Optimizing Pelvic Lymph Node Dissection in Bladder Cancer: Obturator Focus, pN1 Prognosis, and Sentinel Node Feasibility | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Optimizing Pelvic Lymph Node Dissection in Bladder Cancer: Obturator Focus, pN1 Prognosis, and Sentinel Node Feasibility Jun Miki, Shoji Kimura, Fumihiko Urabe, Mahito Atsuta, Kosuke Iwatani, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7458941/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Jan, 2026 Read the published version in International Journal of Clinical Oncology → Version 1 posted 4 You are reading this latest preprint version Abstract Background To determine the optimal extent of pelvic lymph node dissection in bladder cancer, evaluating the prognostic relevance of nodal substaging, and assessing the feasibility of sentinel lymph node biopsy and omission of contralateral dissection. Methods This retrospective study included 180 patients undergoing laparoscopic or robot-assisted radical cystectomy. Sentinel lymph node detection was assessed in 30 cases as a pilot. The obturator region was defined according to lymphatic drainage patterns. The prognostic impact of nodal substaging was evaluated using Kaplan–Meier and Cox proportional hazards models. Laterality of tumor location and node metastasis was also analyzed. Results Sentinel lymph node biopsy demonstrated a 63% detection rate with a 1.6% false-negative rate. nodal metastases were observed in 8.9% of pN1 and 8.3% of pN2–3 cases, predominantly in the obturator region (87.5% and 100%, respectively). Lymph node metastases were most frequently located in the obturator region, including 87.5% of stage pN1 and 100% of stage pN2–3 cases. Cancer-specific survival was significantly better in pN1 than in pN2–3 cases (median 61 vs. 7 months, p < 0.001). Cox proportional hazards regression models identified pN2–3 as the strongest prognostic factor (HR for CSS: 25.4). Ipsilateral nodal metastasis was observed in 87.5% of lateral wall tumors. Conclusions Although sentinel lymph node biopsy demonstrated limited utility, the obturator region appears to represent the optimal diagnostic target for nodal metastasis. In pN1 disease, this region may be therapeutic, resembling sentinel nodes and showing limited spread with better prognosis than pN2-3 disease. Bladder cancer pelvic lymph node dissection nodal substaging sentinel lymph node prognosis Figures Figure 1 Figure 2 Figure 3 Introduction Radical cystectomy (RC) with bilateral PLND is the standard treatment for muscle-invasive bladder cancer (MIBC). PLND is crucial for accurate staging, with lymph node (LN) metastases found in 20–30% of RC cases, and representing a major risk factor for poor oncologic outcomes alongside pathological tumor stage[ 1 ]. Sentinal lymph node (SLN) is a standard alternative to axillary dissection in breast cancer [ 2 ] and is increasingly used in gynecologic cancers, reducing the need for full lymphadenectomy [ 3 ]. In contrast, SLN biopsy is rarely used in bladder cancer[ 4 ]. In the current 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system, nodal substaging is defined by both the number and location of metastatic LNs: pN1 corresponds to a single LN metastasis, pN2 to multiple regional LN metastases, and pN3 to metastasis involving the common iliac LNs[ 5 ]. Although this is conceptually similar to the SLN model, few studies report on their prognostic differences or detailed anatomy[ 6 , 7 ]. Notably, two recent randomized controlled trials (RCTs) found that extended PLND did not improve survival and was associated with increased morbidity[ 8 , 9 ]. Conversely, emerging evidence supporting the use of adjuvant nivolumab therapy[ 10 ] has increased the diagnostic importance of PLND, emphasizing the need to define the optimal extent of this procedure. Analysis of lymphatic drainage patterns and metastatic LN sites in bladder cancer may inform the feasibility of SLN biopsy and the potential omission of unilateral dissection as strategies to minimize the extent of PLND, thereby potentially shortening operative time and reducing complications. We analyzed metastatic LN distribution by lymphatic drainage, assessed prognostic impact of nodal substaging, and explored optimal PLND extent with attention to SLNs and laterality. Patients and Methods Patient cohort This retrospective, single-center study included patients with bladder cancer who underwent laparoscopic RC (LRC) or robot-assisted RC (RARC) with PLND. The type of urinary diversion was determined based on tumor characteristics, patient performance status, and shared decision-making between the patient and the attending physician. Clinical data were collected between April 2014 and February 2025. The following patients were excluded: those with pre-existing distant metastases, those who underwent open RC, those who underwent simultaneous nephroureterectomy, and those who did not undergo PLND. This study was approved by the Institutional Review Board of Jikei University (approval number: 36 − 005[12104]) and adhered to the ethical principles outlined in the Declaration of Helsinki. Lymph node metastasis substaging was conducted according to the 8th edition of the AJCC staging system [ 11 , 5 ]. Survival data were obtained from electronic medical records, including information on diagnosis, neoadjuvant chemotherapy (NAC), age at surgery, follow-up status, cancer recurrence, date of recurrence, date of death, and cause of death, if known. Statistical analysis Continuous variables are presented as medians with interquartile ranges (IQRs). The Mann–Whitney U test was used to compare continuous variables, such as age, while the chi-square test was applied to compare categorical variables, including sex, between groups. Kaplan–Meier curves estimated RFS, CSS, and OS from RC. Log-rank tests compared outcomes by nodal substage. The Kaplan–Meier method was applied to estimate recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) from the date of RC. Log-rank tests compared outcomes by nodal substage. Cox proportional hazards regression analysis was also performed, with independent variables including age, sex[ 12 ], pT stage (≥ pT3)[ 13 ], NAC[ 14 ], LVI[ 15 ], and pN stage[ 16 ]. A p-value of < 0.05 was considered statistically significant. Laterality concordance of LN metastasis was assessed using Cohen’s kappa coefficient, which was interpreted as follows: poor agreement (κ = 0.00–0.40), fair agreement (κ = 0.41–0.75), and excellent agreement (κ = 0.76–1.00).[ 17 ]. Statistical analysis was conducted using SPSS software, version 29.0.2.0 . Imaging with ICG We assessed SLN detection using indocyanine green (ICG) in 30 LRC cases as a pilot. Under general anesthesia, 0.5–1.0 mL of 0.25 mg/mL ICG was injected into the submucosa surrounding the main tumor under cystoscopic guidance. The method for ICG-based SLN identification has been described in our previous reports[ 18 ]. All resected LNs were examined using hematoxylin-eosin and/or immunohistochemical staining. Diagnostic accuracy was assessed on a per-patient basis using identification rate, sensitivity, specificity, and false-negative rates, according to the definitions established in previous systematic reviews[ 19 ]. We also evaluated the proportion of cases in which lymphatic drainage was observed ipsilateral to the tumor, indicating concordant laterality. PLND Our PLND template, which included bilateral obturator, external, internal, and common iliac LNs (Fig. 1 ), was based on vascular landmarks and anatomical membrane structures as proposed by the JSES Working Group[ 20 ] and endorsed by the consensus meeting of the Japanese Society of Endourology and Robotics (JSER) [ 21 ]. The external iliac LN area is bordered cranially by the bifurcation of the common iliac artery, caudally by the deep circumflex iliac vein, laterally by the genitofemoral nerve, medially by the external iliac vein, and dorsally by the external iliac vein and iliopsoas muscle. The common iliac LN area is bordered cranially by the aortic bifurcation, caudally by the bifurcation of the common iliac artery, laterally by the genitofemoral nerve, medially by the inner aspect of the common iliac artery, and dorsally by the iliopsoas muscle and common iliac vein. The internal iliac LN area is bordered cranially by the bifurcation of the common iliac artery, caudally by the inferior vesical vein, laterally by the vesico-hypogastric fascia (located dorsal to the superior vesical artery), medially by the uretero-hypogastric nerve fascia, and dorsally by the internal iliac vessels. The presacral LN area is bordered cranially by the aortic bifurcation, caudally by the level of the common iliac artery bifurcation, laterally by the inner aspect of the common iliac artery, and dorsally by the common iliac vein and sacrum. The obturator LN area is bordered cranially by the bifurcation of the common iliac artery, caudally by the levator ani muscle, laterally by the external iliac vein and pelvic wall, medially by the vesico-hypogastric fascia, and dorsally by the anterior surface of the sacral plexus and the coccygeus muscle (Fig. 1 A and B). In the obturator region, we identified two distinct LN groups, classified according to their anatomical locations and lymphatic drainage patterns.” The first node, previously described, is located between the external and internal iliac vessels and is referred to as the “junctional lymph node” [ 18 ] (Fig. 1 A). The second node, also previously described, is located dorsal to the obturator nerve and lateral to the inferior vesical artery, and is referred to as the “deep obturator lymph node” [ 22 , 23 ] (Fig. 1 B), which was identified as the distal internal iliac node in our previous study[ 18 ]. Results Patient demographics Patient demographics, disease characteristics, and perioperative outcomes are summarized in Table 1 . A total of 236 patients with bladder cancer were identified in this retrospective review. Among these, 17 patients who underwent open RC, 16 patients who did not undergo PLND, and 19 patients who underwent simultaneous nephroureterectomy were excluded. In addition, 4 patients who received adjuvant immuno-oncology therapy were excluded. As a result, 180 patients were included in the statistical analysis, comprising 156 LRC cases (86%) and 24 RARC cases (14%). Of the 180 patients, 149 (82.8%) were classified as pN0, 16 (8.9%) as pN1, and 15 (8.3%) as pN2–3. The median follow-up duration was 44.5 months (range: 15.0–75.0 months). Table 1 Baseline characteristics Characteristic Overall, N = 180 pTanyN0 N = 149 (83%) pTanyN1 N = 16 (9%) pTanyN2-3 N = 15 (8%) p value Median age at radical cystectomy (range), year 71 (45–90) 71 (50–90) 72 (52–88) 75 (45–82) 0.882 Sex, no. (%) Female 32 (17.8) 26 (17.4) 4 (25) 2 (13.3) 0.675 Male 148 (82.2) 123 (82.6) 12 (75) 13 (86.7) ECOG performance status, no. (%) 0 165 (91.7) 139 (93.3) 13 (81.5) 13 (86.7) 0.194 1 15 (8.3) 10 (6.7) 3 (18.5) 2 (13.3) Clinical T stage, no. (%) cTa or cT1 45 (25) 42 (28.2) 2 (12.5) 1 (6.7) 0.008 cT2 88 (49.9) 76 (51) 6 (37.5) 6 (40) cT3 or cT4 47 (26.1) 31 (20.8) 8 (50) 8 (53.3) Clinical N stage, no. (%) cN0 158 (87.7) 135 (90.6) 13 (81.2) 10 (66.7) 0.076 cN1-3 22 (12.3) 14 (9.4) 3 (18.8) 5 (33.3) Surgical approach, no. (%) Laparoscopic 159 (88.3) 130 (87.2) 16 (10) 13 (86.7) 0.313 Robotic 21 (11.7) 19 (12.8) 0 2 (13.3) Number of lymph nodes removed, median (range) 16 (0 − 47) 16 (0–47) 15 (7–32) 16 (7–30) 0.554 Urinary tract diversion, no. (%) Ileal conduit 110 (61.1) 90 (60.4) 13 (81.5) 7 (46.7) 0.07 Orthotopic neobladder 53 (29.4) 46 (30.9) 3 (18.5) 4 (26.7) Other 17 (9.4) 13 (8.7) 0 4 (26.7) Clavien-Dindo complications, no. (%) 0.707 0 111 (61.7) 93 (62.4) 10 (62.5) 8 (53.3) Grade 1,2 43 (23.9) 33 (22.1) 5 (31.3) 5 (33.3) Grade 3–5 26 (14.1) 23 (15.4) 1 (6.3) 2 (13.3) Pathological T stage, no. (%) pTa or cT1 98 (54.4) 94 (63.1) 2 (12.5) 2 (13.3) < 0.001 pT2 26(14.4) 24 (16.1) 2 (12.5) 0 pT3 or pT4 56 (31.2) 31 (20.8) 12 (75) 13 (86.7) Soft-tissue resection margin, no. (%) Negative 178(99.4) 148 (99.9) 16 (100) 14 (93.3) 0.098 Positive 2 (0.6) 1 (0.1) 0 1 (6.7) Lymphovascular invasion, no. (%) No 102 (56.7) 99 (66.4) 3 (18.5) 0 < 0.001 Yes 58 (32.2) 30 (20.1) 13 (81.5) 15 (100) Missing 20 (11.1) 20 (13.4) 0 0 Neoadjuvant chemotherapy, no. (%) No 60 (33.3) 50 (33.6) 6 (37.5) 4 (26.7) 0.807 Yes 120 (66.6) 99 (66.4) 10 (62.5) 11 (73.3) Outcome of SLN detection as a pilot study Outcome of SLN detection as a pilot study The SLN detection rate was 63% (19/30 cases). On a per-lymph node basis, sensitivity, specificity, and false-negative rate were 57% (8/14), 81% (333/408), and 1.6% (6/339), respectively. Ipsilateral SLN-positive findings were obtained in 86.7% of cases (13/15). We have previously reported three representative SLN-related lymphatic drainage patterns in prostate cancer[ 18 ], and similar patterns were identified in bladder cancer as well (Fig. 1 A, B and C). Among these, pattern A was the most common, observed in 78% (15/19), followed by pattern B in 42% (8/19), and pattern C in 15% (3/19). Characteristics of lymph node metastasis LN metastasis was identified in 31 