Comprehensive Versus Primary Tumor Radiotherapy in Oligometastatic Prostate Cancer

NCT ID: NCT07015138

Last Updated: 2025-08-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

390 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-01

Study Completion Date

2027-12-31

Brief Summary

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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

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Conditions

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Prostate Cancer Oligometastatic Prostate Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
This study established a blinded assessment and endpoint adjudication committee.

Study Groups

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ARM A

Comprehensive Radiotherapy + Standard Systemic Therapy

Group Type EXPERIMENTAL

TRT

Intervention Type RADIATION

Comprehensive 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)

Arm B

Primary Radiotherapy + Standard Systemic Therapy

Group Type ACTIVE_COMPARATOR

NTRT

Intervention Type RADIATION

Standard primary radiotherapy:

* Targets: Prostate primary tumor only
* Concurrent therapy: Same systemic treatment as experimental arm

Interventions

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TRT

Comprehensive 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)

Intervention Type RADIATION

NTRT

Standard primary radiotherapy:

* Targets: Prostate primary tumor only
* Concurrent therapy: Same systemic treatment as experimental arm

Intervention Type RADIATION

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Peking University First Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hong-zhen Li

Role: STUDY_CHAIR

Peking University First Hospital

Locations

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Peking University First Hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Peking University Cancer Hospital

Beijing, Beijing Municipality, China

Site Status NOT_YET_RECRUITING

Peking University Third Hospital

Beijing, Beijing Municipality, China

Site Status NOT_YET_RECRUITING

Countries

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China

Central Contacts

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Hong-zhen Li

Role: CONTACT

+8613718895126

Facility Contacts

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Hongzhen Li

Role: primary

+86 13718895126

Yongheng Li

Role: primary

+86 13810277398

Hao Wang

Role: primary

+86 18611207267

Other Identifiers

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PROLONG-3

Identifier Type: -

Identifier Source: org_study_id

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