Cisplatin-based neoadjuvant chemotherapy (NAC) in bladder cancer patients (Pts) with borderline renal function: Implications for clinical practice.

Abstract

390 Background: Cisplatin-based NAC prior to cystectomy is a standard of care in muscle-invasive bladder cancer (MIBC). There are limited data for pts with borderline glomerular filtration rate (GFR) who get cisplatin-based NAC. Methods: A retrospective review of pts who received cisplatin-based NAC at Cleveland Clinic (2005-2016) was done. Pts with pre-NAC GFR of 40-59 mL/min by either CG or MDRD formula (low GFR group; n = 17) were compared to pts with GFR ≥ 60 (nl GFR group; n = 74) for treatment-related toxicities and outcomes, such as pathologic complete (pCR, pT0N0) and partial response (pPR, < pT2N0), overall survival (OS) and recurrence-free survival (RFS). Comparisons were made using Fisher’s exact, Wilcoxon, or log-rank tests. Results: Pts with low GFR were older (median age 69 vs 64, p = .02) with worse PS (44% vs 20% ECOG > 0, p < .05). Gender, race, hydronephrosis rates and TURBT features (stage, grade, LVI, CIS) did not differ. For NAC, 64 pts got Gem/Cis (49 normal GFR, 15 low GFR), 23 got MVAC (22 normal GFR, 1 low GFR), 4 got other. Low GFR pts were less likely to get MVAC (6% vs 30%, p = .08) and more likely to get split-dose cisplatin (38% vs 18%, p = .10) and have NAC modified (delayed, dose reduced or stopped) (69% vs 36%, p = .02). 4/17 pts (24%) with low GFR and 9/73 (12%) with normal GFR did not complete all planned NAC cycles (p = .26). Hematologic toxicity caused most dose delays but renal toxicity was the most common cause of NAC stoppage (4/9 normal GFR, 3/4 low GFR). NAC cycles completed (median 3 / group) and G-CSF use (31/61 normal GFR, 3/9 low GFR) were comparable. No difference was noted in time to cystectomy (mean 107 days for normal vs 103 days for low GFR from NAC start), surgical complications, length of stay, and either post-NAC or post-cystectomy GFR decline from baseline. Combined pathologic response (pCR/pPR) was higher in normal GFR pts (50% vs 18%, p = .02). OS and RFS at 2 years were 89% and 79% for normal GFR and 78% and 58% for low GFR. Conclusions: Low GFR pts were older with worse PS, had more NAC modifications, lower pCR/pPR and trend for shorter OS & RFS, but most completed planned NAC cycles. For very carefully selected pts with GFR 40-59, cisplatin-based NAC is a treatment option.