Long-term biochemical progression-free survival following brachytherapy for prostate cancer: Further insight into the role of short-term androgen deprivation and intermediate risk group subclassification

Abstract

Introduction: Brachytherapy is a well-established treatment of localized prostate cancer. Few studies have documented long-term results, specifically biochemical progression-free survival (bPFS) in men with brachytherapy alone, with or without short-term androgen deprivation therapy (ADT), or in combination with external beam radiotherapy (EBRT). Our aim was to analyze long-term bPFS of brachytherapy treated patients.

Materials and methods: Retrospective analysis of 1457 patients with low and intermediate risk prostate cancer treated with brachytherapy alone (1255) or combined with EBRT (202). Six-months ADT was administrated for all EBRT combined patients and for prostate volume downsizing when >55 cc (328). Failure was by the Phoenix definition. Kaplan-Meier analysis and multivariate Cox regression estimated and compared 10-yr and 15-yr rates of bPFS.

Results: Median follow-up was 6.1 yr. Ten and 15-yr bPFS rates of the entire cohort were 93.2% and 89.2%, respectively. On multivariate analysis, PSA density (PSAD), ADT and clinical stage were significantly associated with failure. The most powerful independent factor was PSAD with a HR of 3.5 (95% CI, 1.7-7.4) for PSAD above 0.15. No significant difference was found between low and intermediate risks patients regardless of treatment regimen. However, comparison of two intermediate risk groups, Gleason score (GS) 7, PSA<20 ng/ml versus GS≤6 and PSA = 10-20 ng/ml, revealed 10- and 15-yr bPFS rates of 94.2% and 94.2% compared to 88.2% and 79.9%, (P = 0.022), respectively. ADT improved bPFS rates in low risk patients. The ten and 15-yr bPFS rates were 97.6% and 94.6% compared to 92.3% and 88.2%, (P = 0.020), respectively.

Conclusions: Our retrospective large scale study suggests that brachytherapy provides excellent long-term bPFS rates in low and intermediate risk disease. Combination of brachytherapy with EBRT yields favorable outcomes in GS 7 intermediate risk patients and short-term ADT has a positive effect on outcomes in low risk patients. Further prospective studies are warranted to discriminate the role of adding either EBRT and/or ADT to brachytherapy protocols.

Fig 1. Kaplan-Meier curves for biochemical progression-free survival of all study patients.

Fig 2

(A) Kaplan-Meier curves for biochemical progression-free survival of all patients stratified according to pretreatment blood prostate-specific antigen (PSA) levels: ≤ 10 ng/ml vs. > 10 ng.ml. (B) Kaplan-Meier curves for biochemical progression-free survival of patients with Gleason score (GS) ≤ 6 stratified according to pretreatment blood PSA levels: ≤ 10 ng/ml vs. > 10 ng.ml.

Fig 3. Kaplan-Meier curves for biochemical progression-free survival of all patients stratified according to Gleason score (GS): ≤ 6 vs. 7.

Fig 4

(A) Kaplan-Meier curves for biochemical progression-free survival of all patients stratified according to D’Amico risk grouping: low vs. intermediate. (B) Kaplan-Meier curves for biochemical progression-free survival of two intermediate risk groups: patient with Gleason score (GS) ≤ 6 and pretreatment blood prostate-specific (PSA) levels > 10 ng.ml vs. patients with GS = 7 and any pretreatment PSA levels.

Fig 5. Kaplan-Meier curves for biochemical progression-free survival of all patients stratified according to prostate-specific antigen density (PSAD): ≤ 0.15 vs. > 0.15.

Fig 6

(A) Kaplan-Meier curves for biochemical progression-free survival of all patients stratified according to whether they received (Yes) androgen deprivation therapy (ADT) or did not receive ADT (No). (B) Kaplan-Meier curves for biochemical progression-free survival of patients with Gleason score (GS) ≤ 6 and prostate-specific antigen (PSA) ≤ 10 ng/ml stratified according to whether they received (Yes) ADT or did not receive ADT (No). (C) Kaplan-Meier curves for biochemical progression-free survival of patients with Gleason score (GS) ≤ 6 and PSA > 10 ng/ml stratified according to whether they received (Yes) ADT or did not receive ADT (No).

Fig 7. Kaplan-Meier curves for biochemical progression-free survival of all patients stratified according to the prostate biopsy percent of positive cores (PPC): ≤ 50 vs. > 50.