Comprehensive Versus Primary Tumor Radiotherapy in Oligometastatic Prostate Cancer

Not Applicable

Not yet recruiting

• Conditions: Prostate Cancer; Oligometastatic Prostate Cancer

• Registration Number: NCT07015138
• Lead Sponsor: Peking University First Hospital

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-05
• Study First Submitted: 2025-05-20
• Study Start: 2025-06-01
• Study First Submitted QC: 2025-06-10
• Last Update Submitted: 2025-06-10
• Study First Posted: 2025-06-11
• Last Update Posted: 2025-06-11
• Primary Completion: 2027-01-01
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Male
• Target Recruitment: 390

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
3-year progression-free survival (PFS)	Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months
3-year treatment discontinuation rate	Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months
Time to PSA progression	Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months
Quality of life (QoL)	Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months	Measure Tools: EORTC QLQ-C30 (Version 3.0): Global health status (Items 29-30), functional scales (physical, role, emotional, cognitive, social), and symptom scales (fatigue, pain, nausea, etc.).; Scale Range: 0-100 for all domains. Interpretation: Higher scores = better functioning (global/functional scales) or worse symptoms (symptom scales).; QLQ-PR25: Prostate cancer-specific module (symptoms, treatment side effects, sexual function).; Scale Range: 0-100 for all subscales; Interpretation: Higher scores = worse symptoms (urinary, bowel, treatment-related). Sexual Activity Subscale: Higher scores = more sexual activity (better functioning).; Sexual Functioning Subscale: Higher scores = worse sexual function (e.g., erectile dysfunction).
Adverse events (AEs) / Toxicity	Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months
Time to initiation of subsequent anti-tumor therapy	Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months
3-year treatment discontinuation rate (in patients with normalized testosterone)	Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months
Radiographic progression-free survival (rPFS)	Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months
Complete PSA response rate	6 months after radiotherapy	Definition: According to Prostate Cancer Working Group 3 (PCWG3) criteria, the following conditions must be met: PSA level decreases to undetectable levels (≤0.2 ng/mL). Confirmed by two consecutive measurements (≥4 weeks apart) with no clinical/radiographic progression (per RECIST 1.1).; Measurement Tools: PSA Assay Method: Electrochemiluminescence immunoassay (ECLIA) or isotope dilution liquid chromatography-mass spectrometry (ID-LC/MS), with a lower limit of quantification (LLoQ) of 0.02 ng/mL.; Radiographic Confirmation: Exclude disease progression (bone scan/CT/MRI per RECIST 1.1).; Statistical Analysis: Proportion (%) of patients meeting the above criteria, with two-sided 95% confidence intervals.