This is a a randomized phase II/III trial comparing salvage SBRT with standard of care (SOC) regimens for patients with a persistent detectable PSA or biochemical progression during follow-up after radical prostatectomy.

This is a multicentric randomized seamless phase II/III study comparing SBRT to conventional RT or moderately hypofractionated RT on the prostate bed.

All subjects will be randomly assigned in a 1:1 ratio:

1. Experimental arm: Radiotherapy treatment in 5 fractions.
2. Control arm: Radiotherapy treatment within a normofractionated or mildly hypofractionated schedule. For the control arm, each participating center can choose between a normofractionated schedule (32 to 35 treatment sessions) and a moderately hypofractionated schedule (20 sessions).

INCLUSION CRITERIA

1. Localized adenocarcinoma (cN0M0) of the prostate treated primarily with radical prostatectomy with definitive intent.
2. Either persistent PSA after prostatectomy (PSA ≥ 0.1 ng/mL at least 6 weeks after prostatectomy), or biochemical progression (two consecutive rising PSA amounts with a PSA >0.1 ng/mL , or three consecutive PSA rises)
3. WHO PS 0-1
4. Age ≥18 years
5. Ability to understand and willingness to sign a study-specific informed consent prior to study entry
6. Ability to understand and answer the EPIC-26 form in one of the languages available

EXCLUSION CRITERIA

1. Patients with a pT4 tumor at prostatectomy
2. Patients with previously pathologically confirmed N1
3. Patients with macroscopically involved margin at surgery (R2)
4. Patients with a history of distant metastases
5. Patients with a recurrence visible on imaging (local, pelvic, or distant). Pelvic nodes with a small diameter >1cm and/or positive on PSMA without other explanation, are considered as a pelvic recurrence.
6. Latest PSA > 2ng/ml
7. Patients with a IPSS >20
8. Gleason 10 tumor
9. Prior history of high-intensity focused ultrasound ablation (HIFU), cryosurgery or brachytherapy of the prostate
10. Prior pelvic radiotherapy
11. Prior hormonal therapy started more than 6 weeks before randomization
12. History of inflammatory bowel disease, ataxia telangiectasia, prior rectal or bladder surgery.
13. Other active malignancy, except non-melanoma skin cancer, superficial bladder cancer, or malignancies with a documented disease-free survival for a minimum of 3 years before randomization.