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Comparative Study
. 2025 Jul;132(1):235-242.
doi: 10.1002/jso.70014. Epub 2025 Jun 13.

Cancer-Specific Survival of Trimodal Therapy Versus Radical Cystectomy in T2N0M0 Non-Urothelial Bladder Cancer

Mattia Longoni  1   2   3 , Andrea Marmiroli  1   4 , Fabian Falkenbach  1   5 , Quynh Chi Le  1   6 , Michele Nicolazzini  1   7   8 , Calogero Catanzaro  1   9 , Federico Polverino  1   10 , Jordan A Goyal  1 , Matteo Ferro  11 , Markus Graefen  5 , Felix K H Chun  6 , Carlotta Palumbo  7   8 , Riccardo Schiavina  9 , Nicola Longo  10 , Fred Saad  1 , Shahrokh F Shariat  12   13   14   15 , Marco Moschini  2   3 , Giorgio Gandaglia  2   3 , Francesco Montorsi  2   3 , Alberto Briganti  2   3 , Pierre I Karakiewicz  1
Affiliations
Comparative Study

Cancer-Specific Survival of Trimodal Therapy Versus Radical Cystectomy in T2N0M0 Non-Urothelial Bladder Cancer

Mattia Longoni et al. J Surg Oncol. 2025 Jul.

Abstract

Introduction: We hypothesized that, within organ-confined (OC, T2N0M0) non-urothelial carcinoma of urinary bladder (non-UCUB) patients, trimodal therapy (TMT) use does not differ from radical cystectomy (RC) regarding cancer control outcomes.

Methods: Within the SEER database (2004-2021), rates of TMT versus RC use in OC non-UCUB patients were calculated. Nearest-neighbor 1:1 propensity score matching (PSM) for age, sex, race/ethnicity, and histological subtype was applied. Cumulative incidence plots depicted 5-year cancer-specific (CSM) and other-cause mortality (OCM) rates. Multivariable competing risks regression (CRR) models were fitted. Sensitivity analyses were performed within squamous cell (SCC), neuroendocrine (NEC), and adenocarcinoma (ADK) and other histological subtypes.

Results: Of 814 OC non-UCUB patients, 310 (38%) received TMT versus 504 (62%) RC. After PSM, 5-year CSM rate was 50% after TMT versus 29% after RC and TMT was associated with 2.1-fold higher CSM relative to RC (multivariable HR [mHR]: 2.1, p < 0.001). In sensitivity analyses within 229 (28%) SCC, TMT patients had higher 5-year CSM rates relative to their RC-counterparts (67% vs. 22%, mHR: 4.3, p < 0.001). Similarly, within 314 (39%) NEC, TMT patients had higher 5-year CSM rates relative to their RC-counterparts (mHR: 1.8, p < 0.001). Conversely, within 118 (28%) ADK and 153 (19%) other subtypes, CSM after TMT did not differ from CSM after RC (33% vs. 15%, mHR: 1.4 and 43% vs. 33%, mHR: 1.4; p = 0.4).

Conclusion: In OC non-UCUB patients TMT is associated with significantly higher CSM than RC. Most pronounced survival disadvantage was recorded within SCC and NEC patients.

Keywords: bladder cancer; non‐urothelial; radical cystectomy; subtypes; trimodal therapy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Estimated annual percent changes (EAPC) depicting temporal trends in trimodal therapy (TMT) (A) and TMT rates according to specific histological subtypes (B) in 814 patients harbouring organ‐confined (OC) non‐urothelial cancer of urinary bladder (non‐UCUB) patients from the Surveillance, Epidemiology, and End Results database (2004–2021).
Figure 2
Figure 2
Cumulative incidence curves depicting cancer specific mortality (CSM) in patients harbouring organ‐confined (OC) non‐urothelial cancer of urinary bladder (non‐UCUB) after 1:1 propensity score matching (PSM) between trimodal therapy (TMT) versus radical cystectomy (RC) from the Surveillance, Epidemiology, and End Results database (2004–2021).
Figure 3
Figure 3
Forest plot depicting separate competing risks multivariable regression models predicting cancer specific (CSM) according to treatment in patients harboring organ‐confined (NOC) non‐urothelial cancer of urinary bladder (non‐UCUB) treated with either trimodal therapy (TMT) versus radical cystectomy (RC) from the Surveillance, Epidemiology, and End Results database (2004–2021).
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