patients (17%), comprising 16 (9%) with pN1, 12 (7%) with pN2, and 3 (1%) with pN3 disease. Characteristics of LN metastases in pN1 and pN2–3 groups are summarized in Table 2 . The median number of LNs removed was 15 (range, 7–32) in pN1 and 16 (range, 7–30) in pN2–3. The median number of positive LNs was 1 in pN1 and 4 (range, 2–21) in pN2–3. In total, 90 positive lymph nodes were identified among the 31 patients with LN metastases, including 16 in the pN1 group and 74 in the pN2–3 group. The most common site of LN metastasis was the obturator region (68.9%), followed by the external iliac (12.2%) and internal iliac regions (8.9%). The predominant site of metastasis per patient was the obturator region in both pN1 (87.5%) and pN2–3 (100%) groups, with the junctional node being the most frequently involved. No significant difference was observed between the pN1 and pN2–3 groups in the distribution of LN metastases (p = 0.456). Table 2 Characteristics of lymph node metastasis Total N = 31 pN1 N = 16 pN2-3 N = 15 p value Number of lymph nodes removed, median (range) 15 (7–32) 15 (7–32) 16 (7–30) 0.973 Number of positive lymph nodes, median (range) 2 (1–21) 1 (1) 4 (2–21) 0.003 Distribution of positive lymph nodes, n (%) 90 16 74 Obturator 62 (68.9) 14 (87.5) 48 (64.9) junctional/ deep obturator/ other 26/13/23 10/4/0 16/9/23 External iliac 11 (12.2) 1 (6.6) 10 (13.5) Internal iliac 8 (8.9) 1 (6.6) 7 (9.5) Common iliac 7 (7.8) 0 7 (9.5) Presacral 2 (2.2) 0 2 (2.7) Distribution of positive lymph nodes per patient, n (%) 31 16 15 Obturator 29 (93.5) 14 (87.5) 15 (100) 0.193 junctional/ deep obturator/ other 25/13/10 10/4/0 15/9/10 External iliac 8 (25.8) 1 (6.3) 7 (46.7) Internal iliac 5 (16.1) 1 (6.3) 4 (26.7) Common iliac 2 (6.5) 0 2 (13.3) Presacral 1 (3.2) 0 1 (6.7) Main tumor location, n (%) Lateral wall 16 (51.6) 9 (56.3) 7 (46.7) 0.862 Trigone, anterior or posterior wall 15 (48.4) 7 (43.7) 8 (53.3) Lymph node metastasis laterality, n (%) Unilateral 26 (83.9) 16 (100) 10 (66.7) 0.042 Bilateral 5 (16.1) 0 5 (33.3) Laterality Among those patients with LN metastases (n = 31), 16 (pN1: n = 9; pN2–3: n = 7) had tumors located in the lateral wall of the bladder, excluding cases of tumors located in the trigone or posterior wall. Of these 16 cases, ipsilateral LN metastasis was observed in 14 (87.5%), comprising 8 cases with pN1 and 6 with pN2–3 (Fig. 2 ). Tumor lateralization in the bladder showed a strong correlation with ipsilateral LN metastasis (Cohen's kappa coefficient, κ = 0.696). An even stronger correlation was observed among the 9 cases with pN1; laterality matched in 8 cases (88.9%) and the Cohen's kappa coefficient was 0.727. Survival in sub-stage of lymph node metastasis During the follow-up period, 64 patients (35%) experienced disease recurrence. A total of 49 patients (27.2%) died, with 36 of those deaths (20%) attributed to bladder cancer. Kaplan–Meier analysis revealed significant differences in RFS among pN0, pN1, and pN2–3 groups, with median RFS times of 44 months (95% confidence interval [CI], 28.8–59.1), 23 months (95% CI, 12.4–52.1), and 4 months (95% CI, 2.8–5.2), respectively (global p < 0.001) (Fig. 3 A). The CSS was 127 months (95% CI, 119.8–135.2) for pN0 patients, 61 months (95% CI, 41.3–80.4) for pN1 patients, and 7 months (95% CI, 3.2–10.7) for pN2–3 patients (global p < 0.001) (Fig. 3 B). The median OS differed significantly among groups: 115 months (95% CI, 106.4–125.1) for pN0 patients, 61 months (95% CI, 26.1–95.8) for pN1 patients, and 7 months (95% CI, 3.3–10.7) for pN2–3 patients (global p < 0.001) (Fig. 3 C). The results of the Cox proportional hazards regression models for oncological outcomes are presented in Table 3 . Female sex was significantly associated with worse CSS (hazard ratio [HR]: 1.75, p = 0.018). A higher pathological T stage (pT ≥ 3) was associated with an increased risk of RFS (HR: 2.49, p = 0.016), but showed no significant association with CSS or OS. Notably, pN2–3 was strongly associated with worse RFS (HR: 4.73, p = 0.001), CSS (HR: 25.4, p < 0.001), and OS (HR: 9.94, p < 0.001), whereas pN1 was not significantly associated with any of these outcomes. Age, LVI, and receipt of NAC were not significantly associated with oncological outcomes. Table 3 Cox proportional hazards regression models for oncological outcomes RFS CSS OS Covariant Reference HR 95% CI p value HR 95% CI p value HR 95% CI p value Age (continuous) 1.04 0.99–1.08 0.078 1.01 0.96–1.07 0.66 1.03 0.99–1.08 0.16 Sex Female 1.32 0.89–1.99 0.17 1.75 1.1–2.78 0.018 1.27 0.84–1.94 0.26 Pathological T stage pT ≥ 3 ≤pT2 2.49 1.19–5.21 0.016 1.2 0.45–3.18 0.71 1.57 0.68–3.61 0.29 Pathological N stage pN1 pN0 1.27 0.51–3.16 0.6 2.77 0.84–9.11 0.095 1.75 0.63–4.89 0.28 pN2-3 pN0 5.16 1.93–13.74 0.001 25.4 8.43–76.4 < 0.001 9.94 3.77–26.2 < 0.001 LVI LVI (+) LVI (-) 0.94 0.47–1.89 0.87 1.09 0.42–2.8 0.86 0.96 0.466–1.993 0.92 Neoadjuvant chemotherapy Present Absent 1.29 0.62–2.68 0.49 1.56 0.57–4.26 0.39 1.17 0.549–2.494 0.69 HR: hazard ratio; RFS: recurrence-free survival; CSS: cancer-specific survival; OS: overall survival Discussion In this study, we examined the distribution of metastatic LNs based on lymphatic drainage patterns, evaluated the prognostic impact of nodal substaging on survival, and explored the optimal extent of PLND, including considerations of SLNs and laterality in patients treated with radical cystectomy. Our results demonstrated that the obturator region – including the SLNs, as defined by lymphatic drainage patterns – has high diagnostic value for detecting LN metastases in both pN1 and pN2–3 stages. Dissection of this region showed consistently high diagnostic utility and may also provide therapeutic benefit, particularly in patients with pN1 disease, who exhibited significantly better oncological outcomes than those with pN2–3 involvement. Although the anatomical boundaries of PLND, particularly between the obturator and internal iliac regions, have historically been poorly defined, our study was able to clearly delineate them based on lymphatic drainage patterns. Our findings are consistent with prior reports emphasizing the obturator fossa as a predominant site of nodal metastasis in MIBC[ 22 , 24 ]. Notably, our study extends previous anatomical work by incorporating the deep obturator nodes—previously described as internal iliac nodes[ 23 , 22 ]—into the obturator region definition. Because LN metastases in bladder cancer are subclassified into pN1 and pN2–3 stages according to the AJCC 8th edition[ 5 , 11 ], our analysis indicates that patients with pN1 disease have a more favorable prognosis than those with pN2–3 disease, with pN2–3 serving as an independent adverse prognostic factor. Importantly, prior research has not extensively examined the relationship between these nodal substages and the specific anatomical locations of LN metastases. While a few previous studies on SLN biopsy in MIBC have reported high detection rates and sensitivity, the adoption of this procedure in clinical practice has remained limited[ 4 ]. The detection rate in our study was not particularly high, but we achieved a low false-negative rate and successfully identified characteristic pelvic lymphatic drainage patterns. Other researchers have identified several major pelvic lymphatic pathways[ 25 ], and we have reported separately that SLNs are located in close proximity to the prostate based on lymphatic mapping using ICG[ 18 ]. Notably, our findings showed three distinct lymphatic drainage pathways in the bladder, as well. Our definition of the obturator region encompasses both the junctional SLN—recognized as the most frequent metastatic site within the conventional obturator fossa—and the deep obturator SLN, which includes the space dorsal to the obturator nerve, previously referred to as the distal internal iliac nodes located around the inferior vesical artery in our study[ 18 ]. This broader and deeper interpretation of the obturator region has already been proposed as the standard obturator region by the JSES Working Group—a multidisciplinary consortium of gastrointestinal surgeons, urologists, and gynecologists in Japan[ 20 ]. In addition to the obturator region, the extent of PLND used in this study—based on the definitions established at the consensus meeting of the JSER—also included the common iliac, external iliac, internal iliac, and presacral areas, as determined by vascular landmarks and anatomical membrane structures[ 21 ]. Although the internal iliac region has traditionally been broadly defined as the area along the internal iliac vessels, [ 26 ], in this classification, it is clearly defined as the area medial to the internal iliac artery. These anatomical subdivisions not only clarified the previously complex boundary between the obturator and internal iliac regions, but also enabled the integration of the frequently metastatic obturator fossa and deep obturator lymph nodes—both considered SLNs—into a single obturator region. In the 8th edition of the AJCC staging system, nodal classification shifted from Stage IV to Stage III, and substaging was refined based on the number and location of LN metastases (pN1: single regional node; pN2: multiple regional nodes; pN3: common iliac involvement)[ 5 , 11 ]. This shift reflects the growing recognition that not all nodal metastases carry the same prognostic weight. Indeed, while the overall prognosis of nodal disease remains poor, emerging evidence—including findings from Hara et al.[ 6 ] and our current study—suggests that pN1 disease may represent a biologically and clinically distinct subset. Our long-term follow-up data revealed that patients with pN1 disease had a 40% long-term cancer-specific or overall survival, whereas those with pN2–3 involvement fared significantly worse. These findings suggest that pN1 nodes and SLNs share common features both anatomically and oncologically. This implies that lymphatic spread in pN1 disease may be more localized and amenable to therapeutic intervention via PLND, whereas pN2–3 disease likely reflects more extensive systemic dissemination with limited potential benefit from local surgical control alone. Previous mapping studies have supported the traditional emphasis on bilateral PLND[ 26 ]. However, studies using radioactive tracers injected into the non-tumor lateral bladder wall have shown minimal or no drainage to contralateral nodes[ 27 ], findings consistent with our ICG-based observations. Gurwin et al. also reported an 80% concordance rate for ipsilateral LN metastasis in lateral wall tumors, although they emphasized the need for contralateral PLND to avoid missing the remaining 20%[ 28 ]. In clinical practice, PLND is often omitted; population-based data from the United States indicated that this procedure was omitted in approximately 20% of all cases during the 2010s[ 29 ]. Given the increased risk of complications and the limited therapeutic benefit of PLND in certain cases[ 9 ], we believe that omitting contralateral PLND may be acceptable in carefully selected patients—particularly elderly individuals or those with comorbidities for whom adjuvant therapy is less feasible. Notably, two recent randomized controlled trials failed to demonstrate a survival benefit from extended PLND in patients with MIBC[ 8 , 9 ], raising doubts about the therapeutic value of extensive dissection. Meanwhile, the diagnostic role of PLND has gained renewed importance, particularly given the proven efficacy of adjuvant nivolumab in high-risk urothelial carcinoma, with especially favorable outcomes among patients with nodal metastases[ 10 , 30 ]. Our results suggest that, in patients with pN1 disease, comprehensive dissection of the obturator region may provide therapeutic benefit, and in both pN1 and pN2 cases, it may aid in identifying candidates for adjuvant immunotherapy. The present study contributes to the growing body of evidence supporting lymphatic anatomy-guided PLND and offers a template for future prospective trials to validate selective dissection strategies. This study has several limitations. The retrospective design introduces potential selection bias, and the single-institution setting may limit external validity. Although we excluded patients who were receiving adjuvant therapy, variations in post-recurrence management could have influenced long-term outcomes. Additionally, the relatively modest sample size may underpower subgroup analyses, and the applicability of our lymphatic mapping findings to non-lateral wall tumors requires further investigation. Conclusion Our findings demonstrate that the obturator region, as defined by lymphatic drainage anatomy, is a highly relevant target for PLND in bladder cancer, and that dissection of this anatomically guided region can yield crucial diagnostic value. In pN1 disease, this region offers potential therapeutic benefit, as it shares key features with SLNs and appears to represent a biologically and clinically distinct subset with more localized spread and better prognosis than pN2–3. Declarations Acknowledgments The authors express their gratitude for the expert English language editing provided by Lee Seaman of Seaman Medical, Inc., Bellingham WA, USA. Conflicts of Interest Takahiro Kimura has received honoraria from Astellas, AstraZeneca, Bayer, Janssen, Sanofi, and Takeda. Data Availability Statement The data supporting the findings of this study are available upon reasonable request from the corresponding author. Ethics Approval The institutional review board approved the study protocol 36-005[12104]. Study Registration Not applicable. Animal Studies Not applicable. Funding : none Author Contributions: Project development: J Miki Data collection: Data analysis: J Miki Manuscript writing/editing: J Miki References Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, Skinner E, Bochner B, Thangathurai D, Mikhail M, Raghavan D, Skinner DG (2001) Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 19(3):666–675. 