In an individual patient-level meta-analysis reported in The Lancet Oncology, Amar U. Kishan, MD, and colleagues found that the addition of androgen-deprivation therapy (ADT) to definitive radiotherapy prolonged metastasis-free and overall survival in patients with localized prostate cancer. Longer vs shorter duration of adjuvant—but not neoadjuvant—ADT was associated with improved outcomes.
Study Details
The meta-analysis included 12 randomized trials, with data from 10,853 individual patients accessed through the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium. A total of six trials with seven randomized comparisons evaluated the addition of ADT to radiotherapy (n = 5,136, median follow-up = 12.9 years), three trials evaluated neoadjuvant ADT extension (n = 2,213, median follow-up = 10.3 years), and four trials evaluated adjuvant ADT prolongation (n = 3,774 patients, median follow-up = 10.9 years). Among all patients, median follow-up was 11.4 years (interquartile range = 9.0–15.0 years). The primary outcome measure was metastasis-free survival. Hazard ratios (HRs) were derived from stratified Cox models for ADT use (radiotherapy vs radiotherapy plus ADT), neoadjuvant ADT duration extension (3–4 vs 6–9 months), and adjuvant ADT extension (4–6 vs 18–36 months).
Adding ADT and prolonging the portion of ADT that follows radiotherapy is associated with improved metastasis-free survival in men, regardless of risk group, age, and radiotherapy dose delivered; however, the magnitude of the benefit could vary and shared decision-making with patients is recommended.— Amar U. Kishan, MD, and colleagues
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Key Findings
The addition of ADT to radiotherapy significantly improved metastasis-free survival (HR = 0.83, 95% confidence interval [CI] = 0.77–0.89, P < .0001); 10-year estimates were 61% vs 52%, corresponding to a 10-year absolute benefit of 8.6% (95% CI = 5.8%–11.4%). ADT use also significantly improved rates of biochemical recurrence, distant metastasis, and overall survival. Estimated 10-year overall survival was 65% vs 57% (HR = 0.86, 95% CI = 0.80–0.92, P < .0001).
Prolongation of adjuvant ADT significantly improved metastasis-free survival vs no prolongation (HR = 0.84, 95% CI = 0.78–0.91, P < .0001); 10-year estimates were 55% vs 47%, corresponding to a 10-year absolute benefit of 7.7% (95% CI = 4.0%–11.4%). Adjuvant ADT prolongation also significantly improved rates of biochemical recurrence, distant metastasis, and overall survival. Estimated 10-year overall survival was 63% vs 57% (HR = 0.85, 95% CI = 0.78–0.94, P = .001).
Neoadjuvant ADT extension was not associated with an improvement in metastasis-free survival vs no extension (HR = 0.95, 95% CI = 0.83–1.09, P = .50); 10-year estimates were 63% vs 62%. Extension was not associated with improved rates of biochemical recurrence or distant metastasis or overall survival. Estimated 10-year overall survival was 67% vs 66% (HR = 0.95, 95% CI = 0.82–1.10, P = .47).
No significant interactions were observed between: radiotherapy dose and metastasis-free survival benefit of ADT use (P = .96) or adjuvant ADT prolongation (P = .41); National Comprehensive Cancer Network risk group and metastasis-free survival treatment effect from ADT use (P = .091) or adjuvant ADT prolongation (P = .72); or age and metastasis-free survival treatment effect from ADT use (P = .088) or adjuvant ADT prolongation (P = .72).
The investigators concluded, “Our findings provide the strongest level of evidence so far to the magnitude of the benefit of ADT treatment intensification with radiotherapy for men with localized prostate cancer. Adding ADT and prolonging the portion of ADT that follows radiotherapy is associated with improved metastasis-free survival in men, regardless of risk group, age, and radiotherapy dose delivered; however, the magnitude of the benefit could vary and shared decision-making with patients is recommended.”
Dr. Kishan, of the Department of Radiation Oncology, University of California, Los Angeles, and Daniel E. Spratt, MD, of University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, are the corresponding authors for The Lancet Oncology article.
Disclosure: The study was funded by the University Hospitals Seidman Cancer Center, Prostate Cancer Foundation, and American Society for Radiation Oncology. For full disclosures of the study authors, visit thelancet.com.
