Do androgen deprivation and the biologically equivalent dose matter in low‐dose‐rate brachytherapy for intermediate‐risk prostate cancer?

The objective of this study was to investigate the impact of the biologically equivalent dose (BED) on treatment outcomes after iodine‐125 low‐dose‐rate brachytherapy (LDR‐BT) with or without supplemental external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) for intermediate‐risk prostate cancer (PCa). We retrospectively evaluated 292 Japanese patients. The impact of the BED and ADT on treatment outcomes was investigated. Cox proportional hazard models were used for univariate and multivariate analysis with biological progression‐free survival (bPFS) and clinical progression‐free survival (cPFS) as the primary outcome measures. The median follow‐up was 66 months. The bPFS and cPFS rates at 5‐/7‐years were 91.6/87.7% and 95.9/94.0%, respectively. When stratified by BED levels, the bPFS rates at 5‐/7‐years were 92.1/89.3% for <178.0 Gy2, and 91.2/86.0% for ≥178.0 Gy2, respectively (P > 0.05). Based on ADT duration, the bPFS rates at 5‐/7‐years were 89.8/83.5%, 89.7/89.7%, and 97.5/97.5% for none, 1–3 months, and 4–12 months, respectively (P = 0.03). For the univariate analysis, the use of ADT and its duration were significant predictors for bPFS, whereas BED was not significant. A multivariate analysis did not indicate the use of ADT itself was significant, however, when covariates were accounted for by the duration of ADT, the longer use of ADT was found to significantly improve bPFS. Although cPFS was associated neither with the BED levels nor ADT duration (P > 0.05), ADT duration had a trend of improving cPFS (P = 0.053). The higher levels of BED did not significantly impact bPFS for intermediate‐risk PCa after LDR‐BT with or without supplemental EBRT and ADT. The longer duration of ADT could provide an additional benefit in the context of high‐dose irradiation generated by LDR‐BT.

[1]  F. Calvo,et al.  High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial. , 2015, The Lancet. Oncology.

[2]  Tomoki Tanaka,et al.  Permanent prostate brachytherapy with or without supplemental external beam radiotherapy as practiced in Japan: outcomes of 1300 patients. , 2015, Brachytherapy.

[3]  J. Asaumi,et al.  Optimal contouring of seminal vesicle for definitive radiotherapy of localized prostate cancer: comparison between EORTC prostate cancer radiotherapy guideline, RTOG0815 protocol and actual anatomy , 2014, Radiation oncology.

[4]  Jiming Liu,et al.  Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range , 2014, BMC Medical Research Methodology.

[5]  N. Shigematsu,et al.  Assessing protection against radiation exposure after prostate (125)I brachytherapy. , 2014, Brachytherapy.

[6]  Hiroyuki Takahashi,et al.  Mid‐term outcome of permanent prostate iodine‐125 brachytherapy in Japanese patients , 2014, International journal of urology : official journal of the Japanese Urological Association.

[7]  R. Stock,et al.  The relative importance of hormonal therapy and biological effective dose in optimizing prostate brachytherapy treatment outcomes , 2013, BJU international.

[8]  N. Keating,et al.  Does comorbidity influence the risk of myocardial infarction or diabetes during androgen-deprivation therapy for prostate cancer? , 2013, European urology.

[9]  Howard Pai,et al.  Population‐based 10‐year oncologic outcomes after low‐dose‐rate brachytherapy for low‐risk and intermediate‐risk prostate cancer , 2013, Cancer.

[10]  Y. Kanda,et al.  Investigation of the freely available easy-to-use software ‘EZR' for medical statistics , 2012, Bone Marrow Transplantation.

[11]  B. Dubray,et al.  Does short-term androgen depletion add to high-dose radiotherapy (80 Gy) in localized intermediate-risk prostate cancer? Intermediary analysis of GETUG 14 randomized trial (EU-20503/NCT00104741). , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  P. Unger,et al.  Influence of pretreatment and treatment factors on intermediate to long-term outcome after prostate brachytherapy. , 2011, The Journal of urology.

[13]  Hiroyuki Takahashi,et al.  Transperineal prostate brachytherapy, using I-125 seed with or without adjuvant androgen deprivation, in patients with intermediate-risk prostate cancer: study protocol for a phase III, multicenter, randomized, controlled trial , 2010, BMC Cancer.

[14]  K. Wallner,et al.  Androgen deprivation therapy: a survival benefit or detriment in men with high-risk prostate cancer? , 2010, Oncology.

[15]  W. J. Morris,et al.  Population-based study of biochemical and survival outcomes after permanent 125I brachytherapy for low- and intermediate-risk prostate cancer. , 2009, Urology.

[16]  M. Kattan,et al.  Multicenter analysis of effect of high biologic effective dose on biochemical failure and survival outcomes in patients with Gleason score 7-10 prostate cancer treated with permanent prostate brachytherapy. , 2009, International journal of radiation oncology, biology, physics.

[17]  Michael W Kattan,et al.  Customized dose prescription for permanent prostate brachytherapy: insights from a multicenter analysis of dosimetry outcomes. , 2007, International journal of radiation oncology, biology, physics.

[18]  Paul Schellhammer,et al.  Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. , 2006, International journal of radiation oncology, biology, physics.

[19]  Barry S Rosenstein,et al.  Biologically effective dose values for prostate brachytherapy: effects on PSA failure and posttreatment biopsy results. , 2005, International journal of radiation oncology, biology, physics.

[20]  M. Piérart,et al.  High conformality radiotherapy in Europe: thirty-one centres participating in the quality assurance programme of the EORTC prostate trial 22991. , 2004, European journal of cancer.

[21]  M. Piérart,et al.  Late toxicity following conventional radiotherapy for prostate cancer: analysis of the EORTC trial 22863. , 2004, European journal of cancer.

[22]  Jacques Bernier,et al.  Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial , 2002, The Lancet.

[23]  M. Benson,et al.  A prospective analysis of time to normalization of serum testosterone after withdrawal of androgen deprivation therapy. , 2000, The Journal of urology.

[24]  T. Matsuda,et al.  Radical retropubic prostatectomy: time trends, morbidity and mortality in Japan , 1999, Prostate Cancer and Prostatic Diseases.

[25]  S B Malkowicz,et al.  Biochemical Outcome After Radical Prostatectomy , External Beam Radiation Therapy , or Interstitial Radiation Therapy for Clinically Localized Prostate Cancer , 2000 .

[26]  R. Stock,et al.  A dose-response study for I-125 prostate implants. , 1998, International journal of radiation oncology, biology, physics.

[27]  G. Tirelli,et al.  Prognosis of oral cancer: a comparison of the staging systems given in the 7th and 8th editions of the American Joint Committee on Cancer Staging Manual. , 2018, The British journal of oral & maxillofacial surgery.

[28]  R. Stock,et al.  Treatment outcomes and morbidity following definitive brachytherapy with or without external beam radiation for the treatment of localized prostate cancer: 20-year experience at Mount Sinai Medical Center. , 2014, Urologic oncology.

[29]  T. H. van der Kwast,et al.  EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. , 2014, European urology.