Metastases-directed therapy in addition to standard systemic therapy in oligometastatic castration-resistant prostate cancer in Canada (GROUQ-PCS 9): a multicentre, open-label, randomised, phase 2 trial

Abstract

Background

The role of metastasis-directed therapy (MDT) in castration-resistant prostate cancer (CRPC) remains unclear. Prostate Cancer Study 9 (PCS-9) aimed to evaluate the benefits of stereotactic body radiotherapy (SBRT) in addition to standard systemic therapy in patients with oligometastatic CRPC.

Methods

This open-label, randomised, phase 2 trial was conducted across 13 Canadian academic and community oncology centres. Male patients aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0–2, and histologically confirmed oligometastatic CRPC (≤5 metastases), who had progressed on androgen deprivation therapy (ADT), were randomly assigned (1:1) to ADT–enzalutamide (ENZA; 160 mg once daily) or ADT–ENZA–SBRT to all oligometastatic sites. Randomisation was completed by sequentially numbered, sealed opaque envelopes, and stratified by the location of the metastasis. The primary endpoint was radiographic progression-free survival. Analysis was performed on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT02685397, and was halted and completed at the phase 2 stage.

Findings

Between Oct 18, 2016, and July 31, 2023, 102 male patients were randomly assigned to ADT–ENZA (n=49) or ADT–ENZA–SBRT (n=53); after excluding one patient per treatment group due to early withdrawal and insufficient data, 48 patients in the ADT–ENZA group and 52 patients in the ADT–ENZA–SBRT group were included in the final analysis. Most patients were White (80 [80%]) and median age was 73·0 years (IQR 67·0–79·5). At a median follow-up of 4·8 years (IQR 3·4–5·0), ADT–ENZA–SBRT significantly improved radiographic progression-free survival compared with ADT–ENZA alone (median radiographic progression-free survival, 4·6 years [95% CI 3·7–not reached] vs 2·3 years [1·4–3·7]; hazard ratio 0·48 [95% CI 0·27–0·86]; p=0·014). The most common grade 3 treatment related adverse event was impotence (eight [57%] of 14 patients in the ADT–ENZA group and nine [75%] of 12 patients in the ADT–ENZA–SBRT group). There were no grade 4 toxicities and no treatment-related deaths.

Interpretation

These results demonstrate that SBRT, when combined with ADT–ENZA, 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.

Funding

Jewish General Hospital (Astellas Canada).