Comprehensive radiotherapy to all metastases plus primary prostate radiotherapy versus prostate-only radiotherapy for men with oligometastatic prostate cancer

A Multicenter, Randomized Controlled Clinical Trial Comparing Comprehensive Radiotherapy Versus Primary Tumor Radiotherapy in Oligometastatic Prostate Cancer

This tests whether adding radiation to all PSMA-PET-visible metastases along with standard systemic therapy helps men with newly diagnosed oligometastatic prostate cancer stay progression-free longer than treating the prostate alone.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 390 (estimated)
• Ages: 18 Years to 85 Years
• Sex: Male
• Sponsor: Peking University First Hospital (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 3 sites (Beijing, Beijing Municipality and 2 other locations)
• Trial ID: NCT07015138 on ClinicalTrials.gov

What this trial studies

PROLONG-3 is a multicenter, randomized phase III trial that enrolled 390 men with newly diagnosed oligometastatic prostate cancer (1–10 metastases on PSMA PET) and randomized them 2:1 to comprehensive radiotherapy plus standard systemic therapy versus primary tumor radiotherapy plus standard systemic therapy. Treatment arms received radiotherapy to the prostate with or without radiation to all PSMA-PET-detected metastatic lesions in addition to guideline systemic therapy such as androgen-deprivation therapy. Randomization was stratified by Gleason score (≤8 vs 9–10) and number of metastases (1–3 vs 4–10), using stratified block randomization with blinded endpoint adjudication to reduce bias. The primary endpoint is 3-year progression-free survival and secondary endpoints include overall survival, intermittent treatment rate, adverse events (CTCAE v5.0), and quality of life measured by EORTC QLQ questionnaires.

Who should consider this trial

Good fit: Ideal candidates are men aged 18–85 with histologically confirmed acinar prostate adenocarcinoma and 1–10 metastatic lesions on PSMA PET who are fit for radiotherapy and standard systemic therapy.

Not a fit: Patients with more than ten metastases, disease not confirmed by PSMA PET, poor performance status or significant comorbidities, or those unsuitable for radiotherapy or systemic therapy are unlikely to benefit.

Why it matters

Potential benefit: If successful, it could lengthen progression-free and potentially overall survival and increase the chance of intermittent systemic therapy for men with limited metastatic prostate cancer.

How similar studies have performed: Smaller randomized and phase II studies of metastasis-directed therapy in oligometastatic prostate cancer have shown delayed progression, but a clear survival benefit from comprehensive radiotherapy remains unproven.

Eligibility criteria

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:

1. 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.
2. 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.
3. 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.

Where this trial is running

Beijing, Beijing Municipality and 2 other locations

• Peking University First Hospital — Beijing, Beijing Municipality, China (Recruiting)
• Peking University Cancer Hospital — Beijing, Beijing Municipality, China (Not_yet_recruiting)
• Peking University Third Hospital — Beijing, Beijing Municipality, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Hong-zhen Li

Conditions Prostate Cancer; Oligometastatic Prostate Cancer