Comprehensive Versus Primary Tumor Radiotherapy in Oligometastatic Prostate Cancer

Inclusion criteria

• Male patients aged 18-85 years.
• Histopathologically confirmed acinar adenocarcinoma of the prostate. The presence of a minor component of ductal adenocarcinoma, intraductal carcinoma, and/or neuroendocrine differentiation is permitted.
• PSMA PET performed within 4 weeks prior to the start of study drug therapy or up to 4 weeks after initiation, demonstrating the presence of 1 to 10 metastatic lesions.Metastasis within pelvic lymph nodes (N1 disease) is permitted but not counted towards the total number of metastatic lesions. Metastasis to non-regional lymph nodes is permitted and counted towards the total number.The pelvis is anatomically divided into 4 regions: left hemipelvis (ilium/ischium/pubis), right hemipelvis (ilium/ischium/pubis), sacrum, and coccyx. Multiple lesions within a single anatomical division are aggregated and counted as one metastatic lesion.
• Prior androgen deprivation therapy (ADT) is permitted if the total duration was ≤ 12 months before enrollment. ADT includes luteinizing hormone-releasing hormone (LHRH) agonists or antagonists and novel hormonal agents (e.g., abiraterone, enzalutamide, apalutamide, darolutamide).
• Eastern Cooperative Oncology Group (ECOG) score 0-2.
• Hematology: Neutrophil count >=1.0×10^9/L; Platelet count >=75×10^9/L; Hemoglobin >=90 g/L.

Exclusion criteria

• Small cell carcinoma of the prostate or prostate sarcoma.
• The primary focus has received external radiation therapy, brachytherapy, and radical prostatectomy.
• Received non-endocrine systemic therapies prior to enrollment (e.g., chemotherapy, targeted therapy, radionuclide therapy).
• Metastatic castration-resistant prostate cancer (mCRPC) phase (EAU Guidelines*).
• Presence of visceral metastases (e.g., liver, lung).
• Previous bilateral orchiectomy.
• Comorbidities: Severe comorbidities affecting survival or treatment tolerance, including: Cardiovascular diseases (NYHA Class III/IV heart failure, uncontrolled arrhythmias); Renal insufficiency (eGFR <30 mL/min/1.73m^2); Neuropsychiatric disorders impairing protocol compliance.

• Definition of mCRPC (EAU Guidelines):

Metastatic castration-resistant prostate cancer (mCRPC) is defined as disease progression despite serum testosterone levels below 50 ng/dL (or 1.7 nmol/L), concurrently with one or more of the following:

• PSA progression: A sequence of at least three consecutive rises in PSA, measured ≥1 week apart, resulting in a ≥50% increase from the nadir (lowest) level, with a minimum absolute PSA value >2 ng/mL.
• Radiographic progression: The appearance of new lesions, defined as either:

• ≥2 new lesions on bone scan (Tc-99m bone scintigraphy), or
• New measurable soft tissue lesions according to RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 criteria.
• Unequivocal clinical progression: Clinical progression in the absence of concurrent PSA or radiographic progression should be viewed with suspicion and mandates further investigation to confirm disease progression.