The lack of well-defined oligometastasis, high disease burden in mCRPC and high sensitivity of PSMA-PET scan, PMSABR study was made with high ambition and the assumption on recruitment was found to be invalid.

In this study, the investigator aim to evaluate the role of PMSA-PET guided SABR on progression free survival (PFS) in patients with oligoprogressive mCRPC with Enzalutamide. The potential improvement in PFS with SABR while continuing the initial-responding Enzalutamide is potentially benefiting to patients in terms of overall disease control.

Inclusion Criteria:

• Histological confirmation of prostate adenocarcinoma

• Evidence of stage IV disease (as defined by AJCC criteria) on previous bone, CT, and/or MRI scan

• Ongoing ADT with a gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy (ie, surgical or medical castration) confirmed by testosterone level ≤ 1.73 nmol/L (50 ng/dL) at the screening visit

• ECOG performance score 0-2

• Age ≥ 18

• History/physical examination within 2 weeks prior to registration

• Able to sign informed-consent

• Patient with mCRPC who received Enzalutamide during the past 6-8 weeks and must have been delivered for a total of at least 3 months with an initial ≥50% decline of PSA from baseline.

• Documented disease progression with Enzalutamide as defined by PCWG3 with at least one of the followings:

  1. PSA progression: defined by PSA increase that is ≥ 25% and ≥ 2 ng/mL above the nadir. A minimum of 2 rising PSA levels with an interval of ≥ 1 week between each determination.
  2. Radiographic disease progression in soft tissue based on RECIST 1.1 criteria. Participants whose disease spread is limited to regional pelvic lymph nodes (N1) measuring at least 2 cm in short axis will be considered eligible.
  3. Radiographic disease progression in bone defined as appearance of 2 or more new bone lesions on bone scan

• A maximum of 5 extracranial metastases in any organ system (except brain), with ≤ 4 tumours within any given organ system, confirmed with PSMA PET-CT scan

• All sites of oligometastasis can be safely treated with SABR

• Adequate baseline organ function to allow SABR to all relevant targets

• Participants already receiving agents for the management of skeletal-related events (SREs) are allowed to continue with anti-bone resorptive therapy (including, but not limited to bisphosphonate or receptor activator of nuclear factor kappa ligand inhibitor) if on stable dose for more than 28 days prior to treatment arm assignment

Exclusion Criteria:

• Patients with active cancer other than prostate cancer and non-melanoma skin cancer.
• Prior treatment with docetaxel, another chemotherapy agent or second generation hormonal therapy (e.g. abiraterone acetate or enzalutamide) for metastatic castration-resistant prostate cancer. Prior docetaxel, abiraterone acetate or enzalutamide for metastatic hormone-sensitive prostate cancer is allowed if ≥ 12 months elapsed from last dose of these treatments.
• PSA at inclusion >20 ng/ml
• Serum creatinine and total bilirubin > 3 times the upper limit of normal
• Liver Transaminases > 5-times the upper limit of normal
• Unstable angina and/or congestive heart failure requiring hospitalization, transmural myocardial infarction within the last 6 months, acute bacterial or fungal infection requiring intravenous antibiotics, chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
• Patients with oligometastases that have been previously treated with SABR.
• Serious medical comorbidities precluding radiotherapy, such as ataxia-telangiectasia or scleroderma. For patients with oligoprogressive lesions in the lung or thorax, this includes interstitial lung disease
• Clinical or radiological evidence of spinal cord compression or tumor within 1.5mm of spinal cord on MRI
• Malignant pleural effusion
• Malignant peritoneal disease
• Intra-cranial metastases