Adjuvant Chemotherapy Postcystectomy Elongates Survival in Bladder Cancer

February 6, 2016
Greg Kennelty

Adjuvant chemotherapy was associated with improved overall survival (OS) compared with observation postcystectomy in patients with pathologic T3/4 and/or pathologic node-positive bladder cancer, according to a retrospective analysis published in the Journal of Clinical Oncology.

Matthew D. Galsky, MD

Adjuvant chemotherapy was associated with improved overall survival (OS) compared with observation postcystectomy in patients with pathologic T3/4 and/or pathologic node-positive bladder cancer, according to a retrospective analysis published in theJournal of Clinical Oncology.

The observational study compared OS using propensity score analyses based on patient-level, facility-level, and tumor-level characteristics. Overall, the 5-year OS rate for the adjuvant chemotherapy cohort was 37% (95% CI, 34.3% to 39.7%) versus 29.1% (95% CI, 27.7% to 30.5%) in the observational group (P<.001). Moreover, a sensitivity analysis did not indicate a difference associated with performance status.

"In this observational study, adjuvant chemotherapy was associated with improved survival in patients with locally advanced bladder cancer," Matthew D. Galsky, MD, director, Genitourinary Medical Oncology, Mount Sinai School of Medicine, and colleagues wrote. "Although neoadjuvant chemotherapy remains the preferred approach based on level I evidence, these data lend further support for the use of adjuvant chemotherapy in patients with locally advanced bladder cancer postcystectomy who did not receive chemotherapy preoperatively."

The study analyzed a total of 5,653 patients, of which 4,360 (77%) did not undergo adjuvant chemotherapy. The median time of initiation on adjuvant chemotherapy from a patient's cystectomy was 52 days. Patients had undergone a cystectomy between 2003 and 2006. Those who received adjuvant chemotherapy tended to be younger, live in a more affluent area with a higher median income, had a positive surgical margin or pathologic node-positive disease, and were less likely to have comorbidities (P<.05).

Median follow-up for patients in the adjuvant chemotherapy cohort was 6.8 years, as opposed to 6.7 years in the observational group. The advantage of adjuvant chemotherapy was shown to be "relatively robust" in comparison to the effects of poor performance statuses.

For this analysis, a performance status of 2 or greater was assumed to be associated with an HR of 1.3 to 2.0, based literature review. With this in mind, the benefit for chemotherapy in the group with the best status was 0.84 (95% Ci, 0.77-0.91). In the worst performance status group, the HR was 0.95 (95% CI, 0.87-1.04).

In the sensitivity analysis, OS was similar across groups, including in those who were older than 85 years of age and those deemed unfit for chemotherapy by the National Cancer Data Base (NCDB). In the older group, there was a 31% improvement in OS seen with chemotherapy versus observation (stratified HR, 0.69; 95% CI, 0.64-0.75). For those deemed unfit, there was a 28% improvement with chemotherapy versus observation (stratified HR, 0.72; 95% CI, 0.67-0.78).

"There are several potential strengths to our study. To our knowledge, this is the largest cohort used to assess the role of adjuvant chemotherapy in bladder cancer. The NCBD includes data from approximately 70% of all newly diagnosed patients with cancer in the United States, suggesting a high level of generalizability," the authors wrote..

In the discussion portion of the article, Galsky pointed out that there were some limitations to the study, such as unmeasured adjuvant chemotherapy patient selection factors and the fact that the study was a retrospective analysis, which could be subject to residual confounding. Moreover, he noted, the specific chemotherapy regimen, dose, and treatment duration were not included.

"Whereas single-agent versus multiagent chemotherapy is recorded in the NCBD, specific chemotherapy regimens, doses, and treatment durations are not included,” the authors wrote. “Our cohort included patients with bladder cancer treated from 2003 through 2006, the upper limit imposed by NCDB conventions for releasing survival data to limit censoring bias. There have been no changes in adjuvant chemotherapy regimens commonly used since that time period, supporting the applicability of our results to contemporary patients."

References

  1. Galsky M, Stensland K, Moshier E et al. Effectiveness of Adjuvant Chemotherapy for Locally Advanced Bladder Cancer [published online January 19, 2016]. J Clin Oncol. 2016. doi:10.1200/jco.2015.64.1076