Neoadjuvant Therapy For Lateral Pelvic Lymph Nodes: Choosing Between Long Course Chemoradiation Or Short Course Radiotherapy With Consolidation Chemotherapy

Neoadjuvant Therapy For Lateral Pelvic Lymph Nodes: Choosing Between Long Course Chemoradiation Or Short Course Radiotherapy With Consolidation Chemotherapy | 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 Neoadjuvant Therapy For Lateral Pelvic Lymph Nodes: Choosing Between Long Course Chemoradiation Or Short Course Radiotherapy With Consolidation Chemotherapy Subhathira Manohkaran, Tejas Vispute, Akash Mor, Kartik Prakash, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5858266/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Jul, 2025 Read the published version in Techniques in Coloproctology → Version 1 posted 8 You are reading this latest preprint version Abstract Background The response of lateral pelvic lymph nodes (LPLNs) to various neoadjuvant treatments has not been thoroughly investigated. This study aims to compare the effects of long-course chemoradiotherapy (LCCRT) and total neoadjuvant therapy (TNT), i.e., short-course radiotherapy (SCRT) with consolidation chemotherapy, on LPLNs size reduction. The secondary objective is to compare the pathological positivity rates of LPLNs dissection (LPLND), post-neoadjuvant treatment. Methods This is a retrospective analysis based on a prospectively maintained database. Rectal cancer patients registered between January 2020 and December 2021 with radiologically positive LPLNs who underwent neoadjuvant radiation therapy were included. Patients were divided into two groups: LCCRT and TNT. Results Among 1,200 registered rectal cancer cases, 160 had positive LPLNs, with 142 included in the analysis. Sixty-one patients received LCCRT, and 81 patients received TNT. No significant differences were found in T and N staging between the groups. However, the TNT cohort had a significantly higher proportion of metastatic patients (p < 0.001), poorly differentiated tumours (p = 0.021), and extramural venous invasion (p = 0.002). Baseline mean nodal sizes were similar between groups. Post-neoadjuvant nodal sizes were 5.3mm for LCCRT and 6.2mm for TNT, with mean reductions of 5.7mm and 4.6mm, respectively (p = 0.136 & 0.54). Surgery was conducted in 77% of the LCCRT group and 59% of the TNT group, with 22 (46.8%) and 26 (54.1%) undergoing LPLND in their respective groups. The pathological positivity rates for LPLNs were similar (27.3% vs. 23.1%, p = 0.731) Conclusion SCRT with consolidation chemotherapy does not provide a significant advantage over LCCRT in reducing LPLNs size or reducing the need for LPLND. LCCRT (Long Course Chemoradiotherapy) LPLNs (Lateral Pelvic Lymph Nodes) LPLND (Lateral Pelvic Lymph Nodes Dissection) SCRT (Short Course Radiotherapy) TNT (Total Neoadjuvant Therapy) Figures Figure 1 Figure 2 INTRODUCTION The treatment of rectal cancer is complex and requires a multidisciplinary approach. Advances such as total mesorectal excision (TME) and neoadjuvant therapy have improved patient outcomes; however, local recurrence continues to occur in a significant number of cases [ 1 , 2 ]. Mid and low rectal cancers are known to metastasize to lateral pelvic lymph nodes (LPLNs), primarily to the internal iliac and obturator basins, which is a well-documented pathway for lateral pelvic recurrence. The reported incidence of lateral node involvement in low to mid rectal cancer ranges from 10–27% [ 3 , 4 ]. The management of enlarged LPLNs is continuously evolving, with several treatment options available, including neoadjuvant chemotherapy, radiation therapy, radiation boosts, and total neoadjuvant therapy (TNT) (5). When residual nodes are present, lateral pelvic lymph node dissection (LPLND) may be performed; however, this surgical procedure is technically challenging, particularly following radiation therapy. In the RAPIDO, PRODIGE 23, and OPRA trials, TNT has been utilized in patients with LPLN involvement. However, the specifics of management and outcomes for these nodes have not been thoroughly addressed [ 6 , 7 , 8 ]. Our study aims to evaluate whether TNT (short-course radiotherapy (SCRT) with consolidation chemotherapy) can achieve a better response in LPLN shrinkage and reduce the need for LPLND. By concentrating on nodal size reduction, we aim to gain insight into how these regimens influence LPLNs size, a crucial aspect of treatment efficacy, that was not addressed in previous studies. METHODS This is a retrospective study from a prospectively maintained database. The study was conducted in a high-volume tertiary cancer center in Mumbai, India (Tata Memorial Hospital). All patients with rectal adenocarcinoma registered between January 2020 and December 2021, who had radiologically positive LPLNs, including metastatic cases, were included in the study. Criteria for positive LPLNs were based on MRI imaging, where a short-axis diameter of ≥ 7 mm on the baseline MRI was considered significant. MRI interpretation was performed by two oncologists subspecialized in abdominal and oncoimaging, each with more than ten years of experience in interpreting rectal MRIs. The short-axis diameter of each LPLN was measured on the baseline MRI and reassessed on post-neoadjuvant MRI to evaluate size reduction. If multiple nodes or bilateral LPLNs were present, the largest node was selected for analysis. Measurements were recorded in millimetres to the first decimal place, ensuring consistency with baseline documentation. This cohort was classified into two groups based on neoadjuvant treatment: the LCCRT and TNT groups. The multidisciplinary tumor board decided on the treatment regimen based on risk factors and patients’ logistical considerations. In cases with metastatic disease, TNT was preferred. Patients from other regions of the country who were unable to stay for the full 6-week treatment period due to financial constraints and logistical reasons were offered SCRT at our institution, followed by chemotherapy administered in medical centers closer to their homes. In the LCCRT group, radiation therapy of 50 Gray over 25 fractions was administered to the primary tumor and regional nodes including the LPLN, with or without simultaneous or sequential integrated boost. In the TNT group, radiation therapy of 25 Gray over 5 fractions was given to the primary tumor and regional nodes, followed by 4 to 6 cycles of chemotherapy (CAPEOX, FOLFOX or FOLFIRINOX). FOLFIRINOX was specifically given to those patients with metastatic disease and had high-risk features (poorly differentiated, EMVI), who had the potential for curative resection. Reassessment MRI was performed 6 to 8 weeks after the last fraction of radiotherapy in the LCCRT group. In the TNT group, a reassessment MRI was performed upon completion of consolidation chemotherapy, either just before or immediately after the last cycle. Patients were reassessed in the tumor board; post-neoadjuvant scans were evaluated for response, and decisions were made regarding further management. For patients with a good response and resectable disease based on the re-evaluation scan, surgery was planned to achieve curative resection. Patients whose re-evaluation scans showed unresectable disease were managed with palliative intent, and no further surgery was performed. Definitive surgery was performed 8 to 12 weeks post-LCCRT and 4 to 6 weeks after the last cycle of chemotherapy in the TNT group. LPLND was performed selectively when residual nodes larger than 4 mm were observed on reassessment MRI. The primary outcome that we are evaluating in this study is the degree of nodal size reduction in response to TNT versus LCCRT. We hypothesize that TNT, which combines chemotherapy and radiotherapy, leads to greater LPLNs shrinkage compared to LCCRT alone. The secondary outcome is the pathological positivity rate in LPLND specimens after neoadjuvant treatment. This study focuses solely on assessing the response of LPLNs to these treatments, under the assumption that their local response remains consistent regardless of metastatic status, rather than evaluating overall survival or disease-free survival outcomes. Statistical Analysis SPSS Version 28.0 by IBM was used for statistical analysis. Categorical values are presented as frequencies and percentages and a chi-squared test was used for statistical comparison. Continuous variables are presented in mean and independent t-test used for statistical comparison. To account for baseline differences between the groups, a multivariable linear regression was performed. Covariates that showed significant differences between the groups were included in the model. Ethics The study protocol followed the ethical standards of the institutional research committee with approval from the institutional ethics committee (Ref: IRB project No:4570). The local ethics committee waived the requirement for informed consent because of the retrospective nature of the study and the use of anonymized patient data. This study adheres to the STROBE guidelines. RESULTS A total of 1,200 cases of rectal cancer were registered between January 2020 and December 2021, of which 160 (13.3%) had positive LPLN (baseline nodal size ≥7 mm). Hundred and forty-two patients received neoadjuvant radiation treatment, whereas 18 patients did not receive radiotherapy (palliative systemic