POst-Prostatectomy Ablative Radiation Therapy

Study Overview
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Brief Summary
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The use of hypofractionated radiotherapy for prostate cancer has matured to a point that in current guidelines extremely hypofractionated image-guided IMRT regimens (6 Gy per fraction or greater) can be considered an alternative to conventionally fractionated regimens at clinics with appropriate technology, physics and clinical expertise. The delivery of fewer and larger fractions with hypofractionation compared to conventional radiotherapy might effectively improve the therapeutic ratio while maintaining isoeffective tumour doses, thus, shortening overall treatment time. In the present study, patients will undergo postoperative image-guided SBRT by means of volumetric intensity-modulated arc radiotherapy (IGRT-VMAT) with state-of-the-art treatment-planning and quality assurance procedures. Normal tissue sparing and delivery accuracy are accomplished by the use of devices that ensure stability and beam location reproducibility. The primary endpoint is to evaluate the cumulative incidence of treatment related toxicities and adverse events in the acute (< 90 days from the end of treatment) and late (> 90 days) setting.

Detailed Description
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In this observational prospective trial eligible patients are those with adverse pathological features or rising PSA after radical prostatectomy proposed for receiving 31 Gy in 5 sessions each of 6.2 Gy to the prostatic bed delivered in one week, and up to 32.5 Gy in 5 sessions each of 6.5 Gy delivered in one week, respectively, in case of clinical relapse. Patients will be treated by means of image guided volumetric modulated radiotherapy (IGRT-VMAT). A real time non-ionizing target monitoring might be used to account for intra-fractional errors, if deemed appropriate. Whether the dose constraints to the normal tissues are at risk, these will be prioritised over the prescription dose to the target. The primary endpoint of the trial is to assess the treatment related toxicity measured by the CTCAE v5.0. Secondary endpoints are quality of life in different domains (sexual, rectal , urinary) and biochemical outcome. Patients will be followed at approximately one month, then every 3 months for the first 12 months and every 6 months thereafter. Quality of Life will be prospectively evaluated through validated tools (ECOG, EPIC, IIEF-5, ICIQ-SF) at various timepoints. Percentage or total mean score will be reported according to the questionnaires, whether they grade values in a scale or use descriptive statistics. Kaplan-Meier curve analysis of biochemical relapse free survival (b-RFS) at 2 and 5-year bRFS for all patients will be estimated.

Official Title
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POst-Prostatectomy Ablative Radiation Therapy

Conditions
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Radiation Toxicity

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Adenocarcinoma of the prostate treated with radical prostatectomy (any type of radical prostatectomy is permitted including retropubic, perineal, laparoscopic or robotically assisted; there is no time limit for the date of radical prostatectomy). Pathologic T3N0/Nx disease or pathologic T2N0/Nx disease, with or without a positive prostatectomy surgical margin Post-radical prostatectomy PSA of ≥ 0.1 - < 2.0 ng/mL. Clinical local relapse assessed by Magnetic Resonance Imaging (MRI) of the pelvis ECOG performance status of 0-1 No distant metastases at restaging (in case of biochemical failure), within 60 days prior to registration Patients can be on androgen deprivation therapy Ability to understand and willingness to sign a study-specific informed consent prior to study entry EXCLUSION CRITERIA N1 and or M1 patients Prior radiation of any kind to the prostate gland or pelvis Prior brachytherapy is not allowed History of inflammatory colitis or other active severe comorbidities Patients who are on immunosuppressant medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v.5.0 | To assess treatment related acute (< 90 days from the end of treatment) and late (> 90 days) gastrointestinal (GI) and genitourinary (GU) toxicity in patients who undergo postoperative SBRT using CTCAE v.5.0 | 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QUALITY OF LIFE (QOL) assessed by Expanded Prostate Cancer Index Composite (EPIC-26) Questionnaire. For each domain minimum symptom score (=0) means best QOL and maximum symptom score (=12) means worst QOL | To measure symptom scores for each QOL domain (urinary incontinence, urinary irritative/obstructive, bowel, sexual) after SDRT by EPIC-26 Questionnaire | 60 months | 
| Number of participants with urinary incontinence assessed by International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), ranging from 0 (best) to 21 (worst) | To assess urinary continence after postoperative SBRT using ICIQ-SF | 60 months | 
| Number of participants with erectile dysfunction assessed by International Index of Erectile Function Questionnaire ranging from 5 (worst ) to 25 (best) | To assess erectile function after postoperative SBRT using IIEF 5 | 60 months | 
| Number of participants with biochemical relapse assessed by PSA (cut off 0.20 ng/mL) | To assess biochemical outcome after postoperative SBRT using serum PSA levels | 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SBRT, adjuvant RT, salvage RT, prostatectomy, prostatic bed