Single Fraction Urethra-Sparing Prostate Cancer SBRT: Phase I Results of a Multicenter, Single Arm, Phase I/II Trial

Abstract

To present the phase I results of a single fraction urethra-sparing stereotactic body radiotherapy (SBRT) schedule for localized prostate cancer (PCa) from the single arm, multicenter phase I/II ONE SHOT trial. From 08/2017 through 12/2018, 6 patients from two among the 5 participating institutions with low- and intermediate-risk localized PCa (cT1c-2cN0M0, Gleason ≤3+4, PSA ≤15 ng/ml, with ≤70 cc prostate volume and without significant tumor in the transitional zone) were recruited and treated with a 19 Gy single fraction to the prostate ± seminal vesicles (PTV= CTV + 5 mm isotropic expansion, except 3 mm posteriorly) using a VMAT technique and intrafractional motion control using intraprostatic electromagnetic transponders. The prostatic urethra, with a surrounding margin of 2 mm, received a lesser dose of 17 Gy. Genitourinary (GU) and gastrointestinal (GI) toxicity (CTCAE v4.03 grading scale), IPSS, IIEF-25 and QOL scores (EPIC) were assessed at baseline, at 5 days (D5), 6th (W6) and 12th weeks (W12) (acute toxicity) since SBRT. Primary endpoint of the phase I was safety as assessed by occurrence of Grade ≥3 acute side effects during the first 3 months in a "3 + 3” cohort-based. Median age and PSA at SBRT were 75 years old and 8.1 ng/ml. All patients underwent SBRT without interruption and doses constraints were respected for all plans. The toxicity stopping rule was never triggered, with no Grade ≥3 acute side effects observed during the first 3 months. Patients experienced mostly grade 1 or 2 GU toxicities (frequency/urgency) resolving from W6 (50% of grade 2 GU) with no grade 2 GI side effects and no rectal toxicity at W12 (33% of grade 1 GI). IPSS increased from baseline to D5 and W6 (mean, from 3.5 to 13.2 and 16.2, respectively) decreasing progressively at W12 (mean, 7.2). The EPIC urinary domain mean score was 92 pretreatment, 73 at D5, 79 at W6 and 87 at W12, while the EPIC bowel domain mean score remained overall stable over weeks (95, 91, 85, 90 at the four endpoints). No impact of SBRT was observed on IIEF-25 scores and the EPIC sexual domain between baseline and W12 (mean, from 10 to 9 and from 46 to 44, respectively). The PSA values showed a bounce at D5 (mean, from 7.9 to 18.3 ng/ml) decreasing successively up to a value of 3.3 ng/ml at W12. 19 Gy single-fraction SBRT irradiation of the whole prostate with urethra sparing to 17 Gy was feasible and well tolerated. This trial represents the first multicenter phase I/II trial assessing the efficacy and safety of a single-fraction SBRT monotherapy in the exclusive treatment of localized disease.