treatment with no reassessment). Sixty-one patients received LCCRT, and 81 patients received TNT (SCRT with consolidation chemotherapy). Two types of chemotherapy regimens were used in the TNT group: FOLFOX/CAPOX (82%) and FOLFIRINOX (18%). The chemotherapy completion rate was 80%. The median number of chemotherapy cycles administered was four. Fourteen patients in the LCCRT group and 33 in the TNT group did not proceed to surgery. Among them, 5 in the LCCRT group and 30 in the TNT group were deemed unresectable based on reassessment MRI and CT scans and were classified as palliative cases. The remaining 9 patients in the LCCRT group and 3 in the TNT group were lost to follow-up. These patients were included in the analysis of LPLN size reduction, as they had received radiation therapy and underwent reassessment MRI for evaluation. Baseline characteristics are shown in Table 1. There were more male patients in both groups; the mean age was 50 years (range: 23–77) in LCCRT group and 48 years (range: 22–80) in TNT group 2, with no significant difference between groups (p = 0.451). More than half of these patients had low rectal tumours (68.9% and 59.3%). There were no statistically significant differences in T and N staging between the two groups; however, there were more metastatic patients in the TNT group (11.5%, vs. 43.2%, p<0.001). There were significantly more poorly differentiated and signet cell tumours in the TNT group (21.3% vs. 39.5%, p=0.021), and extramural venous invasion (EMVI) was also more prevalent in the TNT cohort (37.7% vs. 64.2% p=0.002). Table 1: Baseline Characteristic LCCRT (61) TNT (81) P value Sex Male Female 60.7% (37) 39.3% (24) 65.4% (53) 34.6% (28) 0.559 Age Mean Median Range 50 51 23-77 48 47 22-80 0.451 Location High rectal Mid rectal Low rectal 4.9% (3) 26.2% (16) 68.9% (42) 16.0% (13) 24.7% (20) 59.3% (48) 0.113 T Staging T2 T3 T4 0% 59.0% (36) 41.0% (25) 2.5% (2) 39.5% (32) 58.0% (47) 0.089 N Staging N1 N2 9.8% (6) 90.2% (55) 10.6% (9) 89.4 (72) 0.807 M Staging 11.5% (7 pt) 43.2% (35pt) <0.001 Histopathology Well differentiated Poorly differentiated & signet 78.7% (48) 21.3% (13) 60.5% (49) 39.5% (32) 0.021 EMVI positive 37.7% (23) 64.2% (52) 0.002 EMVI: Extramural venous invasion A multivariable linear regression was performed for the variables that showed significant differences between the two groups (histology, EMVI, and metastatic status). After controlling for baseline differences, the reduction in nodal size was not significantly different between the LCCRT and TNT groups (Figure 2, Table 2, and Table 4). Table 2: Linear regression for LPLN response with covariates that are different on baseline characteristics Predictor Estimate SE t P Lower Bound 95% CI Upper Bound 95% CI Histology Type -2.064 0.896 -2.305 0.023 -3.839 -0.289 EMVI -0.728 0.805 -0.904 0.68 -4.125 -0.114 M stage -2.119 1.012 -2.095 0.039 -2.325 0.868 Type of Neoadjuvant -1.464 0.839 -1.745 0.084 -3.127 0.199 EMVI: Extramural vascular invasion Table 3 shows the LPLNs profile. Bilateral LPLNs was seen in 31.1% in the LCCRT group and 43.2% in the TNT group. The baseline nodal size in both groups was almost the same, with mean sizes of 11 mm in the LCCRT group and 10.8 mm in the TNT group, whereas post-neoadjuvant treatment, the sizes were 5.3 mm and 6.2 mm, respectively. The shrinkage was 5.7 mm in the LCCRT group and 4.6 mm in the TNT group. Although the mean nodal size reduction and nodal size reduction to <4mm higher in the LCCRT group, the differences were not statistically significant (p=0.136 and p=0.54). Table 3: LPLN Profile LCCRT (n=61) TNT(n=81) P value Bilateral LPLNs 19 (31.1%) 35 (43.2%) 0.143 Mean baseline LPLN size 11.0 mm 10.8 mm 0.809 Mean size post neoadjuvant 5.3 mm 6.2 mm 0.337 Mean nodal size reduction 5.7 mm 4.6 mm 0.136 Nodal size <4mm 29 (48.3%) 27 (42.9%) 0.54 Multivariate logistic regression analysis (Table 4) identified pretreatment nodal size as the only significant predictor of LPLN response. A larger pretreatment nodal size was associated with a lower likelihood of achieving a response (<4 mm) (OR: 0.84, 95% CI: 0.73–0.94, p = 0.005). The type of neoadjuvant therapy showed a trend toward significance, with TNT demonstrating a lower likelihood of LPLN response compared to LCRT (OR: 0.48, 95% CI: 0.23–1.01, p=0.054). While this finding did not reach conventional statistical significance, it suggests a potential difference in nodal response between treatment modalities, possibly due to a higher proportion of high-risk tumours in the TNT group. Other factors, including tumour location, histological subtype, EMVI status, T stage, and N stage, did not show a significant association with LPLN response. Table 4: Multivariate Logistic Regression Analysis for LPLN Response (<4 mm vs. ≥4 mm) Dependent: LPLN Response No Yes OR (univariable) OR (multivariable) Tumour location Mid rectum 33 (63.5) 19 (36.5) - - Low rectum 62 (68.9) 28 (31.1) 0.78 (0.38-1.62, p=0.508) Histological subtype Well/Moderate 60 (61.9) 37 (38.1) - - Poor/signet 35 (77.8) 10 (22.2) 0.46 (0.20-1.02, p=0.064) Mucinous Yes 31 (75.6) 10 (24.4) - - No 64 (63.4) 37 (36.6) 1.79 (0.81-4.23, p=0.163) T stage T3 43 (61.4) 27 (38.6) - - T4a 14 (70.0) 6 (30.0) 0.68 (0.22-1.93, p=0.484) T4b 38 (73.1) 14 (26.9) 0.59 (0.26-1.27, p=0.180) N stage N1 9 (60.0) 6 (40.0) - - N2 86 (67.7) 41 (32.3) 0.72 (0.24-2.26, p=0.549) EMVI Yes 51 (68.0) 24 (32.0) - - No 44 (65.7) 23 (34.3) 1.11 (0.55-2.24, p=0.769) Pretreatment nodal Size Mean (SD) 11 (5.3) 9 (2.7) 0.85 (0.74-0.94, p=0.006) 0.84 (0.73-0.94, p=0.005) Neoadjuvant therapy LCCRT 36 (59.0) 25 (41.0) - - TNT 59 (72.8) 22 (27.2) 0.54 (0.26-1.09, p=0.085) 0.48 (0.23-1.01, p=0.054) At the end of neoadjuvant treatment, fewer patients underwent surgery in the TNT group. Surgery was performed on 47 patients (77%) in the LCCRT group and, 48 patients (59%) in the TNT group. Among the operated patients, LPLND was performed in 22 patients (46.8%) in LCCRT group, and 26 patients (54.1%) in TNT group. The pathological positivity rate for LPLN was almost similar in both groups, with no statistical significance (27.3% vs. 23.1%, p=0.731). Pathological complete response (pCR) of the rectal tumour was observed in 10.6% of patients in the LCCRT group and 14.6% in the TNT group. None of the pCR patients had positive LPLN in the resected specimen. Table 5: Pathology results LCCRT (n=47) TNT (n=48) P value LPLND 22 (46.8%) 26 (54.1%) 0.537 LPLNs pathological positivity 6 (27.3%) 6 (23.1%) 0.731 pCR in the primary lesion 5 (10.6%) 7 (14.6%) 0.619 LPLND: Lateral Pelvic Lymph Nodes Dissection; pCR: Pathological complete response DISCUSSION The response of LPLNs to different types of neoadjuvant treatment in rectal cancer has not been extensively studied. TNT is a novel strategy for rectal cancer that gained popularity after the RAPIDO, PRODIGE-23 and OPRA trials [6,7,8]. These trials demonstrated higher rates of clinical complete response (cCR) and pathological complete response (pCR), but their effects on LPLNs remain unexplored. The possibility of TNT achieving a similar response in LPLN and potentially reducing the need for LPLND remains inadequately explored. This is the first study that directly compares TNT with LCCRT in terms of LPLN downstaging. Our study showed no differences in the efficacy of the two regimes in downstaging LPLN. The pathological positivity rate in lateral pelvic lymph node dissection specimens was also almost similar in both groups with no significant statistical differences. Neoadjuvant radiotherapy has been shown to downstage and potentially sterilize mesorectal and LPLNs, as evidenced by the Dutch TME and MERCURY trials. [9,10]. However, LPLN does not completely regress in all cases. Akiyoshi et al. found that two-thirds of patients had lymph node metastasis in LPLND specimens after neoadjuvant radiotherapy, with no local recurrences observed in those who underwent LPLND after radiotherapy [11]. This finding highlights the therapeutic value of LPLND. Similarly, Kim et al. demonstrated that lateral pelvic recurrence was a major contributor to locoregional recurrence in patients who received neoadjuvant radiotherapy followed by TME without LPLND [12]. Various nodal sizes have been used to define positive LPLN in pre and post-radiotherapy imaging, which ranging from 5mm to 10mm [13,14,15]. During the study period (January 2020 to December 2021), our practice was based on the best available evidence at the time, defining LPLNs with a short axis of ≥7mm before neoadjuvant treatment as positive and considering nodes >4mm post-treatment as indications for LPLND [16]. This approach aligns with Ogura et al.'s findings based on an analysis of 1216 rectal cancer patients with LPLN. A baseline LPLN with a short axis of ≥7mm resulted in a significantly higher risk of lateral local recurrence without LPLND (19.5% vs 5.7%) [14]. They also reported that nodes measuring ≤4mm on the internal iliac and ≤6mm on the obturator on restaging MRI did not necessitate LPLND, with a 0% recurrence rate over three years. [16]. However, all these data were derived from the LCCRT cohort. The effect of TNT or SCRT has not been studied before. The presence of LPLN has been reported in two main TNT trials: the RAPIDO (15%) and PRODIGE 23 (10%). Other trials, such as POLISH 2, STELLAR, and FORWARC, did not address the LPLN, and none of