10.1200/jco.2001.19.3.666 Krag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Costantino JP, Ashikaga T, Weaver DL, Mamounas EP, Jalovec LM, Frazier TG, Noyes RD, Robidoux A, Scarth HM, Wolmark N (2010) Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol 11(10):927–933. 10.1016/s1470-2045(10)70207-2 Kanbergs A, Melamed A, Viveros-Carreño D, Wu CF, Wilke RN, Zamorano A, Paladugu K, Havrilesky L, Rauh-Hain JA, Agusti N (2025) Surgical Deescalation Within Gynecologic Oncology. JAMA Netw Open 8(1):e2453604. 10.1001/jamanetworkopen.2024.53604 Zarifmahmoudi L, Ghorbani H, Sadri K, Tavakkoli M, Keshvari M, Salehi M, Sadeghi R (2019) Sentinel Node Biopsy in Urothelial Carcinoma of the Bladder: Systematic Review and Meta-Analysis. Urol Int 103(4):373–382. 10.1159/000497310 Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR, Winchester DP (2017) The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more personalized approach to cancer staging. CA Cancer J Clin 67(2):93–99. 10.3322/caac.21388 Hara S, Fukuokaya W, Miki J, Taoka R, Saito R, Matsui Y, Hatakeyama S, Kawahara T, Matsuda A, Kawai T, Kato M, Sazuka T, Sano T, Urabe F, Kashima S, Naito H, Murakami Y, Miyake M, Daizumoto K, Matsushita Y, Hayashi T, Inokuchi J, Sugino Y, Shiga K, Yamaguchi N, Yamamoto S, Yasue K, Abe T, Nakanishi S, Hashine K, Fujii M, Nishihara K, Matsumoto H, Tatarano S, Wada K, Sekito S, Maruyama R, Nishiyama N, Nishiyama H, Kitamura H, Kimura T (2025) Stage III substaging and outcomes in patients with bladder cancer undergoing radical cystectomy. Int J urology: official J Japanese Urol Association. 10.1111/iju.70005 Abdel-Rahman O (2017) Validation of the Eighth AJCC New Substages for Bladder Cancer Among Different Staging Contexts. Clin Genitourin Cancer 15(6):e1095–e1106. 10.1016/j.clgc.2017.07.025 Gschwend JE, Heck MM, Lehmann J, Rübben H, Albers P, Wolff JM, Frohneberg D, de Geeter P, Heidenreich A, Kälble T, Stöckle M, Schnöller T, Stenzl A, Müller M, Truss M, Roth S, Liehr UB, Leißner J, Bregenzer T, Retz M (2019) Extended Versus Limited Lymph Node Dissection in Bladder Cancer Patients Undergoing Radical Cystectomy: Survival Results from a Prospective, Randomized Trial. Eur Urol 75(4):604–611. 10.1016/j.eururo.2018.09.047 Lerner SP, Tangen C, Svatek RS, Daneshmand S, Pohar KS, Skinner E, Schuckman A, Sagalowsky AI, Smith ND, Kamat AM, Kassouf W, Plets M, Bangs R, Koppie TM, Alva A, La Rosa FG, Pal SK, Kibel AS, Canter DJ, Thompson IM Jr (2024) Standard or Extended Lymphadenectomy for Muscle-Invasive Bladder Cancer. N Engl J Med 391(13):1206–1216. 10.1056/NEJMoa2401497 Bajorin DF, Witjes JA, Gschwend JE, Schenker M, Valderrama BP, Tomita Y, Bamias A, Lebret T, Shariat SF, Park SH, Ye D, Agerbaek M, Enting D, McDermott R, Gajate P, Peer A, Milowsky MI, Nosov A, Neif Antonio J Jr., Tupikowski K, Toms L, Fischer BS, Qureshi A, Collette S, Unsal-Kacmaz K, Broughton E, Zardavas D, Koon HB, Galsky MD (2021) Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med 384(22):2102–2114. 10.1056/NEJMoa2034442 Paner GP, Stadler WM, Hansel DE, Montironi R, Lin DW, Amin MB (2018) Updates in the Eighth Edition of the Tumor-Node-Metastasis Staging Classification for Urologic Cancers. Eur Urol 73(4):560–569. 10.1016/j.eururo.2017.12.018 Kluth LA, Rieken M, Xylinas E, Kent M, Rink M, Rouprêt M, Sharifi N, Jamzadeh A, Kassouf W, Kaushik D, Boorjian SA, Roghmann F, Noldus J, Masson-Lecomte A, Vordos D, Ikeda M, Matsumoto K, Hagiwara M, Kikuchi E, Fradet Y, Izawa J, Rendon R, Fairey A, Lotan Y, Bachmann A, Zerbib M, Fisch M, Scherr DS, Vickers A, Shariat SF (2014) Gender-specific differences in clinicopathologic outcomes following radical cystectomy: an international multi-institutional study of more than 8000 patients. Eur Urol 66(5):913–919. 10.1016/j.eururo.2013.11.040 Drakaki A, Pantuck A, Mhatre SK, Dhillon PK, Davarpanah N, Degaonkar V, Surinach A, Chamie K, Grivas P (2021) Real-world outcomes and prognostic indicators among patients with high-risk muscle-invasive urothelial carcinoma. Urol Oncol 39(1):76. .e15-76.e22 Xia L, Dadabhoy A, Wood EL, Mehta SV, Roberson DS, Guzzo TJ, Bivalacqua TJ, Daneshmand S (2024) Pathologic and survival outcomes following radical cystectomy for progressive and de novo muscle-invasive bladder cancer: A meta-analysis stratified by neoadjuvant chemotherapy status. Urol Oncol 42(10):333. .e331-333.e313 Mari A, Kimura S, Foerster B, Abufaraj M, D'Andrea D, Gust KM, Shariat SF (2018) A systematic review and meta-analysis of lymphovascular invasion in patients treated with radical cystectomy for bladder cancer. Urol Oncol 36(6):293–305. 10.1016/j.urolonc.2018.03.018 Ghoneim MA, Abdel-Latif M, el-Mekresh M, Abol-Enein H, Mosbah A, Ashamallah A, el-Baz MA (2008) Radical cystectomy for carcinoma of the bladder: 2,720 consecutive cases 5 years later. J Urol 180(1):121–127. 10.1016/j.juro.2008.03.024 Landis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33(1):159–174 Miki J, Yanagisawa T, Tsuzuki S, Mori K, Urabe F, Kayano S, Yorozu T, Sato S, Kimura T, Takahashi H, Kishimoto K, Egawa S (2018) Anatomical localization and clinical impact of sentinel lymph nodes based on patterns of pelvic lymphatic drainage in clinically localized prostate cancer. Prostate 78(6):419–425. 10.1002/pros.23486 Wit EMK, Acar C, Grivas N, Yuan C, Horenblas S, Liedberg F, Valdes Olmos RA, van Leeuwen FWB, van den Berg NS, Winter A, Wawroschek F, Hruby S, Janetschek G, Vidal-Sicart S, MacLennan S, Lam TB, van der Poel HG (2017) Sentinel Node Procedure in Prostate Cancer: A Systematic Review to Assess Diagnostic Accuracy. Eur Urol 71(4):596–605. 10.1016/j.eururo.2016.09.007 Takemasa I, Hamabe A, Takenaka A, Kobayashi H, Mandai M, Kinugasa Y, Saika T, Shimbo M, Morizane S, Sekiyama K, Togami S, Hanaoka M, Inoue S, Nagaishi K, Sakai Y, Watanabe M (2024) Standardization of robot-assisted pelvic lymph node dissection-Development of a common understanding of regional anatomy and surgical technique based on cross-disciplinary discussion among colorectal surgery, urology, and gynecology. Asian J Endosc Surg 17(1):e13274. 10.1111/ases.13274 Morizane S, Miki J, Shimbo M, Kanno T, Miura N, Yamada Y, Yamasaki T, Saika T, Takenaka A (2024) Japanese expert consensus on the standardization of robot-assisted pelvic lymph node dissection in urological surgery: Extent of pelvic lymph node and surgical technique. Int J urology: official J Japanese Urol Association. 10.1111/iju.15563 Leissner J, Ghoneim MA, Abol-Enein H, Thüroff JW, Franzaring L, Fisch M, Schulze H, Managadze G, Allhoff EP, el-Baz MA, Kastendieck H, Buhtz P, Kropf S, Hohenfellner R, Wolf HK (2004) Extended radical lymphadenectomy in patients with urothelial bladder cancer: results of a prospective multicenter study. J Urol 171(1):139–144. 10.1097/01.ju.0000102302.26806.fb Dangle PP, Gong MC, Bahnson RR, Pohar KS (2010) How do commonly performed lymphadenectomy templates influence bladder cancer nodal stage? J Urol 183(2):499–503. 10.1016/j.juro.2009.09.080 Perera M, McGrath S, Sengupta S, Crozier J, Bolton D, Lawrentschuk N (2018) Pelvic lymph node dissection during radical cystectomy for muscle-invasive bladder cancer. Nat Rev Urol 15(11):686–692. 10.1038/s41585-018-0066-1 Pedersen CK, Babu AS (2021) Understanding the Lymphatics: An Updated Review of the N Category of the AJCC 8th Edition for Urogenital Cancers. AJR Am J Roentgenol 217(2):368–377. 10.2214/ajr.20.22997 Roth B, Wissmeyer MP, Zehnder P, Birkhäuser FD, Thalmann GN, Krause TM, Studer UE (2010) A new multimodality technique accurately maps the primary lymphatic landing sites of the bladder. Eur Urol 57(2):205–211. 10.1016/j.eururo.2009.10.026 Roth B, Zehnder P, Birkhäuser FD, Burkhard FC, Thalmann GN, Studer UE (2012) Is bilateral extended pelvic lymphadenectomy necessary for strictly unilateral invasive bladder cancer? J Urol 187(5):1577–1582. 10.1016/j.juro.2011.12.106 Gurwin A, Karwacki J, Dorochowicz M, Kowalczyk K, Nowak Ł, Jędrzejuk D, Krajewski W, Hałoń A, Bolanowski M, Szydełko T, Małkiewicz B (2024) Topography and Lateralization of Nodal Metastases in Muscle-Invasive Bladder Cancer Using Super-Extended Pelvic Lymph Node Dissection with the Sentinel Lymph Node Technique. J Clin Med 13(17). 10.3390/jcm13175127 Sodagum L, Passarelli R, Pfail J, Patel HV, Chua K, Doppalapudi SK, Golombos D, Elsamra SE, Singer EA, Jang TL, Srivastava A, Ghodoussipour S (2024) Pelvic lymphadenectomy: Evaluating nodal stage migration and will rogers effect in bladder cancer. Urol Oncol 42(1):21. .e29-21.e20 Galsky MD, Witjes JA, Gschwend JE, Milowsky MI, Schenker M, Valderrama BP, Tomita Y, Bamias A, Lebret T, Shariat SF, Park SH, Agerbaek M, Jha G, Stenner F, Ye D, Giudici F, Dutta S, Askelson M, Nasroulah F, Zhang J, Brophy L, Bajorin DF (2025) Adjuvant Nivolumab in High-Risk Muscle-Invasive Urothelial Carcinoma: Expanded Efficacy From CheckMate 274. J Clin Oncol 43(1):15–21. 10.1200/jco.24.00340 Cite Share Download PDF Status: Published Journal Publication published 27 Jan, 2026 Read the published version in International Journal of Clinical Oncology → Version 1 posted Reviewers agreed at journal 02 Sep, 2025 Reviewers invited by journal 02 Sep, 2025 Editor assigned by journal 26 Aug, 2025 First submitted to journal 25 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7458941","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":508889234,"identity":"414f4190-ad20-4ae3-bd16-5913e21718a7","order_by":0,"name":"Jun Miki","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIiWNgGAWjYBACxgYgkXBAgoGxmQ3IqADymJkbSNFyBqSFEb8WCDgAIoBaGNvgxuAGzDNyj254cMaCgbmdLfHBw3m10fztQC0/KrbhdtiMvLQbCTfADjtskLjteO6Mw4wNjD1nbuPRkmN2I+EDSAt7m0TitmO5DUAtzIxtxGlp/5E451jufOK0QBx2jCGxoSZ3A0EtPW+AWs5I8AC1JEskHDuQuxGo5SA+vxi255jd/HGsTs6w/5jhxx81dbnzzh8++OBHBR4tDRCaB8o4DCYP4FQPBPJojDp8ikfBKBgFo2CEAgAZc171QMzgUwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-4638-8640","institution":"The Jikei University Kashiwa Hospital: Tokyo Jikeikai Ika Daigaku Fuzoku Kashiwa Byoin","correspondingAuthor":true,"prefix":"","firstName":"Jun","middleName":"","lastName":"Miki","suffix":""},{"id":508889235,"identity":"af6a235f-455f-4915-b730-b60fdf2e0332","order_by":1,"name":"Shoji Kimura","email":"","orcid":"","institution":"Toneri Urology Clinic","correspondingAuthor":false,"prefix":"","firstName":"Shoji","middleName":"","lastName":"Kimura","suffix":""},{"id":508889236,"identity":"bb322e09-5b43-471a-9e96-e27678a20a25","order_by":2,"name":"Fumihiko Urabe","email":"","orcid":"","institution":"Jikei University School of Medicine: Tokyo Jikeikai Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Fumihiko","middleName":"","lastName":"Urabe","suffix":""},{"id":508889237,"identity":"8004590d-413b-4256-9a98-49ed7fc1d087","order_by":3,"name":"Mahito Atsuta","email":"","orcid":"","institution":"The Jikei University Kashiwa Hospital: Tokyo Jikeikai Ika Daigaku Fuzoku Kashiwa Byoin","correspondingAuthor":false,"prefix":"","firstName":"Mahito","middleName":"","lastName":"Atsuta","suffix":""},{"id":508889238,"identity":"9f2bc58f-eab8-48ae-913e-9e783bfd9050","order_by":4,"name":"Kosuke Iwatani","email":"","orcid":"","institution":"The Jikei University Kashiwa Hospital: Tokyo Jikeikai Ika Daigaku Fuzoku Kashiwa Byoin","correspondingAuthor":false,"prefix":"","firstName":"Kosuke","middleName":"","lastName":"Iwatani","suffix":""},{"id":508889239,"identity":"9d223652-cb17-4321-9610-464ef8f2cfdc","order_by":5,"name":"Kazuhiro Takahashi","email":"","orcid":"","institution":"The Jikei University Kashiwa Hospital: Tokyo Jikeikai Ika Daigaku Fuzoku Kashiwa Byoin","correspondingAuthor":false,"prefix":"","firstName":"Kazuhiro","middleName":"","lastName":"Takahashi","suffix":""},{"id":508889240,"identity":"4e514140-7d05-44b1-9442-03fa2fecce15","order_by":6,"name":"Naoki Uchida","email":"","orcid":"","institution":"Jikei University School of Medicine: Tokyo Jikeikai Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Naoki","middleName":"","lastName":"Uchida","suffix":""},{"id":508889241,"identity":"c1891c9c-eafe-4ac1-8963-0c10b92e8bde","order_by":7,"name":"Hirokazu Kagawa","email":"","orcid":"","institution":"Jikei University School of Medicine: Tokyo Jikeikai Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Hirokazu","middleName":"","lastName":"Kagawa","suffix":""},{"id":508889242,"identity":"02025e5c-f5a2-4acb-b60a-abe05844ded4","order_by":8,"name":"Naoya