Dose-Escalated External-Beam Radiation to Prostate and Pelvic Nodes in High-Risk Prostate Cancer: Long-Term Toxicities and Outcomes at a Tertiary Center

Abstract

A previous prospective study of dose escalated pelvic nodal irradiation in high-risk prostate cancer patients resulted in the adoption of this strategy as a standard treatment policy at our center. Here we report the long-term outcomes and toxicities of a cohort of high-risk prostate cancer patients treated with dose escalated external-beam radiotherapy (DE-RT) to the prostate and pelvic lymph nodes with or without androgen deprivation therapy (ADT).This was a retrospective REB approved study of 189 patients with high (HRPCa) and very high risk (VHRPCa) prostate cancer, treated with DE-RT between the years 2003 to 2016. All patients receiving at least 74 Gy to the prostate and 52 Gy to the pelvic nodes were included. Acute and late toxicities were retrospectively graded and scored according to CTCAEv.4 criteria from patient charts. The cumulative incidence of endpoints including biochemical failure (BCF), local recurrence (LR), and distant metastases (DM) were estimated considering death as a competing risk. Kaplan-Meier method was used to estimate the actuarial BCF-free and DM-free survival statistics with death as composite endpoint. Univariable and multivariable Cox proportional hazard models were fitted to identify prognostic factors associated with BCF-free and DM-free survival.Median (IQR) age of patients was 69 years (62,74) and median pre-treatment PSA was 21.5 ng/ml (1.6-228). Majority had a T1-2 tumor (67%) and a Gleason Score > 8 (61%). VHRPCa was seen in 36% of the total patients. The median prostatic and pelvic node dose was 78 Gy (74-84 Gy, < 78 Gy n = 6, 84 Gy n = 1) and 54 Gy (52-60 Gy, < 54 Gy n = 17, > 55 Gy n = 6), respectively. Of the patients, 44% (83/188) had less than 24 months of ADT and 56% (105/188) had at least 24 months. At a median follow-up of 6 years (0.5-13.8) the cumulative incidence of BCF, LR and DM at 5 and 10 years are 15.8%, 1.7%, 8.8% and 39.4%, 9.8%, 24.7% respectively. Estimated BCF-free survival was 81.7% at 5 years and 54.4% at 10 years. Estimated DM-free survival was 88.7% at 5 years and 67% at 10 years. Percentage of positive cores and PSA nadir value were statistically significant prognostic factors for both BCF-free (HR 1.01 95% CI 1.01-1.04 P = 0.0011; HR 2.6 95% CI 1.79-3.77 P < 0.001 respectively) and DM-free survival (HR 1.01 95% CI 1-1.04 P = 0.019; HR 2.03 95% CI 1.21-3.41 P = 0.0076 respectively). Late GI and GU Grade 2 toxicity was 8.4% (16/189) and 2.6% (5/189) with 1.6% (3/189) Grade 3 GI toxicity and 0.5% (1/189) Grade 3 GU toxicity.A policy of moderate pelvic nodal dose escalation in HRPC patients is associated with low rates of severe late toxicity although these were possibly underestimated. Long term biochemical control and DM rates were acceptable. Increasing percentage of positive biopsy cores and higher PSA nadir values were associated with worse BCF and DM-free. Further study to determine the utility of these factors for treatment intensification in a subset of HRPC patients is needed.