. 2025 May 7.

doi: 10.1007/s11255-025-04566-3. Online ahead of print.

Oncological outcomes after non-surgical management versus radical cystectomy in non-organ-confined non-urothelial bladder cancer

Mattia Longoni^{1

2

3}, Andrea Marmiroli^{4

5}, Fabian Falkenbach^{4

6}, Quynh Chi Le^{4

7}, Michele Nicolazzini^{4

8

9}, Calogero Catanzaro^{4

10}, Federico Polverino^{4

11}, Jordan A Goyal⁴, Gennaro Musi⁵, Markus Graefen⁶, Felix K H Chun⁷, Alessandro Volpe⁸, Riccardo Schiavina¹⁰, Nicola Longo¹¹, Fred Saad⁴, Shahrokh F Shariat^{12

13

14

15}, Marco Moschini^{16

17}, Giorgio Gandaglia^{16

17}, Francesco Montorsi^{16

17}, Alberto Briganti^{16

17}, Pierre I Karakiewicz⁴

Affiliations

¹ Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada. longoni.mattia@hsr.it.
² Division of Experimental Oncology/Unit of Urology, URI; IRCCS Ospedale San Raffaele, Milan, Italy. longoni.mattia@hsr.it.
³ Urological Research Institute (URI), Unit of Urology, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy. longoni.mattia@hsr.it.
⁴ Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.
⁵ Department of Urology, IEO European Institute of Oncology, IRCCS, Via Ripamonti 435, Milan, Italy.
⁶ Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
⁷ Department of Urology, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany.
⁸ Division of Urology, Department of Translational Medicine, University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy.
⁹ Division of Urology, Department of Oncology, University of Turin, Orbassano, Italy.
¹⁰ Department of Urology, University of Bologna, St. Orsola-Malpighi Hospital, Bologna, Italy.
¹¹ Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, Naples, Italy.
¹² Department of Urology, Weill Cornell Medical College, New York, NY, USA.
¹³ Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁴ Hourani Center of Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan.
¹⁵ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
¹⁶ Division of Experimental Oncology/Unit of Urology, URI; IRCCS Ospedale San Raffaele, Milan, Italy.
¹⁷ Urological Research Institute (URI), Unit of Urology, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy.

PMID: 40332661
DOI: 10.1007/s11255-025-04566-3

Oncological outcomes after non-surgical management versus radical cystectomy in non-organ-confined non-urothelial bladder cancer

Mattia Longoni et al. Int Urol Nephrol. 2025.

. 2025 May 7.

doi: 10.1007/s11255-025-04566-3. Online ahead of print.

Authors

Affiliations

¹ Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada. longoni.mattia@hsr.it.
² Division of Experimental Oncology/Unit of Urology, URI; IRCCS Ospedale San Raffaele, Milan, Italy. longoni.mattia@hsr.it.
³ Urological Research Institute (URI), Unit of Urology, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy. longoni.mattia@hsr.it.
⁴ Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, Québec, Canada.
⁵ Department of Urology, IEO European Institute of Oncology, IRCCS, Via Ripamonti 435, Milan, Italy.
⁶ Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
⁷ Department of Urology, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany.
⁸ Division of Urology, Department of Translational Medicine, University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy.
⁹ Division of Urology, Department of Oncology, University of Turin, Orbassano, Italy.
¹⁰ Department of Urology, University of Bologna, St. Orsola-Malpighi Hospital, Bologna, Italy.
¹¹ Department of Neurosciences, Science of Reproduction and Odontostomatology, University of Naples Federico II, Naples, Italy.
¹² Department of Urology, Weill Cornell Medical College, New York, NY, USA.
¹³ Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁴ Hourani Center of Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan.
¹⁵ Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
¹⁶ Division of Experimental Oncology/Unit of Urology, URI; IRCCS Ospedale San Raffaele, Milan, Italy.
¹⁷ Urological Research Institute (URI), Unit of Urology, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy.

PMID: 40332661
DOI: 10.1007/s11255-025-04566-3

Abstract

Introduction: We hypothesized that among non-organ-confined (NOC, T3-4 and/or N1-3) non-urothelial carcinoma of urinary bladder (non-UCUB) patients, bladder-sparing non-surgical management (NSM) provides cancer-specific mortality (CSM) rates comparable to those of radical cystectomy (RC).

