Comparative analysis of oncological outcomes between trimodal therapy and radical cystectomy in muscle-invasive bladder cancer utilizing propensity score matching

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Methods: Patients treated with either TMT or RC for MIBC at our institution between January 1998 and December 2022 were included. Propensity score matching was used to compare cancer-specific survival and overall survival rates. Results: A total of 93 patients who underwent TMT and 84 who underwent RC for MIBC were analyzed. In the TMT cohort, the pathological complete response rate was 65%; the 5-year recurrence-free survival rate, including intravesical recurrence, was 41.1%; and the 5-year bladder intact event-free survival rate was 55.8%. Using propensity score matching, 66 patients from each treatment group were selected for a comparative analysis of oncological outcomes. The 5-year distant metastasis-free, cancer-specific, and overall survival rates were 64.3% and 51.8% (P=0.096), 83.3% and 69.2% (P=0.104), and 77.8% and 64.2% (P=0.274) for TMT and RC, respectively. Subgroup analyses revealed that TMT for primary tumors significantly improved cancer-specific survival rates compared with RC. The two treatment types had similar adverse events related to hematologic toxicity during perioperative chemotherapy. Conclusion: TMT exhibited oncological outcomes comparable to those of RC in the treatment of MIBC, indicating that TMT provides favorable outcomes, particularly in cases of primary MIBC. Muscle-invasive bladder cancer Trimodal therapy Radical cystectomy Chemoradiation Propensity score Survival Figures Figure 1 Figure 2 Introduction In 2020, bladder cancer was responsible for 573,000 new cases and 213,000 deaths globally [ 1 ]. It is the sixth most prevalent cancer in men, seventh in women, and tenth overall [ 1 , 2 ]. Approximately 75% of affected patients present with non-muscle invasive bladder cancer, which has a favorable prognosis [ 2 ]. Conversely, muscle-invasive bladder cancer (MIBC) has a poor prognosis, with 5-year overall survival (OS) and cancer-specific survival (CSS) rates of 69.1% and 73.1% post-radical cystectomy (RC), respectively [ 3 ]. In Japan, the established protocol for MIBC treatment involves neoadjuvant chemotherapy followed by RC, necessitating urinary tract alteration [ 4 ], which leads to a potential postoperative decline in quality of life and body image [ 5 ]. Despite the advent of less invasive techniques, total cystectomy remains invasive, possibly unsuitable for older adults or those with severe comorbidities [ 6 , 7 ]. Post-RC mortality rates are higher among octogenarians than among septuagenarians [ 8 ]. Bladder-sparing approaches are recommended to patients unfit for total bladder resection or those with T2 stage tumors without concurrent carcinoma in situ (CIS) [ 9 , 10 ]. Over a decade-long observation period, the 5-year recurrence-free survival (RFS) and OS rates for trimodal therapy (TMT) were 63% and 49%, respectively [ 11 ]. To date, no prospective randomized controlled trials have compared RC and TMT in MIBC treatment. In a recent multicenter, retrospective study in which propensity score-matched and weighted analysis were used, TMT and RC had comparable oncological outcomes in patients with MIBC [ 12 ]. While favorable outcomes for TMT in MIBC have been reported in Japan [ 13 , 14 ], comparative studies on oncological outcomes against RC are scarce. This study aimed to compare the oncological outcomes between TMT and RC for MIBC using a retrospective design and propensity score-matched analysis. Patients and methods Study design This study was a single-center retrospective study. The inclusion criteria were MIBC treatment (cT2-4N0-2M0) with RC or TMT at Yamaguchi University Hospital between January 1998 and December 2022. Patients previously subjected to radiotherapy for bladder cancer or treated with TMT non-curatively were excluded. Propensity scores were generated based on patient and tumor characteristics. Matching was performed using a caliper width of 0.2, comparing oncological outcomes between the TMT and RC cohorts. Surgical procedures for RC RC was conducted using open, laparoscopic, or robot-assisted techniques involving the resection of the bladder and prostate (men) or bladder and uterus (women), including the urethra. Lymph node dissection typically encompasses the common and external iliac, internal iliac, and obturator regions, with the method of urinary diversion at the surgeon’s discretion. Perioperative chemotherapy was administered predominantly following platinum-based regimens as recommended by the guidelines, subject to the treating physician’s judgment. TMT treatment protocol TMT was aimed at patients who were ineligible or refused RC and desired bladder preservation. Radiation therapy was administered at 1.8–2.0 Gy/day, totaling 48.6–60.0 Gy, focusing on true pelvic irradiation (excluding the common iliac lymph node area) and enhanced irradiation of the entire bladder. Chemotherapy options include cisplatin alone or in combination with gemcitabine. The gemcitabine plus cisplatin regimen was implemented in a phase 2 study [ 14 ]. The cisplatin regimen was administered at 70 mg/m 2 once every 2 weeks; the combined regimen was administered at 300 mg/m 2 gemcitabine and 30 mg/m 2 cisplatin once a week. Dose reductions in chemotherapy were implemented based on renal function and the occurrence of Grade 3 or higher adverse events. Statistical analysis Clinical and pathological parameters were compared using Fisher’s exact or Mann–Whitney U test. Survival rates were assessed using Kaplan–Meier plots and the log-rank test. RFS of bladder cancer was defined as the interval from treatment initiation to intravesical recurrence, extravesical recurrence, distant metastasis, or death from any cause. Bladder intact event-free survival was the interval from treatment initiation to MIBC occurrence, cystectomy for any cause, extravesical recurrence, distant metastasis, or death from any cause. RFS was the interval from treatment initiation to the MIBC recurrence, extravesical recurrence, distant