Tomomasa","email":"","orcid":"","institution":"Jikei University School of Medicine: Tokyo Jikeikai Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Naoya","middleName":"","lastName":"Tomomasa","suffix":""},{"id":508889243,"identity":"b62db6c4-abf1-4768-bb5d-485109f29aeb","order_by":9,"name":"Shun Saito","email":"","orcid":"","institution":"Jikei University School of Medicine: Tokyo Jikeikai Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Shun","middleName":"","lastName":"Saito","suffix":""},{"id":508889244,"identity":"6e851d9c-3f80-4147-bf82-f601fd718993","order_by":10,"name":"Wataru Fukuokaya","email":"","orcid":"","institution":"Jikei University School of Medicine: Tokyo Jikeikai Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Wataru","middleName":"","lastName":"Fukuokaya","suffix":""},{"id":508889245,"identity":"a8496051-0113-49aa-b50b-76cacf44898d","order_by":11,"name":"Akihiro Matsukawa","email":"","orcid":"","institution":"Jikei University School of Medicine: Tokyo Jikeikai Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Akihiro","middleName":"","lastName":"Matsukawa","suffix":""},{"id":508889246,"identity":"79fa3196-1ca6-44f1-aebf-b25a1b3df1e4","order_by":12,"name":"Keiichiro Mori","email":"","orcid":"","institution":"Jikei University School of Medicine: Tokyo Jikeikai Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Keiichiro","middleName":"","lastName":"Mori","suffix":""},{"id":508889247,"identity":"80c22546-979c-4063-bbaa-d8b7417e0004","order_by":13,"name":"Takafumi Yanagisawa","email":"","orcid":"","institution":"Jikei University School of Medicine: Tokyo Jikeikai Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Takafumi","middleName":"","lastName":"Yanagisawa","suffix":""},{"id":508889248,"identity":"036e5c82-ac30-4f49-b16c-c24b530c9ebc","order_by":14,"name":"Shunsuke Tsuzuki","email":"","orcid":"","institution":"Jikei University School of Medicine: Tokyo Jikeikai Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Shunsuke","middleName":"","lastName":"Tsuzuki","suffix":""},{"id":508889249,"identity":"07ea4014-9afd-4f54-8c8b-3f6af5e5a5ee","order_by":15,"name":"Takahiro Kimura","email":"","orcid":"","institution":"Jikei University School of Medicine: Tokyo Jikeikai Ika Daigaku","correspondingAuthor":false,"prefix":"","firstName":"Takahiro","middleName":"","lastName":"Kimura","suffix":""}],"badges":[],"createdAt":"2025-08-26 05:33:52","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7458941/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7458941/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10147-026-02969-5","type":"published","date":"2026-01-27T15:59:16+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":90899657,"identity":"511a8ea2-2b2e-44f7-8cd3-bd53ac05bd5a","added_by":"auto","created_at":"2025-09-09 12:02:25","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":141849,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Slide1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7458941/v1/d872ac44aee83c2c57943333.jpg"},{"id":90900836,"identity":"59a509fa-5282-4726-bcec-6273524254fd","added_by":"auto","created_at":"2025-09-09 12:10:25","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":95311,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Slide2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7458941/v1/1e33bc3a27ba403727782e70.jpg"},{"id":90899660,"identity":"cc147399-43e3-4ba3-818d-1a2aaca90194","added_by":"auto","created_at":"2025-09-09 12:02:25","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":74154,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Slide3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7458941/v1/70dc74ecb8ad020e05e08c1b.jpg"},{"id":101691848,"identity":"d39009f4-9622-43c7-85c5-400f418769ec","added_by":"auto","created_at":"2026-02-02 16:15:30","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1359550,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7458941/v1/563c296d-4a3c-418e-bce5-7308466c4b64.pdf"}],"financialInterests":"","formattedTitle":"Optimizing Pelvic Lymph Node Dissection in Bladder Cancer: Obturator Focus, pN1 Prognosis, and Sentinel Node Feasibility","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRadical cystectomy (RC) with bilateral PLND is the standard treatment for muscle-invasive bladder cancer (MIBC). PLND is crucial for accurate staging, with lymph node (LN) metastases found in 20\u0026ndash;30% of RC cases, and representing a major risk factor for poor oncologic outcomes alongside pathological tumor stage[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSentinal lymph node (SLN) is a standard alternative to axillary dissection in breast cancer [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] and is increasingly used in gynecologic cancers, reducing the need for full lymphadenectomy [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In contrast, SLN biopsy is rarely used in bladder cancer[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn the current 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system, nodal substaging is defined by both the number and location of metastatic LNs: pN1 corresponds to a single LN metastasis, pN2 to multiple regional LN metastases, and pN3 to metastasis involving the common iliac LNs[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Although this is conceptually similar to the SLN model, few studies report on their prognostic differences or detailed anatomy[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eNotably, two recent randomized controlled trials (RCTs) found that extended PLND did not improve survival and was associated with increased morbidity[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Conversely, emerging evidence supporting the use of adjuvant nivolumab therapy[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] has increased the diagnostic importance of PLND, emphasizing the need to define the optimal extent of this procedure. Analysis of lymphatic drainage patterns and metastatic LN sites in bladder cancer may inform the feasibility of SLN biopsy and the potential omission of unilateral dissection as strategies to minimize the extent of PLND, thereby potentially shortening operative time and reducing complications.\u003c/p\u003e\u003cp\u003eWe analyzed metastatic LN distribution by lymphatic drainage, assessed prognostic impact of nodal substaging, and explored optimal PLND extent with attention to SLNs and laterality.\u003c/p\u003e"},{"header":"Patients and Methods","content":"\u003cp\u003ePatient cohort\u003c/p\u003e\u003cp\u003eThis retrospective, single-center study included patients with bladder cancer who underwent laparoscopic RC (LRC) or robot-assisted RC (RARC) with PLND. The type of urinary diversion was determined based on tumor characteristics, patient performance status, and shared decision-making between the patient and the attending physician. Clinical data were collected between April 2014 and February 2025. The following patients were excluded: those with pre-existing distant metastases, those who underwent open RC, those who underwent simultaneous nephroureterectomy, and those who did not undergo PLND. This study was approved by the Institutional Review Board of Jikei University (approval number: 36\u0026thinsp;\u0026minus;\u0026thinsp;005[12104]) and adhered to the ethical principles outlined in the Declaration of Helsinki.\u003c/p\u003e\u003cp\u003eLymph node metastasis substaging was conducted according to the 8th edition of the AJCC staging system [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSurvival data were obtained from electronic medical records, including information on diagnosis, neoadjuvant chemotherapy (NAC), age at surgery, follow-up status, cancer recurrence, date of recurrence, date of death, and cause of death, if known.\u003c/p\u003e\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eContinuous variables are presented as medians with interquartile ranges (IQRs). The Mann\u0026ndash;Whitney U test was used to compare continuous variables, such as age, while the chi-square test was applied to compare categorical variables, including sex, between groups.\u003c/p\u003e\u003cp\u003eKaplan\u0026ndash;Meier curves estimated RFS, CSS, and OS from RC. Log-rank tests compared outcomes by nodal substage. The Kaplan\u0026ndash;Meier method was applied to estimate recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) from the date of RC. Log-rank tests compared outcomes by nodal substage. Cox proportional hazards regression analysis was also performed, with independent variables including age, sex[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], pT stage (\u0026ge;\u0026thinsp;pT3)[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], NAC[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], LVI[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], and pN stage[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eA p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant. Laterality concordance of LN metastasis was assessed using Cohen\u0026rsquo;s kappa coefficient, which was interpreted as follows: poor agreement (κ\u0026thinsp;=\u0026thinsp;0.00\u0026ndash;0.40), fair agreement (κ\u0026thinsp;=\u0026thinsp;0.41\u0026ndash;0.75), and excellent agreement (κ\u0026thinsp;=\u0026thinsp;0.76\u0026ndash;1.00).[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eStatistical analysis was conducted using SPSS software, version 29.0.2.0 .\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eImaging with ICG\u003c/h2\u003e\u003cp\u003eWe assessed SLN detection using indocyanine green (ICG) in 30 LRC cases as a pilot. Under general anesthesia, 0.5\u0026ndash;1.0 mL of 0.25 mg/mL ICG was injected into the submucosa surrounding the main tumor under cystoscopic guidance. The method for ICG-based SLN identification has been described in our previous reports[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. All resected LNs were examined using hematoxylin-eosin and/or immunohistochemical staining. Diagnostic accuracy was assessed on a per-patient basis using identification rate, sensitivity, specificity, and false-negative rates, according to the definitions established in previous systematic reviews[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. We also evaluated the proportion of cases in which lymphatic drainage was observed ipsilateral to the tumor, indicating concordant laterality.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003ePLND\u003c/h3\u003e\n\u003cp\u003eOur PLND template, which included bilateral obturator, external, internal, and common iliac LNs (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), was based on vascular landmarks and anatomical membrane structures as proposed by the JSES Working Group[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] and endorsed by the consensus meeting of the Japanese Society of Endourology and Robotics (JSER) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe external iliac LN area is bordered cranially by the bifurcation of the common iliac artery, caudally by the deep circumflex iliac vein, laterally by the genitofemoral nerve, medially by the external iliac vein, and dorsally by the external iliac vein and iliopsoas muscle. The common iliac LN area is bordered cranially by the aortic bifurcation, caudally by the bifurcation of the common iliac artery, laterally by the genitofemoral nerve, medially by the inner aspect of the common iliac artery, and dorsally by the iliopsoas muscle and common iliac vein. The internal iliac LN area is bordered cranially by the bifurcation of the common iliac artery, caudally by the inferior vesical vein, laterally by the vesico-hypogastric fascia (located dorsal to the superior vesical artery), medially by the uretero-hypogastric nerve fascia, and dorsally by the internal iliac vessels. The presacral LN area is bordered cranially by the aortic bifurcation, caudally by the level of the common iliac artery bifurcation, laterally by the inner aspect of the common iliac artery, and dorsally by the common iliac vein and sacrum. The obturator LN area is bordered cranially by the bifurcation of the common iliac artery, caudally by the levator ani muscle, laterally by the external iliac vein and pelvic wall, medially by the vesico-hypogastric fascia, and dorsally by the anterior surface of the sacral plexus and the coccygeus muscle (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA and B). In the obturator region, we identified two distinct LN groups, classified according to their anatomical locations and lymphatic drainage patterns.