Comprehensive Versus Primary Tumor Radiotherapy in Oligometastatic Prostate Cancer
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexMale
Age18-85
SponsorPeking University First Hospital
About this trial
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
This trial does not accept healthy volunteersQualifiers
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).
Disqualifiers
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*).
Trial design
Design model
Parallel
Treatments tested in this trial
TRT
RadiationComprehensive metastasis-directed radiotherapy: * Targets: Primary prostate tumor + all metastatic lesions (≤10 sites confirmed by PSMA PET) * Concurrent therapy: Standard systemic treatment (ADT + novel hormonal agents)
NTRT
RadiationStandard primary radiotherapy: * Targets: Prostate primary tumor only * Concurrent therapy: Same systemic treatment as experimental arm
Treatment groups
390 Participants
are divided into 2 treatment groupsGroup A: ARM AExperimental treatment 1 intervention
Group B: Arm BActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
3-year progression-free survival (PFS)
Time frame
Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 monthsSecondary outcomes
1
Time to PSA progression
Time frame
Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months2
Overall survival (OS)
Time frame
Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months3
3-year treatment discontinuation rate
Time frame
Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 months4
Quality of life (QoL)
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).
Time frame
Post-radiotherapy follow-up at 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, and 36 monthsSponsors and contacts
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Source ClinicalTrials.gov