Neoadjuvant Radiohormonal Therapy for Oligometastatic Prostate Cancer

Study Overview
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Brief Summary
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The optimal treatment for oligometastatic prostate cancer (OMPC) is still on its way. Accumulating evidence has proven the safety and feasibility of radical prostatectomy and local or metastasis-directed radiotherapy for oligometastatic patients. The aim of this trial is to compare the safety and feasibility outcomes of metastasis-directed neoadjuvant radiotherapy (naRT) and neoadjuvant androgen deprivation therapy (naADT) followed by robotic-assisted radical prostatectomy (RARP) to ADT combined with abiraterone for treating OMPC.

Detailed Description
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The present study will be conducted as a prospective, open-label, two arms clinical trial. Patients with ≤ 3 de novo oligometastatic PCa, diagnosed on Ga-68 prostate-specific membrane antigen (PSMA) PET/CT, will be randomized in a 1:1 ratio between arm A (hormone) and arm B (neoadjuvant hormone and RT). The patients in arm A with oligometastatic PCa will receive long-term ADT combined with abiraterone. The patients in arm B with oligometastatic PCa will receive 1 month of naADT, followed by metastasis-directed radiation and abdominal or pelvic radiotherapy. Then, radical prostatectomy will be performed at intervals of 5-15 weeks after radiotherapy, and long-term ADT will be continued. The primary endpoints of the study are progression-free survival (PFS) including biochemical recurrence-free survival (bPFS), and radiological progression-free survival (RPFS). The secondary endpoints include quality of life (QoL), time to CRPC, positive surgical margin (pSM), overall survival (OS), postoperative continence, and toxicities parameters.

Official Title
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Safety and Efficacy Study of Neoadjuvant Radiohormonal Therapy for Oligometastatic Prostate Cancer: a Multi-center Randomized Controlled Clinical Trial

Conditions
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Oligometastatic Prostate Carcinoma

Intervention / Treatment
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* Drug: ADT combined with abiraterone
* Radiation: neoadjuvant hormone and RT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed adenocarcinoma of the prostate without small cell features Oligometastatic PCa assessed by Ga-68 prostate-specific membrane antigen (PSMA), PET/CT <4 bone oligometastases, lymph node metastasis below the renal artery level Expected survival time >5 years World Health Organization (WHO) performance status 0-1 Be willing to give written informed consent. Exclusion Criteria: Any previous or ongoing treatment for PCa, including radiotherapy, ADT, chemotherapy, focal treatment, etc. Patients who have previously undergone transurethral resection or enucleation of the prostate. Patients who have undergone other abdominal surgery within the last 3 months Patients who have visceral metastases Patients with a history of long-term anticoagulant use and anti-platelet drug use and who stopped anticoagulant therapy less than 1 week before registration Patients with other malignancies and acute or chronic infections such as human immunodeficiency virus (HIV) (+), hepatitis C virus (HCV) (+) and/or positive syphilis Severe or active comorbidities likely to impact the advisability of radiotherapy Any other serious underlying medical, psychiatric, psychological, familial, or geographical condition, which, according to the judgement of the investigator, may affect the planned staging, treatment and follow-up or patient compliance or may cause high-risk treatmentrelated complications for the patient Patients who have participated in other clinical trials within the last 3 months Patients who refuse to undergo RALP Patients unsuitable for participation in this clinical trial as per the judgement of the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized in a 1:1 ratio between arm A (hormone) and arm B (neoadjuvant hormone and RT).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A (hormone)<br>The patients in arm A with oligometastatic PCa will receive long-term ADT combined with abiraterone. | Drug: ADT combined with abiraterone<br>* The patients will receive long-term ADT combined with abiraterone.<br>|
| Experimental: B (neoadjuvant hormone and RT)<br>The patients in arm B with oligometastatic PCa will receive 1 month of naADT, followed by metastasis-directed radiation and abdominal or pelvic radiotherapy. Then, radical prostatectomy will be performed at intervals of 5-15 weeks after radiotherapy, and long-term ADT will be continued. | Radiation: neoadjuvant hormone and RT<br>* The patients will receive 1 month of naADT, followed by metastasis-directed radiation and abdominal or pelvic radiotherapy. Then, radical prostatectomy will be performed at intervals of 5-15 weeks after radiotherapy, and long-term ADT will be continued.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year progression-free survival (PFS) | To assess progression-free survival (PFS) including biochemical recurrence-free survival (bPFS), and radiological progression-free survival (RPFS). | Assessment progression-free survival (PFS) at 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quality of life (QoL) | quality of life (QoL) | through study completion, an average of 3 years | 
| time to castration-resistant prostate cancer (CRPC) | To assess the time to castration-resistant prostate cancer (CRPC) | through study completion, an average of 3 years | 
| 5-year overall survival (OS) | To assess the overall survival (OS) | Assessment overall survival (OS) at 5 years |