OUTCOMES FOLLOWING NEOADJUVANT CISPLATIN-BASED CHEMOTHERAPY AND CYSTECTOMY FOR MUSCLE INVASIVE UROTHELIAL CARCINOMA WITH CONCOMITANT CARCINOMA IN SITU

Abstract

Introduction

Neoadjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy (RC) is a standard treatment for eligible patients with muscle invasive bladder cancer (MIBC). Studies on the effects of concomitant carcinoma in situ (CIS) at transurethral resection of bladder tumor (TURBT) before NAC are sparse and often limited by including non-cisplatin-based NAC, small samples, or multi-institutional data. Understanding the effect of concomitant CIS on final pathologic staging and survival outcomes is important. Thus, we aimed to compare complete response rates between patients with and without concomitant CIS with MIBC at TURBT using single-institution data from patients undergoing only cisplatin-based NAC prior to RC. We secondarily aimed to compare rates of other pathologic and oncologic outcomes as well.

Methods

This was a single institution retrospective cohort study using data from our prospectively maintained IRB approved database of patients who undergo RC. Patients with clinical stage T2-4aN0M0 MIBC with or without concomitant CIS at most recent TURBT (performed within and outside of our institution) who received at least three cycles of cisplatin-based NAC followed by RC between 2002-2024 were identified. The primary outcome of interest was rate of pathologic complete response (pCR) in patients with concomitant CIS at TURBT compared to those without. Secondary outcomes included comparison of residual CIS (pTis), nodal metastasis, lack of response to NAC (stable or upstage), overall survival, and recurrence free survival.

Results

346 patients (predominantly male (n=280, 80.9%), average age 66.3 (SD=9.2)) who had a median of 25.3 (IQR: 182-1629) months of follow-up were included. Among these patients, 78 (22.5%) had concomitant carcinoma in situ (CIS), while 268 (77.5%) did not. A higher percentage of patients without concomitant CIS received gemcitabine-cisplatin compared to those with concomitant CIS (75.7% vs. 64.1%, p=0.041). Patients with concomitant CIS had longer follow-up than patients without concomitant CIS (37.7 months vs. 18.4 months, p=0.03). The cohorts did not significantly differ in any other baseline characteristics. On multivariable analyses, concomitant CIS was not associated with pCR (OR=0.57, 95% CI=[0.30-1.07], p=0.089), pTisN0M0 (OR=1.68, 95% CI=[0.77-3.60], p=0.185), nodal metastasis (OR=0.86, 95% CI=[0.36-1.92], p=0.719), or lack of response to chemotherapy (OR=1.24, 95% CI=[0.65-2.46], p=0.522). Concomitant CIS was also not significantly associated with overall survival (HR 0.58, 95% CI [0.32-1.05], p=0.07) or recurrence free survival (HR 0.67, [0.38-1.18], p=0.163).

Conclusions

The presence of CIS in the setting of MIBC has no impact on complete response to NAC, pathologic outcomes, overall survival, or recurrence free survival. The current study is the largest single-institution study, and the only study with all patients receiving at least three cycles of only cisplatin-based NAC to assess the effect of concomitant CIS at TURBT for MIBC. The presence of concomitant CIS should not alter treatment decisions regarding NAC in patients with MIBC.