Research Article: 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

Date Published: April 19, 2019

Publisher: Public Library of Science

Author(s): Haim Matzkin, Juza Chen, Rubi Agai, Tomer Ziv-Baran, Nicola J. Mabjeesh, Daniel Grossi Marconi.

http://doi.org/10.1371/journal.pone.0215582

Abstract

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.

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.

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. 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.

Partial Text

Since 1983 a large number of patients have been treated with brachytherapy, generating a large database in many excellence centers [1]. However no randomized controlled studies have been published comparing long-term oncological results of brachytherapy to other current treatment approaches. Therefore high volume and longer prospective follow up reports are welcome to substantiate this treatment modality and perhaps answer some still debated issues, such as the role of adjuvant short term androgen deprivation therapy (ADT), and of combined external beam radiotherapy (EBRT) in appropriate patients. The RTOG 0232 randomized trial aiming to answer the clinical dilemma of treating Gleason score (GS) 7 by brachytherapy or brachytherapy and EBRT has recently been published as Abstract only [2]. Many brachytherapy centers have moved towards the use of brachytherapy only, in cases with intermediate D’Amico risk group patients and do not reserve brachy-monotherapy for low risk patients only [3]. This approach is backed-up by the excellent clinical results achieved with monotherapy in low risk patients, the ever improving computation capabilities in the operating room and the trend for lower risk patients being diagnosed as a result of the widespread use of PSA.

Prostate brachytherapy for low to intermediate risk cancer, has been demonstrated by many to be as effective as EBRT and as good as surgery [10]. Brachytherapy alone has traditionally been selected for low risk prostate cancer and more recently for intermediate risk patients too [11,12], although many authorities still advocate the use of combined brachytherapy and EBRT +/- short term ADT for intermediate and high risk disease [13].

Brachytherapy provides excellent long-term bPFS rates in low and intermediate risk disease. Our retrospective analysis, a hypothesis generating study suggests that 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.

 

Source:

http://doi.org/10.1371/journal.pone.0215582

 

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