metastasis, or death from any cause. Distant metastasis-free survival (DMFS) was the period from treatment initiation to the emergence of distant metastasis or death from any cause. CSS and OS were the time from treatment initiation to cancer-related death and time from treatment initiation to death from any cause, respectively. Pathological complete response (pCR) was the absence of malignant findings on histopathology following treatment. Pathological partial response (pPR) was defined as histopathological findings of less than stage pT2 (pTa, pT1, or pTis). Subgroup analyses via a Cox proportional hazards model were performed to identify patient and tumor factors. Adverse events related to chemotherapy and radiation therapy were assessed according to the Common Terminology Criteria for Adverse Events version 5.0, while postoperative complications were evaluated using the Clavien-Dindo classification. Statistical analyses were performed using JMP Pro version 15.0 (SAS, Cary, NC, USA), with a two-sided test significance level set at 5% and confidence interval estimation at 95%. Results Patient and tumor characteristics We reviewed 93 and 84 patients who underwent TMT and RC, respectively, for MIBC. Patient and tumor characteristics are shown in Table 1. The median follow-up period was 42.2 (interquartile range [IQR]: 19.7–104.8) and 36.5 (IQR: 19.6–88.5) months for the TMT and RC groups, respectively. After propensity score matching, 66 patients from each group were analyzed; patient or tumor characteristics were not significantly different. Outcomes of Each Treatment In the TMT cohort, 52 patients (56%) received cisplatin alone, whereas 41 (44%) were treated with combined gemcitabine and cisplatin. The median total radiation dose was 54.0 (IQR: 48.6–54.0) Gy. Post-TMT, immediate total cystectomy for residual tumor was required in four patients (4%); BCG intravesical therapy for residual CIS was administered to five patients (6%) (Table 2). The pCR and bladder preservation rates were 65% and 91%, respectively, for lesions less than pT2 (Table S1 ). The median RFS in the bladder after TMT was 23.3 months, with 5-year survival rates of 41.1% (Fig. S1 A). Additionally, 5-year bladder intact event-free survival rates were 55.8% (Fig. S1 B). In the RC cohort, neoadjuvant chemotherapy was administered to 60 patients (72%) and adjuvant chemotherapy to 13 (16%) (Table 2). Regarding the histopathological outcomes, the pCR and partial pathological response rates were 18% and 42%, respectively (Table S1 ). Comparison of TMT and RC oncological outcomes Oncological outcomes were compared between 66 matched cases each from the TMT and RC groups. The 2-year RFS rates were 72.4% for TMT and 59.2% for RC, with 5-year rates at 64.3% and 52.6%, respectively (p = 0.209, Fig. 1 A). The 2-year DMFS rates were 81.8% for TMT and 60.5% for RC, with 5-year rates at 64.3% and 51.8%, respectively, without significant differences (p = 0.096, Fig. 1 B). The 5-year CSS rates were 83.3% for TMT and 69.2% for RC (p = 0.104, Fig. 1 C), and the 5-year OS rates were 77.8% for TMT and 64.2% for RC, without significant differences (p = 0.274, Fig. 1 D). In subgroup analyses, TMT demonstrated superior CSS compared to RC for primary tumors (Fig. 2 ). Adverse events and postoperative complications Grade ≥ 3 neutropenia was observed in 48.1%, anemia in 14.3%, and thrombocytopenia in 20.8% of patients who underwent TMT (Table S2 ). Similar proportions were observed in patients who underwent RC and perioperative chemotherapy (47.1%, 14.7%, and 26.5%, respectively) (Table S2 ). Radiation-induced adverse events included grade 3 diarrhea (10.4%), noninfectious cystitis (3.9%), and rectal bleeding (2.6%), without grade 4 events (Table S2 ). Perioperative complications of RC included grade 3 ileus (10.6%), anastomotic leak (2.3%), and wound dehiscence (3.6%), without deaths related to perioperative complications (Table S3 ). Discussion This study evaluated the oncological outcomes of TMT and RC for MIBC treatment. Patient and tumor characteristics were closely matched using propensity score matching. No significant differences in DMFS, CSS, or OS were observed between the two treatment groups. However, the subgroup analysis indicated superior CSS with TMT in primary MIBC cases, compared with RC. Despite the higher proportion of older patients and those with poor performance status in the TMT group, the severity and frequency of adverse events were remarkably similar. Some systematic reviews and meta-analyses have indicated that RC for MIBC treatment yields better oncological outcomes than TMT, although other studies have suggested equivalent results between these treatments [ 15 – 17 ]. The variability in TMT outcomes has been attributed to diverse regimens and radiation doses employed. As RC is supported by substantial evidence as the standard treatment for MIBC and recommended by clinical guidelines, treatment outcomes are not significantly different among studies [ 4 , 18 ]. Reports of long-term outcomes of RC for MIBC treatment have shown 5-year survival rates of approximately 40–50% [ 18 , 19 ], and 50–60% with the addition of neoadjuvant chemotherapy [ 20 , 21 ]. In this study, the 5-year CSS and OS rates for the RC group were 69.2% and 64.2%, respectively, consistent with previously reported figures. Zlotta et al. documented 5-year metastasis-free survival, CSS, and OS rates of 74%, 85%, and 77%, respectively, for TMT in MIBC treatment [ 12 ]. Our findings for TMT were similar at 5-year DMFS, CSS, and OS rates of 64.3%, 83.3%, and 77.8%, respectively. Kulkarni et al. reported equivalent oncological outcomes for TMT and RC using propensity score matching [ 22 ]. However, a definitive comparison of oncological outcomes between TMT and RC for MIBC remains inconclusive owing to the absence of large prospective controlled studies. In this study, TMT led to better oncological outcomes of primary MIBC than RC. The literature presents varied results when comparing the oncological outcomes between primary and secondary MIBC [ 23 , 24 ]. Pones et al. found no significant differences in the oncological outcomes between primary