Autor:innen:
PD Dr. med. Cédric Poyet | University Hospital of Zurich | Switzerland
Charlotte Voskuilen | The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital | Netherlands
Dr. med. Htoo Oo | Vancouver Prostate Centre, University of British Columbia | Canada
Dr. phil. Vera Genitsch | University of Bern | Switzerland
Dr. med. Laura Smit | The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital | Netherlands
Alvaro Vidal | Instituto Oncológico FALP | Chile
Manuel Meneses | Instituto Oncológico FALP | Chile
Andrea Necchi | Fondazione IRCCS Istituto Nazionale dei Tumori | Italy
Maurizio Colecchia | Fondazione IRCCS Istituto Nazionale dei Tumori | Italy
Evanguelos Xylinas | Hôpital Cochin, Paris Descartes University | French Guiana
Jacqueline Fontugne | Institut Curie | France
Mathilde Sibony | Institut Curie | France
Prof. Dr. med. Morgan Rouprêt | Sorbonne Université, Hôpital Pitié-Salpêtrière | France
Luis Lenfant | Sorbonne Université, Hôpital Pitié-Salpêtrière | France
Jean-François Côté Côté | Sorbonne Université, Hôpital Pitié-Salpêtrière | France
Dr. med. Lorenz Buser | University Hospital of Zurich | Switzerland
Karim Saba | University Hospital of Zurich | Switzerland
Marc Furrer | University of Bern | Switzerland
Michiel van der Heijden | The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital | Netherlands
Mads Daugaard | Vancouver Prostate Centre, University of British Columbia | Canada
Peter C. Black | Vancouver Prostate Centre, University of British Columbia | Canada
Bas van Rhijn | The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital | Netherlands
Kees Hendricksen | The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital | Netherlands
Prof. Dr. med. Roland Seiler | University of Bern | Switzerland
Background and aims
Response classification after neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) is based on TNM stage at radical cystectomy (RC). We recently showed that post-NAC histopathologic tumor regression grades (TRG) add prognostic information to TNM. The following study aimed validate the prognostic significance of TRG in MIBC in a multicenter setting.
Material and methods
We enrolled 389 patients who underwent cisplatin-based NAC and RC in 8 centers between 2010 and 2016. Median follow-up was 2.2 years. TRG was determined in RC specimens by local pathologists. Central pathology review (CPR) was conducted in 20% of cases, which were randomly selected. Major response was defined as ≤pT1N0. Remaining patients were grouped in partial-responders (≥ypT2N0-3 and TRG2) and non-responders (≥ypT2N0-3 and TRG3). Response classification with and without TRG was correlated with overall survival (OS). OS was estimated using Kaplan-Meier plots. The association between response and OS was analyzed using Cox proportional hazards models.
Results
TRG was successfully determined in all cases and interobserver agreement in CPR was high (κ=0.83). After combining TRG and TNM, 47%, 15% and 38% of patients were major, partial and non-responders, respectively. Combination of TRG and TNM showed significant prognostic discrimination of OS (Major-responder: ref.; Partial-responder: hazard ratio 3.5 [95%CI 1.8-6.8]; Non-responder: hazard ratio 6.1 [95%CI 3.6-10.3]). This discrimination was superior compared to TNM staging alone, supported by two goodness-of-fit criteria (p=0.041).
Conclusions
TRG is a simple, reproducible measurement of response to NAC in MIBC. In this multicenter cohort, integrating TRG with TNM staging resulted in significantly better prognostic stratification than TNM staging alone.