The present study evaluates the feasibility of postoperative stereotactic hypofractionated external beam radiation therapy delivered in patients who underwent radical prostatectomy with adverse pathological features or early biochemical failure. Regardless the two settings (adjuvant or salvage), external beam radiation therapy for prostate cancer is usually a protracted course, since a total dose of 66 Gy to 70 Gy is needed to be effective. At the typical rate of 1.8 Gy to 2.0 Gy per treatment, it takes approximately 35 treatments over the course of 7 weeks to complete, which is very costly and extremely time consuming. On the other hand, the α/β ratio for prostate cancer has estimated to be as low as 1.5 Gy, significantly lower than the 3 Gy value estimated for late complications.Therefore, the delivery of the same equivalent total dose at 2 Gy/fraction (normalized total dose) to the prostate using a hypofractionation regimen, a part from the practical benefits of reducing the treatment cost and number of sessions for patients to radiotherapy departments, should have a sparing effect on early responding normal tissues through the reduction in the total dose delivered, as well as a reduction in the incidence of late complications. Trials investigating clinical and toxicity outcomes of moderate hypofractionation schedules in the curative setting have reached sufficient follow-up to show similar efficacy and toxicity to conventionally fractionated regimens.

Stereotactic body radiation therapy, or SBRT, is on the shortest end of the hypofractionation spectrum. It is accomplished in a five treatments. With its pinpoint accuracy, many Institutions currently use it for primary treatment at doses up to 9 Gy per treatment, leading to excellent outcomes at least at early time points.Patients enrolled in the study will undergo image-guided, volumetric intensity-modulated arc radiotherapy (IGRT-VMAT) with state-of-the-art treatment-planning and quality assurance procedures with emphasis on normal tissue sparing and delivery accuracy via the use of devices that ensure stability and beam location reproducibility.A rectal balloon with air filling will be used for anatomical reproducibility, while a urethral catheter loaded with beacon transponders will be used to ensure set-up reproducibility and online target tracking. Previously untreated patients who underwent radical prostatectomy with adverse pathologic findings will be enrolled in a phase I study, consisting of 31 Gy (5 fractions of 6.2 Gy), respectively, delivered over a 1-week period at 5 fractions per week. This dosage corresponds to 68.2 Gy (for an α/βratio estimate of 1.5 Gy), compared to 52.7 Gy (for an α/β estimate of 4 Gy) in a conventional schedule. In those who developed early biochemical failure the radiation schedule will consists in 32.5 Gy (5 fractions of 6.5 Gy), respectively, delivered over a 1-week period at 5 fractions per week. This dosage corresponds to 74.3 Gy (for an α/β ratio estimate of 1.5 Gy), compared to 56.9 Gy (for an α/β estimate of 4 Gy) in a conventional schedule.

Patients will be followed at one month post-treatment and every 3 months for up to 12 months (+/- 4 weeks) and every 6 months thereafter. Acute and chronic toxicity evaluations will focus, though not exclusively, on urinary, rectal and sexual functions and will be assessed through validated EPIC questionnaires. Serum PSA values will be drawn on the same schedule as clinical follow-up. The study will be continuously monitored for a minimum of 5 years. In the event unexpected severe (grade ≥3) toxicities are observed in any one of the treatment regimens, the trial will be terminated according to the standard stopping rules: \>3/first 10, and \>5/first 25 patients.