and secondary MIBC after RC [ 23 ]. In contrast, Grossmann et al. observed that secondary MIBC was associated with significantly shorter CSS and OS following RC [ 24 ], similar to our finding. While most reports have focused on outcomes following RC, few studies have examined outcomes following TMT. More comprehensive studies are needed in this area, as secondary MIBC may exhibit a poorer prognosis than primary MIBC when treated with TMT. Recent clinical trials have explored the use of immune checkpoint inhibitors as bladder-sparing therapies, with some protocols omitting radiation therapy [ 25 ]. Kimura et al. reported a phase 2 trial in which bladder preservation therapy, combining atezolizumab with radiotherapy, was administered to patients with T2-3 MIBC and high-risk T1 [ 26 ]. This trial achieved a high pCR rate (84.4%) and low incidence of grade ≥ 3 adverse events (13.3%). Furthermore, Shen et al. demonstrated that neoadjuvant treatment of MIBC with immune checkpoint inhibitors and chemotherapy yielded a complete response in 50% of the patients, surpassing the outcomes of chemotherapy alone in terms of disease control and bladder-intact disease-free survival [ 27 ]. In the future, treatment with bladder preservation therapy may include immune checkpoint inhibitors or involve them as neoadjuvant therapy, with complete response cases treated with bladder preservation therapy and others with RC. This study had limitations. First, this was a retrospective study with a small sample size. Given that RC is the standard MIBC treatment, there was an inherent bias in the difference in patient characteristics between the treatment groups. We attempted to minimize this bias through propensity score matching to accurately compare the oncological outcomes. Nonetheless, discrepancies in the follow-up duration and other variables remained evident between groups. Additionally, the TMT group received two different treatment regimens with varying radiation doses. To date, various TMT regimens have been documented, including agents such as cisplatin and gemcitabine, as single agents and in combination with 5-fluorouracil; however, no definitive conclusions have been reached. The total administered radiation dose has also increased owing to advancements in technology and equipment. Similarly, the use of neoadjuvant chemotherapy in the RC group has become more prevalent since 2009, with nearly all patients receiving this therapy. The retrospective nature of this study means that the treatments were consistent with their respective times but lacked consistency overall. In conclusion, propensity score matching was used to compare the efficacy of TMT for MIBC treatment using cisplatin alone or in combination with gemcitabine with that of RC. Outcomes in terms of DMFS, CSS, and OS were comparable between the two treatments. Consequently, TMT may be considered an effective alternative treatment for primary MIBC. Declarations Acknowledgements We would like to acknowledge the patients who participated in this study. We would like to thank Editage (www.editage.com) for the English language editing. Authors’ contribution Keita Kobayashi: Data curation; Writing – original draft. Nakanori Fujii: Data curation. Kosuke Shimizu: Data curation. Yukihiro Hitaka: Data curation. Shintaro Oka: Data curation. Kimihiko Nakamura: Data curation. Toshiya Hiroyoshi: Data curation. Naohito Isoyama: Data curation. Hiroshi Hirata: Data curation. Koji Shiraishi: Supervision. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflict of interest None. Informed consent This study was conducted in compliance with the Ethical Guidelines for Life Science and Medical Research Involving Human Subjects in Japan. 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Supplementary Files Fig.S1.jpg Fig. S1 Recurrence-free survival curve including intravesical recurrence (A) and bladder intact-event free survival (B) curve in patients treated with TMT for MIBC (n=93) TableS1.xlsx TableS2.xlsx TableS3.xlsx Table1.xlsx Table2.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4496894","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":312215888,"identity":"aa80a3d4-4fdf-4e13-b297-b5fa4f75d0d6","order_by":0,"name":"Keita 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University","correspondingAuthor":false,"prefix":"","firstName":"Naohito","middleName":"","lastName":"Isoyama","suffix":""},{"id":312215902,"identity":"fc0dd63e-4d85-442d-a1a6-0e5f011c2e60","order_by":8,"name":"Hiroshi Hirata","email":"","orcid":"","institution":"Yamaguchi University","correspondingAuthor":false,"prefix":"","firstName":"Hiroshi","middleName":"","lastName":"Hirata","suffix":""},{"id":312215905,"identity":"d583923b-4f4a-4195-9dab-058b57d252e3","order_by":9,"name":"Koji Shiraishi","email":"","orcid":"","institution":"Yamaguchi University","correspondingAuthor":false,"prefix":"","firstName":"Koji","middleName":"","lastName":"Shiraishi","suffix":""}],"badges":[],"createdAt":"2024-05-29 11:59:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4496894/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4496894/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58248283,"identity":"3cdd82e4-63f5-4bc6-adaa-0294962eed22","added_by":"auto","created_at":"2024-06-13 02:46:16","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":189238,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of recurrence free survival (A), distant metastatic-free survival (B), cancer-specific survival (C) and overall survival (D) curves of patients treated with TMT (n=66) and RC (n=66) for MIBC following propensity score matching\u003c/p\u003e","description":"","filename":"Fig.1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4496894/v1/b774063eb0539f282b498dd9.jpg"},{"id":58248282,"identity":"313922f2-f1dc-4f1c-a494-b913c6203857","added_by":"auto","created_at":"2024-06-13 02:46:16","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":96042,"visible":true,"origin":"","legend":"\u003cp\u003eSubgroup analysis of cancer-specific survival in patients treated with TMT (n=66) and RC (n=66)\u003c/p\u003e","description":"","filename":"Fig.2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4496894/v1/b9aa70344b3e9b3b35b8f542.jpg"},{"id":66095461,"identity":"55cef937-c398-4d82-b98b-2115d88d8577","added_by":"auto","created_at":"2024-10-07 15:46:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":669323,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4496894/v1/a68e4522-eccb-4acc-a917-358739340307.pdf"},{"id":58248279,"identity":"7cd72753-861c-4369-887b-11df32206aa1","added_by":"auto","created_at":"2024-06-13 02:46:16","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":73737,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFig. S1\u003c/strong\u003e Recurrence-free survival curve including intravesical recurrence (A) and bladder intact-event free survival (B) curve in patients treated with TMT for MIBC (n=93)\u003c/p\u003e","description":"","filename":"Fig.S1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4496894/v1/271cb042d02dc2c6105ddb03.jpg"},{"id":58249228,"identity":"a9f42a48-8190-4cc1-8ad8-ea774b9aeae7","added_by":"auto","created_at":"2024-06-13 02:54:16","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":10139,"visible":true,"origin":"","legend":"","description":"","filename":"TableS1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4496894/v1/d67ba7ae94b141386e5b6e24.xlsx"},{"id":58248284,"identity":"2b9e25cb-c7a9-49f9-a387-7985115ce626","added_by":"auto","created_at":"2024-06-13 02:46:17","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":10552,"visible":true,"origin":"","legend":"","description":"","filename":"TableS2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4496894/v1/950320f99a108d25d0527097.xlsx"},{"id":58248287,"identity":"213385e3-fc4c-4378-aadc-f35ae56a6afd","added_by":"auto","created_at":"2024-06-13 02:46:17","extension":"xlsx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":10060,"visible":true,"origin":"","legend":"","description":"","filename":"TableS3.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4496894/v1/65c3db7f47db8ce9bf1ee7e8.xlsx"},{"id":58248286,"identity":"6ac1b435-424d-45e7-9752-44783379224d","added_by":"auto","created_at":"2024-06-13 02:46:17","extension":"xlsx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":13107,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4496894/v1/7128b8df59870135216f5781.xlsx"},{"id":58248285,"identity":"833b9f61-e94d-4ae1-b398-a9c53317d7e5","added_by":"auto","created_at":"2024-06-13 02:46:17","extension":"xlsx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":10423,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-4496894/v1/a0e76d96b1e2b48c93574c43.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparative analysis of oncological outcomes between trimodal therapy and radical cystectomy in muscle-invasive bladder cancer utilizing propensity score matching","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn 2020, bladder cancer was responsible for 573,000 new cases and 213,000 deaths globally [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It is the sixth most prevalent cancer in men, seventh in women, and tenth overall [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Approximately 75% of affected patients present with non-muscle invasive bladder cancer, which has a favorable prognosis [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Conversely, muscle-invasive bladder cancer (MIBC) has a poor prognosis, with 5-year overall survival (OS) and cancer-specific survival (CSS) rates of 69.1% and 73.1% post-radical cystectomy (RC), respectively [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In Japan, the established protocol for MIBC treatment involves neoadjuvant chemotherapy followed by RC, necessitating urinary tract alteration [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], which leads to a potential postoperative decline in quality of life and body image [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Despite the advent of less invasive techniques, total cystectomy remains invasive, possibly unsuitable for older adults or those with severe comorbidities [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Post-RC mortality rates are higher among octogenarians than among septuagenarians [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Bladder-sparing approaches are recommended to patients unfit for total bladder resection or those with T2 stage tumors without concurrent carcinoma in situ (CIS) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Over a decade-long observation period, the 5-year recurrence-free survival (RFS) and OS rates for trimodal therapy (TMT) were 63% and 49%, respectively [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. To date, no prospective randomized controlled trials have compared RC and TMT in MIBC treatment. In a recent multicenter, retrospective study in which propensity score-matched and weighted analysis were used, TMT and RC had comparable oncological outcomes in patients with MIBC [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. While favorable outcomes for TMT in MIBC have been reported in Japan [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], comparative studies on oncological outcomes against RC are scarce.\u003c/p\u003e \u003cp\u003eThis study aimed to compare the oncological outcomes between TMT and RC for MIBC using a retrospective design and propensity score-matched analysis.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThis study was a single-center retrospective study. The inclusion criteria were MIBC treatment (cT2-4N0-2M0) with RC or TMT at Yamaguchi University Hospital between January 1998 and December 2022. Patients previously subjected to radiotherapy for bladder cancer or treated with TMT non-curatively were excluded. Propensity scores were generated based on patient and tumor characteristics. Matching was performed using a caliper width of 0.2, comparing oncological outcomes between the TMT and RC cohorts.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eSurgical procedures for RC\u003c/h2\u003e \u003cp\u003eRC was conducted using open, laparoscopic, or robot-assisted techniques involving the resection of the bladder and prostate (men) or bladder and uterus (women), including the urethra. Lymph node dissection typically encompasses the common and external iliac, internal iliac, and obturator regions, with the method of urinary diversion at the surgeon\u0026rsquo;s discretion. Perioperative chemotherapy was administered predominantly following platinum-based regimens as recommended by the guidelines, subject to the treating physician\u0026rsquo;s judgment.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eTMT treatment protocol\u003c/h2\u003e \u003cp\u003eTMT was aimed at patients who were ineligible or refused RC and desired bladder preservation. Radiation therapy was administered at 1.8\u0026ndash;2.0 Gy/day, totaling 48.6\u0026ndash;60.0 Gy, focusing on true pelvic irradiation (excluding the common iliac lymph node area) and enhanced irradiation of the entire bladder. Chemotherapy options include cisplatin alone or in combination with gemcitabine. The gemcitabine plus cisplatin regimen was implemented in a phase 2 study [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The cisplatin regimen was administered at 70 mg/m\u003csup\u003e2\u003c/sup\u003e once every 2 weeks; the combined regimen was administered at 300 mg/m\u003csup\u003e2\u003c/sup\u003e gemcitabine and 30 mg/m\u003csup\u003e2\u003c/sup\u003e cisplatin once a week. Dose reductions in chemotherapy were implemented based on renal function and the occurrence of Grade 3 or higher adverse events.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eClinical and pathological parameters were compared using Fisher\u0026rsquo;s exact or Mann\u0026ndash;Whitney U test. Survival rates were assessed using Kaplan\u0026ndash;Meier plots and the log-rank test. RFS of bladder cancer was defined as the interval from treatment initiation to intravesical recurrence, extravesical recurrence, distant metastasis, or death from any cause. Bladder intact event-free survival was the interval from treatment initiation to MIBC occurrence, cystectomy for any cause, extravesical recurrence, distant metastasis, or death from any cause. RFS was the interval from treatment initiation to the MIBC recurrence, extravesical recurrence, distant metastasis, or death from any cause. Distant metastasis-free survival (DMFS) was the period from treatment initiation to the emergence of distant metastasis or death from any cause. CSS and OS were the time from treatment initiation to cancer-related death and time from treatment initiation to death from any cause, respectively. Pathological complete response (pCR) was the absence of malignant findings on histopathology following treatment. Pathological partial response (pPR) was defined as histopathological findings of less than stage pT2 (pTa, pT1, or pTis). Subgroup analyses via a Cox proportional hazards model were performed to identify patient and tumor factors. Adverse events related to chemotherapy and radiation therapy were assessed according to the Common Terminology Criteria for Adverse Events version 5.0, while postoperative complications were evaluated using the Clavien-Dindo classification. Statistical analyses were performed using JMP Pro version 15.0 (SAS, Cary, NC, USA), with a two-sided test significance level set at 5% and confidence interval estimation at 95%.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePatient and tumor characteristics\u003c/h2\u003e \u003cp\u003eWe reviewed 93 and 84 patients who underwent TMT and RC, respectively, for MIBC. Patient and tumor characteristics are shown in Table\u0026nbsp;1. The median follow-up period was 42.2 (interquartile range [IQR]: 19.7\u0026ndash;104.8) and 36.5 (IQR: 19.6\u0026ndash;88.5) months for the TMT and RC groups, respectively. After propensity score matching, 66 patients from each group were analyzed; patient or tumor characteristics were not significantly different.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes of Each Treatment\u003c/h2\u003e \u003cp\u003eIn the TMT cohort, 52 patients (56%) received cisplatin alone, whereas 41 (44%) were treated with combined gemcitabine and cisplatin. The median total radiation dose was 54.0 (IQR: 48.6\u0026ndash;54.0) Gy. Post-TMT, immediate total cystectomy for residual tumor was required in four patients (4%); BCG intravesical therapy for residual CIS was administered to five patients (6%) (Table\u0026nbsp;2). The pCR and bladder preservation rates were 65% and 91%, respectively, for lesions less than pT2 (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). The median RFS in the bladder after TMT was 23.3 months, with 5-year survival rates of 41.1% (Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003eA). Additionally, 5-year bladder intact event-free survival rates were 55.8% (Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003eB). In the RC cohort, neoadjuvant chemotherapy was administered to 60 patients (72%) and adjuvant chemotherapy to 13 (16%) (Table\u0026nbsp;2). Regarding the histopathological outcomes, the pCR and partial pathological response rates were 18% and 42%, respectively (Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eComparison of TMT and RC oncological outcomes\u003c/h2\u003e \u003cp\u003eOncological outcomes were compared between 66 matched cases each from the TMT and RC groups. The 2-year RFS rates were 72.4% for TMT and 59.2% for RC, with 5-year rates at 64.3% and 52.6%, respectively (p\u0026thinsp;=\u0026thinsp;0.209, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). The 2-year DMFS rates were 81.8% for TMT and 60.5% for RC, with 5-year rates at 64.3% and 51.8%, respectively, without significant differences (p\u0026thinsp;=\u0026thinsp;0.096, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). The 5-year CSS rates were 83.3% for TMT and 69.2% for RC (p\u0026thinsp;=\u0026thinsp;0.104, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eC), and the 5-year OS rates were 77.8% for TMT and 64.2% for RC, without significant differences (p\u0026thinsp;=\u0026thinsp;0.274, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eD). In subgroup analyses, TMT demonstrated superior CSS compared to RC for primary tumors (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eAdverse events