Adding Chemo Postsurgery Improves Survival in Locally Advanced Bladder Cancer

San Francisco, California—Results from a recent study presented at the 2019 ASCO Genitourinary Cancers Symposium support the use of adjuvant therapies to address local and distant disease in patients with locally advanced bladder cancer.

“The role of post-operative chemotherapy after radical cystectomy…is not well-defined. While some retrospective studies have shown a benefit, trials have been under-powered,” according to lead investigator Mohamed S. Zaghloul, MD, MSc, MB.BCh, Professor, National Cancer Institute (NCI), Department of Radiation Oncology, Cairo University, Egypt, and colleagues.

In the Egypt-based, phase 3 clinical trial of patients with locally advanced bladder cancer, Dr Zaghloul and colleagues sought to determine the benefit of using adjuvant chemotherapy in patients receiving postoperative radiotherapy (PORT).

“We hypothesized that the addition of adjuvant chemo would improve disease-free survival (DFS) compared to PORT alone for [locally advanced bladder cancer],” they said.

A total of 153 patients (median age, 55 years) with bladder cancer were enrolled between 2002 and 2008 at the NCI in Cairo, Egypt, and randomized to receive PORT or sequential chemotherapy (n = 40) plus PORT (n = 41) after radical cystectomy. Radiotherapy 45Gy was administered via the pelvis, and the chemotherapy regimen included 2 cycles of gemcitabine and cisplatin before and after radiotherapy.

The primary end point of the trial by Dr Zaghloul and colleagues was DFS; secondary end points included overall survival (OS) and late GI toxicity.

Approximately 50% of the patients in the study had urothelial carcinoma. In the chemotherapy plus PORT and PORT-only arms, median follow-up was 21 months and 15 months, respectively. According to the investigators, “local failures” occurred in only 2 patients receiving PORT and in no patients receiving chemotherapy plus PORT.

Findings demonstrated a 2-year DFS of 62% (95% confidence interval [CI], 53%-71%) and 48% (95% CI, 39%-58%) for the chemotherapy plus PORT and PORT-only arms, respectively (log-rank P = .031). In addition, the 2-year OS was 71% (95% CI, 63%-80%) and 51% (95% CI, 40%-61%), respectively (log-rank P = .048).

On multivariable analysis, Dr Zaghloul and colleagues found chemotherapy plus PORT to be a significant prognosticator of improved DFS (HR, 0.42; 95% CI, 0.21-0.85; P = .016) and OS (HR, 0.45; 95% CI, 0.21-0.96; P = .039). Late GI toxicity of grade ≥3 occurred in 5 (7%) patients receiving chemotherapy plus PORT and in 6 (8%) patients receiving PORT alone.

“The addition of adjuvant chemo to PORT improved DFS & OS for LABC [locally advanced bladder cancer] after RC [radical cystectomy] with acceptable late GI toxicity,” Dr Zaghloul and colleagues said.

“The results suggest a role for adjuvant therapies to address both local & distant disease,” they concluded.—Hina Khaliq

Zaghloul MS, Christodouleas JP, Hwang WT, et al. Randomized phase III trial of adjuvant sequential chemotherapy plus radiotherapy versus adjuvant radiotherapy alone for locally advanced bladder cancer after radical cystectomy: Urothelial carcinoma subgroup analysis. Presented at: the 2019 Genitourinary Cancers Symposium; February 14-16, 2019; San Francisco, CA. Abstract 351.