these trials included LPLN in their protocol or results. RAPIDO trial was a study on locally advanced rectal cancers, and the objective was to reduce distant failure [6]. The 3-year result was promising with a higher pCR rate, however, the 5-year outcome showed that locoregional failure was higher in the experimental arm as compared to the conventional LCCRT group (12% vs 8%). Multivariate analysis showed that the presence of enlarged LPLN was significantly associated with the local recurrence rate in the experimental group (p=0.042) [17]. This raised the question regarding the possibility of SCRT being less effective in treating the LPLN as compared to LCCRT. In our study, the TNT group, which followed a treatment regimen similar to the RAPIDO trial and included high-risk patients comparable to the RAPIDO cohort, demonstrated a pathology-negative rate for LPLN comparable to that of the LCCRT group. However, both regimens still exhibited high nodal positivity rates, indicating that CRT alone, or even TNT, is insufficient, and LPLND remains necessary after both treatment strategies. It is important to note, however, that the efficacy of TNT in treating LPLN may have been underestimated due to inherent bias within our cohort. As patients with high-risk and metastatic rectal cancers are more likely to benefit from TNT, balancing the baseline characteristics between TNT and LCCRT groups for direct comparison would be both impractical and ethically inappropriate. Designing a study to achieve a perfectly balanced cohort by ignoring the established benefits of TNT in such cases could compromise patient care. Therefore, while baseline differences are inevitable, they reflect the clinical reality that TNT is prioritized for patients at higher risk, and this should be acknowledged when interpreting the results. Beets et. al revisited the OPRA trial and analysed the subgroup of 57 patients with positive LPLN [18]. Here, TNT (LCCRT and chemotherapy) was given to all patients. The complete regression rate was 53%, and the disease recurrence was significantly low (3.5%). All patients with recurrence in LPLN also had distant metastasis, and LPLND was performed only in 3 patients. In this study, more than half (30 patients) achieved complete regression of LPLNs with LCCRT and this figure is slightly higher than our study (53% VS 48.3%). However, the high nodal response rate and the low recurrence rate can be explained by the tumour histology of this subgroup, where all the positive LPLN patients had low-grade tumours with no information about mesorectal involvement and EMVI as compared to subjects in the RAPIDO group and our patients. Another possibility would be the combination of LCCRT and the longer duration of the chemotherapy may have improved the response rate. The main limitation of our study is the inherent bias between the two groups, with the TNT group containing more stage four cases and high-risk features. Balancing these risk factors across both groups would improve the study’s accuracy, but this is challenging, as high-risk cancer cases, such as those with a propensity for distant metastasis (e.g., EMVI and positive nodes) or existing metastasis, typically require chemotherapy in addition to radiotherapy rather than radiotherapy alone. Despite these challenges, our study aims to specifically assess how these two neoadjuvant regimens affect LPLNs, assuming their response is independent of metastatic status. Our primary focus remains on evaluating LPLN response rather than overall survival or disease-free survival outcomes. Other drawbacks are; (I)It is a single-center study, (II) The sample size is small, (III) The data was collected retrospectively, (IV) There was no strict protocol in the treatment regime, and (V) We did not look at the recurrence rate. Our study concludes that SCRT with consolidation chemotherapy and LCCRT provide a similar nodal response to LPLNs. Both regimes do not treat the nodal disease completely and in fact, there are a significant number of non-responders who need further treatment. At this point, patients with positive LPNDs are best treated with neoadjuvant chemoradiation or TNT, followed by surgery based on post-radiation MRI imaging. Declarations Author Contribution 1. Study concepts and design: Avanish Saklani;2. Manuscript preparation (Wrote the main manuscript): Subhathira Manohkaran;3. Manuscript editing: Subhathira Manohkaran, Avanish Saklani, Mufaddal Kazi, Tejas Vispute;4. Data acquisition: Karthik Prakash, Akash Mor;5. Quality control of data and algorithms: Avanish Saklani, Suman Kumar, Ashwin Desouza;6. Statistical analysis and interpretation: Subhathira Manohkaran, Mufaddal Kazi;7. All authors reviewed the manuscript Conflict Of Interest We declare that there are no conflicts of interest, and no financial incentives influenced the content. Data Availability Statement The data of this study are available from the corresponding author upon reasonable request. PROVENANCE AND PEER REVIEW Not commissioned, externally peer-reviewed Funding/Support: None reported. Financial Disclosure: None reported. References You, Y. N., Hardiman, K. M., Bafford, A., Poylin, V., Francone, T. D., Davis, K., … Feingold, D. L. (2020). The American society of colon and rectal surgeons clinical practice guidelines for the management of rectal cancer. Diseases of the Colon & Rectum, 63 (9), 1191–1222. Langenfeld, S. J., Davis, B. R., Vogel, J. D., Davids, J. S., Temple, L. K., Cologne, K. G., … Paquette, I. M. (2024). The American Society of Colon and Rectal Surgeons clinical practice guidelines for the management of rectal cancer 2023 Supplement. Diseases of the Colon & Rectum, 10–1097. Singhal, N., Bankar, S., & Saklani, A. Lateral Pelvic Lymph Node Dissection in Rectal Cancers. Does it have a Place in Era of Neoadjuvant Chemoradiation. 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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-5858266","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":442177733,"identity":"34975a44-c0d8-483d-85e4-f64acecc6892","order_by":0,"name":"Subhathira Manohkaran","email":"","orcid":"","institution":"Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI)","correspondingAuthor":false,"prefix":"","firstName":"Subhathira","middleName":"","lastName":"Manohkaran","suffix":""},{"id":442177734,"identity":"9b20b90b-a27c-4cbf-bf39-6b87657a2e91","order_by":1,"name":"Tejas Vispute","email":"","orcid":"","institution":"Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI)","correspondingAuthor":false,"prefix":"","firstName":"Tejas","middleName":"","lastName":"Vispute","suffix":""},{"id":442177735,"identity":"d33d0920-2642-4dfd-bf99-ef6570f7c30e","order_by":2,"name":"Akash Mor","email":"","orcid":"","institution":"Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI)","correspondingAuthor":false,"prefix":"","firstName":"Akash","middleName":"","lastName":"Mor","suffix":""},{"id":442177736,"identity":"eed638f3-2cd4-4cd5-a510-6bbc050e976d","order_by":3,"name":"Kartik Prakash","email":"","orcid":"","institution":"Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI)","correspondingAuthor":false,"prefix":"","firstName":"Kartik","middleName":"","lastName":"Prakash","suffix":""},{"id":442177737,"identity":"51c14beb-2437-4e94-9d55-8abdfe10d824","order_by":4,"name":"Mufaddal Kazi","email":"","orcid":"","institution":"Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI)","correspondingAuthor":false,"prefix":"","firstName":"Mufaddal","middleName":"","lastName":"Kazi","suffix":""},{"id":442177738,"identity":"98ec420f-a970-4f5f-8c97-0d5a570f708a","order_by":5,"name":"Ankit Sharma","email":"","orcid":"","institution":"Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI)","correspondingAuthor":false,"prefix":"","firstName":"Ankit","middleName":"","lastName":"Sharma","suffix":""},{"id":442177739,"identity":"6a0c1431-62b4-4be3-9eb1-70090b69d492","order_by":6,"name":"Suman Kumar Ankathi","email":"","orcid":"","institution":"Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI)","correspondingAuthor":false,"prefix":"","firstName":"Suman","middleName":"Kumar","lastName":"Ankathi","suffix":""},{"id":442177740,"identity":"d17461ca-fd4b-47a5-9f15-deeef8b1b0db","order_by":7,"name":"Ashwin Desouza","email":"","orcid":"","institution":"Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI)","correspondingAuthor":false,"prefix":"","firstName":"Ashwin","middleName":"","lastName":"Desouza","suffix":""},{"id":442177741,"identity":"7b84e3de-f9bb-4c0b-9989-1fd91d5d4ddf","order_by":8,"name":"Avanish Saklani","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA20lEQVRIie3PsQrCMBCA4ROhLgddI4i+QkqguPkqKUKndHIVEQqOuhZ8CcEXCATTsWtAB1FwFgodi9FVqXVzyD8lcB/JAbhc/1kXzgDok9eFDNoRbkk/g87SEmxNgJoXge/E36gr5fPTgB3T/GLmY4SeOuyaCDEx41zfMDzpKBXafgzj2DQ+Y4BJ7ikMjQhS4VlC7LlJjIq8lLxWyLInqVsQKgXj0UohJZYkqxYkMGJGo7VCu1S0TdYEvW+7DIt8T+6VmvjZVJaiWgz9ntLN67/l/Tbucrlcrk89AH6lSEy/ZaEhAAAAAElFTkSuQmCC","orcid":"","institution":"Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute (HBNI)","correspondingAuthor":true,"prefix":"","firstName":"Avanish","middleName":"","lastName":"Saklani","suffix":""}],"badges":[],"createdAt":"2025-01-19 