Outcomes of patients following dose-dense neoadjuvant chemotherapy for muscle-invasive bladder cancer: Implications for organ-sparing strategies.

Abstract

426 Background: Locoregional management of muscle-infiltrating bladder cancer (MIBC) after neoadjuvant chemotherapy (NAC) is controversial, because of both the morbidity of radical cystectomy (RC). Bladder preservation may be feasible after complete tumor response. Methods: This single-center retrospective study included 120 MIBC patients (stages ypT2-4aN0-3M0) treated between 2011 and 2017 with up to 6 cycles of neoadjuvant dose-dense Methotrexate, Vinblastin, Doxorubicin and Cisplatin (DD-MVAC). The primary outcome was relapse-free survival (RFS) depending on pathological findings on RC specimens, classified as either pathological complete response (pCR: ypT0N0/x), residual organ-confined disease (yOCD: ypTa/is/1/2N0/x), residual non-organ-confined disease (yNOCD: ypT≥3Nany or ypTanyN1-3). Secondary objectives included the rate of pCR in RC patients, the rate of ypT0 in the intention-to-treat population, and RFS in ypT0 patients according to locoregional management. Results: After a median number of 5 cycles of NAC, RC was performed in 75% of the patients, concurrent radiochemotherapy (CRC) in 11% and cystoscopic surveillance (CS) in 8%. In the intention-to-treat population, the ypT0 rate was 47%. Among 90 patients who underwent RC, 49% achieved pCR, 16% had yOCD and 34% yNOCD. Median follow-up in RC patients alive at last follow-up was 40 months. Three-year RFS was 86% in RC patients with pCR, 69% in patients with yOCD and 21% in patients with yNOCD (p < 0.0001). Outcomes were similar between ypT0 patients treated with either RC or CRC/CS (3-year RFS: 81% vs 100%, p = 0.20). Limitations to this study included its restrospective design and the lower number of patients treated with CRC/CS. Conclusions: Patients reaching ypT0 after dose-dense NAC show improved prognosis regardless of locoregional treatment. Patients with yOCD are frequently cured by RC, as opposed to patients with yNOCD. Prospective trials are needed to compare upfront cystectomy and bladder-sparing management in patients with both pCR or yNOCD.