MP55-06 OUTCOME OF NON-RESPONDERS TO NEOADJUVANT IMMUNOTHERAPY COMPARED TO CISPLATIN-BASED CHEMOTHERAPY BEFORE RADICAL CYSTECTOMY IN MUSCLE-INVASIVE BLADDER CANCER

Abstract

INTRODUCTION AND OBJECTIVE: Patients (pts) with ypT3-4 or ypN+ response after neoadjuvant chemotherapy (CT) have a dismal prognosis regardless the use of adjuvant therapies. It is possible that similar pathologic responses after neoadjuvant immunotherapy (IO) portend different prognosis. Here, we compared the relapse-free survival (RFS) after RC in ypT3-4 or yN+ pts after IO vs CT METHODS: Between 2014 and 2019, we identified all patients with cT2-4N0 MIBC treated with neoadjuvant CT or IO (pembrolizumab), followed by RC, at our tertiary care institution. For this study purpose, only ypT3-4 or ypN+ pts were considered. Kaplan-Meier analyses examined the RFS according to neoadjuvant therapy group (CT VS IO). Cox regression analysis examined the risk of relapse after adjusting for pT, pN, age at surgery, gender and use of adjuvant CT. Finally, actual rate of 1-year RFS after RC was plotted against pT, pN, and adjuvant CT-based risk of recurrence for pts treated with neoadjuvant CT or IO RESULTS: We retrospectively identified 37 and 31 ypT3-4 or ypN+ MIBC pts. Median follow-up was 12months (interquartile range [IQR] 6-17months). No baseline differences emerged between neoadjuvant treatment groups in terms of age, gender, ypT stage, ypN stage, and use of adjuvant CT (all p>0.1). At Kaplan-Meier and multivariable Cox-regression analyses, non-responder pts treated with IO (pembrolizumab) showed higher 1-year RFS (79% vs. 47%, adjusted HR: 0.32, 95% CI: 0.11-0.93, p=0.03) compared with patients treated with neoadjuvant CT. The interaction between the use of neoadjuvant therapies (IO vs. CHT) and the risk of 1-year recurrence derived from ypT, ypN, and use of adjuvant CT-based model was statistically significant (p=0.0014). Here, non-responder neoadjuvant IO-treated patients presented a clinically significant lower rate of 1-year recurrence for predicted probabilities of recurrence higher than 20%. CONCLUSIONS: The paradigm that non-responder ypT3-4 or ypN+ MIBCa patients present adverse oncologic outcomes was confirmed after standard neoadjuvant chemotherapy, but not after neoadjuvant pembrolizumab. Neoadjuvant immunotherapy still shows an oncologic benefit even in patients with apparently unresponsive disease.Source of Funding: none