07:53:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5858266/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5858266/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10151-025-03177-5","type":"published","date":"2025-07-25T15:57:21+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":80789755,"identity":"6761a716-b0d9-43be-8e71-eb8e53241994","added_by":"auto","created_at":"2025-04-17 06:36:34","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":63309,"visible":true,"origin":"","legend":"\u003cp\u003eConsort diagram of patient selection\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-5858266/v1/48f999f1c03f5a04d95d5e3f.png"},{"id":80790969,"identity":"78616db0-ecdf-428c-b1b0-deb4df1d0e61","added_by":"auto","created_at":"2025-04-17 06:44:34","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":33347,"visible":true,"origin":"","legend":"\u003cp\u003eEstimated Marginal means for type of radiation with nodal response (controlled for M stage, Histopathology, and EMVI)\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-5858266/v1/321a761b6be289c3e76f61ca.png"},{"id":88506156,"identity":"abfb3d8d-428d-4fc9-a655-f6a73c2004ac","added_by":"auto","created_at":"2025-08-07 07:31:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":863690,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5858266/v1/c596a232-b64d-4759-a76d-cf3575fdedf8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Neoadjuvant Therapy For Lateral Pelvic Lymph Nodes: Choosing Between Long Course Chemoradiation Or Short Course Radiotherapy With Consolidation Chemotherapy","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eThe treatment of rectal cancer is complex and requires a multidisciplinary approach. Advances such as total mesorectal excision (TME) and neoadjuvant therapy have improved patient outcomes; however, local recurrence continues to occur in a significant number of cases [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Mid and low rectal cancers are known to metastasize to lateral pelvic lymph nodes (LPLNs), primarily to the internal iliac and obturator basins, which is a well-documented pathway for lateral pelvic recurrence. The reported incidence of lateral node involvement in low to mid rectal cancer ranges from 10\u0026ndash;27% [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe management of enlarged LPLNs is continuously evolving, with several treatment options available, including neoadjuvant chemotherapy, radiation therapy, radiation boosts, and total neoadjuvant therapy (TNT) (5). When residual nodes are present, lateral pelvic lymph node dissection (LPLND) may be performed; however, this surgical procedure is technically challenging, particularly following radiation therapy. In the RAPIDO, PRODIGE 23, and OPRA trials, TNT has been utilized in patients with LPLN involvement. However, the specifics of management and outcomes for these nodes have not been thoroughly addressed [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study aims to evaluate whether TNT (short-course radiotherapy (SCRT) with consolidation chemotherapy) can achieve a better response in LPLN shrinkage and reduce the need for LPLND. By concentrating on nodal size reduction, we aim to gain insight into how these regimens influence LPLNs size, a crucial aspect of treatment efficacy, that was not addressed in previous studies.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eThis is a retrospective study from a prospectively maintained database. The study was conducted in a high-volume tertiary cancer center in Mumbai, India (Tata Memorial Hospital). All patients with rectal adenocarcinoma registered between January 2020 and December 2021, who had radiologically positive LPLNs, including metastatic cases, were included in the study.\u003c/p\u003e \u003cp\u003eCriteria for positive LPLNs were based on MRI imaging, where a short-axis diameter of \u0026ge;\u0026thinsp;7 mm on the baseline MRI was considered significant. MRI interpretation was performed by two oncologists subspecialized in abdominal and oncoimaging, each with more than ten years of experience in interpreting rectal MRIs. The short-axis diameter of each LPLN was measured on the baseline MRI and reassessed on post-neoadjuvant MRI to evaluate size reduction. If multiple nodes or bilateral LPLNs were present, the largest node was selected for analysis. Measurements were recorded in millimetres to the first decimal place, ensuring consistency with baseline documentation.\u003c/p\u003e \u003cp\u003eThis cohort was classified into two groups based on neoadjuvant treatment: the LCCRT and TNT groups. The multidisciplinary tumor board decided on the treatment regimen based on risk factors and patients\u0026rsquo; logistical considerations. In cases with metastatic disease, TNT was preferred. Patients from other regions of the country who were unable to stay for the full 6-week treatment period due to financial constraints and logistical reasons were offered SCRT at our institution, followed by chemotherapy administered in medical centers closer to their homes.\u003c/p\u003e \u003cp\u003eIn the LCCRT group, radiation therapy of 50 Gray over 25 fractions was administered to the primary tumor and regional nodes including the LPLN, with or without simultaneous or sequential integrated boost. In the TNT group, radiation therapy of 25 Gray over 5 fractions was given to the primary tumor and regional nodes, followed by 4 to 6 cycles of chemotherapy (CAPEOX, FOLFOX or FOLFIRINOX). FOLFIRINOX was specifically given to those patients with metastatic disease and had high-risk features (poorly differentiated, EMVI), who had the potential for curative resection.\u003c/p\u003e \u003cp\u003eReassessment MRI was performed 6 to 8 weeks after the last fraction of radiotherapy in the LCCRT group. In the TNT group, a reassessment MRI was performed upon completion of consolidation chemotherapy, either just before or immediately after the last cycle. Patients were reassessed in the tumor board; post-neoadjuvant scans were evaluated for response, and decisions were made regarding further management. For patients with a good response and resectable disease based on the re-evaluation scan, surgery was planned to achieve curative resection. Patients whose re-evaluation scans showed unresectable disease were managed with palliative intent, and no further surgery was performed. Definitive surgery was performed 8 to 12 weeks post-LCCRT and 4 to 6 weeks after the last cycle of chemotherapy in the TNT group. LPLND was performed selectively when residual nodes larger than 4 mm were observed on reassessment MRI.\u003c/p\u003e \u003cp\u003eThe primary outcome that we are evaluating in this study is the degree of nodal size reduction in response to TNT versus LCCRT. We hypothesize that TNT, which combines chemotherapy and radiotherapy, leads to greater LPLNs shrinkage compared to LCCRT alone. The secondary outcome is the pathological positivity rate in LPLND specimens after neoadjuvant treatment. This study focuses solely on assessing the response of LPLNs to these treatments, under the assumption that their local response remains consistent regardless of metastatic status, rather than evaluating overall survival or disease-free survival outcomes.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eSPSS Version 28.0 by IBM was used for statistical analysis. Categorical values are presented as frequencies and percentages and a chi-squared test was used for statistical comparison. Continuous variables are presented in mean and independent t-test used for statistical comparison. To account for baseline differences between the groups, a multivariable linear regression was performed. Covariates that showed significant differences between the groups were included in the model.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEthics\u003c/h3\u003e\n\u003cp\u003eThe study protocol followed the ethical standards of the institutional research committee with approval from the institutional ethics committee (Ref: IRB project No:4570). The local ethics committee waived the requirement for informed consent because of the retrospective nature of the study and the use of anonymized patient data. This study adheres to the STROBE guidelines.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eA total of 1,200 cases of rectal cancer were registered between January 2020 and December 2021, of which 160 (13.3%) had positive LPLN (baseline nodal size \u0026ge;7 mm). Hundred and forty-two patients received neoadjuvant radiation treatment, whereas 18 patients did not receive radiotherapy (palliative systemic treatment with no reassessment). Sixty-one patients received LCCRT, and 81 patients received TNT (SCRT with consolidation chemotherapy).\u003c/p\u003e\n\u003cp\u003eTwo types of chemotherapy regimens were used in the TNT group: FOLFOX/CAPOX (82%) and FOLFIRINOX (18%). The chemotherapy completion rate was 80%. The median number of chemotherapy cycles administered was four.\u003c/p\u003e\n\u003cp\u003eFourteen patients in the LCCRT group and 33 in the TNT group did not proceed to surgery. Among them, 5 in the LCCRT group and 30 in the TNT group were deemed unresectable based on reassessment MRI and CT scans and were classified as palliative cases. The remaining 9 patients in the LCCRT group and 3 in the TNT group were lost to follow-up. These patients were included in the analysis of LPLN size reduction, as they had received radiation therapy and underwent reassessment MRI for evaluation.