In a pooled analysis (SANDSTORM) reported in the Journal of Clinical Oncology, Ma et al found that concurrent/adjuvant short-term androgen-deprivation therapy (ADT) with prostate-only radiotherapy (PORT) was associated with better outcomes in multiple measures vs neoadjuvant/concurrent ADT with PORT in patients with nonmetastatic prostate cancer. No differences in most outcomes were associated with sequencing of ADT among patients receiving whole-pelvis radiotherapy (WPRT).
As stated by the investigators, “The sequencing of ADT with radiotherapy may affect outcomes for prostate cancer in a radiotherapy-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with PORT or WPRT.”
Study Details
The study included individual patient data from 12 randomized trials including patients receiving neoadjuvant/concurrent or concurrent/adjuvant ADT for 4 to 6 months with radiotherapy for localized disease; data were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate Consortium. Inverse probability of treatment weighting was performed with propensity scores accounting for age, initial prostate-specific antigen level, Gleason score, T stage, radiotherapy dose, and midtrial enrollment year. Metastasis-free survival was the primary outcome measure.
Key Points
A total of 7,409 patients were included in the analysis, including 6,325 in the neoadjuvant/concurrent group and 1,084 in the concurrent/adjuvant group. Median follow-up was 10.2 years (interquartile range = 7.2–14.9 years).
A significant interaction between ADT sequencing and radiotherapy field size (PORT vs WPRT) was observed for all outcome measures (metastasis-free survival, prostate cancer–specific mortality, and rates of distant metastasis and biochemical recurrence; P for interaction < .02 for all) except overall survival.
Among 4,355 patients receiving PORT, compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved:
- Metastasis-free survival (10-year risk benefit = 8.0%, hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.54–0.79, P < .0001)
- Cumulative incidence of distant metastasis (risk benefit = 3.4%, HR = 0.52, 95% CI = 0.33–0.82, P = .0046)
Cumulative incidence of biochemical recurrence (risk benefit = 14.4%, HR = 0.46, 95% CI = 0.35–0.59, P < .0001) - Prostate cancer–specific mortality (risk benefit = 4.5%, HR = 0.30, 95% CI = 0.16–0.54, P < .0001)
- Overall survival (risk benefit = 6.2%, HR = 0.69, 95% CI = 0.57–0.83, P = .0001).
Among 3,049 patients receiving WPRT, no significant differences were observed in any outcome measures for concurrent/adjuvant ADT vs neoadjuvant/concurrent ADT, except for worse cumulative incidence of distant metastasis (10-year risk increase = 7.9%, HR = 1.57, 95% CI = 1.20–2.05, P = .0009) with concurrent/adjuvant ADT.
The investigators concluded, “ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with radiotherapy field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.”
Amar U. Kishan, MD, of the Department of Radiation Oncology, University of California, Los Angeles, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by the Prostate Cancer Foundation, American Society for Radiation Oncology (ASTRO), and others. For full disclosures of the study authors, visit ascopubs.org.
