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Urology. 2017 Apr;102:148-158. doi: 10.1016/j.urology.2016.10.064. Epub 2017 Jan 16.

Assessing Cancer Progression and Stable Disease After Neoadjuvant Chemotherapy for Organ-confined Muscle-invasive Bladder Cancer.

Author information

1
The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address: mchappi1@jhmi.edu.
2
The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, MD.
3
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD.
4
Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.

Abstract

OBJECTIVE:

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

METHODS:

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

RESULTS:

In the institutional cohort, NAC stable patients (n = 17) had better OS (P = .05) and RFS (P = .04) than NAC progressors (n = 50), and had comparable OS (P = .7) and CSS (P = .09) with non-NAC stable patients (n = 27). Multivariable Cox proportional hazard models showed that larger tumor size predicted worse OS (hazard ratio [HR] = 1.20 per centimeter, 95% confidence interval [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 National Cancer Database, NAC stable patients (n = 223) had improved OS (P < .0001) compared with NAC progressors (n = 232) and comparable (P = .4) OS with non-NAC stable patients (n = 950). Multivariable Cox proportional hazard model showed that larger tumor size (HR = 1.03 per centimeter, 95% CI [1.02, 1.03]) and progression (HR = 2.69, 95% CI [2.40, 3.01]) predicted worse OS.

CONCLUSION:

Distinct survival outcomes suggest that NAC non-responders should be further stratified into stable disease and progressors. Comparable survival between non-NAC and NAC stable disease patients suggests that NAC stable disease may represent a chemoresistant but more indolent phenotype on the disease spectrum. Moreover, 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 disease progression.

PMID:
28104421
PMCID:
PMC5376379
DOI:
10.1016/j.urology.2016.10.064
[Indexed for MEDLINE]
Free PMC Article

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