In a Canadian phase II trial (GROUQ-PCS 9) reported in The Lancet Oncology, Niazi et al found that the addition of metastasis-directed stereotactic body radiotherapy (SBRT) to standard systemic therapy improved radiographic progression-free survival in patients with oligometastatic castration-resistant prostate cancer (CRPC).
Study Details
In the multicenter open-label trial, 100 patients with up to five metastases who had progressed on androgen-deprivation therapy (ADT) were randomly assigned between October 2016 and July 2023 to receive ADT, enzalutamide at 160 mg once daily with (n = 52) or without (n = 48) SBRT to all oligometastatic sites. SBRT doses depended on metastasis site. Enzalutamide was continued until radiographic progression or unacceptable toxicity. The primary endpoint was radiographic progression-free survival in the intention-to-treat population.
Key Findings
At a median follow-up of 4.8 years (interquartile range = 3.4–5.0 years), median radiographic progression-free survival was 4.6 years (95% confidence interval [CI] = 3.7 years to not reached) in the SBRT group vs 2.3 years (95% CI = 1.4–3.7 years) in the control group (hazard ratio [HR] = 0.48, 95% CI = 0.27–0.86, P = .014).
Median biochemical progression-free survival was 4.6 years (95% CI = 3.7 years to not reached) in the SBRT group vs 3.1 years (95% CI = 1.9–4.7 years) in the control group (HR = 0.58, 95% CI = 0.31–1.07, P = .065).
Median time to subsequent antineoplastic therapy was 5.1 years (95% CI = 4.0 years to not reached) in the SBRT group vs 2.9 years (95% CI = 1.8–4.7 years) in the control group (HR = 0.42, 95% CI = 0.22–0.80, P = .009).
Median overall survival was not reached in either group (HR for SBRT group vs control group = 0.71, 95% CI = 0.31–1.59, P = .407).
No treatment-related grade 4 or 5 adverse events were observed; the most common grade 3 events were erectile impotence (17%) and fatigue, hypertension, and fracture (n = 1, 2% each) in the SBRT group and erectile impotence (17%) and hypertension and fracture (n = 2, 4% each) in the control group.
The investigators concluded: “These results demonstrate that SBRT, when combined with ADT–[enzalutamide], prolongs disease control in oligometastatic CRPC by doubling median radiographic progression-free survival, with similar toxicity profiles between the groups. These findings support integrating SBRT into the treatment paradigm for oligometastatic CRPC.”
Tamim Niazi, MD, of Jewish General Hospital, McGill University, Montreal, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Astellas Canada. For full disclosures of all study authors, visit thelancet.com.
