In a meta-analysis reported in JAMA Oncology, Zaorsky et al found that longer durations of androgen-deprivation therapy given with definitive radiotherapy were associated with nonlinear relative benefits in patients with localized prostate cancer.
Study Details
The meta-analysis used patient-level data from 13 randomized phase III trials evaluating definitive radiotherapy alone or with androgen-deprivation therapy. The primary outcome of interest was overall survival.
Key Findings
Among 10,266 patients included in the analysis, median age was 70 years (interquartile range [IQR] = 65–74 years), 7,392 (72%) had National Comprehensive Cancer Network (NCCN) high-risk or very high-risk disease, and androgen-deprivation therapy duration was 0 months (randomized to radiotherapy alone in randomized trials) to 36 months. Median duration of follow-up was 11.3 years (IQR = 9.5–14.5 years).
Compared with 36 months of androgen-deprivation therapy, poorer overall survival was observed with 3 months (hazard ratio [HR] = 1.75, 95% confidence interval [CI] = 1.37–2.24) and 9 months (HR = 1.50, 95% CI = 1.07–2.10) among all patients. No significant difference was observed between 36 and 18 months of treatment (HR = 1.02, 95% CI = 0.83–1.26).
Longer durations of androgen-deprivation therapy were also associated with nonlinear improvement in relative benefits in risk of distant metastases and prostate cancer–specific mortality, with reduced estimated benefits being observed beyond androgen-deprivation therapy durations of 9 to 12 months.
A near-linear increase in risk of mortality from causes other than prostate cancer was observed with longer duration of androgen-deprivation therapy (HR for 28 vs 0 months = 1.28, 95% CI = 1.09–1.50, P = .002). Compared with 36 months of treatment, risk of other-cause mortality was lower with 3 months (HR = 0.60, 95% CI = 0.45–0.80) and 6 months (HR = 0.77, 95% CI = 0.66–0.89).
The optimal androgen-deprivation therapy durations based on 10-year risk of distant metastasis were 0, 6, and 12 months and “undefined” for patients with one NCCN intermediate-risk factor, two or more NCCN intermediate-risk factors, NCCN high-risk disease, and NCCN very high-risk disease, respectively.
The investigators concluded: “The results of this meta-analysis suggest that, for men with localized prostate cancer treated with definitive radiotherapy and [androgen-deprivation therapy], there are relative and absolute benefits from increasing durations of [androgen-deprivation therapy] that help provide individualized risk estimates.”
Daniel E. Spratt, MD, of the Department of Radiation Oncology, University Hospitals Seidman Cancer, Case Western Reserve University, Cleveland, Ohio, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by the National Institutes of Health. For full disclosures of the study authors, visit jamanetwork.com.
