Comprehensive one-day management of prostate cancer patients: PRO-FAST single-fraction ablative, urethral-sparing, HDR-like, robotic SBRT.

backgroundRadiotherapy (RT) is a standard curative treatment for prostate cancer (PCa) and there is growing evidence of the high efficacy of moderate and ultra-hypofractionated RT. Reducing treatment duration to one week or less is a major advance, but very few studies have explored single-fraction therapy. This study evaluates the feasibility, safety, and efficacy of single-fraction stereotactic body RT (SBRT) while delivering the entire procedure in one day, with a potentially high benefit in terms of patient comfort and therapy cost and logistics.

methodsThis prospective, non-randomized monocentric trial uses Robotic Radiosurgery (CyberKnife v.7 system) to deliver a single 24 Gy fraction to the prostate (± seminal vesicles) with a "urethral sparing HDR-like" technique, and target tracking. The first phase will enroll 13 PCa patients following Simon's optimal design. Treatment is to be stopped if ≥ 2 patients develop ≥ G3 toxicity (CTCAE v5.0) within a month from RT end; otherwise, 52 more patients will be added, totaling 65. To account for minimal drop-out, 5 extra patients will be enrolled, reaching 70. All procedures are performed in a single day, including fiducial implantation, imaging acquisition, contouring, planning, dosimetry quality control, and treatment. Apart from treatment feasibility in terms of one-month acute toxicity, secondary endpoints include late toxicity, biochemical and clinical control. DISCUSSION: Few others have investigated the 24 Gy single-fraction schedule using different delivery modalities (not including tracking), which has proved to be non-inferior to 5 fraction SBRT. Our approach aims to maintain (and possibly improve) the previously reported acute, subacute and late toxicity as well as disease control, adding evidence in favor of single-fraction delivery. Another significant goal of the study is the demonstration that all the complex treatment procedures can be safely delivered in a single day. This would be especially appealing for patients far from radiotherapy centers and those with work commitments not allowing daily hospital visits. The study of response to RT can also provide useful information about PCa radiobiology. Planned additional analyses may help in better assessing the clinical value of PSMA PET/CT in the selection of high-risk patients with true limited disease, and in identifying radiomic features associated to outcome.

trial registrationThe study was prospectively registered at clinicaltrials.gov (NCT05936736).