Radiotherapy - Adjuvant Versus Early Salvage

Study Overview
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Brief Summary
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Radical prostatectomy (RP) is the most common curative approach offered to men with newly diagnosed prostate cancer. Unfortunately, up to half of these patients will have factors placing them at high risk of their cancer recurring. Having radiotherapy after RP is known to improve cure rates, but what is not known is whether it should be given straight after the operation or only when there is a rising PSA after surgery indicating active cancer. Immediate RT may not benefit all men, and can cause serious side effects such as bladder and bowel problems and impotence. International lack of consensus on the optimal timing of RT has resulted in varied clinical practice. This phase 3 trial will compare the two approaches.

Detailed Description
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This is a prospective, multi-centre, international, randomised controlled trial with a 1:1 allocation ratio. Patients with positive margins and/or pT3 disease will be randomised to adjuvant RT (Standard Arm) or active surveillance with salvage RT delivered at early relapse (Experimental Arm). 64 Gy in 32 fractions will be delivered to the prostate bed. QoL self-assessment questionnaires, Hospital Anxiety and Depression Score and toxicity will be assessed at baseline, the end of RT and annually for 5 years. Patients will be seen by their doctor 6 monthly for the first 5 years, then annually for the next 5 years. A blood test measuring prostate specific antigen (PSA) is done 3 monthly for the first 5 years for patients randomised to early salvage RT, then 6 monthly from years 5 to 10.

Official Title
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Radiotherapy - Adjuvant Versus Early Salvage. A Phase III Multi-centre Randomised Trial Comparing Adjuvant Radiotherapy (RT) With Early Salvage RT in Patients With Positive Margins or Extraprostatic Disease Following Radical Prostatectomy.

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: Adjuvant Radiotherapy
* Radiation: Early Salvage Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prior Radical Prostatectomy (RP) for adenocarcinoma of the prostate. Histological confirmation of adenocarcinoma of the prostate with the Gleason score reported (Radical Prostatectomy specimen). Patients must have at least one of the following risk factors: 1) Positive margins, 2) Extraprostatic extension (EPE) with or without seminal vesicle involvement (pT3a or pT3b) Capable of starting RT within 4 months of RP (a requirement if randomised to adjuvant RT arm) Most recent PSA ≤ 0.10 ng/ml following RP and prior to randomisation Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1 Patient able to adhere to the specified follow-up schedule and complete the Quality of Life and anxiety/depression self-assessments Written informed consent obtained prior to randomisation Completion of all pre-treatment evaluations 18 years and older Exclusion Criteria: Previous pelvic RT Androgen deprivation (AD) prior to or following RP Evidence of nodal or distant metastases Co-morbidities that would interfere with the completion of treatment and/or 5 years of follow-up Concurrent cytotoxic medication Hip prosthesis

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: Adjuvant Radiotherapy (RT)<br>Adjuvant Radiotherapy (64Gy in 32 Fractions to the prostate bed) | Radiation: Adjuvant Radiotherapy<br>* Adjuvant RT (ART) commenced within 4 months of Radical Prostatectomy. 64Gy in 32 fractions to the prostate bed.<br>* Other names: ART, Radiation;|
| Experimental: Active Surveillance with Early SalvageRT<br>Active Surveillance with Early Salvage Radiotherapy | Radiation: Early Salvage Radiotherapy<br>* Active surveillance with early Salvage RT (SRT). SRT - 64Gy in 32 fractions to the prostate bed. RT should commence no later than 4 months following the first PSA measurement ≥ 0.2ng/mL.<br>* Other names: SRT, Surveillance, Radiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical failure: PSA ≥ 0.4 ng/ml and rising following RT |  | After 160 events have been observed, expected to be 5 years after recruitment closes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life |  | Final Analysis will be after 160 events, estimated to be five years after the end of accrual | 
| Toxicity |  | Final analysis will be after 160 events, estimated to be 5 years after end of accrual. | 
| Anxiety/Depression |  | Final analysis will be after 160 events, estimated to be 5 years after end of accrual. | 
| Biochemical failure-free survival |  | Final analysis will be after 160 events, estimated to be 5 years after end of accrual. | 
| Overall survival |  | Final analysis will be after 160 events, estimated to be 5 years after end of accrual. | 
| Disease-specific survival |  | Final analysis will be after 160 events, estimated to be 5 years after end of accrual. | 
| Time to distant failure |  | Final analysis will be after 160 events, estimated to be 5 years after end of accrual. | 
| Time to local failure |  | Final analysis will be after 160 events, estimated to be 5 years after end of accrual. | 
| Time to the initiation of androgen ablation |  | Final analysis will be after 160 events, estimated to be 5 years after end of accrual. | 
| Quality adjusted life years |  | Final analysis will be after 160 events, estimated to be 5 years after end of accrual. | 
| Cost-utility |  | Final analysis will be after 160 events, estimated to be 5 years after end of accrual. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oncology, Prostate Cancer, Radiotherapy, Radical Prostatectomy, Prior Radical Prostatectomy (RP), Histological Confirmation of adenocarcinoma of the prostate, Positive margins and/or extraprostatic extension (EPE)