and postoperative complications\u003c/h2\u003e \u003cp\u003eGrade\u0026thinsp;\u0026ge;\u0026thinsp;3 neutropenia was observed in 48.1%, anemia in 14.3%, and thrombocytopenia in 20.8% of patients who underwent TMT (Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e). Similar proportions were observed in patients who underwent RC and perioperative chemotherapy (47.1%, 14.7%, and 26.5%, respectively) (Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e). Radiation-induced adverse events included grade 3 diarrhea (10.4%), noninfectious cystitis (3.9%), and rectal bleeding (2.6%), without grade 4 events (Table \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e). Perioperative complications of RC included grade 3 ileus (10.6%), anastomotic leak (2.3%), and wound dehiscence (3.6%), without deaths related to perioperative complications (Table \u003cspan refid=\"MOESM3\" class=\"InternalRef\"\u003eS3\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study evaluated the oncological outcomes of TMT and RC for MIBC treatment. Patient and tumor characteristics were closely matched using propensity score matching. No significant differences in DMFS, CSS, or OS were observed between the two treatment groups. However, the subgroup analysis indicated superior CSS with TMT in primary MIBC cases, compared with RC. Despite the higher proportion of older patients and those with poor performance status in the TMT group, the severity and frequency of adverse events were remarkably similar.\u003c/p\u003e \u003cp\u003eSome systematic reviews and meta-analyses have indicated that RC for MIBC treatment yields better oncological outcomes than TMT, although other studies have suggested equivalent results between these treatments [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The variability in TMT outcomes has been attributed to diverse regimens and radiation doses employed. As RC is supported by substantial evidence as the standard treatment for MIBC and recommended by clinical guidelines, treatment outcomes are not significantly different among studies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Reports of long-term outcomes of RC for MIBC treatment have shown 5-year survival rates of approximately 40\u0026ndash;50% [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], and 50\u0026ndash;60% with the addition of neoadjuvant chemotherapy [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In this study, the 5-year CSS and OS rates for the RC group were 69.2% and 64.2%, respectively, consistent with previously reported figures. Zlotta et al. documented 5-year metastasis-free survival, CSS, and OS rates of 74%, 85%, and 77%, respectively, for TMT in MIBC treatment [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Our findings for TMT were similar at 5-year DMFS, CSS, and OS rates of 64.3%, 83.3%, and 77.8%, respectively. Kulkarni et al. reported equivalent oncological outcomes for TMT and RC using propensity score matching [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. However, a definitive comparison of oncological outcomes between TMT and RC for MIBC remains inconclusive owing to the absence of large prospective controlled studies.\u003c/p\u003e \u003cp\u003eIn this study, TMT led to better oncological outcomes of primary MIBC than RC. The literature presents varied results when comparing the oncological outcomes between primary and secondary MIBC [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Pones et al. found no significant differences in the oncological outcomes between primary and secondary MIBC after RC [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In contrast, Grossmann et al. observed that secondary MIBC was associated with significantly shorter CSS and OS following RC [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], similar to our finding. While most reports have focused on outcomes following RC, few studies have examined outcomes following TMT. More comprehensive studies are needed in this area, as secondary MIBC may exhibit a poorer prognosis than primary MIBC when treated with TMT.\u003c/p\u003e \u003cp\u003eRecent clinical trials have explored the use of immune checkpoint inhibitors as bladder-sparing therapies, with some protocols omitting radiation therapy [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Kimura et al. reported a phase 2 trial in which bladder preservation therapy, combining atezolizumab with radiotherapy, was administered to patients with T2-3 MIBC and high-risk T1 [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. This trial achieved a high pCR rate (84.4%) and low incidence of grade\u0026thinsp;\u0026ge;\u0026thinsp;3 adverse events (13.3%). Furthermore, Shen et al. demonstrated that neoadjuvant treatment of MIBC with immune checkpoint inhibitors and chemotherapy yielded a complete response in 50% of the patients, surpassing the outcomes of chemotherapy alone in terms of disease control and bladder-intact disease-free survival [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In the future, treatment with bladder preservation therapy may include immune checkpoint inhibitors or involve them as neoadjuvant therapy, with complete response cases treated with bladder preservation therapy and others with RC.\u003c/p\u003e \u003cp\u003eThis study had limitations. First, this was a retrospective study with a small sample size. Given that RC is the standard MIBC treatment, there was an inherent bias in the difference in patient characteristics between the treatment groups. We attempted to minimize this bias through propensity score matching to accurately compare the oncological outcomes. Nonetheless, discrepancies in the follow-up duration and other variables remained evident between groups. Additionally, the TMT group received two different treatment regimens with varying radiation doses. To date, various TMT regimens have been documented, including agents such as cisplatin and gemcitabine, as single agents and in combination with 5-fluorouracil; however, no definitive conclusions have been reached. The total administered radiation dose has also increased owing to advancements in technology and equipment. Similarly, the use of neoadjuvant chemotherapy in the RC group has become more prevalent since 2009, with nearly all patients receiving this therapy. The retrospective nature of this study means that the treatments were consistent with their respective times but lacked consistency overall.