\u0026rdquo; The first node, previously described, is located between the external and internal iliac vessels and is referred to as the \u0026ldquo;junctional lymph node\u0026rdquo; [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). The second node, also previously described, is located dorsal to the obturator nerve and lateral to the inferior vesical artery, and is referred to as the \u0026ldquo;deep obturator lymph node\u0026rdquo; [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB), which was identified as the distal internal iliac node in our previous study[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003ePatient demographics\u003c/h2\u003e\u003cp\u003ePatient demographics, disease characteristics, and perioperative outcomes are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. A total of 236 patients with bladder cancer were identified in this retrospective review. Among these, 17 patients who underwent open RC, 16 patients who did not undergo PLND, and 19 patients who underwent simultaneous nephroureterectomy were excluded. In addition, 4 patients who received adjuvant immuno-oncology therapy were excluded. As a result, 180 patients were included in the statistical analysis, comprising 156 LRC cases (86%) and 24 RARC cases (14%). Of the 180 patients, 149 (82.8%) were classified as pN0, 16 (8.9%) as pN1, and 15 (8.3%) as pN2\u0026ndash;3. The median follow-up duration was 44.5 months (range: 15.0\u0026ndash;75.0 months).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOverall, \u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;180\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003epTanyN0\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;149 (83%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003epTanyN1\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;16 (9%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003epTanyN2-3\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;15 (8%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian age at radical cystectomy (range), year\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e71 (45\u0026ndash;90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e71 (50\u0026ndash;90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e72 (52\u0026ndash;88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e75 (45\u0026ndash;82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.882\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex, no. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32 (17.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26 (17.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.675\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e148 (82.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e123 (82.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13 (86.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eECOG performance status, no. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e165 (91.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e139 (93.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (81.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13 (86.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.194\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (8.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (18.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (13.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClinical T stage, no. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecTa or cT1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e45 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42 (28.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (6.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0.008\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecT2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e88 (49.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e76 (51)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6 (40)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecT3 or cT4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e47 (26.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31 (20.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8 (53.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClinical N stage, no. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecN0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e158 (87.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e135 (90.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (81.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e10 (66.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.076\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecN1-3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22 (12.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (9.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (18.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5 (33.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurgical approach, no. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLaparoscopic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e159 (88.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e130 (87.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13 (86.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.313\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRobotic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (11.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (12.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (13.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of lymph nodes removed, median (range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (0\u0026thinsp;\u0026minus;\u0026thinsp;47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (0\u0026ndash;47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15 (7\u0026ndash;32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e16 (7\u0026ndash;30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.554\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrinary tract diversion, no. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIleal conduit\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e110 (61.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e90 (60.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (81.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7 (46.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOrthotopic neobladder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e53 (29.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46 (30.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (18.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4 (26.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (9.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (8.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4 (26.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClavien-Dindo complications, no. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e0.707\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e111 (61.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e93 (62.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10 (62.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8 (53.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade 1,2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e43 (23.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33 (22.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (31.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5 (33.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade 3\u0026ndash;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (14.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23 (15.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (6.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (13.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePathological T stage, no. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epTa or cT1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e98 (54.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e94 (63.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epT2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26(14.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24 (16.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (12.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epT3 or pT4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e56 (31.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31 (20.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12 (75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13 (86.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSoft-tissue resection margin, no. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e178(99.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e148 (99.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14 (93.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.098\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (0.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (0.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (6.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymphovascular invasion, no. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e102 (56.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e99 (66.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (18.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e58 (32.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30 (20.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13 (81.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15 (100)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMissing\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (11.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (13.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeoadjuvant chemotherapy, no. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60 (33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50 (33.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6 (37.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4 (26.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.807\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e120 (66.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e99 (66.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10 (62.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e11 (73.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eOutcome of SLN detection as a pilot study\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003eOutcome of SLN detection as a pilot study\u003c/div\u003e\u003cp\u003eThe SLN detection rate was 63% (19/30 cases). On a per-lymph node basis, sensitivity, specificity, and false-negative rate were 57% (8/14), 81% (333/408), and 1.6% (6/339), respectively. Ipsilateral SLN-positive findings were obtained in 86.7% of cases (13/15). We have previously reported three representative SLN-related lymphatic drainage patterns in prostate cancer[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], and similar patterns were identified in bladder cancer as well (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA, B and C). Among these, pattern A was the most common, observed in 78% (15/19), followed by pattern B in 42% (8/19), and pattern C in 15% (3/19).\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eCharacteristics of lymph node metastasis\u003c/h2\u003e\u003cp\u003eLN metastasis was identified in 31 patients (17%), comprising 16 (9%) with pN1, 12 (7%) with pN2, and 3 (1%) with pN3 disease. Characteristics of LN metastases in pN1 and pN2\u0026ndash;3 groups are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The median number of LNs removed was 15 (range, 7\u0026ndash;32) in pN1 and 16 (range, 7\u0026ndash;30) in pN2\u0026ndash;3. The median number of positive LNs was 1 in pN1 and 4 (range, 2\u0026ndash;21) in pN2\u0026ndash;3. In total, 90 positive lymph nodes were identified among the 31 patients with LN metastases, including 16 in the pN1 group and 74 in the pN2\u0026ndash;3 group. The most common site of LN metastasis was the obturator region (68.9%), followed by the external iliac (12.2%) and internal iliac regions (8.9%). The predominant site of metastasis per patient was the obturator region in both pN1 (87.5%) and pN2\u0026ndash;3 (100%) groups, with the junctional node being the most frequently involved. No significant difference was observed between the pN1 and pN2\u0026ndash;3 groups in the distribution of LN metastases (p\u0026thinsp;=\u0026thinsp;0.456).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCharacteristics of lymph node metastasis\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;31\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003epN1\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;16\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003epN2-3\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;15\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of lymph nodes removed, median (range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (7\u0026ndash;32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15 (7\u0026ndash;32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 (7\u0026ndash;30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.973\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of positive lymph nodes, median (range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (1\u0026ndash;21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (2\u0026ndash;21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDistribution of positive lymph nodes, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eObturator\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62 (68.