Differential outcomes of re-stratified high-risk prostate cancer patients treated with external beam radiation therapy plus high-dose-rate brachytherapy boost

Abstract

Purpose: We report outcomes of high-risk prostate cancer (PCa) patients, initially classified according to a 3-tier NCCN classification system, treated with external beam radiation therapy (EBRT) and high-dose-rate brachytherapy boost (HDR-BT). Patients were analyzed based on a re-stratification of their risk grouping using CAPRA score and a newer 5-tier NCCN classification.

Material and methods: 471 high-risk PCa patients treated with EBRT, HDR-BT, and androgen deprivation therapy (ADT) between 1999 and 2018 were included. Competing risk survival analyses to compare individuals with CAPRA scores < 6 vs. ≥ 6 for biochemical relapse (BCR) and metastasis incidence were conducted. Also, overall survival (OS) for both groups using Kaplan-Meier analysis was assessed. The same analyses were repeated using a 5-tier NCCN stratification comparing those classified as high-risk vs. very high-risk patients.

Results: The median age was 71 years, and the median follow-up period was 72 months. The whole cohort received an EQD₂ of 74 Gy or greater, with a median EQD₂ of 106.89 Gy. Both a CAPRA score ≥ 6 and belonging to the NCCN very high-risk group were associated with BCR, with subdistribution hazard ratios (sHRs) of 3.04 (p = 0.015) and 2.53 (p = 0.013), respectively. For metastasis incidence, both the CAPRA and NCCN groups had similar sHRs of 2.60 (p = 0.094) and 2.71 (p = 0.037), respectively. For 10-year OS, patients with CAPRA score ≥ 6 and belonging to the NCCN very high-risk group presented similar HRs of 2.11 (p = 0.005) and 2.10 (p = 0.002).

Conclusions: We showed that high-risk PCa patients classified according to the 3-tier NCCN system benefit from further stratification using the CAPRA score or the 5-tier NCCN stratification method. Patients with a CAPRA score ≥ 6 or classified as very high-risk demonstrate a higher hazard of BCR, metastasis, and death. These patients might benefit from further intensification of their investigations and treatment, based on ongoing research.

Keywords: high-dose-rate brachytherapy; prostate cancer; risk stratification.

Fig. 1

Number of high-dose-rate (HDR) brachytherapy cases performed each year at our institution between 1999 and 2018 according to number of fractions

Fig. 2

Cumulative incidence plots for biochemical relapse (BCR) according to CAPRA score (A) or NCCN classification (B). Metastasis cumulative incidence depicted by CAPRA score (C) and NCCN classification (D)

Fig. 3

Kaplan-Meier OS plots as assessed according to CAPRA scoring (A) or NCCN classification (B)