924P - Pathologic outcomes after neoadjuvant chemotherapy for high-risk muscle invasive bladder cancer

Abstract

BackgroundNeoadjuvant chemotherapy (NAC) with cisplatin-based chemotherapy for muscle invasive bladder cancer (MIBC) has improves overall survival as compared to radical cystectomy (RC) alone. Our group has previously reported high risk features of MIBC that increase benefit of NAC. We report our institutional experience with NAC for patients with high-risk MIBC. MethodsThe records of consecutive high-risk, clinically node negative MIBC patients who underwent RC at our institution between 2005 and 2017 were reviewed. Pre-operative high-risk criteria included one or more of lymphovascular invasion, hydronephrosis, extravesical disease, and/or variant histology. Clinicopathologic and demographic information was collected, including eGFR and a previously validated frailty index. The primary outcomes were pathologic complete response (pCR=pT0N0M0) and downstaging to <pT2N0M0. ResultsIn our cohort (n=674), 74.3% (n=501) of patients received any NAC, most commonly dose dense MVAC (39.3%, n=265) followed by gemcitabine/cisplatin (GC) (13.1%, n=88), other cisplatin-based regimens (OCBR) (10.4%, n=70), and non-cisplatin regimen (NCBR) (11.6%, n=78) were used with similar frequency. The pCR rate was significantly lower without NAC at only 7.5% (n=13, p<0.01), while ddMVAC (30.2%, n=80), GC (25%, n=22), OCBR (25.7%, n=18), and NCBR (23.1%, n=18) all yielded similar results (p=0.55). When controlling for age, baseline eGFR, frailty index, and clinical T stage the chemotherapeutic regimen was not significantly predictive of achieving <ypT2N0M0 when ddMVAC was used as the reference group: GC (OR 0.75, p=0.28), other cisplatin-based regimens (OR 1.25, p=0.44), and non-cisplatin regimens (OR 0.80, p=0.4). At 5-years, cancer specific and overall survival were: 90% and 63% (MVAC); 85% and 47% (GC); 86% and 54% (OCBR); 81% and 50% (NCBR); 81% and 47% (none). ConclusionsThe benefits of NAC for MIBC have been repeatedly demonstrated, however, the rate of pathologic CR in high-risk muscle invasive disease has not been reported in a large series. In our high risk MIBC group, NAC led to significant higher pCR rate as compared to upfront surgery. These findings will serve as a benchmark for future neoadjuvant studies for evaluation of novel regimens. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureM.T. Campbell: Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): EMD Serono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Apricity health; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Janssen; Non-remunerated activity/ies: BMS; Non-remunerated activity/ies: Roche; Non-remunerated activity/ies: Merck. A.Y. Shah: Honoraria (self), Research grant / Funding (institution): Eisai; Honoraria (self): Oncology Information Group; Honoraria (self): Roche Pharmaceuticals; Research grant / Funding (institution): BMS; Research grant / Funding (institution): EMD Serono. J. Gao: Travel / Accommodation / Expenses: AstraZeneca. A.O. Siefker-Radtke: Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Sharp & Dohme; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Travel / Accommodation / Expenses: Nektar Therapeutics; Advisory / Consultancy, Travel / Accommodation / Expenses: Seattle Genetics; Advisory / Consultancy: Bavarian Nordic. C.P.N. Dinney: Advisory / Consultancy: FKD Therapies Oy; Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (self): NCI; Research grant / Funding (self): The University of Eastern Finland, Faculty of Health Sciences (UEFHS). A.M. Kamat: Advisory / Consultancy: Photocure; Advisory / Consultancy: FKD; Advisory / Consultancy: Abbott Molecular; Advisory / Consultancy: Theralase; Advisory / Consultancy: Merck; Advisory / Consultancy: BMS; Advisory / Consultancy: Eisai; Advisory / Consultancy: BioClin Therapeutics; Advisory / Consultancy: Cold Genesys; Advisory / Consultancy: Roviant; Advisory / Consultancy: Sessen Bio; Advisory / Consultancy: Asieris; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: US Biotest; Advisory / Consultancy: Ferring; Advisory / Consultancy: MDxHealth; Leadership role: IBCG; Advisory / Consultancy: TMC Innovation. N. Navai: Shareholder / Stockholder / Stock options: Allogene; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Pacira. All other authors have declared no conflicts of interest.