10-Year Outcomes Following Proton Therapy for Localized Prostate Cancer.

Abstract

PURPOSE/OBJECTIVE(S)\nTo report 10-year outcomes for patients treated with proton therapy for localized prostate cancer.\n\n\nMATERIALS/METHODS\nThe 10-year outcomes from a prospective outcome tracking protocol were assessed and reported for 1272 men with localized prostate cancer. Risk groups were classified per NCCN guidelines. Median proton therapy dose was 78 GyRBE (72 to 82 GyRBE) delivered at 1.8 to 2 GyRBE per fraction. Androgen deprivation therapy (ADT) was received by 193 men for a median 6 months (range 1 to 36 months). Biochemical control was defined using the Phoenix definition. Common Terminology Criteria for Adverse Events, version 5.0, was used for toxicity scoring. The International Prostate Symptom Score (IPSS) and Expanded Prostate Index Composite (EPIC) was used for patient-reported outcomes. Freedom from biochemical failure (FFBF) and toxicity rates were calculated using the Kaplan Meier method. EPIC domain score changes considered clinically significant were 5 (bowel), 6 (urinary irritative /obstructive), 7 (urinary incontinence), and 11 (sexual).\n\n\nRESULTS\nThe median follow-up time was 10.2 years. The 10-year FFBF rates for patients with very low-risk, low-risk, favorable intermediate-risk, unfavorable intermediate-risk, high-risk, and very high-risk prostate cancer were 97%, 96%, 88%, 82%, 68%, 49%, respectively. Median PSA nadir was 0.2 ng/mL. On multivariate analysis, risk category, PSA, and the presence of perineural invasion predicted 10-year biochemical control. The 7- and 10-year grade 3+ gastrointestinal and urologic toxicity rates were 1.0% and 1.3% and 4.1% and 6.2%, respectively. On multivariate analysis (MVA), the use of prescription blood thinners significantly increased the 10-year risk for grade 3+ gastrointestinal toxicity. The use of prescription blood thinners, the presence of diabetes mellitus, a prostate volume 40+ grams, the use of pretreatment alpha blockers, an IPSS score of 15+, and the use of ADT were associated with late grade 3+ genitourinary (GU) toxicity on MVA. The dose-volume histogram parameter V70 (GyRBE) of bladder volume (< 33 cc vs. 33+ cc) also predicted for late grade 3+ GU toxicity on MVA. A clinically significant decline in EPIC sexual summary scores occurred at 10 years (67 to 41). No other clinically significant change was seen in EPIC summary scores.\n\n\nCONCLUSION\nThese long-term results show that proton therapy can provide favorable biochemical control outcomes for patients with localized prostate cancer. Additional strategies are needed to improve disease control for patients with very high-risk disease. Late grade 3+ GI toxicity rates are low and, as noted with other radiation modalities, the rate of late grade 3+ GU toxicity increases with time even after 5 years. There was an expected decline in overall sexual function as the patient cohort aged following proton therapy. These long-term results establish benchmarks for future comparative trials.