\u003c/p\u003e\n\u003cp\u003eBaseline characteristics are shown in Table 1. There were more male patients in both groups; the mean age was 50 years (range: 23\u0026ndash;77) in LCCRT group and 48 years (range: 22\u0026ndash;80) in TNT group 2, with no significant difference between groups (p = 0.451). More than half of these patients had low rectal tumours (68.9% and 59.3%). There were no statistically significant differences in T and N staging between the two groups; however, there were more metastatic patients in the TNT group (11.5%, vs. 43.2%, p\u0026lt;0.001). There were significantly more poorly differentiated and signet cell tumours in the TNT group (21.3% vs. 39.5%, p=0.021), and extramural venous invasion (EMVI) was also more prevalent in the TNT cohort (37.7% vs. 64.2% p=0.002).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eTable 1: Baseline Characteristic\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"606\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003eLCCRT (61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003eTNT (81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eMale\u003c/li\u003e\n \u003cli\u003eFemale\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e60.7% (37)\u003c/p\u003e\n \u003cp\u003e39.3% (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e65.4% (53)\u003c/p\u003e\n \u003cp\u003e34.6% (28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.559\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eMean\u003c/li\u003e\n \u003cli\u003eMedian\u003c/li\u003e\n \u003cli\u003eRange\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003cp\u003e23-77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003cp\u003e22-80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.451\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eLocation\u0026nbsp;\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eHigh rectal\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMid rectal\u003c/li\u003e\n \u003cli\u003eLow rectal\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4.9% (3)\u003c/p\u003e\n \u003cp\u003e26.2% (16)\u003c/p\u003e\n \u003cp\u003e68.9% (42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16.0% (13)\u003c/p\u003e\n \u003cp\u003e24.7% (20)\u003c/p\u003e\n \u003cp\u003e59.3% (48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.113\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eT Staging\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eT2\u003c/li\u003e\n \u003cli\u003eT3\u003c/li\u003e\n \u003cli\u003eT4\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003cp\u003e59.0% (36)\u003c/p\u003e\n \u003cp\u003e41.0% (25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.5% (2)\u003c/p\u003e\n \u003cp\u003e39.5% (32)\u003c/p\u003e\n \u003cp\u003e58.0% (47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.089\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eN Staging\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eN1\u003c/li\u003e\n \u003cli\u003eN2\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9.8% (6)\u003c/p\u003e\n \u003cp\u003e90.2% (55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10.6% (9)\u003c/p\u003e\n \u003cp\u003e89.4 (72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.807\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eM Staging\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e11.5% (7 pt)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e43.2% (35pt)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eHistopathology\u0026nbsp;\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eWell differentiated\u003c/li\u003e\n \u003cli\u003ePoorly differentiated \u0026amp; signet\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e78.7% (48)\u003c/p\u003e\n \u003cp\u003e21.3% (13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e60.5% (49)\u003c/p\u003e\n \u003cp\u003e39.5% (32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eEMVI positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e37.7% (23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e64.2% (52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eEMVI: Extramural venous invasion\u003c/p\u003e\n\u003cp\u003eA multivariable linear regression was performed for the variables that showed significant differences between the two groups (histology, EMVI, and metastatic status). After controlling for baseline differences, the reduction in nodal size was not significantly different between the LCCRT and TNT groups (Figure 2, Table 2, and Table 4).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eTable 2: Linear regression for LPLN response with covariates that are different on baseline characteristics\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"601\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePredictor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEstimate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u003cstrong\u003et\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLower Bound 95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUpper Bound 95% CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003eHistology Type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e-2.064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0.896\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e-2.305\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e-3.839\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e-0.289\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003eEMVI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;-0.728\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0.805\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e-0.904\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e-4.125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e-0.114\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003eM stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e-2.119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e1.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e-2.095\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 86px;\"\u003e\n \u003cp\u003e0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e-2.325\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e0.868\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 164px;\"\u003e\n \u003cp\u003eType of Neoadjuvant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;-1.464\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e0.839\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e-1.745\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003e\n \u003cp\u003e0.084\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e-3.127\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e0.199\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eEMVI: Extramural vascular invasion\u003c/p\u003e\n\u003cp\u003eTable 3 shows the LPLNs profile. Bilateral LPLNs was seen in 31.1% in the LCCRT group and 43.2% in the TNT group. The baseline nodal size in both groups was almost the same, with mean sizes of 11 mm in the LCCRT group and 10.8 mm in the TNT group, whereas post-neoadjuvant treatment, the sizes were 5.3 mm and 6.2 mm, respectively. The shrinkage was 5.7 mm in the LCCRT group and 4.6 mm in the TNT group. Although the mean nodal size reduction and nodal size reduction to \u0026lt;4mm higher in the LCCRT group, the differences were not statistically significant (p=0.136 and p=0.54).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eTable 3: LPLN Profile\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"606\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003eLCCRT (n=61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003eTNT(n=81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eBilateral LPLNs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e19 (31.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e35 (43.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e0.143\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eMean baseline LPLN size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e11.0 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e10.8 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e0.809\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eMean size post neoadjuvant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e5.3 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e6.2 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e0.337\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eMean nodal size reduction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e5.7 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e4.6 mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e0.136\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 252px;\"\u003e\n \u003cp\u003eNodal size \u0026lt;4mm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e29 (48.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e27 (42.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eMultivariate logistic regression analysis (Table 4) identified pretreatment nodal size as the only significant predictor of LPLN response. A larger pretreatment nodal size was associated with a lower likelihood of achieving a response (\u0026lt;4 mm) (OR: 0.84, 95% CI: 0.73\u0026ndash;0.94, p = 0.005).