Outcomes Following Proton Therapy for the Treatment of Prostate Cancer: Efficacy and Toxicity Results from 2 Prospective Single Institution Cohorts

Abstract

To report the outcomes of prostate cancer patients treated with definitive proton therapy at a single institution. The study population is the combination of two prospective single institution cohorts aimed at evaluating the efficacy and toxicity outcomes of prostate cancer patients treated with proton therapy. For this analysis, outcomes are presented according to NCCN risk group. Eligible patients had a non-pretreated prostate cancer with at least one year of follow-up following treatment. Results are presented as numbers and percentages and survival rates are computed using Kaplan Meier methods, using the end of radiotherapy as start date. Events for biochemical progression free survival (bPFS) are death, clinical or biochemical progression or salvage treatment. Events for clinical PFS (cPFS) are death, clinical progression or salvage treatment. From 2006 to 2015, 1869 prostate cancer patients were treated using proton therapy in these two cohorts, out of which 1628 (87%) had sufficient follow-up for inclusion in the present analysis (low-risk [LR]: n=516, 31.7%, intermediate risk [IR]: n=978, 60%, high-risk [HR]: n=134, 8.2%). Proton therapy delivered a median dose of 76 (range 75.6-78) cobalt gray equivalent (CGE) in 2 CGE fractions according to risk group. Pelvic lymph nodes were not treated. Hormonal therapy was mostly used for IR (56.7%) and HR (96.3%) patients. The median follow-up was 4.1 years for the entire cohort and 4.4, 4.1 and 3.1 years for LR, IR, and HR patients, respectively. Two/five-year overall survival rates were 100%/98.0%, 99.2%/95.9% and 99.2%/87.0% for LR, IR, and HR, respectively (p=0.004 for the differences between groups). Forty-four patients had died, of which 20 (45%) had died due to prostate cancer (5-years prostate cancer specific survival of 98% with no difference between groups, p=0.1). Two/five-year bPFS rates were 99.6%/95.7%, 97.9%/92.3% and 98.4%/80.7% for LR, IR, and HR, respectively (p=0.0001 for the differences between groups). Two/five-year cPFS rates were 99.8%/95.9%, 98.6%/92.7% and 98.0%/78.0% for LR, IR, and HR, respectively (p=0.0001 for the differences between groups). Acute grade 2+ genitourinary and gastrointestinal toxicity occurred in 39.4% (n=641) and 5.2% (n=85) of the entire cohort, with only 2 grade 3 GU and no grade 3 GI toxicity. Two/five-year cumulative incidence of late grade 2+ GU and GI toxicity, defined as occurring 90 days or more after treatment, was 10.4%/15.9% and 8.3%/10.6%, respectively. Late grade 3 and 4 GU toxicity occurred in 0.6% (n=9) and 0.1% (n=1) of patients, respectively. Late grade 3 and 4 GI toxicity occured in 0.6% (n=10) and 0.1% (n=1) of patients, respectively. This prospective single institution cohort of prostate cancer patients treated with proton therapy combined demonstrates the efficacy and safety of this treatment approach. These results need to be confirmed with a longer follow-up and compared with competing treatment options.