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Adjuvant chemotherapy with radiotherapy improves survival in locally advanced bladder cancer
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SAN FRANCISCO — Adding adjuvant chemotherapy to postoperative radiotherapy improved DFS and OS among patients with locally advanced bladder cancer after radical cystectomy, according to results of a randomized phase 3 study presented at Genitourinary Cancers Symposium.
“We all know that the standard-of-care treatment for muscle-invasive bladder cancer is neoadjuvant chemotherapy plus radical cystectomy,” Brian C. Baumann, MD, assistant professor of radiation oncology at Washington University School of Medicine in St. Louis, said during the study presentation. “The role of postoperative chemotherapy after radical cystectomy is more controversial. Unfortunately, trials assessing this question have struggled with accrual, and many closed prematurely around power. Some retrospective studies have shown overall survival improvement and meta-analyses have suggested a benefit, but even some of those have been inconclusive.”
Baumann and colleagues enrolled 153 patients with bladder cancer treated with radical cystectomy and pelvic node dissection with negative margins who had pT3b/T4a disease, grade 3 tumors or positive nodes. Eligible participants were aged 70 years or younger, had ECOG performance status of 0 to 2, and showed no evidence of distant metastases or second malignancies.
Researcher randomly assigned patients to undergo 3-D conformal postoperative radiotherapy to the pelvis (45y Gy in 1.5 Gy fractions twice daily) alone or with chemotherapy (two cycles of gemcitabine and cisplatin before and after radiotherapy).
DFS served as the primary endpoint. OS and late gastrointestinal toxicity served as secondary endpoints.
Of all patients enrolled, 53% (n = 81) had urothelial carcinoma, including 41 (median age, 54 years; 80.5% pT3 stage) in the combination treatment group and 40 (median age, 55 years; 80% pT3 stage) in the postoperative radiotherapy-only group. The groups in the urothelial cohort subset, which researchers analyzed post-hoc, appeared well-balanced.
Median follow-up was 21 months (range, 4-127) for patients receiving combination therapy and 15 months (range, 5-70) for those receiving postoperative radiotherapy alone.
two local failures with postoperative radiotherapy alone and none with chemotherapy and postoperative radiotherapy.
Results showed 2-year DFS of 62% (95% CI, 45-79) with the combination therapy vs. 48% (95% CI, 29-67) with postoperative radiotherapy alone (P = .031).
Two-year OS with the combination was 71% (95% CI, 54-88) vs. 51% (95% CI, 31-71%) with postoperative radiotherapy alone (P = .048).
Multivariable analysis found that chemotherapy plus postoperative radiotherapy significantly improved DFS (HR = 0.42; 95% CI, 0.21-0.85) and OS (HR = 0.45; 95% CI, 0.21-0.96).
Researchers noted that in both groups, treatment was reasonably well-tolerated, with late grade 3 or higher GI toxicities observed in five patients who received combination therapy (7%) and six patients who underwent postoperative radiotherapy only (8%).
The fact that the urothelial analysis was performed post-hoc and the use of standard, rather than extended, lymph node dissection served as limitations to the study.
therapy in this relatively small cohort of 81 patients is somewhat surprising,” Baumann said. “Several large trials have failed to show such a benefit. So how do we explain these results?”
Baumann cited the SWOG 8710 and EORTC/MRC trials, which showed that patients with locally advanced disease have a 30% risk for local failure, and that this risk was not reduced with the addition of chemotherapy. He also discussed findings from a phase 2 trial conducted in Cairo, which found that the addition of adjuvant radiotherapy significantly improved local control vs. adjuvant chemotherapy alone.
“Our hypothesis is that the use of adjuvant radiation, which improves local control, has a synergistic effect on chemotherapy, improving the effectiveness of chemo to prevent disease recurrence,” he said. – by Jennifer Byrne
Reference:
Zaghloul M, et al. Abstract 351. Presented at: Genitourinary Cancers Symposium; Feb. 14-16, 2019; San Francisco.
Disclosures: Baumann reports no relevant financial disclosures. Please see the abstract for a list of all other authors’ relevant financial disclosures.