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

Ryuji Tabata, Takahiro Kimura, Hidetoshi Kuruma, Hiroshi Sasaki, Masahito Kido, Kenta Miki, Hiroyuki Takahashi, Manabu Aoki, Shin Egawa, Ryuji Tabata, Takahiro Kimura, Hidetoshi Kuruma, Hiroshi Sasaki, Masahito Kido, Kenta Miki, Hiroyuki Takahashi, Manabu Aoki, Shin Egawa

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00664456.

Keywords: Androgen deprivation therapy; brachytherapy; dose-response; prostate cancer.

© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Kaplan–Meier curves for (A) biological progression‐free survival (bPFS) rates, (B) clinical progression‐free survival (cPFS), (C) overall survival (OS), and cumulative incidence analysis for (D) Cancer‐specific mortality in the entire cohort (n = 292).
Figure 2
Figure 2
Kaplan–Meier curves for biological progression‐free survival (bPFS) rates based on (A) stratified biologically equivalent dose (BED) levels, and (B) divided androgen deprivation therapy (ADT) duration. Curves in the ADT subgroups had significant trend (P = 0.03).

References

    1. Bolla, M. , Collette L., Blank L., et al. 2002. 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. Lancet 360:103–106.
    1. Morris, W. J. , Keyes M., Palma D., et al. 2009. Population‐based study of biochemical and survival outcomes after permanent 125I brachytherapy for low‐ and intermediate‐risk prostate cancer. Urology 73:860–865.
    1. Stock, R. G. , Buckstein M., Liu J. T., and Stone N. N.. 2013. The relative importance of hormonal therapy and biological effective dose in optimizing prostate brachytherapy treatment outcomes. BJU Int. 112:E44–E50.
    1. Zapatero, A. , Guerrero A., Maldonado X., et al. 2015. High‐dose radiotherapy with short‐term or long‐term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial. Lancet Oncol. 16:320–327.
    1. Qi, X. , Gao X. S., Asaumi J., et al. 2014. Optimal contouring of seminal vesicle for definitive radiotherapy of localized prostate cancer: comparison between EORTC prostate cancer radiotherapy guideline, RTOG0815 protocol and actual anatomy. Radiat. Oncol. 9:288.
    1. Dubray, B. M. , Beckendorf V., Guerif S., et al. 2011. 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). J. Clin. Oncol. 29:abs 4521.
    1. Ataman, F. , Poortmans P., Davis J. B., et al. 2004. High conformality radiotherapy in Europe: thirty‐one centres participating in the quality assurance programme of the EORTC prostate trial 22991. Eur. J. Cancer 40:2411–2416.
    1. Fang, L. C. , Merrick G. S., and Wallner K. E.. 2010. Androgen deprivation therapy: a survival benefit or detriment in men with high‐risk prostate cancer? Oncology (Williston Park) 24:790–798.
    1. Edge S. B., Byrd D. R., Compton C. C., Fritz A. G., Greene F. L., and Trotti A., eds. 2009. American Joint Committee on Cancer Staging Manual, 7th ed. Springer, New York.
    1. D'Amico, A. V. , Whittington R., Malkowicz S. B., et al. 1998. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 280:969–974.
    1. Miki, K. , Kiba T., Sasaki H., et al. 2010. 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. BMC Cancer 10:572.
    1. Kimura, T. , Kido M., Miki K., et al. 2013. Mid‐term outcome of permanent prostate iodine‐125 brachytherapy in Japanese patients. Int. J. Urol. 21:473–478.
    1. Stock, R. G. , Stone N. N., Cesaretti J. A., and Rosenstein B. S.. 2006. Biologically effective dose values for prostate brachytherapy: effects on PSA failure and posttreatment biopsy results. Int. J. Radiat. Oncol. Biol. Phys. 64:527–533.
    1. Roach, M. III , Hanks G., Thames H. Jr, et al. 2006. 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. Int. J. Radiat. Oncol. Biol. Phys. 65:965–974.
    1. Kanda, Y. 2013. Investigation of the freely available easy‐to‐use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 48:452–458.
    1. Japanese Society for Therapeutic Radiology and Oncology/Japanese Urological Association/Japan Radiological Society . 2003. Guideline for safety control of permanent implantation brachytherapy of prostate cancer. Editorial supervision by the Japanese Society for Therapeutic Radiology and Oncology/Japanese Urological Association/Japan Radiological Society.
    1. Hanada, T. , Yorozu A., Kikumura R., Ohashi T., and Shigematsu N.. 2014. Assessing protection against radiation exposure after prostate (125)I brachytherapy. Brachytherapy 13:311–318.
    1. Yorozu, A. , Kuroiwa N., Takahashi A., et al. 2015. Permanent prostate brachytherapy with or without supplemental external beam radiotherapy as practiced in Japan: outcomes of 1300 patients. Brachytherapy 14:111–117.
    1. Morris, W. J. , Keyes M., Spadinger I., et al. 2013. Population‐based 10‐year oncologic outcomes after low‐dose‐rate brachytherapy for low‐risk and intermediate‐risk prostate cancer. Cancer 119:1537–1546.
    1. Marshall, R. A. , Buckstein M., Stone N. N., and Stock R.. 2014. 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. Urol. Oncol. 32: 38.e1–38.e7.
    1. Stock, R. G. , Stone N. N., Tabert A., Iannuzzi C., and DeWyngaert J. K.. 1998. A dose‐response study for I‐125 prostate implants. Int. J. Radiat. Oncol. Biol. Phys. 41:101–108.
    1. Stone, N. N. , Stone M. M., Rosenstein B. S., Unger P., and Stock R. G.. 2011. Influence of pretreatment and treatment factors on intermediate to long‐term outcome after prostate brachytherapy. J. Urol. 185:495–500.
    1. Stone, N. N. , Potters L., Davis B. J., et al. 2009. 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. Int. J. Radiat. Oncol. Biol. Phys. 73:341–346.
    1. Wan, X. , Wang W., Liu J., and Tong T.. 2014. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med. Res. Methodol. 14:135.
    1. Stone, N. N. , Potters L., Davis B. J., et al. 2007. Customized dose prescription for permanent prostate brachytherapy: insights from a multicenter analysis of dosimetry outcomes. Int. J. Radiat. Oncol. Biol. Phys. 69:1472–1477.
    1. Heidenreich, A. , Bastian P. J., Bellmunt J., et al. 2014. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent‐update 2013. Eur. Urol. 65:124–137.
    1. Ataman, F. , Zurlo A., Artignan X., et al. 2004. Late toxicity following conventional radiotherapy for prostate cancer: analysis of the EORTC trial 22863. Eur. J. Cancer 40:1674–1681.
    1. Keating, N. L. , O'Malley A. J., Freedland S. J., and Smith M. R.. 2013. Does comorbidity influence the risk of myocardial infarction or diabetes during androgen‐deprivation therapy for prostate cancer? Eur. Urol. 64:159–166.
    1. Arai, Y. , Egawa S., Tobisu K., et al. 2000. Radical retropubic prostatectomy: time trends, morbidity and mortality in Japan. BJU Int. 85:287–294.
    1. Nejat, R. J. , Rashid H. H., Bagiella E., Katz A. E., and Benson M. C.. 2000. A prospective analysis of time to normalization of serum testosterone after withdrawal of androgen deprivation therapy. J. Urol. 164:1891–1894.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj