OBJECTIVE: To assess the oncological outcomes of patients with high-risk (HR) and very high-risk (VHR) non-muscle-invasive bladder cancer (NMIBC) treated with upfront radical cystectomy (RC) vs Bacillus Calmette-Guérin (BCG) instillations from a contemporary European multicentre cohort. PATIENTS AND METHODS: We conducted a retrospective analysis of 1491 patients diagnosed with HR- or VHR-NMIBC from a European multicentre database between 2015 and 2024. Patients were included if they received either upfront RC or at least five doses of BCG. A 1:1 propensity score matching (PSM) according to clinically relevant variables was applied. Progression was defined as muscle-invasive or metastatic disease. Cumulative incidence plots and multivariable competing risk regression models addressing cancer-specific mortality (CSM) were fitted. RESULTS: Among the 1221 patients with HR- (n = 1221 [90%]) or VHR-NMIBC (n = 121 [10%]), 87 (7.1%) underwent upfront RC. The median follow-up was 2.6 years. After PSM (87 vs 87 patients), the 5-year CSM rate was similar in patients treated with BCG (13%) vs their upfront RC counterparts (16%) (hazard ratio: 1.77, 95% confidence interval [CI] 0.66-4.73; P = 0.3). Of the 1134 patients who initially received BCG, 73 (6.6%) eventually required delayed RC, with 34 (47%) progressing to muscle-invasive bladder cancer before delayed RC. The 3-year CSM rate was comparable in upfront RC (13%) vs delayed RC (11%) among non-progressing patients (P = 0.3). However, patients who progressed before delayed RC had worse 3-year CSM relative to those who did not (13% vs 31%, hazard ratio: 0.32, 95% CI 0.13-0.83; P = 0.018). CONCLUSION: Within a European cohort of patients with HR- and VHR-NMIBC, upfront RC was rarely performed. Patients treated with BCG did not exhibit a CSM disadvantage relative to their upfront RC counterparts. After matching, long-term CSM was similar between BCG therapy and upfront RC. Delayed RC, led to worse outcomes if performed after progression, but matched upfront RC when performed before progression, underscoring importance of timely surgery.

Department of Experimental Oncology Unit of Urology URI IRCCS Ospedale San Raffaele Milan Italy

Department of General Oncological and Functional Urology Medical University of Warsaw Warsaw Poland

Department of Maternal Infant and Urologic Sciences Policlinico Umberto 1 Hospital 'Sapienza' University of Rome Rome Italy

Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology and Oncologic Urology Wrocław Medical University Wroclaw Poland

Department of Urology Claude Huriez Hospital CHU Lille Lille France

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology Fundació Puigvert Autonomous University of Barcelona Barcelona Spain

Department of Urology Gregorio Marañón University Hospital Madrid Spain

Department of Urology Hospital Universitario de Cáceres Cáceres Spain

Department of Urology Humanitas Clinical and Research Institute IRCCS Milan Italy

Department of Urology Instituto Ramón y Cajal de Investigación Sanitaria Hospital Universitario Ramón y Cajal Universidad de Alcalá Madrid Spain

Department of Urology Luzerner Kantonsspital Lucerne Switzerland

Department of Urology Medical University of Innsbruck Innsbruck Austria

Department of Urology Netherlands Cancer Institute Amsterdam The Netherlands

Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology University of Texas Southwestern Dallas TX USA

Department of Urology University of Tor Vergata Rome Italy

Department of Urology UROSUD La Croix Du Sud Hospital Quint Fonsegrives France

Department of Urology Weill Cornell Medical College New York NY USA

Division of Urology Department of Surgical Sciences San Giovanni Battista Hospital University of Studies of Torino Turin Italy

IRCCS 'Regina Elena' National Cancer Institute Rome Italy

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

Unit of Oncologic Minimally Invasive Urology and Andrology Department of Experimental and Clinical Medicine Careggi Hospital University of Florence Florence Italy

Urology GRC 5 Predictive Onco Uro AP HP Pitie Salpetriere Hospital Sorbonne University Paris France

Vita Salute San Raffaele University Milan Italy

Zobrazit více v PubMed

Babjuk M, Burger M, Capoun O et al. European Association of Urology guidelines on non‐muscle‐invasive bladder cancer (Ta, T1, and carcinoma in situ). Eur Urol 2022; 81: 75–94

Sylvester RJ, Rodríguez O, Hernández V et al. European Association of Urology (EAU) prognostic factor risk groups for non‐muscle‐invasive bladder cancer (NMIBC) incorporating the WHO 2004/2016 and WHO 1973 classification systems for grade: an update from the EAU NMIBC guidelines panel. Eur Urol 2021; 79: 480–488

Subiela JD, Krajewski W, González‐Padilla DA et al. Unlocking the potential of adequate Bacillus Calmette‐Guérin immunotherapy in very‐high‐risk non‐muscle‐invasive bladder carcinoma: a multicenter analysis of oncological outcomes and risk dynamics. Eur Urol Oncol 2024; 7: 1367–1375

Contieri R, Hensley PJ, Tan WS et al. Oncological outcomes for patients with European Association of Urology very high‐risk non‐muscle‐invasive bladder cancer treated with Bacillus Calmette‐Guérin or early radical cystectomy. Eur Urol Oncol 2023; 6: 590–596

Matulay JT, Li R, Hensley PJ et al. Contemporary outcomes of patients with nonmuscle‐invasive bladder cancer treated with Bacillus Calmette‐Guérin: implications for clinical trial design. J Urol 2021; 205: 1612–1621

Jacob JM, Guerrero‐Ramos F, Xylinas E et al. Reasons for refusal of or ineligibility for radical cystectomy (RC) in patients (pts) with Bacillus Calmette‐Guérin (BCG)–unresponsive high‐risk non‐muscle‐invasive bladder cancer (HR NMIBC) from the SunRISe‐1 study. J Clin Oncol 2024; 42(4_suppl): 701

