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While conventionally fractionated RT is still being used as a standard treatment in the postoperative setting, ultra-hypofractionated RT has emerged as a viable option with encouraging results in patients with localised disease in the primary setting. In addition, recent technological advancements in RT delivery and precise definition of isolated macroscopic recurrence within the prostate bed using prostate-specific membrane antigen-positron emission tomography (PSMA-PET) and multiparametric MRI (mpMRI) allow the exploration of ultra-hypofractionated schedules in the salvage setting using five fractions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and analysis<\/jats:title><jats:p>In this single-arm prospective phase II multicentre trial, 36 patients with node-negative prostate adenocarcinoma treated with RP at least 6 months before trial registration, tumour stage pT2a\u20133b, R0\u20131, pN0 or cN0 according to the UICC TNM 2009 and evidence of measurable local recurrence within the prostate bed detected by PSMA PET\/CT and mpMRI within the last 3 months, will be included. The patients will undergo focal ultra-hypofractionated salvage RT with 34\u2009Gy in five fractions every other day to the site of local recurrence in combination with 6 months of androgen deprivation therapy. The primary outcome of this study is biochemical relapse-free survival at 2 years. Secondary outcomes include acute side effects (until 90 days after the end of RT) of grade 3 or higher based on Common Terminology Criteria for Adverse Events V.5, progression-free survival, metastasis-free survival, late side effects and the quality of life (based on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30, QLQ-PR25).<\/jats:p><\/jats:sec><jats:sec><jats:title>Ethics and dissemination<\/jats:title><jats:p>The study has received ethical approval from the Ethics Commission of the Canton of Bern (KEK-BE 2022-01026). Academic dissemination will occur through publications and conference presentations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration number<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05746806\">NCT05746806<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2023-075846","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T06:11:53Z","timestamp":1706681513000},"page":"e075846","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["HypoFocal SRT Trial: Ultra-hypofractionated focal salvage radiotherapy for isolated prostate bed recurrence after radical prostatectomy; single-arm phase II study; clinical trial 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