Methods: Within the SEER database (2004-2021) rates of NSM vs. RC use in NOC non-UCUB patients were tabulated. Nearest-neighbor 1:1 propensity score matching (PSM) for age, sex, stage, race/ethnicity, and histological subtype was applied. Cumulative incidence plots depicted five-year CSM. Univariable and multivariable competing risks regression (CRR) models were fitted. Sensitivity analyses were performed within squamous cell carcinoma (SCC), small cell carcinoma (small-CC) and adenocarcinoma (ADK).

Results: Of 775 NOC non-UCUB patients, 290 (37.4%) received NSM vs. 485 (62.6%) RC. After PSM, five-year CSM rate was 70.4% after NSM vs. 60.6% after RC and NSM was associated with 1.6-fold higher CSM relative to RC (multivariable HR [mHR]: 1.61, p < 0.001). In sensitivity analyses within 253 (32.6%) SCC, after re-applying PSM, five-year CSM rate was 85.0% after NSM vs. 53.3% after RC and NSM was associated with 2.8-fold higher CSM relative to RC (mHR: 2.80, p < 0.001). Conversely, within 216 (27.9%) small-CC and 135 (17.4%) ADK patients, CSM after NSM did not differ from CSM after RC (54.3 vs. 62.5%, mHR: 0.85; 69.8 vs. 71.7%, mHR: 1.0; all p > 0.05).

Conclusion: In NOC non-UCUB patients, NSM is associated with higher CSM than RC. Subgroup analyses according to histological subtypes suggest that these differences virtually exclusively originated from SCC patients but not from their small-CC and ADK counterparts.

Keywords: Bladder cancer; Bladder-sparing; Non-organ-confined; Non-urothelial; Radical cystectomy; Variant histology.

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Conflict of interest statement

Declarations. Competing interest: The authors declare no competing interests.

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Artificial intelligence for rare bladder cancer variants: a new hope for detection?
Mantica G, Calarco A, Leonardi R. Mantica G, et al. Int Urol Nephrol. 2025 Jul 4. doi: 10.1007/s11255-025-04647-3. Online ahead of print. Int Urol Nephrol. 2025. PMID: 40610842 No abstract available.

References

1. Holzbeierlein J, Bixler BR, Buckley DI, Chang SS, Holmes RS, James AC et al (2024) Treatment of non-metastatic muscle-invasive bladder cancer: AUA/ASCO/SUO guideline (2017; Amended 2020, 2024). J Urol. https://doi.org/10.1097/JU.0000000000003981 - DOI - PubMed
1. Powles T, Bellmunt J, Comperat E, Santis MD, Huddart R, Loriot Y et al (2022) Bladder cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up☆. Ann Oncol 33:244–58. https://doi.org/10.1016/j.annonc.2021.11.012 - DOI - PubMed
1. Alfred Witjes J, Max Bruins H, Carrión A, Cathomas R, Compérat E, Efstathiou JA et al (2024) European association of urology guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2023 guidelines. Eur Urol 85:17–31. https://doi.org/10.1016/J.EURURO.2023.08.016 - DOI - PubMed
1. Moschini M, D’Andrea D, Korn S, Irmak Y, Soria F, Compérat E et al (2017) Characteristics and clinical significance of histological variants of bladder cancer. Nat Rev Urol 14:651–68. https://doi.org/10.1038/nrurol.2017.125 - DOI - PubMed
1. Brown JT, Narayan VM, Joshi SS, Harik L, Jani AB, Bilen MA (2023) Challenges and opportunities in the management of non-urothelial bladder cancers. Cancer Treat Res Commun 34:100663. https://doi.org/10.1016/j.ctarc.2022.100663 - DOI - PubMed

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Oncological outcomes after non-surgical management versus radical cystectomy in non-organ-confined non-urothelial bladder cancer

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Oncological outcomes after non-surgical management versus radical cystectomy in non-organ-confined non-urothelial bladder cancer

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