Radioablation With or Without Androgen DeprIvation Therapy in Metachronous Prostate Cancer OligometaStAsis

Study Overview
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Brief Summary
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A randomized phase II clinical trial (RADIOSA trial: Radioablation with or without Androgen DeprIvation therapy in metachronous prostate cancer OligometaStAsis). The aim is to compare time to progression between the two study arms: SBRT only or SBRT and hormonotherapy (ADT). The primary objective is to compare the progression-free survival (PFS) defined as the absence of new metastatic lesions (local, regional or distant) between the two arms. The secondary endpoints include the comparison of overall survival (OS), biochemical progression-free survival (BPFS), ADT-free survival, local control, treatment-induced acute and late toxicity, time to castration-resistant disease and QoL between the two arms; the development of a dedicated biobanking (collection of plasma and serum) for further biological investigation of predictive/diagnostic factors for personalized treatment; the preliminary evaluation of prognostic biomarkers; the correlation between imaging-derived parameters and treatment outcome.

Official Title
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Radioablation +/- Hormonotherapy for Prostate Cancer Oligorecurrences (RADIOSA Trial): Potential of Imaging and Biology

Conditions
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Oligometastatic Prostate Cancer

Intervention / Treatment
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* Drug: Androgen deprivation therapy (ADT)
* Radiation: SBRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven initial diagnosis of adenocarcinoma of the prostate; Biochemical relapse of PCa following radical local prostate treatment (radical prostatectomy, primary radiotherapy or radical prostatectomy +/- prostate bed adjuvant/salvage radiotherapy) +/- ADT according to the European Association of Urology (EAU) guidelines 2016 [18] or after any salvage therapy if biochemical progression is diagnosed in the context of castration sensitive PCa; Nodal relapse in the pelvis, extra-regional nodal relapse (M1a), bone metastases (M1b) on Ch-PET/CT or WBMRI with a maximum of 3 lesions; Serum testosterone level >50 ng/dl at the time of randomization (castration sensitive PCa) Eastern Cooperative Oncology Group (ECOG) performance status 0-1; Age ≥18 years; Written informed consent signed Exclusion criteria Serious concomitant comorbidities or contraindication to SBRT and/or ADT; Previous invasive cancer (within 3 years before the prostate cancer diagnosis) apart from non-melanoma skin malignancies; No ability to complete questionnaires about QoL; Presence of mental diseases that cannot ensure valid informed consent;

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stereotactic body Radiotherapy (SBRT) only<br>ARM 1: salvage SBRT for lymph nodes and/or bone metastases. All the radiologically documented lesions will be treated simultaneously. | Radiation: SBRT<br>* SBRT to all radiological documented lesions (bone or lymphnodes)<br>|
| Active Comparator: Stereotactic body Radiotherapy (SBRT) and hormonotherapy (ADT)<br>ARM 2: salvage SBRT (as described for ARM 1) + 6-month ADT (luteinizing hormone-releasing hormone (LHRH) agonist or antagonist). ADT should start within one week before the start of SBRT. | Drug: Androgen deprivation therapy (ADT)<br>* SBRT + ADT<br>Radiation: SBRT<br>* SBRT to all radiological documented lesions (bone or lymphnodes)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Defined as the absence of new metastatic lesions (local, regional or distant) between the two arms. | up 3 months from the end of the treatment up to radiological progression within 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | From the end of RT treatment to the time of clinical progression or mortality from specific disease cause | Up the end of SBRT until death for cancer or other causes up to 3 years | 
| Biochemical progression-free survival (BPFS) | Biochemical progression is defined according to the EAU guidelines [18], namely a rising PSA level >0.2 ng/ml following radical prostatectomy and >2 ng/ml above the nadir after radiation therapy. | up 3 months from the end of the treatment up to 3 years | 
| Numbers of patients who experienced acute and late toxicity | Toxicity will be assessed according to the Common Toxicity Criteria for adverse events (CTCAE) toxicity criteria v4.3 | Up to 1 months after treatment completion and then up to 3 years |