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (87.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e48 (64.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"5\" rowspan=\"6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ejunctional/ deep obturator/ other\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26/13/23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10/4/0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16/9/23\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExternal iliac\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (12.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (6.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10 (13.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInternal iliac\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (8.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (6.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (9.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCommon iliac\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (7.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (9.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePresacral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (2.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (2.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDistribution of positive lymph nodes per patient, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eObturator\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29 (93.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14 (87.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"5\" rowspan=\"6\"\u003e\u003cp\u003e0.193\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ejunctional/ deep obturator/ other\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25/13/10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10/4/0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15/9/10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExternal iliac\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (25.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (6.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (46.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInternal iliac\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (16.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (6.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (26.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCommon iliac\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (6.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (13.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePresacral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (6.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMain tumor location, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLateral wall\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (51.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (56.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (46.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.862\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTrigone, anterior or posterior wall\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (48.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (43.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (53.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymph node metastasis laterality, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnilateral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (83.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10 (66.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.042\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBilateral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (16.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (33.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eLaterality\u003c/h3\u003e\n\u003cp\u003eAmong those patients with LN metastases (n\u0026thinsp;=\u0026thinsp;31), 16 (pN1: n\u0026thinsp;=\u0026thinsp;9; pN2\u0026ndash;3: n\u0026thinsp;=\u0026thinsp;7) had tumors located in the lateral wall of the bladder, excluding cases of tumors located in the trigone or posterior wall. Of these 16 cases, ipsilateral LN metastasis was observed in 14 (87.5%), comprising 8 cases with pN1 and 6 with pN2\u0026ndash;3 (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Tumor lateralization in the bladder showed a strong correlation with ipsilateral LN metastasis (Cohen's kappa coefficient, κ\u0026thinsp;=\u0026thinsp;0.696). An even stronger correlation was observed among the 9 cases with pN1; laterality matched in 8 cases (88.9%) and the Cohen's kappa coefficient was 0.727.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003eSurvival in sub-stage of lymph node metastasis\u003c/h3\u003e\n\u003cp\u003eDuring the follow-up period, 64 patients (35%) experienced disease recurrence. A total of 49 patients (27.2%) died, with 36 of those deaths (20%) attributed to bladder cancer. Kaplan\u0026ndash;Meier analysis revealed significant differences in RFS among pN0, pN1, and pN2\u0026ndash;3 groups, with median RFS times of 44 months (95% confidence interval [CI], 28.8\u0026ndash;59.1), 23 months (95% CI, 12.4\u0026ndash;52.1), and 4 months (95% CI, 2.8\u0026ndash;5.2), respectively (global p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). The CSS was 127 months (95% CI, 119.8\u0026ndash;135.2) for pN0 patients, 61 months (95% CI, 41.3\u0026ndash;80.4) for pN1 patients, and 7 months (95% CI, 3.2\u0026ndash;10.7) for pN2\u0026ndash;3 patients (global p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB). The median OS differed significantly among groups: 115 months (95% CI, 106.4\u0026ndash;125.1) for pN0 patients, 61 months (95% CI, 26.1\u0026ndash;95.8) for pN1 patients, and 7 months (95% CI, 3.3\u0026ndash;10.7) for pN2\u0026ndash;3 patients (global p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe results of the Cox proportional hazards regression models for oncological outcomes are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Female sex was significantly associated with worse CSS (hazard ratio [HR]: 1.75, p\u0026thinsp;=\u0026thinsp;0.018). A higher pathological T stage (pT\u0026thinsp;\u0026ge;\u0026thinsp;3) was associated with an increased risk of RFS (HR: 2.49, p\u0026thinsp;=\u0026thinsp;0.016), but showed no significant association with CSS or OS. Notably, pN2\u0026ndash;3 was strongly associated with worse RFS (HR: 4.73, p\u0026thinsp;=\u0026thinsp;0.001), CSS (HR: 25.4, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and OS (HR: 9.94, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), whereas pN1 was not significantly associated with any of these outcomes. Age, LVI, and receipt of NAC were not significantly associated with oncological outcomes.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCox proportional hazards regression models for oncological outcomes\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"15\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e\u003cp\u003eRFS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e\u003cp\u003eCSS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e\u003cp\u003eOS\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCovariant\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eReference\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eHR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c12\"\u003e\u003cp\u003eHR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c13\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c14\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge (continuous)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.99\u0026ndash;1.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.078\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.96\u0026ndash;1.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e1.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.99\u0026ndash;1.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e0.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.89\u0026ndash;1.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e1.1\u0026ndash;2.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e1.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.84\u0026ndash;1.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e0.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePathological T stage\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epT\u0026thinsp;\u0026ge;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026le;pT2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.19\u0026ndash;5.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.45\u0026ndash;3.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e1.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.68\u0026ndash;3.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e0.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePathological N stage\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epN1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003epN0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.51\u0026ndash;3.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e2.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.84\u0026ndash;9.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.095\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e1.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.63\u0026ndash;4.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e0.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epN2-3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003epN0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.93\u0026ndash;13.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e25.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e8.43\u0026ndash;76.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e9.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e3.77\u0026ndash;26.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLVI\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLVI (+)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLVI (-)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.47\u0026ndash;1.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.42\u0026ndash;2.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.86\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e0.96\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.466\u0026ndash;1.993\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e0.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNeoadjuvant chemotherapy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePresent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAbsent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.62\u0026ndash;2.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e1.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e0.57\u0026ndash;4.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003e0.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c12\"\u003e\u003cp\u003e1.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c13\"\u003e\u003cp\u003e0.549\u0026ndash;2.494\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c14\"\u003e\u003cp\u003e0.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"15\" nameend=\"c15\" namest=\"c1\"\u003e\u003cp\u003eHR: hazard ratio; RFS: recurrence-free survival; CSS: cancer-specific survival; OS: overall survival\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we examined the distribution of metastatic LNs based on lymphatic drainage patterns, evaluated the prognostic impact of nodal substaging on survival, and explored the optimal extent of PLND, including considerations of SLNs and laterality in patients treated with radical cystectomy. Our results demonstrated that the obturator region \u0026ndash; including the SLNs, as defined by lymphatic drainage patterns \u0026ndash; has high diagnostic value for detecting LN metastases in both pN1 and pN2\u0026ndash;3 stages. Dissection of this region showed consistently high diagnostic utility and may also provide therapeutic benefit, particularly in patients with pN1 disease, who exhibited significantly better oncological outcomes than those with pN2\u0026ndash;3 involvement.\u003c/p\u003e\u003cp\u003eAlthough the anatomical boundaries of PLND, particularly between the obturator and internal iliac regions, have historically been poorly defined, our study was able to clearly delineate them based on lymphatic drainage patterns. Our findings are consistent with prior reports emphasizing the obturator fossa as a predominant site of nodal metastasis in MIBC[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Notably, our study extends previous anatomical work by incorporating the deep obturator nodes\u0026mdash;previously described as internal iliac nodes[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u0026mdash;into the obturator region definition. Because LN metastases in bladder cancer are subclassified into pN1 and pN2\u0026ndash;3 stages according to the AJCC 8th edition[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], our analysis indicates that patients with pN1 disease have a more favorable prognosis than those with pN2\u0026ndash;3 disease, with pN2\u0026ndash;3 serving as an independent adverse prognostic factor. Importantly, prior research has not extensively examined the relationship between these nodal substages and the specific anatomical locations of LN metastases.