\u003c/p\u003e \u003cp\u003eIn conclusion, propensity score matching was used to compare the efficacy of TMT for MIBC treatment using cisplatin alone or in combination with gemcitabine with that of RC. Outcomes in terms of DMFS, CSS, and OS were comparable between the two treatments. Consequently, TMT may be considered an effective alternative treatment for primary MIBC.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to acknowledge the patients who participated in this study. We would like to thank Editage (www.editage.com) for the English language editing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKeita Kobayashi: Data curation; Writing \u0026ndash; original draft. Nakanori Fujii: Data curation. Kosuke Shimizu: Data curation. Yukihiro Hitaka: Data curation. Shintaro Oka: Data curation. Kimihiko Nakamura: Data curation. Toshiya Hiroyoshi: Data curation. Naohito Isoyama: Data curation. Hiroshi Hirata: Data curation. Koji Shiraishi: Supervision.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in compliance with the Ethical Guidelines for Life Science and Medical Research Involving Human Subjects in Japan. Informed consent was waived under the condition that information about the research was made publicly available, and maximal efforts were made to ensure opportunities for declining participation. The study received approval from the Research Ethics Committee of Yamaguchi University Hospital (approval number: 2023-129)\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJubber I, Ong S, Bukavina L et al (2023) Epidemiology of bladder cancer in 2023: A systematic review of risk factors. Eur Urol 84(2):176\u0026ndash;190. http://doi.org/10.1016/j.eururo.2023.03.029\u003c/li\u003e\n\u003cli\u003eBabjuk M, Burger M, Capoun O et al (2022) European Association of Urology guidelines on non-muscle-invasive bladder cancer (ta, T1, and carcinoma in situ). Eur Urol 81(1):75\u0026ndash;94. http://doi.org/10.1016/j.eururo.2021.08.010\u003c/li\u003e\n\u003cli\u003eNuhn P, May M, Sun M et al (2012) External validation of postoperative nomograms for prediction of all-cause mortality, cancer-specific mortality, and recurrence in patients with urothelial carcinoma of the bladder. Eur Urol 61(1):58\u0026ndash;64. http://doi.org/10.1016/j.eururo.2011.07.066\u003c/li\u003e\n\u003cli\u003eMatsumoto H, Shiraishi K, Azuma H et al (2020) Clinical practice guidelines for bladder cancer 2019 edition by the Japanese Urological Association: Revision working position paper. Int J Urol 27(5):362\u0026ndash;368. http://doi.org/10.1111/iju.14210\u003c/li\u003e\n\u003cli\u003eChoi H, Park JY, Bae JH, Tae BS (2020) Health-related quality of life after radical cystectomy. Transl Androl Urol 9(6):2997\u0026ndash;3006. http://doi.org/10.21037/tau.2020.02.01\u003c/li\u003e\n\u003cli\u003eFroehner M, Brausi MA, Herr HW, Muto G, Studer UE (2009) Complications following radical cystectomy for bladder cancer in the elderly. Eur Urol 56(3):443\u0026ndash;454. http://doi.org/10.1016/j.eururo.2009.05.008\u003c/li\u003e\n\u003cli\u003eTilki D, Zaak D, Trottmann M et al (2010) Radical cystectomy in the elderly patient: a contemporary comparison of perioperative complications in a single institution series. World J Urol 28(4):445\u0026ndash;450. https://doi.org/10.1007/s00345-009-0482-1\u003c/li\u003e\n\u003cli\u003eHaden TD, Prunty MC, Jones AB, Deroche CB, Murray KS, Pokala N (2018) Comparative perioperative outcomes in septuagenarians and octogenarians undergoing radical cystectomy for bladder cancer\u0026mdash;do outcomes differ? Eur Urol Focus 4(6):895\u0026ndash;899. http://doi.org/10.1016/j.euf.2017.08.005\u003c/li\u003e\n\u003cli\u003eWitjes JA, Bruins HM, Cathomas R et al (2021) European Association of Urology guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2020 guidelines. Eur Urol 79(1):82\u0026ndash;104. http://doi.org/10.1016/j.eururo.2020.03.055\u003c/li\u003e\n\u003cli\u003eGiacalone NJ, Shipley WU, Clayman RH et al (2017) Long-term outcomes after bladder-preserving tri-modality therapy for patients with muscle-invasive bladder cancer: an updated analysis of the Massachusetts General Hospital experience. Eur Urol 71(6):952\u0026ndash;960. http://doi.org/10.1016/j.eururo.2016.12.020\u003c/li\u003e\n\u003cli\u003eHall E, Hussain SA, Porta N et al (2022) Chemoradiotherapy in muscle-invasive Bladder Cancer: 10-yr Follow-up of the Phase 3 Randomised Controlled BC2001 Trial. Eur Urol 82(3):273\u0026ndash;279. http://doi.org/10.1016/j.eururo.2022.04.017\u003c/li\u003e\n\u003cli\u003eZlotta AR, Ballas LK, Niemierko A et al (2023) Radical cystectomy versus trimodality therapy for muscle-invasive bladder cancer: a multi-institutional propensity score matched and weighted analysis. Lancet Oncol 24(6):669\u0026ndash;681. http://doi.org/10.1016/S1470-2045(23)00170-5\u003c/li\u003e\n\u003cli\u003eKijima T, Tanaka H, Koga F et al (2019) Selective tetramodal bladder-preservation therapy, incorporating induction chemoradiotherapy and consolidative partial cystectomy with pelvic lymph node dissection for muscle-invasive bladder cancer: oncological and functional outcomes of 107 patients. BJU Int 124(2):242\u0026ndash;250. http://doi.org/10.1111/bju.14736\u003c/li\u003e\n\u003cli\u003eKobayashi K, Matsumoto H, Misumi T et al (2022) The efficacy of trimodal chemoradiotherapy with gemcitabine and cisplatin as a bladder-preserving strategy for the treatment of muscle-invasive bladder cancer: a single-arm phase II study. Jpn J Clin Oncol 52(10):1201\u0026ndash;1207. http://doi.org/10.1093/jjco/hyac095\u003c/li\u003e\n\u003cli\u003eAl-Qudimat AR, Singh K, Ojha LK et al (2023) Comparing trimodal therapy with radical cystectomy in muscle-invasive bladder cancer: an updated meta-analysis. Front Surg 10:1276746. http://doi.org/10.3389/fsurg.2023.1276746\u003c/li\u003e\n\u003cli\u003eSu X, Dong C, Liao