Assessing Cancer Progression and Stable Disease after Neoadjuvant Chemotherapy for Organ-Confined Muscle-Invasive Bladder Cancer

To propose and validate a new approach to stratify clinically staged organ-confined muscle-invasive bladder cancer patients (cT2N0M0) that are pathologic non-responders to neoadjuvant chemotherapy (NAC) to better characterize NAC non-response.

We retrospectively identified radical cystectomy patients with cT2N0M0 disease at our institution (2005-2014) and in the National Cancer Database (NCDB, 2004-2012) for external validation. Patients were stratified as stable (pT2N0M0) or progressors (>pT2 and/or pN+). Primary endpoints were cancer-specific (CSS), overall (OS), and recurrence free survival (RFS).

In the institutional cohort, NAC stable (n=17) had better OS (p=0.05) and RFS (p=0.04) than NAC progressors (n=50) and comparable OS (p=0.7) and CSS (p=0.09) compared to non-NAC stable (n=27). Multivariable cox proportional hazards models showed larger tumor size (per cm) predicted worse OS (HR=1.20, 95%CI[1.07-1.35]), CSS (HR=1.27, 95%CI[1.11-1.45]), and RFS (HR=1.24, 95%CI[1.09-1.42]). Similarly, in the NCDB, NAC stable (n=223) had improved OS (p<0.0001) than NAC progressors (n=232) and comparable (p=0.4) OS to non-NAC stable (n=950). Multivariable cox proportional hazards model showed larger tumor size (HR=1.03 per cm, 95%CI[1.02, 1.03]) and progression (HR=2.69, 95%CI[2.40-3.01]) predicted worse OS.

Distinct survival outcomes suggest NAC non-responders should be further stratified into stable disease and progressors. Comparable survival between non-NAC and NAC stable disease patients suggests NAC stable disease may represent a chemoresistent, but more indolent phenotype on the disease spectrum. Tumor size is an important prognostic biomarker in NAC non-responders. Clinical predictors of disease progression on NAC were not identified, highlighting the need to explore molecular and genomic subtyping determinants of progression.

Urology. 2017 Jan 16 [Epub ahead of print]

Meera R Chappidi, Max Kates, Aaron Brant, Alexander S Baras, George J Netto, Phillip M Pierorazio, Noah M Hahn, Trinity J Bivalacqua

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine. Electronic address: ., The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine., Department of Pathology, Johns Hopkins University School of Medicine., Department of Oncology, Johns Hopkins University School of Medicine.

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