Long-Term Results from the S1314 Study of Neoadjuvant Chemotherapy for Muscle Invasive Bladder Cancer - Expert Commentary
The standard of care for muscle-invasive bladder cancer (MIBC) is cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy. Studies have documented the clinical benefit of dose-dense methotrexate-vinblastine-adriamycin-cisplatin (ddMVAC) or gemcitabine plus cisplatin (GC). The COXEN approach was developed to use gene expression data as a potential biomarker that predicts patients who are likely to benefit more from GC versus ddMVAC., Flaig et al. recently reported the long-term results of the S1314 trial.
The study cohort consisted of 227 patients, 167 of whom were eligible for the COXEN analysis. The median follow-up duration was 53 months. The researchers first determined the gene expression model (GEM) status for the COXEN subgroup. These were not predictive of progression-free survival (PFS) or overall survival (OS) in the ddMVAC or GC arms. In a pooled analysis, there was a non-significant positive association between favorable GC GEM status and PFS and OS. The XOEN scores were prognostic with a favorable GC COXEN GEM status in the pooled population hazard ratio for OS of 0.45 (95% CI 0.20–0.99; p = 0.047. For ddMVAC compared to GC, the HR was 0.86 (95% CI, 0.59-1.26; p = 0.44) for event-free survival (EFS) and 0.87 (95% CI, 0.54-1.40; p = 0.57) for OS. Among the 193 patients who underwent surgery, the 5-year postsurgical OS rate was 90% for those with stage pT0 at surgery, 89% for those downstaged but at higher than pT0, and 52% for those who did not have a pathologic response. The HR for OS among those with a complete response or downstaging relative to nonresponders was 0.14 (95% CI, 0.06-0.29; p < 0.0001).
The COXEN model provided prognostic value in MIBC patients receiving GC and ddMVAC. Integrating clinical parameters, RNA expression, and other biological signals from prospectively collected clinical trial datasets is a promising avenue to identify prognostic biomarkers.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine
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