Comparing Salvage Radiotherapy and Individualized PSMA PET/CT Targeted Treatment in With Relapsing Prostate Cancer

Study Overview
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Brief Summary
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Less than 50% of patients receiving salvage radiation therapy (SRT) to the pelvis as treatment for prostate cancer relapsing after surgery will achieve undetectable Prostate Specific Antigen (PSA) levels. Despite SRT, two-thirds of patients will again develop elevated PSA, 20% will have distant metastases, and 10% will die from prostate cancer within 10 years. The reason for this is probably preexisting distant metastasis and lymph node metastasises which need to better targeted directly. Additionally , there are well known permanent side effects to SRT. Standard imaging techniques have poor sensitivity detecting recurrence when PSA is below 1.0 ng/ml. The surface protein Prostate-specific membrane antigen (PSMA) is overexpressed on prostate cancer cells and 68Gallium (68Ga)- and 18Fluorine (18F)-targeted radioligands have been developed. PSMA PET/CT is used increasingly but there is limited data of its impact. In this study patients with biochemical relapse of prostate cancer after surgery are randomised to the control or experimental group (1:2) and undergo a PSMA PET/CT scan. The experimental group receives individualised therapy based on the result of the PET/CT. The control group receives standard salvage therapy and the result of the PET/CT is blinded. The patients are followed-up with PSA test and quality of life questionnaires.

Official Title
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A Randomized Trial Comparing Conventional Salvage Radiotherapy and Individualized 68Ga-PSMA-11 or 18F-PSMA-1007 PET/CT Targeted Treatment in Patients With Biochemical Recurrence After Prostate Cancer Surgery

Conditions
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Prostate Cancer

Intervention / Treatment
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* Combination Product: Individualised therapy
* Radiation: Standard salvage therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients previously treated for prostate cancer with radical prostatectomy and now having a biochemical recurrence (BCR) defined as: PSA >0.2 <2.0 ng/mL, and increasing measured twice. Multidisciplinary conference (MDK) decision to offer the patient SRT Signed Informed Consent Exclusion Criteria: Patients previously treated for prostate cancer with biochemical recurrence Previous treatment with androgen deprivation therapy (ADT) after surgery Previous pelvic radiotherapy Patients with positive lymph nodes at surgery

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: Experimental arm<br>Individualised therapy based on results of the PSMA PET/CT. | Combination Product: Individualised therapy<br>* Group I - No uptake: treated with conventional SRT against the prostate bed. Group II -Uptake only in the prostate bed: will receive intensity modulated RT (IMRT) including Volumetric Modulated Arc Therapy (VMAT) for prostate bed with simultaneous-integrated boost (SIB) to the PET positive uptake in the prostate bed. Group III - Uptake in the prostate bed and involvement of regional lymph nodes in the pelvis: will be treated as Group II plus VMAT for the pelvic lymph nodes with SIB to the PET positive lymph nodes or pelvic lymph nodes salvage lymph node dissection (SLND). Group IV - Uptake in regional lymph nodes only: will be treated with VMAT for the pelvic lymph nodes with SIB to the PET positive lymph nodes or pelvic lymph nodes SLND. Group V - Uptake in extra-pelvic lymph nodes or bone metastasis: systemic treatment instead of surgery or radiation. Local treatment with surgery or radiation is acceptable if curative intention.<br>|
| Active Comparator: Control arm<br>Standard salvage therapy. Results of PSMA PET/CT blinded. | Radiation: Standard salvage therapy<br>* Standard salvage radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary PSA progression free survival | Number of patients with progress defined by Prostate-Specific Antigen (PSA) measurement | Throughout the study, approximately 10 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to metastasis | Time to documented metastasis of prostate cancer | At 5, 7 and 10 years | 
| Prostate cancer specific survival | Time to prostate cancer specific death | At 5, 7 and 10 years | 
| Time to secondary treatment | Time to need for secondary treatment for prostate cancer | At 5, 7 and 10 years | 
| Differences in quality of life recorded using Patient Reported Outcome Measure (PROM) | A modified version of the PSMA questionnaire developed by the National Prostate Cancer Register. Scale from 1 to 5 were 1 is very good and 5 is very bad. | Baseline, 6, 12, 36 and 60 months after completed treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PSMA PET/CT