W, Liu W (2023) Oncological effectiveness of bladder-preserving trimodal therapy versus radical cystectomy for the treatment of muscle-invasive bladder cancer: a system review and meta-analysis. World J Surg Oncol 21(1):271. http://doi.org/10.1186/s12957-023-03161-z\u003c/li\u003e\n\u003cli\u003eDitonno F, Veccia A, Montanaro F et al (2024) Trimodal therapy vs radical cystectomy in patients with muscle-invasive bladder cancer: a systematic review and meta-analysis of comparative studies. BJU Int 15. http://doi.org/10.1111/bju.16366\u003c/li\u003e\n\u003cli\u003eStein JP, Lieskovsky G, Cote R, et al (2001) Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 19(3):666\u0026ndash;675. http://doi.org/10.1200/JCO.2001.19.3.666\u003c/li\u003e\n\u003cli\u003eGore JL, Litwin MS, Lai J, et al (2010) Use of radical cystectomy for patients with invasive bladder cancer. J Natl Cancer Inst 102(11):802\u0026ndash;811. http://doi.org/10.1093/jnci/djq121\u003c/li\u003e\n\u003cli\u003eGrossman HB, Natale RB, Tangen CM, et al (2003) Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 349(9):859\u0026ndash;866. http://doi.org/10.1056/NEJMoa022148\u003c/li\u003e\n\u003cli\u003eInternational Collaboration of Trialists, Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group), European Organization for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group et al (2011) International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol 29(16):2171\u0026ndash;2177. http://doi.org/10.1200/JCO.2010.32.3139\u003c/li\u003e\n\u003cli\u003eKulkarni GS, Hermanns T, Wei Y et al (2017) Propensity score analysis of radical cystectomy versus bladder-sparing trimodal therapy in the setting of a multidisciplinary bladder cancer clinic. J Clin Oncol 35(20):2299\u0026ndash;2305. http://doi.org/10.1200/JCO.2016.69.2327\u003c/li\u003e\n\u003cli\u003ePones M, D\u0026rsquo;Andrea D, Mori K et al (2021) Differential Prognosis and Response of DeNovo vs. secondary Muscle-Invasive Bladder Cancer: an Updated Systematic Review and Meta-Analysis. Cancers (Basel) 13(10):2496. http://doi.org/10.3390/cancers13102496\u003c/li\u003e\n\u003cli\u003eGrossmann NC, Rajwa P, Quhal F et al (2022) Comparative outcomes of primary versus recurrent high-risk non-muscle-invasive and primary versus secondary muscle-invasive bladder cancer after radical cystectomy: results from a retrospective multicenter study. Eur Urol Open Sci 39:14\u0026ndash;21. http://doi.org/10.1016/j.euros.2022.02.011\u003c/li\u003e\n\u003cli\u003eMeeks JJ, Black PC, Galsky M et al (2023) Checkpoint inhibitors in urothelial carcinoma-future directions and biomarker selection. Eur Urol 84(5):473\u0026ndash;483. http://doi.org/10.1016/j.eururo.2023.05.011\u003c/li\u003e\n\u003cli\u003eKimura T, Ishikawa H, Nagumo Y et al (2023) Efficacy and safety of bladder preservation therapy in combination with atezolizumab and radiation therapy (BPT-ART) for invasive bladder cancer: interim analysis from a multicenter, open-label, prospective Phase 2 trial. Int J Radiat Oncol Biol Phys 117(3):644\u0026ndash;651. http://doi.org/10.1016/j.ijrobp.2023.05.013\u003c/li\u003e\n\u003cli\u003eShen Y, Wen F, Zhang P, Lin T (2022) Real-world study of chemotherapy plus immunotherapy versus chemotherapy alone as neoadjuvant treatment guided bladder-sparing therapy for localized muscle-invasive bladder cancer. J Clin Oncol 40(6_suppl):499\u0026ndash;499. https://doi.org/10.1200/JCO.2022.40.6_suppl.499\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 and 2 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Muscle-invasive bladder cancer, Trimodal therapy, Radical cystectomy, Chemoradiation, Propensity score, Survival","lastPublishedDoi":"10.21203/rs.3.rs-4496894/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4496894/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eTo compare the outcomes of trimodal therapy (TMT) and radical cystectomy (RC) in the treatment of muscle-invasive bladder cancer (MIBC).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003ePatients treated with either TMT or RC for MIBC at our institution between January 1998 and December 2022 were included. Propensity score matching was used to compare cancer-specific survival and overall survival rates.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eA total of 93 patients who underwent TMT and 84 who underwent RC for MIBC were analyzed. In the TMT cohort, the pathological complete response rate was 65%; the 5-year recurrence-free survival rate, including intravesical recurrence, was 41.1%; and the 5-year bladder intact event-free survival rate was 55.8%. Using propensity score matching, 66 patients from each treatment group were selected for a comparative analysis of oncological outcomes. The 5-year distant metastasis-free, cancer-specific, and overall survival rates were 64.3% and 51.8% (P=0.096), 83.3% and 69.2% (P=0.104), and 77.8% and 64.2% (P=0.274) for TMT and RC, respectively. Subgroup analyses revealed that TMT for primary tumors significantly improved cancer-specific survival rates compared with RC. The two treatment types had similar adverse events related to hematologic toxicity during perioperative chemotherapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eTMT exhibited oncological outcomes comparable to those of RC in the treatment of MIBC, indicating that TMT provides favorable outcomes, particularly in cases of primary MIBC.\u003c/p\u003e","manuscriptTitle":"Comparative analysis of oncological outcomes between trimodal therapy and radical cystectomy in muscle-invasive bladder cancer utilizing propensity score matching","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-13 02:46:12","doi":"10.21203/rs.3.rs-4496894/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0beb4fe0-835b-4eef-a884-838684d220c4","owner":[],"postedDate":"June 13th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-10-07T15:38:49+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-13 02:46:12","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4496894","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4496894","identity":"rs-4496894","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}