ORLANDO—Multi-agent adjuvant chemotherapy (AC) is associated with better survival among patients with advanced nonmetastatic bladder cancer (BCa), according to findings from a retrospective database study (Abstract 292) presented during the 2015 Genitourinary Cancers Symposium.1
“AC was associated with improved survival in patients with ≥pT3 and/or pN+ BCa in this large population-based comparative effectiveness analysis,” reported lead study author Matt D. Galsky, MD, of the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai in New York, NY. “AC was associated with improved overall survival. The results were robust to sensitivity analysis for comorbidities.”
“Neoadjuvant chemotherapy is the preferred approach, based on the available level of evidence,” he concluded. “These data lend further support to consider adjuvant chemotherapy in appropriate patients who have not received neoadjuvant chemotherapy.”
Despite support for neoadjuvant chemotherapy in bladder cancer, the evidence base for AC has been “mixed,” Dr. Galsky noted. Several randomized trials of adjuvant therapy closed early because of a failure to meet patient-enrollment goals, he said—a track record that casts doubt on the feasibility of conducting a much-needed, large randomized clinical trial to settle the matter.
Such problems have “fueled controversy regarding the role of AC in bladder cancer,” he noted.
To help fill the gap left by unfinished randomized clinical trials, Dr. Galsky and coauthors applied biostatistical methods to help reduce the effects of potential confounders in a retrospective database study, such as calculating propensity-score adjustments using stratification, weighting, and matching statistical models.
To compare the effectiveness of AC with that of observation following radical cystectomy for locally advanced BCa, the study authors identified 3,294 de-identified patients in the National Cancer Data Base (NCDB) who had undergone cystectomy for ≥pT3 and/or node-positive nonmetastatic (pN+ M0) BCa.
Selection (eligibility) criteria included ≥pT3 and/or pN+ and M0 urothelial cancer; no neoadjuvant chemotherapy, no radiation to primary tumor; and survival >30 days post-cystectomy; and for the AC arm, receipt of multi-agent chemotherapy within 90 days of cystectomy.
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Patients undergoing AC were “significantly more likely to be younger, have more lymph nodes examined and involved, to have higher pT stage, have positive margins, reside in the Northeast and closer to the hospital, and to have private insurance,” Dr. Galsky noted.
AC was associated with significantly improved hazard ratios (HRs) for overall survival (OS) in all three propensity-score adjusted models (stratification, weighting, and matching: HRs= 0.72, 0.72, and 0.62, respectively; all Ps < 0.0001).
Despite important limitations (including the retrospective nature of the study and the absence of database details regarding chemotherapy regimens or durations, and recurrence or cancer-specific survival data), the effect size was similar to those obtained in meta-analyses of randomized controlled trials, he said. Furthermore, the study speaks to the “real-world, routine-practice effectiveness” of AC in bladder cancer, rather than the “efficacy under ideal conditions” identified in randomized prospective clinical studies.
- Galsky MD, Stensland K, Moshier EL, et al. Comparative effectiveness of adjuvant chemotherapy (AC) versus observation in patients with ≥ pT3 and/or pN+ bladder cancer (BCa). 2015 Genitourinary Cancers Symposium. Abstract 292.