Proton Therapy for Localized Prostate Cancer: Long-Term Clinical Outcomes at a Comprehensive Cancer Center

Purpose/Objective(s)

To assess the effectiveness and toxicity of proton therapy for patients with localized prostate cancer at a comprehensive cancer center.

Materials/Methods

Patients (n=2773) participating in two prospective clinical trials were treated from May 2006 through January 2020 at a comprehensive care center and stratified according to the National Comprehensive Cancer Network guidelines (n=640 low-risk [LR], n=850 favorable-intermediate risk [F-IR], n=851 unfavorable-intermediate risk [U-IR], n=315 high risk [HR], and n=117 very high risk [VHR]). Median patient age was 66 years; median follow-up time was 7.0 years. Median prostate-specific antigen (PSA) level at 7 years was 0.3 ng/mL (interquartile range [IQR] 0.2–0.4). Pelvic lymph node irradiation was given to 29 of 2773 patients (1%) (2/851 [0.2%] U-IR, 11/315 [3.5%] HR, and 16/117 [13.7%] VHR). The median PT dose was 78 Gy in 1.8–2.0 Gy(RBE) per fraction; 63% of patients received 78 Gy(RBE) in 39 fractions, and 29% received 76 Gy(RBE) in 38 fractions. Androgen deprivation therapy (ADT) was used in 1471 patients (53%) (68/640 [10.6%] LR, 329/850 [38.7%] F-IR, 642/851 [75.4%] U-IR, 315/315 [100%] HR, and 117/117 [100%] VHR), with a median duration of 6 months for U-IR and 24 months for HR and VHR groups. Biochemical failure was defined as post-treatment nadir PSA level + 2 ng/mL. Toxicity was graded according to the modified RTOG/EORTC morbidity scale. Descriptive statistics and Kaplan-Meier estimates were used to assess toxicity and survival.

Results

Freedom from biochemical relapse (FFBR) rates at 5 and 10 years were 98.3% (95% confidence interval [CI] 96.9-99.1%) and 97% (95% CI 94.8-98.3%) for the LR group; 98.3% (95% CI 97.0-99.0%) and 93.6% (95% CI 90.6-95.7%) for the F-IR; 94.2% (95% CI 92.1-95.7%) and 90.2% (95% CI 87.3-92.5%) for the U-IR; 94.3% (95% CI 90.1-96.8%) and 85.2% (95% CI 77.1-90.8%) for the HR; and 86.1% (95% CI, 74.7-92.9%) and 68.5% (95% CI, 50.9-82.1%) for the VHR group. Two patients died of prostate cancer, one VHR (at 19.5 months) and the other U-IR (at 28.5 months). The overall rate of acute grade ≥3 genitourinary (GU) toxicity was 6/2773 (0.22%). The overall rates of late grade ≥3 GU and gastrointestinal (GI) toxicities were 23/2773 (0.83%) and 26/2773 (0.94%). Maximum toxicities experienced were grade 4 acute GU in 1 patient, grade 4 late GU in 2 patients, and grade 4 late GI in 6 patients.

Conclusion

Long-term clinical outcomes for men treated with proton therapy for localized prostate cancer were excellent in all risk groups. The benefits of pelvic lymph node radiation therapy may be greatest in the VHR group, whereas the benefits of ADT may be highest in the U-IR, HR, and VHR groups.