This Phase II, single arm study evaluates a PSA-response-adapted approach to salvage radiotherapy after radical prostatectomy for prostate cancer. All participants will receive hypo-fractionated stereotactic radiotherapy to the prostate fossa. At 5 weeks, biochemical response will be assessed. responders will proceed to observation, while non responders will receive sequential pelvic nodal radiotherapy and 4 months of androgen deprivation therapy (ADT). The study aims to determine whether this response base approach achieves non inferior 2 year freedom from progression compared with historical outcomes using routine pelvic nodal radiotherapy and ADT in all patients.
Men aged ≥18 years with histologically confirmed prostate adenocarcinoma treated with prostatectomy in the localized setting within 10 years, with post-operative PSA (persistent or rising) of ≥0.05ng/mL.
Radical prostatectomy ≥4 months prior to enrollment without nodal involvement (pN0 or pNx)
Performance status ECOG 0-2
PSA>=0.2ng/mL: positron emission tomography (PET) with FDA-approved advanced imaging agent for prostate cancer (e.g. PSMA) required.
Prior androgen deprivation therapy (ADT) > 3 months OR anti-androgen therapy (AAT) of > 30 days. For shorter courses of either, at least 30 day "wash out" period is required with confirmation of resolved castration of testosterone to >50ng/mL.
Ongoing testosterone replacement therapy (TRT) with refusal to discontinue (must be stopped with demonstration of detectable PSA ≥0.05ng/mL and non-castrate testosterone >50ng/mL after 14 days of TRT cessation)
Prior pelvic radiotherapy
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements.
Single group
Prostate Fossa Radiotherapy
RadiationStereotactic ultra hypofractionanted radiotherapy delivered to the prostate fossa using the Ethos online adaptive platform. Total dose of 32.5 Gy administered in 5 fractions over 2-4 weeks.
Pelvic nodal Radiotherapy
RadiationSequential pelvic nodal radiotherapy delivered only to PSA non responders. Dose of 25 Gy given in 5 fractions over 4 weeks using the same stereotactic technique as prostate fossa RT.
Androgen Deprivation Therapy (ADT)
DrugGnRH agonist or antagonist (leuprolide, goserelin, degarelix) administered as per institutional standard. Therapy duration is 4 months, starting before or within 14 days of pelvic nodal RT initiation.
Freedom from failure
first occurrence of rise of PSA of 2 ng/dL above post-salvage RT nadir, clinical progression (local/regional/distant) or death due to any cause.
EPIC-26 hormonal summary domain score
Patient reported hormonal symptom severity measure by the EPIC-26 questionnaire
EPIC-26 Genitourinary (GU) summary domain score
Patient reported genitourinary symptom severity measure by EPIC-26
EPIC-26 Gastrointestinal (GI) summary domain score
Patient reported gastrointestinal severity measured by EPIC-26
CTCAE v5.0 toxicity GU and GI
GI and GU adverse events will be assessed and graded according to the National Cancer Institute Common Technology Criteria for Adverse Events (CTCAE), version 5.0.
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