Yang LS, Shan BL, Shan LL et al. A systematic review and meta‐analysis of quality of life outcomes after radical cystectomy for bladder cancer. Surg Oncol 2016; 25: 281–297

Pellegrino F, Scilipoti P, Rosiello G et al. Long‐term functional outcomes after robot‐assisted radical cystectomy with intracorporeal ileal orthotopic neobladder. BJU Int 2024; 134: 48–50

Pellegrino F, Leni R, Basile G et al. Peri‐ and post‐operative outcomes of robot‐assisted radical cystectomy after the implementation of the EAU guidelines recommendations for collecting and reporting complications at a high‐volume referral center. World J Urol 2024; 42: 270

Khetrapal P, Wong JK, Tan WP et al. Robot‐assisted radical cystectomy versus open radical cystectomy: a systematic review and meta‐analysis of perioperative, oncological, and quality of life outcomes using randomized controlled trials. Eur Urol 2023; 84: 393–405

Wang EY, Larsson U, Gårdmark T, Malmström PU. Radical cystectomy compared to intravesical BCG immunotherapy for high‐risk non‐muscle invasive bladder cancer ‐ is there a long‐term survival difference? A Swedish nationwide analysis. Scand J Urol 2021; 55: 46–52

Shen PL, Lin ME, Hong YK, He XJ. Bladder preservation approach versus radical cystectomy for high‐grade non‐muscle‐invasive bladder cancer: a meta‐analysis of cohort studies. World J Surg Oncol 2018; 16: 197

Catto JWF, Gordon K, Collinson M et al. Radical cystectomy against intravesical BCG for high‐risk high‐grade nonmuscle invasive bladder cancer: results from the randomized controlled BRAVO‐feasibility study. J Clin Oncol 2021; 39: 202–214

Bentzen HB, Høstmælingen N. Balancing protection and free movement of personal data: the new European Union general data protection regulation. Ann Intern Med 2019; 170: 335–337

Tan WS, Steinberg G, Witjes JA et al. Intermediate‐risk non‐muscle‐invasive bladder cancer: updated consensus definition and management recommendations from the international bladder cancer group. Eur Urol Oncol 2022; 5: 505–516

Vickers AJ, Sjoberg DD. Guidelines for reporting of statistics in European Urology. Eur Urol 2015; 67: 181–187

Balasubramanian A, Gunjur A, Weickhardt A et al. Adjuvant therapies for non‐muscle‐invasive bladder cancer: advances during BCG shortage. World J Urol 2022; 40: 1111–1124

Scilipoti P, Liedberg F, Garmo H, Wilberg Orrason A, Stattin P, Westerberg M. Risk of prostate cancer death in men diagnosed with prostate cancer at cystoprostatectomy: a nationwide population‐based study. Scand J Urol 2024; 59: 98–103

Lonati C, Afferi L, Mari A et al. Immediate radical cystectomy versus BCG immunotherapy for T1 high‐grade non‐muscle‐invasive squamous bladder cancer: an international multi‐centre collaboration. World J Urol 2022; 40: 1167–1174

Lobo N, Shariat SF, Guo CC et al. What is the significance of variant histology in urothelial carcinoma? Eur Urol Focus 2020; 6: 653–663

Subiela JD, Rodríguez Faba Ó, Aumatell J et al. Long‐term recurrence and progression patterns in a contemporary series of patients with carcinoma in situ of the bladder with or without associated Ta/T1 disease treated with Bacillus Calmette‐Guérin: implications for risk‐adapted follow‐up. Eur Urol Focus 2023; 9: 325–332

Jakse G, Hall R, Bono A et al. Intravesical BCG in patients with carcinoma in situ of the urinary bladder: long‐term results of EORTC GU Group phase II protocol 30861. Eur Urol 2001; 40: 144–150

Moschini M, Sharma V, Dell'oglio P et al. Comparing long‐term outcomes of primary and progressive carcinoma invading bladder muscle after radical cystectomy. BJU Int 2016; 117: 604–610

Hensley PJ, Bree KK, Campbell MT et al. Progression of disease after Bacillus Calmette‐Guérin therapy: refining patient selection for neoadjuvant chemotherapy before radical cystectomy. J Urol 2021; 206: 1258–1267

Robesti D, Moschini M, Tenace NP et al. The impact of second opinion expert pathology review in patient management at the time of transurethral resection of the bladder. Eur Urol Focus 2024:S2405‐4569(24)00096‐8. https://doi.org/10.1016/j.euf.2024.06.007

Yanagisawa T, Kawada T, von Deimling M et al. Repeat transurethral resection for non‐muscle‐invasive bladder cancer: an updated systematic review and meta‐analysis in the contemporary era. Eur Urol Focus 2024; 10: 41–56

Grabe‐Heyne K, Henne C, Odeyemi I, Pöhlmann J, Ahmed W, Pollock RF. Evaluating the cost‐utility of intravesical Bacillus Calmette‐Guérin versus radical cystectomy in patients with high‐risk non‐muscle‐invasive bladder cancer in the UK. J Med Econ 2023; 26: 411–421

Scilipoti P, Moschini M, Li R, et al. The Financial Burden of Localized and Metastatic Bladder Cancer. Eur Urol. Published online December 26, 2024. https://doi.org/10.1016/j.eururo.2024.12.002

Gore JL, Wolff EM, Comstock BA et al. Protocol of the comparison of intravesical therapy and surgery as treatment options (CISTO) study: a pragmatic, prospective multicenter observational cohort study of recurrent high‐grade non‐muscle invasive bladder cancer. BMC Cancer 2023; 23: 1127