As reported in the Journal of Clinical Oncology by Deek et al, long-term follow-up of the pooled phase II STOMP and ORIOLE trials suggest maintained benefit of metastasis-directed therapy vs observation in patients with oligometastatic castration-sensitive prostate cancer.
Study Details
As noted by the investigators, the two trials are the only studies that have assessed stereotactic ablative radiation vs observation in metachronous oligometastatic (defined as ≤ three metastases) castration-sensitive prostate cancer. The initial results of the trials showed that metastasis-directed therapy was associated with prolonged androgen deprivation–free survival and progression-free survival.
The current analysis included 116 patients (62 from STOMP and 54 from ORIOLE). The primary outcome measure was progression-free survival. Outcomes were assessed according to presence or absence of high-risk mutations, defined as pathogenic somatic mutations in ATM, BRCA1/2, Rb1, or TP53.
Long-term outcomes from the only two randomized trials in oligometastatic castration-sensitive prostate cancer suggest a sustained clinical benefit to metastasis-directed therapy over observation. A high-risk mutational signature may help risk stratify treatment outcomes after metastasis-directed therapy.— Deek et al
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Key Findings
Median follow-up was 52.5 months (range = 5.8–92.0 months).
In the pooled population, median progression-free survival was 11.9 months (95% confidence interval [CI] = 8.0–18.3 months) in the metastasis-directed therapy group vs 5.9 months (95% CI = 3.2–7.1 months) in the observation group (hazard ratio [HR] = 0.44, 95% CI = 0.29–0.66, P < .001).
The greatest relative progression-free survival benefit of metastasis-directed therapy vs observation was seen among patients with high-risk mutations. Median progression-free survival was 7.5 months (95% CI = 5.9 months–not reached) vs 2.8 months (95% CI = 2 months–not reached) among patients with high-risk mutations (HR = 0.05, 95% CI = 0.01–0.28, P < .01) and 13.4 months (95% CI = 7.0–36 months) vs 7.0 months (95% CI = 4.0–15.4 months) among patients without high-risk mutations (HR = 0.42, 95% CI = 0.23–0.77, P = .01; P for interaction = .12). Within the metastasis-directed therapy group, the hazard ratio for the median progression-free survival durations of 13.4 vs 7.5 months was 0.53 (95% CI = 0.25–1.11, P = .09). In analysis of radiographic progression-free survival within the metastasis-directed therapy group, median durations were 25.3 months with no high-risk mutations vs 8.0 months with high-risk mutations (HR = 0.43, 95% CI = 0.20–0.95, P = .04).
No significant differences between the metastasis-directed therapy group vs observation group were observed for median radiographic progression–free survival (18.3 vs 17 months, HR = 0.81, 95% CI = 0.50–1.29, P = .37), time to castration-resistant disease (not reached vs 63 months, HR = 0.67, 95% CI = 0.34–1.31, P = .24), or overall survival (not reached vs not reached, HR = 0.53, 95% CI = 0.13–2.11, P = .36).
The investigators concluded, “Long-term outcomes from the only two randomized trials in oligometastatic castration-sensitive prostate cancer suggest a sustained clinical benefit to metastasis-directed therapy over observation. A high-risk mutational signature may help risk stratify treatment outcomes after metastasis-directed therapy.”
Phuoc T. Tran, MD, PhD, of the Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Movember Foundation-Distinguished Gentleman’s Ride-Prostate Cancer Foundation, Barbara’s Fund, National Cancer Institute, and others. For full disclosures of the study authors, visit ascopubs.org.