\u003c/p\u003e\u003cp\u003eWhile a few previous studies on SLN biopsy in MIBC have reported high detection rates and sensitivity, the adoption of this procedure in clinical practice has remained limited[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The detection rate in our study was not particularly high, but we achieved a low false-negative rate and successfully identified characteristic pelvic lymphatic drainage patterns. Other researchers have identified several major pelvic lymphatic pathways[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], and we have reported separately that SLNs are located in close proximity to the prostate based on lymphatic mapping using ICG[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Notably, our findings showed three distinct lymphatic drainage pathways in the bladder, as well. Our definition of the obturator region encompasses both the junctional SLN\u0026mdash;recognized as the most frequent metastatic site within the conventional obturator fossa\u0026mdash;and the deep obturator SLN, which includes the space dorsal to the obturator nerve, previously referred to as the distal internal iliac nodes located around the inferior vesical artery in our study[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. This broader and deeper interpretation of the obturator region has already been proposed as the standard obturator region by the JSES Working Group\u0026mdash;a multidisciplinary consortium of gastrointestinal surgeons, urologists, and gynecologists in Japan[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In addition to the obturator region, the extent of PLND used in this study\u0026mdash;based on the definitions established at the consensus meeting of the JSER\u0026mdash;also included the common iliac, external iliac, internal iliac, and presacral areas, as determined by vascular landmarks and anatomical membrane structures[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Although the internal iliac region has traditionally been broadly defined as the area along the internal iliac vessels, [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], in this classification, it is clearly defined as the area medial to the internal iliac artery. These anatomical subdivisions not only clarified the previously complex boundary between the obturator and internal iliac regions, but also enabled the integration of the frequently metastatic obturator fossa and deep obturator lymph nodes\u0026mdash;both considered SLNs\u0026mdash;into a single obturator region.\u003c/p\u003e\u003cp\u003eIn the 8th edition of the AJCC staging system, nodal classification shifted from Stage IV to Stage III, and substaging was refined based on the number and location of LN metastases (pN1: single regional node; pN2: multiple regional nodes; pN3: common iliac involvement)[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. This shift reflects the growing recognition that not all nodal metastases carry the same prognostic weight. Indeed, while the overall prognosis of nodal disease remains poor, emerging evidence\u0026mdash;including findings from Hara et al.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and our current study\u0026mdash;suggests that pN1 disease may represent a biologically and clinically distinct subset. Our long-term follow-up data revealed that patients with pN1 disease had a 40% long-term cancer-specific or overall survival, whereas those with pN2\u0026ndash;3 involvement fared significantly worse. These findings suggest that pN1 nodes and SLNs share common features both anatomically and oncologically. This implies that lymphatic spread in pN1 disease may be more localized and amenable to therapeutic intervention via PLND, whereas pN2\u0026ndash;3 disease likely reflects more extensive systemic dissemination with limited potential benefit from local surgical control alone.\u003c/p\u003e\u003cp\u003ePrevious mapping studies have supported the traditional emphasis on bilateral PLND[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. However, studies using radioactive tracers injected into the non-tumor lateral bladder wall have shown minimal or no drainage to contralateral nodes[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], findings consistent with our ICG-based observations. Gurwin et al. also reported an 80% concordance rate for ipsilateral LN metastasis in lateral wall tumors, although they emphasized the need for contralateral PLND to avoid missing the remaining 20%[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In clinical practice, PLND is often omitted; population-based data from the United States indicated that this procedure was omitted in approximately 20% of all cases during the 2010s[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Given the increased risk of complications and the limited therapeutic benefit of PLND in certain cases[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], we believe that omitting contralateral PLND may be acceptable in carefully selected patients\u0026mdash;particularly elderly individuals or those with comorbidities for whom adjuvant therapy is less feasible.\u003c/p\u003e\u003cp\u003eNotably, two recent randomized controlled trials failed to demonstrate a survival benefit from extended PLND in patients with MIBC[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], raising doubts about the therapeutic value of extensive dissection. Meanwhile, the diagnostic role of PLND has gained renewed importance, particularly given the proven efficacy of adjuvant nivolumab in high-risk urothelial carcinoma, with especially favorable outcomes among patients with nodal metastases[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Our results suggest that, in patients with pN1 disease, comprehensive dissection of the obturator region may provide therapeutic benefit, and in both pN1 and pN2 cases, it may aid in identifying candidates for adjuvant immunotherapy. The present study contributes to the growing body of evidence supporting lymphatic anatomy-guided PLND and offers a template for future prospective trials to validate selective dissection strategies.\u003c/p\u003e\u003cp\u003eThis study has several limitations. The retrospective design introduces potential selection bias, and the single-institution setting may limit external validity. Although we excluded patients who were receiving adjuvant therapy, variations in post-recurrence management could have influenced long-term outcomes. Additionally, the relatively modest sample size may underpower subgroup analyses, and the applicability of our lymphatic mapping findings to non-lateral wall tumors requires further investigation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur findings demonstrate that the obturator region, as defined by lymphatic drainage anatomy, is a highly relevant target for PLND in bladder cancer, and that dissection of this anatomically guided region can yield crucial diagnostic value. In pN1 disease, this region offers potential therapeutic benefit, as it shares key features with SLNs and appears to represent a biologically and clinically distinct subset with more localized spread and better prognosis than pN2\u0026ndash;3.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors express their gratitude for the expert English language editing provided by Lee Seaman of Seaman Medical, Inc., Bellingham WA, USA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTakahiro Kimura has received honoraria from Astellas, AstraZeneca, Bayer, Janssen, Sanofi, and Takeda.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this study are available upon reasonable request from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe institutional review board approved the study protocol 36-005[12104].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnimal Studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: none\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eProject development: J Miki\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData collection:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData analysis: J Miki\u003c/p\u003e\n\u003cp\u003eManuscript writing/editing: J Miki\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eStein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, Skinner E, Bochner B, Thangathurai D, Mikhail M, Raghavan D, Skinner DG (2001) Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 19(3):666\u0026ndash;675. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1200/jco.2001.19.3.666\u003c/span\u003e\u003cspan address=\"10.1200/jco.2001.19.3.666\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKrag DN, Anderson SJ, Julian TB, Brown AM, Harlow SP, Costantino JP, Ashikaga T, Weaver DL, Mamounas EP, Jalovec LM, Frazier TG, Noyes RD, Robidoux A, Scarth HM, Wolmark N (2010) Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol 11(10):927\u0026ndash;933. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s1470-2045(10)70207-2\u003c/span\u003e\u003cspan address=\"10.1016/s1470-2045(10)70207-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKanbergs A, Melamed A, Viveros-Carre\u0026ntilde;o D, Wu CF, Wilke RN, Zamorano A, Paladugu K, Havrilesky L, Rauh-Hain JA, Agusti N (2025) Surgical Deescalation Within Gynecologic Oncology. JAMA Netw Open 8(1):e2453604. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamanetworkopen.2024.53604\u003c/span\u003e\u003cspan address=\"10.1001/jamanetworkopen.2024.53604\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZarifmahmoudi L, Ghorbani H, Sadri K, Tavakkoli M, Keshvari M, Salehi M, Sadeghi R (2019) Sentinel Node Biopsy in Urothelial Carcinoma of the Bladder: Systematic Review and Meta-Analysis. Urol Int 103(4):373\u0026ndash;382. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000497310\u003c/span\u003e\u003cspan address=\"10.1159/000497310\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAmin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR, Winchester DP (2017) The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more personalized approach to cancer staging. CA Cancer J Clin 67(2):93\u0026ndash;99. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3322/caac.21388\u003c/span\u003e\u003cspan address=\"10.3322/caac.21388\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHara S, Fukuokaya W, Miki J, Taoka R, Saito R, Matsui Y, Hatakeyama S, Kawahara T, Matsuda A, Kawai T, Kato M, Sazuka T, Sano T, Urabe F, Kashima S, Naito H, Murakami Y, Miyake M, Daizumoto K, Matsushita Y, Hayashi T, Inokuchi J, Sugino Y, Shiga K, Yamaguchi N, Yamamoto S, Yasue K, Abe T, Nakanishi S, Hashine K, Fujii M, Nishihara K, Matsumoto H, Tatarano S, Wada K, Sekito S, Maruyama R, Nishiyama N, Nishiyama H, Kitamura H, Kimura T (2025) Stage III substaging and outcomes in patients with bladder cancer undergoing radical cystectomy. Int J urology: official J Japanese Urol Association. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/iju.70005\u003c/span\u003e\u003cspan address=\"10.1111/iju.70005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAbdel-Rahman O (2017) Validation of the Eighth AJCC New Substages for Bladder Cancer Among Different Staging Contexts. Clin Genitourin Cancer 15(6):e1095\u0026ndash;e1106. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.clgc.2017.07.025\u003c/span\u003e\u003cspan address=\"10.1016/j.clgc.2017.07.025\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGschwend JE, Heck MM, Lehmann J, R\u0026uuml;bben H, Albers P, Wolff JM, Frohneberg D, de Geeter P, Heidenreich A, K\u0026auml;lble T, St\u0026ouml;ckle M, Schn\u0026ouml;ller T, Stenzl A, M\u0026uuml;ller M, Truss M, Roth S, Liehr UB, Lei\u0026szlig;ner J, Bregenzer T, Retz M (2019) Extended Versus Limited Lymph Node Dissection in Bladder Cancer Patients Undergoing Radical Cystectomy: Survival Results from a Prospective, Randomized Trial. Eur Urol 75(4):604\u0026ndash;611. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.eururo.2018.09.047\u003c/span\u003e\u003cspan address=\"10.1016/j.eururo.2018.09.047\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLerner SP, Tangen C, Svatek RS, Daneshmand S, Pohar KS, Skinner E, Schuckman A, Sagalowsky AI, Smith ND, Kamat AM, Kassouf W, Plets M, Bangs R, Koppie TM, Alva A, La Rosa FG, Pal SK, Kibel AS, Canter DJ, Thompson IM Jr (2024) Standard or Extended Lymphadenectomy for Muscle-Invasive Bladder Cancer. N Engl J Med 391(13):1206\u0026ndash;1216. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa2401497\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa2401497\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBajorin DF, Witjes JA, Gschwend JE, Schenker M, Valderrama BP, Tomita Y, Bamias A, Lebret T, Shariat SF, Park SH, Ye D, Agerbaek M, Enting D, McDermott R, Gajate P, Peer A, Milowsky MI, Nosov A, Neif Antonio J Jr., Tupikowski K, Toms L, Fischer BS, Qureshi A, Collette S, Unsal-Kacmaz K, Broughton E, Zardavas D, Koon HB, Galsky MD (2021) Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med 384(22):2102\u0026ndash;2114. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa2034442\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa2034442\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePaner GP, Stadler WM, Hansel DE, Montironi R, Lin DW, Amin MB (2018) Updates in the Eighth Edition of the Tumor-Node-Metastasis Staging Classification for Urologic Cancers. Eur Urol 73(4):560\u0026ndash;569. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.eururo.2017.12.018\u003c/span\u003e\u003cspan address=\"10.1016/j.eururo.2017.12.018\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKluth LA, Rieken M, Xylinas E, Kent M, Rink M, Roupr\u0026ecirc;t M, Sharifi N, Jamzadeh A, Kassouf W, Kaushik D, Boorjian SA, Roghmann F, Noldus J, Masson-Lecomte A, Vordos D, Ikeda M, Matsumoto K, Hagiwara M, Kikuchi E, Fradet Y, Izawa J, Rendon R, Fairey A, Lotan Y, Bachmann A, Zerbib M, Fisch M, Scherr DS, Vickers A, Shariat SF (2014) Gender-specific differences in clinicopathologic outcomes following radical cystectomy: an international multi-institutional study of more than 8000 patients. Eur Urol 66(5):913\u0026ndash;919. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.eururo.2013.11.040\u003c/span\u003e\u003cspan address=\"10.1016/j.eururo.2013.11.040\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDrakaki A, Pantuck A, Mhatre SK, Dhillon PK, Davarpanah N, Degaonkar V, Surinach A, Chamie K, Grivas P (2021) Real-world outcomes and prognostic indicators among patients with high-risk muscle-invasive urothelial carcinoma. Urol Oncol 39(1):76. .e15-76.e22\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eXia L, Dadabhoy A, Wood EL, Mehta SV, Roberson DS, Guzzo TJ, Bivalacqua TJ, Daneshmand S (2024) Pathologic and survival outcomes following radical cystectomy for progressive and de novo muscle-invasive bladder cancer: A meta-analysis stratified by neoadjuvant chemotherapy status. Urol Oncol 42(10):333. .e331-333.e313\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMari A, Kimura S, Foerster B, Abufaraj M, D'Andrea D, Gust KM, Shariat SF (2018) A systematic review and meta-analysis of lymphovascular invasion in patients treated with radical cystectomy for bladder cancer. Urol Oncol 36(6):293\u0026ndash;305. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.urolonc.2018.03.018\u003c/span\u003e\u003cspan address=\"10.1016/j.urolonc.2018.03.018\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGhoneim MA, Abdel-Latif M, el-Mekresh M, Abol-Enein H, Mosbah A, Ashamallah A, el-Baz MA (2008) Radical cystectomy for carcinoma of the bladder: 2,720 consecutive cases 5 years later. J Urol 180(1):121\u0026ndash;127. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.juro.2008.03.024\u003c/span\u003e\u003cspan address=\"10.1016/j.juro.2008.03.024\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLandis JR, Koch GG (1977) The measurement of observer agreement for categorical data. Biometrics 33(1):159\u0026ndash;174\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMiki J, Yanagisawa T, Tsuzuki S, Mori K, Urabe F, Kayano S, Yorozu T, Sato S, Kimura T, Takahashi H, Kishimoto K, Egawa S (2018) Anatomical localization and clinical impact of sentinel lymph nodes based on patterns of pelvic lymphatic drainage in clinically localized prostate cancer. Prostate 78(6):419\u0026ndash;425. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/pros.23486\u003c/span\u003e\u003cspan address=\"10.1002/pros.23486\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWit EMK, Acar C, Grivas N, Yuan C, Horenblas S, Liedberg F, Valdes Olmos RA, van Leeuwen FWB, van den Berg NS, Winter A, Wawroschek F, Hruby S, Janetschek G, Vidal-Sicart S, MacLennan S, Lam TB, van der Poel HG (2017) Sentinel Node Procedure in Prostate Cancer: A Systematic Review to Assess Diagnostic Accuracy. Eur Urol 71(4):596\u0026ndash;605. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.eururo.2016.09.007\u003c/span\u003e\u003cspan address=\"10.1016/j.eururo.2016.09.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTakemasa I, Hamabe A, Takenaka A, Kobayashi H, Mandai M, Kinugasa Y, Saika T, Shimbo M, Morizane S, Sekiyama K, Togami S, Hanaoka M, Inoue S, Nagaishi K, Sakai Y, Watanabe M (2024) Standardization of robot-assisted pelvic lymph node dissection-Development of a common understanding of regional anatomy and surgical technique based on cross-disciplinary discussion among colorectal surgery, urology, and gynecology. Asian J Endosc Surg 17(1):e13274. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/ases.13274\u003c/span\u003e\u003cspan address=\"10.1111/ases.13274\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMorizane S, Miki J, Shimbo M, Kanno T, Miura N, Yamada Y, Yamasaki T, Saika T, Takenaka A (2024) Japanese expert consensus on the standardization of robot-assisted pelvic lymph node dissection in urological surgery: Extent of pelvic lymph node and surgical technique. Int J urology: official J Japanese Urol Association. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/iju.15563\u003c/span\u003e\u003cspan address=\"10.1111/iju.15563\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLeissner J, Ghoneim MA, Abol-Enein H, Th\u0026uuml;roff JW, Franzaring L, Fisch M, Schulze H, Managadze G, Allhoff EP, el-Baz MA, Kastendieck H, Buhtz P, Kropf S, Hohenfellner R, Wolf HK (2004) Extended radical lymphadenectomy in patients with urothelial bladder cancer: results of a prospective multicenter study. J Urol 171(1):139\u0026ndash;144. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/01.ju.0000102302.26806.fb\u003c/span\u003e\u003cspan address=\"10.1097/01.ju.0000102302.26806.fb\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDangle PP, Gong MC, Bahnson RR, Pohar KS (2010) How do commonly performed lymphadenectomy templates influence bladder cancer nodal stage? J Urol 183(2):499\u0026ndash;503. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.juro.2009.09.080\u003c/span\u003e\u003cspan address=\"10.1016/j.juro.2009.09.080\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePerera M, McGrath S, Sengupta S, Crozier J, Bolton D, Lawrentschuk N (2018) Pelvic lymph node dissection during radical cystectomy for muscle-invasive bladder cancer. Nat Rev Urol 15(11):686\u0026ndash;692. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41585-018-0066-1\u003c/span\u003e\u003cspan address=\"10.1038/s41585-018-0066-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePedersen CK, Babu AS (2021) Understanding the Lymphatics: An Updated Review of the N Category of the AJCC 8th Edition for Urogenital Cancers. AJR Am J Roentgenol 217(2):368\u0026ndash;377. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2214/ajr.20.22997\u003c/span\u003e\u003cspan address=\"10.2214/ajr.20.22997\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRoth B, Wissmeyer MP, Zehnder P, Birkh\u0026auml;user FD, Thalmann GN, Krause TM, Studer UE (2010) A new multimodality technique accurately maps the primary lymphatic landing sites of the bladder. Eur Urol 57(2):205\u0026ndash;211. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.eururo.2009.10.026\u003c/span\u003e\u003cspan address=\"10.1016/j.eururo.2009.10.026\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRoth B, Zehnder P, Birkh\u0026auml;user FD, Burkhard FC, Thalmann GN, Studer UE (2012) Is bilateral extended pelvic lymphadenectomy necessary for strictly unilateral invasive bladder cancer? J Urol 187(5):1577\u0026ndash;1582. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.juro.2011.12.106\u003c/span\u003e\u003cspan address=\"10.1016/j.juro.2011.12.106\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGurwin A, Karwacki J, Dorochowicz M, Kowalczyk K, Nowak Ł, Jędrzejuk D, Krajewski W, Hałoń A, Bolanowski M, Szydełko T, Małkiewicz B (2024) Topography and Lateralization of Nodal Metastases in Muscle-Invasive Bladder Cancer Using Super-Extended Pelvic Lymph Node Dissection with the Sentinel Lymph Node Technique. J Clin Med 13(17). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/jcm13175127\u003c/span\u003e\u003cspan address=\"10.3390/jcm13175127\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSodagum L, Passarelli R, Pfail J, Patel HV, Chua K, Doppalapudi SK, Golombos D, Elsamra SE, Singer EA, Jang TL, Srivastava A, Ghodoussipour S (2024) Pelvic lymphadenectomy: Evaluating nodal stage migration and will rogers effect in bladder cancer. Urol Oncol 42(1):21. .e29-21.e20\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGalsky MD, Witjes JA, Gschwend JE, Milowsky MI, Schenker M, Valderrama BP, Tomita Y, Bamias A, Lebret T, Shariat SF, Park SH, Agerbaek M, Jha G, Stenner F, Ye D, Giudici F, Dutta S, Askelson M, Nasroulah F, Zhang J, Brophy L, Bajorin DF (2025) Adjuvant Nivolumab in High-Risk Muscle-Invasive Urothelial Carcinoma: Expanded Efficacy From CheckMate 274. J Clin Oncol 43(1):15\u0026ndash;21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1200/jco.24.00340\u003c/span\u003e\u003cspan address=\"10.1200/jco.24.00340\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Bladder cancer, pelvic lymph node dissection, nodal substaging, sentinel lymph node, prognosis","lastPublishedDoi":"10.21203/rs.3.rs-7458941/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7458941/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo determine the optimal extent of pelvic lymph node dissection in bladder cancer, evaluating the prognostic relevance of nodal substaging, and assessing the feasibility of sentinel lymph node biopsy and omission of contralateral dissection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study included 180 patients undergoing laparoscopic or robot-assisted radical cystectomy. Sentinel lymph node detection was assessed in 30 cases as a pilot. The obturator region was defined according to lymphatic drainage patterns. The prognostic impact of nodal substaging was evaluated using Kaplan–Meier and Cox proportional hazards models. Laterality of tumor location and node metastasis was also analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSentinel lymph node biopsy demonstrated a 63% detection rate with a 1.6% false-negative rate. nodal metastases were observed in 8.9% of pN1 and 8.3% of pN2–3 cases, predominantly in the obturator region (87.5% and 100%, respectively). Lymph node metastases were most frequently located in the obturator region, including 87.5% of stage pN1 and 100% of stage pN2–3 cases. Cancer-specific survival was significantly better in pN1 than in pN2–3 cases (median 61 vs. 7 months, p \u0026lt; 0.001). Cox proportional hazards regression models identified pN2–3 as the strongest prognostic factor (HR for CSS: 25.4). Ipsilateral nodal metastasis was observed in 87.5% of lateral wall tumors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAlthough sentinel lymph node biopsy demonstrated limited utility, the obturator region appears to represent the optimal diagnostic target for nodal metastasis.\u003c/p\u003e\n\u003cp\u003eIn pN1 disease, this region may be therapeutic, resembling sentinel nodes and showing limited spread with better prognosis than pN2-3 disease.\u003c/p\u003e","manuscriptTitle":"Optimizing Pelvic Lymph Node Dissection in Bladder Cancer: Obturator Focus, pN1 Prognosis, and Sentinel Node Feasibility","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-09 11:54:20","doi":"10.21203/rs.3.rs-7458941/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-09-02T08:37:40+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-02T06:42:20+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-26T18:09:36+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Journal of Clinical Oncology","date":"2025-08-26T01:33:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"international-journal-of-clinical-oncology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijco","sideBox":"Learn more about [International Journal of Clinical Oncology](http://link.springer.com/journal/10147)","snPcode":"10147","submissionUrl":"https://www.editorialmanager.com/ijco/default2.aspx","title":"International Journal of Clinical Oncology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"019e4247-e647-494a-b4c5-082eed67b1e5","owner":[],"postedDate":"September 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-02T16:10:52+00:00","versionOfRecord":{"articleIdentity":"rs-7458941","link":"https://doi.org/10.1007/s10147-026-02969-5","journal":{"identity":"international-journal-of-clinical-oncology","isVorOnly":false,"title":"International Journal of Clinical Oncology"},"publishedOn":"2026-01-27 15:59:16","publishedOnDateReadable":"January 27th, 2026"},"versionCreatedAt":"2025-09-09 11:54:20","video":"","vorDoi":"10.1007/s10147-026-02969-5","vorDoiUrl":"https://doi.org/10.1007/s10147-026-02969-5","workflowStages":[]},"version":"v1","identity":"rs-7458941","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7458941","identity":"rs-7458941","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.