Oncologic Outcomes of Conventionally Fractionated, Hypofractionated, and Stereotactic Body Spot-Scanned Proton Radiation Therapy for Prostate Cancer: The Mayo Clinic Experience.

PURPOSE/OBJECTIVE(S): Spot/pencil beam scanned proton therapy is a relatively new technology with fundamental differences from double scattered or IMRT. We aimed to report the long-term oncologic outcomes of a contemporary prospective series of patients treated with spot-scanned proton therapy (SSPT).

MATERIALS/METHODS: An IRB-approved prospective registry identified patients with prostate cancer treated with proton therapy between January 2016 and December 2018. Descriptive statistics were calculated for all patients. Clinical, demographic, and treatment characteristics were gathered and analyzed. Kaplan-Meier curves were generated to estimate survival and recurrence rates. Outcomes assessed included 5-year overall survival (OS), 5-year local control (LC), biochemical failure (BF), regional and distant failures, and physician-reported adverse events (AEs). Biochemical failure was defined as rise in PSA ≥ 2.0 ng/mL above nadir PSA. Acute and chronic gastrointestinal (GI) and genitourinary (GU) grade 2+ and grade 3+ baseline-adjusted AEs were assigned using CTCAE v5.0. All failures were re-staged with PET C-11 or PSMA.

RESULTS: With a median follow up of 4.4 years (IQR 3.7 - 5), two hundred and eighty-six prostate cancer patients with a median age of 72 (IQR 67.5 - 77) were treated with spot-scanned proton radiation. The median Gleason grade group was 3 (IQR 2 - 4). The median pre-RT PSA was 6.9 ng/mL (IQR 4.3 - 10.5). Median T-stage was T1c. Nearly 64% of all patients were on androgen deprivation therapy at the time of initiating radiation treatment. The median total radiation dose was 79.2 Gy delivered over 44 fractions, 70 Gy over 28 fractions, and 38 Gy over 5 fractions for CF, HF, and SBRT regimens, respectively. The BF rate for all patients was 8.4%. The 5-year LC rates for CF, HF, and SBRT were 100% (95% CI: 100 - 100), 100% (95% CI: 100 - 100), and 97.3% (95% CI: 92.2 - 100), respectively (p = 0.07). Regional recurrences occurred in 12 (4.2%) patients: 8 (5.6%) treated with CF, 2 (2.1%) with HF, and 2 (4.3%) with SBRT (p = 0.62). Distant metastatic failures occurred in 12 patients (4.2%): 5 (3.5%) treated with CF, 7 (7.4%) with HF, and none with SBRT (0%) (p = 0.052). The 5-year OS for patients treated with CF, HF, and SBRT SSPT were 88.2% (95% CI: 81.8 - 95), 86.2% (95% CI: 77.6 - 95.6), and 97.2% (95% CI: 92 - 100), respectively (p = 0.1). Acute and chronic grade 2+ GI baseline-adjusted AEs occurred in 8 (2.8%) and 51 (17.8%) patients, respectively. Acute and chronic grade 3+ GI baseline-adjusted AEs occurred in 3 (1%) and 4 (1.4%) patients, respectively. Acute and chronic grade 2+ GU-related AEs were observed in 72 (25.2%) and 63 (22%) patients, respectively. Acute and chronic grade 3+ GU toxicity was observed in 3 (1%) and 6 (2.1%) patients, respectively.

CONCLUSION: Spot-scanned proton radiation therapy provides high local control rates and excellent oncologic outcomes across different fractionation schedules with low long-term AE rates.