\u003c/p\u003e\n\u003cp\u003eThe type of neoadjuvant therapy showed a trend toward significance, with TNT demonstrating a lower likelihood of LPLN response compared to LCRT (OR: 0.48, 95% CI: 0.23\u0026ndash;1.01, p=0.054). While this finding did not reach conventional statistical significance, it suggests a potential difference in nodal response between treatment modalities, possibly due to a higher proportion of high-risk tumours in the TNT group.\u003c/p\u003e\n\u003cp\u003eOther factors, including tumour location, histological subtype, EMVI status, T stage, and N stage, did not show a significant association with LPLN response.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eTable 4: Multivariate Logistic Regression Analysis for LPLN Response (\u0026lt;4 mm vs. \u0026ge;4 mm)\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"557\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDependent: LPLN Response\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR (univariable)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR (multivariable)\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTumour location\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eMid rectum\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e33 (63.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e19 (36.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eLow rectum\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e62 (68.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e28 (31.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e0.78 (0.38-1.62, p=0.508)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHistological subtype\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eWell/Moderate\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e60 (61.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e37 (38.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003ePoor/signet\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e35 (77.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e10 (22.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e0.46 (0.20-1.02, p=0.064)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMucinous\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e31 (75.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e10 (24.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e64 (63.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e37 (36.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e1.79 (0.81-4.23, p=0.163)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT stage\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eT3\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e43 (61.4)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e27 (38.6)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eT4a\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e14 (70.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e6 (30.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e0.68 (0.22-1.93, p=0.484)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eT4b\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e38 (73.1)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e14 (26.9)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e0.59 (0.26-1.27, p=0.180)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN stage\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eN1\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e9 (60.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e6 (40.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eN2\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e86 (67.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e41 (32.3)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e0.72 (0.24-2.26, p=0.549)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEMVI\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e51 (68.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e24 (32.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eNo\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e44 (65.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e23 (34.3)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e1.11 (0.55-2.24, p=0.769)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePretreatment nodal Size\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eMean (SD)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e11 (5.3)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e9 (2.7)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e0.85 (0.74-0.94, p=0.006)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e0.84\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(0.73-0.94, p=0.005)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNeoadjuvant therapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eLCCRT\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e36 (59.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e25 (41.0)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e-\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eTNT\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e59 (72.8)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58px;\"\u003e\n \u003cp\u003e22 (27.2)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 140px;\"\u003e\n \u003cp\u003e0.54 (0.26-1.09, p=0.085)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 114px;\"\u003e\n \u003cp\u003e0.48\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(0.23-1.01, p=0.054)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt the end of neoadjuvant treatment, fewer patients underwent surgery in the TNT group. Surgery was performed on 47 patients (77%) in the LCCRT group and, 48 patients (59%) in the TNT group. Among the operated patients, LPLND was performed in 22 patients (46.8%) in LCCRT group, and 26 patients (54.1%) in TNT group. The pathological positivity rate for LPLN was almost similar in both groups, with no statistical significance (27.3% vs. 23.1%, p=0.731). Pathological complete response (pCR) of the rectal tumour was observed in 10.6% of patients in the LCCRT group and 14.6% in the TNT group. None of the pCR patients had positive LPLN in the resected specimen.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eTable 5: Pathology results\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 228px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eLCCRT (n=47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003eTNT (n=48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 228px;\"\u003e\n \u003cp\u003eLPLND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e22 (46.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e26 (54.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e0.537\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 228px;\"\u003e\n \u003cp\u003eLPLNs pathological positivity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e6 (27.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e6 (23.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e0.731\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 228px;\"\u003e\n \u003cp\u003epCR in the primary lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e5 (10.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 126px;\"\u003e\n \u003cp\u003e7 (14.6%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 115px;\"\u003e\n \u003cp\u003e0.619\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eLPLND: Lateral Pelvic Lymph Nodes Dissection; pCR: Pathological complete response\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe response of LPLNs to different types of neoadjuvant treatment in rectal cancer has not been extensively studied. TNT is a novel strategy for rectal cancer that gained popularity after the RAPIDO, PRODIGE-23 and OPRA trials [6,7,8]. These trials demonstrated higher rates of clinical complete response (cCR) and pathological complete response (pCR), but their effects on LPLNs remain unexplored. The possibility of TNT achieving a similar response in LPLN and potentially reducing the need for LPLND remains inadequately explored. This is the first study that directly compares TNT with LCCRT in terms of LPLN downstaging. Our study showed no differences in the efficacy of the two regimes in downstaging LPLN. The pathological positivity rate in lateral pelvic lymph node dissection specimens was also almost similar in both groups with no significant statistical differences.\u003c/p\u003e\n\u003cp\u003eNeoadjuvant radiotherapy has been shown to downstage and potentially sterilize mesorectal and LPLNs, as evidenced by the Dutch TME and MERCURY trials.\u0026nbsp;[9,10]. However, LPLN does not completely regress in all cases.\u0026nbsp;Akiyoshi et al. found that two-thirds of patients had lymph node metastasis in\u0026nbsp;LPLND specimens after neoadjuvant radiotherapy, with no local recurrences observed in those who underwent LPLND after radiotherapy\u0026nbsp;[11]. This finding highlights the therapeutic value of LPLND. Similarly, Kim et al. demonstrated that lateral pelvic recurrence was a major contributor to locoregional recurrence in patients who received neoadjuvant radiotherapy followed by TME without LPLND\u0026nbsp;[12].\u003c/p\u003e\n\u003cp\u003eVarious nodal sizes have been used to define positive LPLN in pre and post-radiotherapy imaging, which ranging from 5mm to 10mm [13,14,15]. During the study period (January 2020 to December 2021), our practice was based on the best available evidence at the time, defining LPLNs with a short axis of \u0026ge;7mm before neoadjuvant treatment as positive and considering nodes \u0026gt;4mm post-treatment as indications for LPLND [16].