PURPOSE: Optimal management of oligoprogressive prostate cancer whilst on androgen receptor pathway inhibitors (ARPi) is not known. The **** trial tests the role of stereotactic body radiotherapy (SBRT) in this setting. The objective of this Phase II prospective, non-randomised, single arm trial was to determine if local control of oligoprogressive disease with SBRT can delay further progression by more than four months, postponing time to next therapy. METHODS: Men with castration resistant prostate cancer with ≤ 2 oligoprogressive sites developing on treatment with an ARPi, after initial response to therapy, were recruited. All patients were treated to a dose of 30 Gy in 5 fractions (alternate days) or 36 Gy in 6 fractions weekly (prostate only). RESULTS: 86 men were recruited between October 2018 and February 2023. SBRT was delivered to 81 men. Mean age was 74 years. Most patients (67%) had 1 OPD lesion. Sites irradiated were bone (59%), lung (1%), lymph node (32%) and prostate (7%). Median follow-up was 22.9 months at the time of analysis. Fifty-five (68%) patients had progressed, 33 (41%) of patients progressed within 6 months of radiotherapy. Median progression free survival (PFS) was 6.4 months (95% CI 5.9-11.4). An estimated 39% (95% CI 29-49) of patients have a prolonged PFS of >
12 months. Thirty-three (41%) of patients had started new treatment or died. Median time to either next treatment or death was 27 months (95% CI 14.9-29.6). Median overall survival was 27.2 months (95% CI 24.7-36.6). Four deaths occurred within 6 months of SBRT
none were related to radiotherapy treatment. CONCLUSIONS: The **** trial has demonstrated a median PFS of 6.4 months after SBRT for oligoprogression of prostate cancer, meeting the primary endpoint. Further analysis of biomarker panel including circulating DNA and whole-body magnetic resonance imaging will promote better patient selection.