PURPOSE: To compare cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and Bacillus Calmette-Guérin (BCG) immunotherapy for T1 squamous bladder cancer (BCa). METHODS: We retrospectively analysed 188 T1 high-grade squamous BCa patients treated between 1998 and 2019 at fifteen tertiary referral centres. Median follow-up time was 36 months (interquartile range: 19-76). The cumulative incidence and Kaplan-Meier curves were applied for CSM and OM, respectively, and compared with the Pepe-Mori and log-rank tests. Multivariable Cox models, adjusted for pathological findings at initial transurethral resection of bladder (TURB) specimen, were adopted to predict tumour recurrence and tumour progression after BCG immunotherapy. RESULTS: Immediate RC and conservative management were performed in 20% and 80% of patients, respectively. 5-year CSM and OM did not significantly differ between the two therapeutic strategies (Pepe-Mori test p = 0.052 and log-rank test p = 0.2, respectively). At multivariable Cox analyses, pure squamous cell carcinoma (SqCC) was an independent predictor of tumour progression (p = 0.04), while concomitant lympho-vascular invasion (LVI) was an independent predictor of both tumour recurrence and progression (p = 0.04) after BCG. Patients with neither pure SqCC nor LVI showed a significant benefit in 3-year recurrence-free survival and progression-free survival compared to individuals with pure SqCC or LVI (60% vs. 44%, p = 0.04 and 80% vs. 68%, p = 0.004, respectively). CONCLUSION: BCG could represent an effective treatment for T1 squamous BCa patients with neither pure SqCC nor LVI, while immediate RC should be preferred among T1 squamous BCa patients with pure SqCC or LVI at initial TURB specimen.

APHP Department of Urology Hôpital Saint Louis Université de Paris Paris France

Clinica Luganese Moncucco Lugano Switzerland

Clinica S Anna Swiss Medical Group Sorengo Switzerland

Clinica Santa Chiara Locarno Switzerland

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

Department of Medical Oncology IRCCS Ospedale San Raffaele Milan Italy

Department of Surgery Prince of wales Hospital The Chinese University of Hong Kong Hong Kong China

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

Department of Urology and Oncological Urology Wrocław Medical University Wrocław Poland

Department of Urology Centre Hospitalier Universitaire de Toulouse Toulouse France

Department of Urology Charité Universitätsmedizin Berlin Berlin Germany

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

Department of Urology Fundación Instituto Valenciano de Oncologia Valencia Spain

Department of Urology IRCCS Humanitas Research Hospital Rozzano Milan Italy

Department of Urology Ludwig Maximilians University Munich Germany

Department of Urology Luzerner Kantonsspital Lucerne Switzerland

Department of Urology Policlinico San Martino Hospital University of Genova Genova Italy

Department of Urology Spedali Civili di Brescia piazzale Spedali Civili 1 25123 Brescia Italy

Department of Urology The Netherlands Cancer Institute Amsterdam The Netherlands

Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology University of Texas Southwestern Medical Center Dallas TX USA

Department of Urology University of Verona Azienda Ospedaliera Universitaria Integrata Verona Verona Italy

Department of Urology Weill Cornell Medical College New York NY USA

Division of Experimental Oncology Unit of Urology Urological Research Institute IRCCS Ospedale San Raffaele Milan Italy

Division of Surgery and Interventional Science University College London London UK

Division of Urology Department of Surgical Sciences AOU Città della Salute e della Scienza di Torino Torino School of Medicine Torino Italy

GRC 5 Predictive Onco Uro AP HP Urology Sorbonne University Pitie Salpetriere Hospital 75013 Paris France

Institute for Urology and Reproductive Health Sechenov University Moscow Russia

University Vita Salute San Raffaele Milan Italy

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