3263 - Prospective Analysis on Tumor Control, Survival, Toxicity and Quality of Life Outcomes of an HDR-Brachytherapy Boost for Prostate Cancer

M. Peters¹, T. Nuver¹, M. Rasing¹, M. Noordhoek¹, M. Haverkort², E. Schimmel², W. Schoevers¹, M. Czerwinski², K. Pasma², R. Kattevilder¹, and A. W. Minken¹; ¹Radiotherapiegroep Deventer, Deventer, Netherlands, ²Radiotherapiegroep Arnhem, Arnhem, Netherlands

Purpose/Objective(s): A brachytherapy boost for intermediate to high-risk prostate cancer increases biochemical disease-free survival (bDFS) at the risk of increased toxicity. We performed a prospective evaluation of tumor control, survival, toxicity and quality of life (QoL) in a large modern cohort of intermediate to high-risk patients treated with high-dose-rate (HDR) brachytherapy boost after hypo-fractionated external beam radiotherapy (EBRT). Materials/

Methods: Patients treated from February 2010-August 2020 were prospectively followed. Treatment consisted of EBRT (58 Gy in 20 fractions to prostate and seminal vesicles or 62.5 Gy in 25 fractions with 50 Gy in 25 fractions to elective pelvic nodes), followed by a single fraction HDR-brachytherapy boost of 10 Gy, combined with androgen deprivation therapy (ADT) up to two years. Data on bDFS, overall survival (OS), toxicity and QoL were registered up to ten years. The Phoenix-definition (PSA-nadir + 2 ng/ml) was used for biochemical recurrence. Toxicity was scored with CTCAE v3.0. QoL was measured using IPSS for urinary, and a Likert scale for erectile and bowel complaints. bDFS and OS were analyzed using Kaplan-Meier analysis and Cox-regression.
Results: Baseline characteristics are shown in Table 1. With median follow-up of 95 months (IQR 66-120) 8-year bDFS was 76% (95% confidence interval [CI] 70-83%) and OS 76% (95%-CI 71-82%). For biochemical failure, PSA nadir >0.1 ng/ml was the strongest predictor: univariable hazard ratio (HR) 9.2 (95%-CI 5.2-16.3, p<0.0001) and multivariable 11.9 (6.4-22.0, p<0.0001), corrected for PSA, T-stage, Gleason score, age, ADT and number of fractions. Patients with PSA nadir <0.1 ng/ml (n=209) had 8-year bDFS of 88% (95%-CI 83-94) versus 31% (18-54%) with nadir >0.1 ng/ml (p<0.0001). Competing risk analysis gave similar results. PSA nadir >0.1 ng/ml was also the most significant predictor for mortality: univariable HR 1.9 (95%-CI 1.2-3.1, p=0.009) and multivariable 2.0 (1.2-3.3, p=0.01), resulting in a 15% 8-year survival advantage (80% versus 65%). Late grade 3 genitourinary toxicity occurred in 12 patients (crude rate 4.4%), and grade 3 gastro-intestinal toxicity in 2 (0.7%). IPSS increased from minor to moderate bother: 6 (IQR 3-10) to 9 (IQR 6-15) (p<0.0001). Minor bowel complaints transiently increased and complete erectile dysfunction increased from 39 (14%) to 88 (32%) patients (p<0.0001).
Conclusion: EBRT combined with ADT followed by a 10 Gy HDR-brachytherapy boost leads to high bDFS and OS in a large prospective cohort of mostly high-risk prostate cancer patients, with acceptable toxicity and small impact on QoL. PSA nadir is a powerful predictor of recurrence and mortality.

Table 1: baseline characteristics
Age, mean	69
PSA, median	11.7
Gleason score
6	35
7	123
8-10	115
Missing	1
MRI T-stage
T1b-T2b	60
T2c	28
T3a-T3b	185
T4	1
D’Amico risk group
Intermediate	7
High	267
ADT
No	12
Three months neoadjuvant	118
Three months neoadjuvant and adjuvant	144