Clinical trial NCT07015138: Comprehensive Versus Primary Tumor Radiotherapy in Oligometastatic Prostate Cancer
Official title: A Multicenter, Randomized Controlled Clinical Trial Comparing Comprehensive Radiotherapy Versus Primary Tumor Radiotherapy in Oligometastatic Prostate Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Prostate Cancer
Oligometastatic Prostate Cancer
Lead sponsor: Peking University First Hospital
Sponsor class: OTHER
First posted: 2025-06-11
Enrollment: 390
Sex: MALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a multicenter, randomized controlled phase III clinical trial (PROLONG-3) designed to evaluate the survival benefit of comprehensive radiotherapy combined with primary tumor radiotherapy versus primary tumor radiotherapy alone in patients with newly diagnosed oligometastatic prostate cancer. The trial enrolled 390 patients with ≤10 metastatic lesions confirmed by PSMA PET imaging, who were randomized in a 2:1 ratio to either the intervention group (comprehensive radiotherapy + standard systemic therapy) or control group (primary radiotherapy + standard systemic therapy).

Stratification factors included Gleason score (GS ≤8 vs. GS 9-10) and number of metastases (1-3 vs. 4-10). The primary endpoint was 3-year progression-free survival (PFS), with secondary endpoints encompassing overall survival (OS), intermittent treatment rate, adverse events (CTCAE v5.0), and quality of life (EORTC QLQ questionnaires). To minimize bias, stratified block randomization and blinded endpoint adjudication were implemented, with treatment effects analyzed using Kaplan-Meier survival curves and Cox proportional hazards models.

The study's innovation lies in its definitive evaluation of the added value of comprehensive radiotherapy, combined with exploratory biomarker analyses (including genomic testing) to identify predictive markers of therapeutic response. Should the results demonstrate significant PFS improvement with comprehensive radiotherapy, this would provide high-level evidence to guide clinical practice, potentially influencing treatment guideline updates while optimizing patient quality of life and reducing healthcare burdens.


Eligibility criteria: Inclusion Criteria:

* Male patients aged 18-85 years.
* Histologically proven prostate adenocarcinoma, with cases exhibiting partial neuroendocrine differentiation permitted.
* \<=10 metastatic lesions confirmed by pre-treatment PSMA PET imaging, excluding regional lymph nodes; Pelvic lymph node involvement (N1) is allowed but not counted toward the total metastatic lesion count; Pelvic metastases are anatomically categorized into 4 regions: left iliac bone, right iliac bone, sacrum, and coccyx. Multiple lesions within a single pelvic region are counted as 1 metastatic site .
* Endocrine therapy duration \<=12 months before enrollment, including: Luteinizing hormone-releasing hormone analogs (LHRHa), Novel endocrine therapies (e.g., abiraterone, enzalutamide).
* 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.
* 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.

Primary outcomes:
measure: 3-year progression-free survival (PFS)
timeFrame: Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months
Secondary outcomes:
measure: Time to PSA progression
timeFrame: Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months
measure: Overall survival (OS)
timeFrame: Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months
measure: 3-year treatment discontinuation rate
timeFrame: Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months
measure: Quality of life (QoL)
timeFrame: Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months
measure: Adverse events (AEs) / Toxicity
timeFrame: Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months
measure: Time to initiation of subsequent anti-tumor therapy
timeFrame: Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months
measure: 3-year treatment discontinuation rate (in patients with normalized testosterone)
timeFrame: Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months
measure: Radiographic progression-free survival (rPFS)
timeFrame: Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months
measure: Complete PSA response rate
timeFrame: 6 months after radiotherapy
Other outcomes:
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