\u0026nbsp;This approach aligns with Ogura et al.\u0026apos;s findings based on an analysis of 1216 rectal cancer patients with LPLN. A baseline LPLN with a short axis of \u0026ge;7mm resulted in a significantly higher risk of lateral local recurrence without LPLND (19.5% vs 5.7%) [14]. They also reported that nodes measuring \u0026le;4mm on the internal iliac and \u0026le;6mm on the obturator on restaging MRI did not necessitate LPLND, with a 0% recurrence rate over three years. [16]. However, all these data were derived from the LCCRT cohort. The effect of TNT or SCRT has not been studied before.\u003c/p\u003e\n\u003cp\u003eThe presence of LPLN has been reported in two main TNT trials: the RAPIDO (15%) and PRODIGE 23 (10%). Other trials, such as POLISH 2, STELLAR, and FORWARC, did not address the LPLN, and none of these trials included LPLN in their protocol or results. RAPIDO trial was a study on locally advanced rectal cancers, and the objective was to reduce distant failure [6]. The 3-year result was promising with a higher pCR rate, however, the 5-year outcome showed that locoregional failure was higher in the experimental arm as compared to the conventional LCCRT group (12% vs 8%). Multivariate analysis showed that the presence of enlarged LPLN was significantly associated with the local recurrence rate in the experimental group (p=0.042) [17]. This raised the question regarding the possibility of SCRT being less effective in treating the LPLN as compared to LCCRT. In our study, the TNT group, which followed a treatment regimen similar to the RAPIDO trial and included high-risk patients comparable to the RAPIDO cohort, demonstrated a pathology-negative rate for LPLN comparable to that of the LCCRT group. However, both regimens still exhibited high nodal positivity rates, indicating that CRT alone, or even TNT, is insufficient, and LPLND remains necessary after both treatment strategies.\u003c/p\u003e\n\u003cp\u003eIt is important to note, however, that the efficacy of TNT in treating LPLN may have been underestimated due to inherent bias within our cohort. As patients with high-risk and metastatic rectal cancers are more likely to benefit from TNT, balancing the baseline characteristics between TNT and LCCRT groups for direct comparison would be both impractical and ethically inappropriate. Designing a study to achieve a perfectly balanced cohort by ignoring the established benefits of TNT in such cases could compromise patient care. Therefore, while baseline differences are inevitable, they reflect the clinical reality that TNT is prioritized for patients at higher risk, and this should be acknowledged when interpreting the results.\u003c/p\u003e\n\u003cp\u003eBeets et. al revisited the OPRA trial and analysed the subgroup of 57 patients with positive LPLN [18]. Here, TNT (LCCRT and chemotherapy) was given to all patients. The complete regression rate was 53%, and the disease recurrence was significantly low (3.5%). All patients with recurrence in LPLN also had distant metastasis, and LPLND was performed only in 3 patients. In this study, more than half (30 patients) achieved complete regression of LPLNs with LCCRT and this figure is slightly higher than our study (53% VS 48.3%). However, the high nodal response rate and the low recurrence rate can be explained by the tumour histology of this subgroup, where all the positive LPLN patients had low-grade tumours with no information about mesorectal involvement and EMVI as compared to subjects in the RAPIDO group and our patients. Another possibility would be the combination of LCCRT and the longer duration of the chemotherapy may have improved the response rate.\u003c/p\u003e\n\u003cp\u003eThe main limitation of our study is the inherent bias between the two groups, with the TNT group containing more stage four cases and high-risk features. Balancing these risk factors across both groups would improve the study\u0026rsquo;s accuracy, but this is challenging, as high-risk cancer cases, such as those with a propensity for distant metastasis (e.g., EMVI and positive nodes) or existing metastasis, typically require chemotherapy in addition to radiotherapy rather than radiotherapy alone. Despite these challenges, our study aims to specifically assess how these two neoadjuvant regimens affect LPLNs, assuming their response is independent of metastatic status. Our primary focus remains on evaluating LPLN response rather than overall survival or disease-free survival outcomes. Other drawbacks are; (I)It is a single-center study, (II) The sample size is small, (III) The data was collected retrospectively, (IV) There was no strict protocol in the treatment regime, and (V) We did not look at the recurrence rate.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur study concludes that SCRT with consolidation chemotherapy and LCCRT provide a similar nodal response to LPLNs. Both regimes do not treat the nodal disease completely and in fact, there are a significant number of non-responders who need further treatment. At this point, patients with positive LPNDs are best treated with neoadjuvant chemoradiation or TNT, followed by surgery based on post-radiation MRI imaging.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003e1. Study concepts and design: Avanish Saklani;2. Manuscript preparation (Wrote the main manuscript): Subhathira Manohkaran;3. Manuscript editing: Subhathira Manohkaran, Avanish Saklani, Mufaddal Kazi, Tejas Vispute;4. Data acquisition: Karthik Prakash, Akash Mor;5. Quality control of data and algorithms: Avanish Saklani, Suman Kumar, Ashwin Desouza;6. Statistical analysis and interpretation: Subhathira Manohkaran, Mufaddal Kazi;7. All authors reviewed the manuscript\u003c/p\u003e \u003cp\u003e\u003cstrong\u003e\u003cu\u003eConflict Of Interest\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe declare that there are no conflicts of interest, and no financial incentives influenced the content.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eData Availability Statement\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003ePROVENANCE AND PEER REVIEW\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot commissioned, externally peer-reviewed\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding/Support:\u0026nbsp;\u003c/strong\u003eNone reported.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial Disclosure:\u0026nbsp;\u003c/strong\u003eNone reported.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eYou, Y. N., Hardiman, K. M., Bafford, A., Poylin, V., Francone, T. D., Davis, K., \u0026hellip; Feingold, D. L. (2020). The American society of colon and rectal surgeons clinical practice guidelines for the management of rectal cancer. Diseases of the Colon \u0026amp; Rectum, \u003cem\u003e63\u003c/em\u003e(9), 1191\u0026ndash;1222.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLangenfeld, S. J., Davis, B. R., Vogel, J. D., Davids, J. S., Temple, L. K., Cologne, K. G., \u0026hellip; Paquette, I. M. (2024). The American Society of Colon and Rectal Surgeons clinical practice guidelines for the management of rectal cancer 2023 Supplement. Diseases of the Colon \u0026amp; Rectum, 10\u0026ndash;1097.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSinghal, N., Bankar, S., \u0026amp; Saklani, A. Lateral Pelvic Lymph Node Dissection in Rectal Cancers. Does it have a Place in Era of Neoadjuvant Chemoradiation. \u003cem\u003eWorld J Surg Surgical Res.\u003c/em\u003e 2020; \u003cem\u003e3\u003c/em\u003e, \u003cem\u003e1204\u003c/em\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOgawa, S., Itabashi, M., Inoue, Y., Ohki, T., Bamba, Y., Koshino, K., \u0026hellip; Yamamoto,M. (2021). Lateral pelvic lymph nodes for rectal cancer: a review of diagnosis and management. \u003cem\u003eWorld Journal of Gastrointestinal Oncology\u003c/em\u003e, \u003cem\u003e13\u003c/em\u003e(10), 1412.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRomero-Zoghbi, S. E., L\u0026oacute;pez-Campos, F., \u0026amp; Cou\u0026ntilde;ago, F. (2024). Management of lateral pelvic lymph nodes in rectal cancer: Is it time to reach an Agreement?. World Journal of Clinical Oncology, \u003cem\u003e15\u003c/em\u003e(4), 472.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBahadoer, R. R., Dijkstra, E. A., van Etten, B., Marijnen, C. A., Putter, H., Kranenbarg,E. M. K., \u0026hellip; Silviera, M. L. (2021). Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME,and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised,open-label, phase 3 trial. \u003cem\u003eThe Lancet Oncology\u003c/em\u003e, \u003cem\u003e22\u003c/em\u003e(1), 29\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eConroy, T., Bosset, J. F., Etienne, P. L., Rio, E., Fran\u0026ccedil;ois, \u0026Eacute;., Mesgouez-Nebout,N., \u0026hellip; Marquis, I. (2021). Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. \u003cem\u003eThe Lancet Oncology\u003c/em\u003e, \u003cem\u003e22\u003c/em\u003e(5), 702\u0026ndash;715.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarcia-Aguilar, J., Patil, S., Gollub, M. J., Kim, J. K., Yuval, J. B., Thompson,H. M., \u0026hellip; Saltz, L. B. (2022). Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. \u003cem\u003eJournal of clinical oncology\u003c/em\u003e, \u003cem\u003e40\u003c/em\u003e(23), 2546\u0026ndash;2556.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMERCURY STUDY: Brown, G., \u0026amp; Daniels, I. R. (2005). Preoperative staging of rectal cancer: the MERCURY research project. Rectal cancer treatment, 58\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTME TRIAL: Kusters, M., Marijnen, C. A., Van de Velde, C. J., Rutten, H. J., Lahaye,M. J., Kim, J. H., \u0026hellip; Beets, G. L. (2010). Patterns of local recurrence in rectal cancer;a study of the Dutch TME trial. \u003cem\u003eEuropean Journal of Surgical Oncology (EJSO)\u003c/em\u003e, \u003cem\u003e36\u003c/em\u003e(5), 470\u0026ndash;476.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkiyoshi T, Ueno M, Matsueda K, Konishi T, Fujimoto Y, Nagayama S, Fukunaga Y, Unno T, Kano A, Kuroyanagi H, Oya M, Yamaguchi T, Watanabe T, et al. Selective lateral pelvic lymph node dissection in patients with advanced low rectal cancer treated with preoperative chemoradiotherapy based on pretreatment imaging. Ann Surg Oncol. 2014; 21:189\u0026ndash;196.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim TH, Jeong SY, Choi DH, et al. Lateral lymph node metastasis is a major cause of locoregional recurrence in rectal cancer treated with preoperative chemoradiotherapy and curative resection. Ann Surg Oncol 2008;15:729\u0026ndash;37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalakorn S, Yang Y, Bednarski BK, Kaur H, You YN, Holliday EB, Dasari A, Skibber JM, Rodriguez-Bigas MA, Chang GJ. Who Should Get Lateral Pelvic Lymph Node Dissection After Neoadjuvant Chemoradiation? Dis Colon Rectum. 2019;62(10):1158\u0026ndash;1166. doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/DCR.0000000000001465\u003c/span\u003e\u003cspan address=\"10.1097/DCR.0000000000001465\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 31490825.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOgura A, Konishi T, Cunningham C, Garcia-Aguilar J, Iversen H, Toda S, et al. Neoadjuvant (Chemo) radiotherapy with total mesorectal excision only is not sufficient to prevent lateral local recurrence in enlarged nodes: results of the multicenter lateral node study of patients with low ct3/4 rectal cancer. J Clin Oncol. 2019;37(1):33\u0026ndash;43\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHassanzadeh, C., Mirza, K., Kalaghchi, B., Fallahian, F., Chin, R. I., Roy, A., \u0026hellip;Kim, H. (2024). Lateral Pelvic Nodal Management and Patterns of Failure in Patients Receiving Short-Course Radiation for Locally Advanced Rectal Cancer. \u003cem\u003eDiseases of the Colon \u0026amp; Rectum\u003c/em\u003e, \u003cem\u003e67\u003c/em\u003e(1), 54\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOgura A, Konishi T, Beets GL, Cunningham C, Garcia-Aguilar J, Iversen H, et al. Lateral nodal features on restaging magnetic resonance imaging associated with lateral local recurrence in low rectal cancer after neoadjuvant chemoradiotherapy or radiotherapy. JAMA Surg. 2019:e192172.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDijkstra, E. A., Nilsson, P. J., Hospers, G. A., Bahadoer, R. R., Kranenbarg, E. M.K., Roodvoets, A. G., \u0026hellip; Collaborative Investigators. (2023). Locoregional failure during and after short-course radiotherapy followed by chemotherapy and surgery compared with long-course chemoradiotherapy and surgery: a 5-year follow-up of the RAPIDO trial.\u003cem\u003eAnnals of surgery\u003c/em\u003e, \u003cem\u003e278\u003c/em\u003e(4), e766-e772\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBeets, N. R., Verheij, F. S., Williams, H., Omer, D. M., Lin, S. T., Qin, L. X., \u0026hellip;Garcia-Aguilar, J. (2024). Association of Lateral Pelvic Lymph Nodes with Disease Recurrence and Organ Preservation in Patients with Distal Rectal Adenocarcinoma Treated with Total Neoadjuvant Therapy. \u003cem\u003eAnnals of Surgery\u003c/em\u003e, 10-1097.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoshino, N., Fukui, Y., Ueno, K., Hida, K., Obama, K., Sakamoto, K., \u0026hellip; Ajioka, Y.(2024). Identification of lateral pelvic nodes without metastasis in patients with rectal cancer treated with preoperative chemoradiotherapy or chemotherapy based on magnetic resonance imaging. Annals of Gastroenterological Surgery.\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":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"techniques-in-coloproctology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"tcol","sideBox":"Learn more about [Techniques in Coloproctology](http://link.springer.com/journal/10151)","snPcode":"10151","submissionUrl":"https://submission.nature.com/new-submission/10151/3","title":"Techniques in Coloproctology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"LCCRT (Long Course Chemoradiotherapy), LPLNs (Lateral Pelvic Lymph Nodes), LPLND (Lateral Pelvic Lymph Nodes Dissection), SCRT (Short Course Radiotherapy), TNT (Total Neoadjuvant Therapy)","lastPublishedDoi":"10.21203/rs.3.rs-5858266/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5858266/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe response of lateral pelvic lymph nodes (LPLNs) to various neoadjuvant treatments has not been thoroughly investigated. This study aims to compare the effects of long-course chemoradiotherapy (LCCRT) and total neoadjuvant therapy (TNT), i.e., short-course radiotherapy (SCRT) with consolidation chemotherapy, on LPLNs size reduction. The secondary objective is to compare the pathological positivity rates of LPLNs dissection (LPLND), post-neoadjuvant treatment.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis is a retrospective analysis based on a prospectively maintained database. Rectal cancer patients registered between January 2020 and December 2021 with radiologically positive LPLNs who underwent neoadjuvant radiation therapy were included. Patients were divided into two groups: LCCRT and TNT.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 1,200 registered rectal cancer cases, 160 had positive LPLNs, with 142 included in the analysis. Sixty-one patients received LCCRT, and 81 patients received TNT. No significant differences were found in T and N staging between the groups. However, the TNT cohort had a significantly higher proportion of metastatic patients (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), poorly differentiated tumours (p\u0026thinsp;=\u0026thinsp;0.021), and extramural venous invasion (p\u0026thinsp;=\u0026thinsp;0.002). Baseline mean nodal sizes were similar between groups. Post-neoadjuvant nodal sizes were 5.3mm for LCCRT and 6.2mm for TNT, with mean reductions of 5.7mm and 4.6mm, respectively (p\u0026thinsp;=\u0026thinsp;0.136 \u0026amp; 0.54). Surgery was conducted in 77% of the LCCRT group and 59% of the TNT group, with 22 (46.8%) and 26 (54.1%) undergoing LPLND in their respective groups. The pathological positivity rates for LPLNs were similar (27.3% vs. 23.1%, p\u0026thinsp;=\u0026thinsp;0.731)\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eSCRT with consolidation chemotherapy does not provide a significant advantage over LCCRT in reducing LPLNs size or reducing the need for LPLND.\u003c/p\u003e","manuscriptTitle":"Neoadjuvant Therapy For Lateral Pelvic Lymph Nodes: Choosing Between Long Course Chemoradiation Or Short Course Radiotherapy With Consolidation Chemotherapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-17 06:36:29","doi":"10.21203/rs.3.rs-5858266/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-05-22T06:04:06+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-28T15:49:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-26T08:56:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"293403301168184964154726210255642620219","date":"2025-04-15T08:28:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"17087356573399261276481165735083570724","date":"2025-04-15T05:36:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-13T05:00:23+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-04T01:58:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"Techniques in Coloproctology","date":"2025-04-03T23:28:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"techniques-in-coloproctology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"tcol","sideBox":"Learn more about [Techniques in Coloproctology](http://link.springer.com/journal/10151)","snPcode":"10151","submissionUrl":"https://submission.nature.com/new-submission/10151/3","title":"Techniques in Coloproctology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"a43ddb43-9c0b-4f9b-bcee-dbd5f4ee2986","owner":[],"postedDate":"April 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-08-07T07:20:00+00:00","versionOfRecord":{"articleIdentity":"rs-5858266","link":"https://doi.org/10.1007/s10151-025-03177-5","journal":{"identity":"techniques-in-coloproctology","isVorOnly":false,"title":"Techniques in Coloproctology"},"publishedOn":"2025-07-25 15:57:21","publishedOnDateReadable":"July 25th, 2025"},"versionCreatedAt":"2025-04-17 06:36:29","video":"","vorDoi":"10.1007/s10151-025-03177-5","vorDoiUrl":"https://doi.org/10.1007/s10151-025-03177-5","workflowStages":[]},"version":"v1","identity":"rs-5858266","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5858266","identity":"rs-5858266","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}