Elective Pelvic Nodal Irradiation With A Simultaneous Hypofractionated Integrated Prostate Boost for Localized High Risk Prostate Cancer: Long Term Results From a Prospective Clinical Trial

Abstract

To report on the long-term results of patients with localized high risk prostate cancer treated with elective pelvic nodal irradiation (EPNI) and a simultaneous hypofractionated prostate boost along with adjuvant androgen deprivation therapy (ADT).This was a prospective single-institution single-arm phase II study. Patients with high-risk prostate cancer (any of cT3 disease, PSA > 20 ng/mL, or Gleason score 8-10) were eligible. Patients underwent radiotherapy to a dose of 45 Gy in 25 fractions to the prostate and pelvic lymph nodes with a simultaneous image-guided (matched to prostatic fiducial markers) IMRT boost of 22.5 Gy to the prostate for a total of 67.5 Gy in 25 fractions (2.7 Gy per fraction) over 5 weeks. Patients were to receive ADT for 2-3 years. Endpoints included biochemical failure (Phoenix definition), distant radiographic failure, and overall survival. Univariate and multivariable analyses were performed to look for predictive factors. Late toxicity was assessed using CTCAE v3.0 for 5 years.Two hundred thirty patients (median age 71 years) were enrolled from 2004-2010. Median follow-up was 11.2 years (IQR 8.1-12.9). 67% of patients had Gleason score ≥ 8, 44% had PSA > 20 ng/mL, and 27% had cT3 disease. Median ADT duration was 30 months (IQR 21-33). Median PSA nadir was 0.02 ng/mL (IQR 0.02-0.02). Cumulative incidence of testosterone recovery (> 1.7 nmol/L) was 47.6% and 77.5% at 5 and 10 years, respectively. Cumulative incidence of biochemical failure was 15% and 33.4% at 5 and 10 years, respectively. At 10 years, the cumulative incidence of distant metastasis was 16.5%, and overall survival was 76.3%. On multivariable analysis, PSA nadir > 0.05 ng/mL was predictive of biochemical failure (HR 6.8, 95% CI 4-11.8, P < 0.001) and development of distant metastases (HR 7.5, 95% CI 3.9-14.5, P < 0.0001). PSA nadir > 0.1 ng/mL (HR 5.2, 95% 2.2-12, P = 0.0001) and ADT use < 12 months (versus > 24 months) (HR 2.3, 95% CI 1.3-3.9, P = 0.004) were predictive of worse survival. The 5-year cumulative incidence of any late grade ≥ 3 gastrointestinal and genitourinary toxicity was 2.3% and 7.5%, respectively.This was a large prospective study evaluating EPNI and a simultaneous hypofractionated prostate boost over 5 weeks combined with 2-3 years of ADT for localized high risk prostate cancer with very mature follow-up. Ten-year biochemical control and overall survival rates were favorable. Lower PSA nadir predicted for higher biochemical control, less distant failure, and longer overall survival. ADT duration of ≤ 12 months was associated with decreased overall survival.