Patients that received chemotherapy after bladder cancer surgery demonstrated an approximately 30% lower risk of death than those that underwent surgery alone, according to an analysis to be presented by researchers at the Icahn School of Medicine at Mount Sinai at the 2015 Genitourinary Cancers Symposium.
Clear Level I evidence backs the effectiveness of cisplatin-based chemotherapy in both the neo-adjuvant setting and the metastatic setting in urothelial carcinoma. In contrast, convincing data in the adjuvant setting are paltry, largely because randomised controlled trials have been consistently undermined by poor accrual.
Given that an adequately powered trial to definitively assess the role of adjuvant chemotherapy is unlikely to reach completion based on historical trends, Dr Matthew D Galsky, of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai Hospital, and colleagues applied an alternative approach to evaluate the benefit of adjuvant chemotherapy using population-based data.
"Randomised controlled trials and population-based observational studies can serve as partners in the evolution of medical evidence," he explained. Particular strengths of population-based studies include good external validity, insight into therapeutic effectiveness in the real-world clinical setting, and the ability to answer questions that might never be addressed by clinical trials.
According to the researchers’ population-based analysis of 5,653 patients with pT3/pT4 and/or node-positive bladder cancer, the 1,293 individuals who received adjuvant chemotherapy following radical cystectomy consistently demonstrated improved overall survival compared to patients who underwent observation across three separate analyses. Before the overall survival numbers were crunched, logistic regression was used to calculate propensity scores accounting for multiple variables that might influence the likelihood of whether patients underwent chemotherapy or observation. For example, patients who received adjuvant chemotherapy were more likely to be younger and have private insurance, a higher median income, lymph node involvement, positive margins, and a lower Charlson/Deyo score compared with patients managed with observation, and these confounders were factored into the propensity score calculations.
Regardless of whether the data were stratified by propensity-score quintiles (hazard ratio (HR) 0.72, 95% CI (0.65, 0.80); p < 0.0001), subjected to inverse probability-of-treatment weighting (HR 0.72, 95% CI (0.69, 0.76); p < 0.0001), or matched 1:1 by propensity score for those managed with adjuvant chemotherapy versus observation (HR 0.62, 95% CI (0.56, 0.70); p < 0.0001), adjuvant chemotherapy always yielded prolonged survival compared with observation. The results also stood up in sensitivity analyses exploring the influence of poor performance status, as well as in different patient subsets.
Patients in the population-based cohort were pulled from a de-identified National Cancer Data Base Participant User File that encompasses approximately 70% of incident cancer cases in the US. The patients included in the study underwent cystectomy between 2003 and 2007, with adjuvant chemotherapy administered within 90 days of surgery. None had previously received neo-adjuvant chemotherapy or radiation to the primary tumour.
Galsky noted that the effect size favouring adjuvant chemotherapy in bladder cancer in this large comparative-effectiveness analysis of real-world data is similar to that seen in meta-analyses of randomised controlled trials of adjuvant chemotherapy. Still, he stressed, "Neo-adjuvant chemotherapy is the preferred approach based on the available level of evidence. However, for patients who do not receive neo-adjuvant chemotherapy, these data lend further support to consider adjuvant chemotherapy." Galsky hopes that these findings might help end exhaustive discourse regarding the need for more data evaluating adjuvant therapy in bladder cancer.
[link url="http://gucasym.org/large-observational-study-investigates-adjuvant-chemotherapy-locally-advanced-bladder-cancer"]Genitourinary Cancers Symposium material[/link]
[link url="http://meetinglibrary.asco.org/content/141139-159"]ASCO abstract[/link]
[link url="https://www.medicalbrief.co.za/archives/new-drug-brings-hope-to-bladder-cancer-sufferers/"]See also: New drug for bladder cancer[/link]