PSMA-PET Guided Hypofractionated Salvage Prostate Bed Radiotherapy

Study Overview
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Brief Summary
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After radical prostatectomy approximately 15-40% of men develop a biochemical recurrence (BR) within 5 years. The standard treatment of post-prostatectomy BR is salvage external beam radiation therapy (sEBRT). sEBRT can provide long-term disease control; with 5 year biochemical progression-free survival (bPFS) up to 60% and with most treatment failures in the first 2 years after sEBRT. The main goal of this project is to investigate whether the oncologic outcome in patients with post-prostatectomy recurrent PCa can be improved, by increasing the biological effective radiation dose using a hypofractionated schedule of 20 x 3 = 60 Gy. The study is designed as a prospective open phase III randomized multicenter trial. All patients with biochemical recurrence with a PSA < 1.0 ng/ml after radical prostatectomy for prostate cancer without evidence of lymph nodes or distance metastases will be included. PSA progression after prostatectomy defined as two consecutive rises with the final PSA > 0.1 ng/mL or three consecutive rises will be included. All eligible patients will be randomized to one of the following two treatment arms: Arm 1 = Conventional sEBRT to apply a total dose of 70 Gy in 35 daily fractions of 2 Gy during 7 weeks. Arm 2 = Hypofractionated sEBRT to apply a total dose of 60 Gy in 20 fractions of 3 Gy during 4 weeks. The primary endpoint will be the 5-year progression-free survival (PFS) after treatment.

Official Title
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PSMA-PET Guided Hypofractionated Salvage Prostate Bed Radiotherapy of Biochemical Failure After Radical Prostatectomy for Prostate Cancer

Conditions
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Prostate Cancer, Cancer Recurrence

Intervention / Treatment
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* Radiation: Conventional sEBRT
* Radiation: Hypofractionated sEBRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with prostate adenocarcinoma treated with radical prostatectomy; Tumour stage pT2-4, R0-1, pN0, or cN0, cNx according to the UICC TNM 2009, only with Gleason score available; No lymph node or distant metastases. A recent PSMA-PET scan (< 60 days) without evidence of lymph node or distant metastases; PSA progression after prostatectomy defined as two consecutive rises with the final PSA > 0.1 ng/mL or 3 consecutive rises. The first value must be measured at least 6 weeks after radical prostatectomy; PSA at inclusion < 1.0 ng/mL; WHO performance status 0-2 at inclusion; Age at inclusion between 18 and 80 years; Written (signed and dated) informed consent prior to registration. Exclusion Criteria: Prior pelvic irradiation, (chemo)hormonal therapy or orchiectomy; Previous or concurrent active invasive cancers other than superficial non-melanoma skin cancers; Patients with positive nodes or with distant metastases based on the surgical specimen of lymphadenectomy or the following minimum diagnostic workup: PSMA-PET/CT scan, 60 days prior to registration; Double-sided metallic hip prosthesis; Inability or unwillingness to understand the information on trial-related topics, to give informed consent or to fill out QoL questionnaires.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: 2 randomised arms
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional<br>Conventional sEBRT | Radiation: Conventional sEBRT<br>* A total dose of70 Gy in 35 daily fractions of 2 Gy during 7 weeks<br>* Other names: Conventional salvage external beam radiation therapy;|
| Experimental: Hypofractionation<br>Hypofractionated sEBRT | Radiation: Hypofractionated sEBRT<br>* A total dose of 60 Gy in 20 daily fractions of 3 Gy during 4 weeks<br>* Other names: Hypofractionated salvage external beam radiation therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5-year progression-free survival | Defined as biochemical progression, clinical progression, loco-regional or distant progression or start with hormonal therapy, whichever occurs first | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute grade ≥ 2 gastrointestinal toxicity | As assessed using physician-reported score: Common Terminology Criteria for adverse events version 5.0 (CTCAE-5) toxicity score with a scale of 1 - 4. | Up to 3 months after completion of the RT | 
| Acute grade ≥ 2 genitourinary toxicities | As assessed using physician-reported score using questionnaires (CTCAE 5.0 toxicity score). | Up to 3 months after completion of the RT | 
| Late grade ≥ 2 gastrointestinal toxicity | As assessed using physician-reported score (CTCAE 5.0 toxicity score). | Up to 5 years after completion of the RT | 
| Late grade ≥ 2 genitourinary toxicity | Using physician-reported score (CTCAE 5.0 toxicity score). | Up to 5 years after completion of the RT | 
| Quality of life after radiation | As assessed using patient-reported questionnaires: measurend with European platform of cancer research-QLQ C30 | Up to 5 years after completion of the RT | 
| Metastasis-free survival | Time from randomisation to the date of metastases reported by CT scan, MRI scan or PSMA-PET/CT during the follow up (date scan). | 5 years | 
| Prostate cancer-specific mortality | Prostate cancer-specific mortality. | 5 years | 
| Overall survival | Overall survival | 5 years | 
| Acute grade ≥ 2 gastrointestinal toxicity | Using patient-reported questionnaires (Radiation Therapy Oncology Group (RTOG) / European platform of cancer research (EORTC) toxicity questionnaires with grade 1 to 4). | Up to 3 months after completion of the RT | 
| Acute grade ≥ 2 genitourinary toxicities | Using patient-reported questionnaires (Radiation Therapy Oncology Group (RTOG) / European platform of cancer research (EORTC) toxicity questionnaires with grade 1 to 4). | Up to 3 months after completion of the RT | 
| Late grade ≥ 2 genitourinary toxicity | Using patient-reported questionnaires (Radiation Therapy Oncology Group (RTOG) / European platform of cancer research (EORTC) toxicity questionnaires with grade 1 to 4). | Up to 5 years after completion of the RT | 
| Quality of life after radiation | As assessed using patient reported quatinnaires: European platform of cancer research-Quality of Life Questionnaire - Prostate Cancer Module (PR 25). | Up to 5 years after completion of the RT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PSMA-PET/CT, Salvage, Hypofractionation, Radiotherapy, Prostatectomy