To evaluate outcomes of patients achieving <ypT2N0 disease at radical cystectomy (RC) following neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) to identify an optimal definition of pathologic response.
Patients from 10 international centers who underwent NAC for cT2-4aN0-1 MIBC and achieved <ypT2N0 disease at RC were included. The primary outcome was time to recurrence, either local or distant. Kaplan-Meier and Cox proportional hazards regression were used to evaluate associations between clinicopathologic variables and outcomes.
625 patients were included. Median age was 66 years and 80% were male. Gemcitabine and cisplatin (GC, 56%) and methotrexate, vinblastine, doxorubicin and cisplatin (MVAC)/dose-dense (dd) MVAC (32%) were the most common NAC regimens. ypT0, pure ypTis, ypTa+/-ypTis and ypT1+/-ypTis were attained in 58.1%, 20.0%, 7.6% and 14.2% of patients respectively. The cumulative incidence of recurrence at 5 years was 9%, 16%, 29% and 30% respectively. Pathologic stage was prognostic for recurrence, with ypTa+/-Tis (HR=3.20 [1.40-7.30]) and ypT1+/-Tis disease (HR=4.03 [2.13-7.63]) associated with a significantly higher recurrence risk. Pure ypTis (HR=1.66 [0.82-3.38]) and the type of NAC regimen (ddMVAC: HR=1.59 [0.55-4.56]; MVAC: HR=1.18 [0.25-5.54]; ref: GC) were not associated with recurrence.
We propose that optimal pathologic response after NAC be defined as attainment of ypT0N0/ypTisN0 at RC. Patients with ypTaN0 or ypT1N0 disease (with or without Tis) at RC displayed a significantly higher risk of recurrence and may be candidates for trials investigating adjuvant therapy.
BJU international. 2021 Apr 28 [Epub ahead of print]
Praful Ravi, Gregory R Pond, Leonidas N Diamantopoulos, Christopher Su, Ajjai Alva, Rohit K Jain, William P Skelton, Sumati Gupta, Jonathan D Tward, Kathleen M Olson, Parminder Singh, Camilla M Grunewald, Guenter Niegisch, Jae-Lyun Lee, Andrea Gallina, Marco Bandini, Andrea Necchi, Matthew Mossanen, Bradley A McGregor, Catherine Curran, Petros Grivas, Guru P Sonpavde
Dana-Farber Cancer Institute, Boston, MA, USA., McMaster University, Hamilton, Ontario, Canada., University of Washington, Fred Hutchinson Cancer Research Center Seattle, Washington, WA, USA., University of Michigan, Ann Arbor, MI, USA., Moffitt Cancer Center, Tampa, FL, USA., Huntsman Cancer Institute, Salt Lake City, UT, USA., Mayo Clinic College of Medicine, Scottsdale, AZ, USA., Department of Urology, Medical Faculty, Heinrich-Heine-University Düsseldorf., University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea., Vita-Salute San Raffaele University, Milan, Italy., Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.