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      Does supplemental external beam radiation therapy impact urinary, bowel, and erectile function following permanent prostate brachytherapy?: results of two prospective randomized trials

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          Abstract

          Purpose

          To evaluate the impact of supplemental external beam radiation therapy (EBRT) prior to permanent prostate brachytherapy on long term urinary, bowel, and erectile function.

          Material and methods

          Patient administered urinary, bowel, and erectile quality of life (QoL) instrument were obtained prior to treatment and following brachytherapy. The study population was comprised of the 457 patients who were alive as of June 2016, had been randomized to two markedly different supplemental EBRT dose regimens and a third arm without supplemental EBRT, and had completed the June 2016 QoL survey. The need for urinary or bowel surgical intervention was prospectively recorded during routine follow-up. Multiple parameters were evaluated for effect on outcomes.

          Results

          The urinary catheter was removed on day 0 in 92.1% of patients and 0.4% required a post-implant transurethral prostatic resection (TURP). On average, the International Prostate Symptom Score (IPSS) normalized at week 14. The 10-year rate of urethral strictures was 5.3%. No significant differences were discerned between baseline and post-implant rectal function assessment score (RFAS), and no patient developed a rectal ulcer or fistula. The 10-year potency preservation rate was 50.3%. Supplemental EBRT did not affect urinary, bowel, or erectile function. Urethral strictures were most closely related to bulbomembranous urethral brachytherapy doses, post-implant rectal function to pre-implant hemorroidal bleeding, and RFAS and erectile function to pre-brachytherapy international index of erectile function and age.

          Conclusions

          Supplemental EBRT did not significantly effect catheter dependency, IPSS resolution, urethral stricture rate, the need for post-implant TURP, bowel, or erectile function. Careful attention to brachytherapy dose distributions appears to be most important in minimizing post-brachytherapy morbidity.

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          Most cited references 31

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          Incidence of urethral stricture after primary treatment for prostate cancer: data From CaPSURE.

          We determined the incidence of treatment for urethral stricture, including bladder neck contracture, after primary treatment for clinically localized prostate cancer. A total of 6,597 men with newly diagnosed, localized prostate cancer and no history of urethral stricture disease were identified in the CaPSURE database. Treatment modalities included radical prostatectomy, external beam radiotherapy, brachytherapy, cryotherapy, androgen deprivation therapy, radical prostatectomy plus external beam radiotherapy, brachytherapy plus external beam radiotherapy and watchful waiting. The database was queried for patient reported history or International Classification of Diseases, 9th revision/Common Procedural Terminology codes consistent with stricture treatment after prostate cancer therapy. Time to obstruction was examined by the Kaplan-Meier method. Risk factors for stricture were examined in a multivariate Cox proportional hazards model. The incidence of stricture treatment was 344 of 6,597 cases (5.2%, range 1.1% to 8.4% by prostate cancer treatment type). Median followup was 2.7 years. In the multivariate model primary treatment type (p <0.0001), body mass index (p <0.0001) and age (p = 0.0002) were significant predictors of stricture treatment. After controlling for age and body mass index the HR for treatments compared to watchful waiting was significantly higher for radical prostatectomy (HR = 10.4, p <0.0001) and brachytherapy plus external beam radiotherapy (HR = 4.6, p = 0.0231). After radical prostatectomy most failures occurred within the first 6 months and failures were rare after 24 months, whereas after radiation failures occurred later. The risk of urethral stricture treatment after prostate cancer therapy is 1.1% to 8.4% depending on cancer treatment type. Risk was highest after radical prostatectomy or brachytherapy plus external beam radiotherapy and in those with advanced age or obesity. Stricture after radical prostatectomy occurred within the first 24 months, whereas onset was delayed after radiation.
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            Comparison of high-dose (86.4 Gy) IMRT vs combined brachytherapy plus IMRT for intermediate-risk prostate cancer.

            To compare tumour control and toxicity outcomes with the use of high-dose intensity-modulated radiation therapy (IMRT) alone or brachytherapy combined with IMRT (combo-RT) for patients with intermediate-risk prostate cancer. Between 1997 and 2010, 870 consecutive patients with intermediate-risk prostate cancer were treated at our institution with either 86.4 Gy of IMRT alone (n = 470) or combo-RT consisting of brachytherapy combined with 50.4 Gy of IMRT (n = 400). Brachytherapy consisted of low-dose-rate permanent interstitial implantation in 260 patients and high-dose-rate temporary implantation in 140 patients. The median (range) follow-up for the entire cohort was 5.3 (1-14) years. For IMRT alone vs combo-RT, 7-year actuarial prostate-specific antigen (PSA)-relapse-free survival (PSA-RFS) rates were 81.4 vs 92.0% (P < 0.001), and distant metastases-free survival (DMFS) rates were 93.0 vs 97.2% (P = 0.04), respectively. Multivariate analysis showed that combo-RT was associated with better PSA-RFS (hazard ratio [HR], 0.40 [95% confidence interval, 0.24-0.66], P < 0.001), and better DMFS (HR, 0.41 [0.18-0.92], P = 0.03). A higher incidence of acute genitourinary (GU) grade 2 (35.8 vs 18.9%; P < 0.01) and acute GU grade 3 (2.3 vs 0.4%; P = 0.03) toxicities occurred in the combo-RT group than in the IMRT-alone group. Most acute toxicity resolved. Late toxicity outcomes were similar between the treatment groups. The 7-year actuarial late toxicity rates for grade 2 gastrointestinal (GI) toxicity were 4.6 vs 4.1% (P = 0.89), for grade 3 GI toxicity 0.4 vs 1.4% (P = 0.36), for grade 2 GU toxicity 19.4 vs 21.2% (P = 0.14), and grade 3 GU toxicity 3.1 vs 1.4% (P = 0.74) for the IMRT vs the combo-RT group, respectively. Enhanced dose escalation using combo-RT was associated with superior PSA-RFS and DMFS outcomes for patients with intermediate-risk prostate cancer compared with high-dose IMRT alone at a dose of 86.4 Gy. While acute GU toxicities were more prevalent in the combo-RT group, the incidence of late GI and GU toxicities was similar between the treatment groups. © 2013 The Authors. BJU International © 2013 BJU International.
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              Local control following permanent prostate brachytherapy: effect of high biologically effective dose on biopsy results and oncologic outcomes.

              To determine factors that influence local control and systemic relapse in patients undergoing permanent prostate brachytherapy (PPB). A total of 584 patients receiving PPB alone or PPB with external beam radiation therapy (19.5%) agreed to undergo prostate biopsy (PB) at 2 years postimplantion and yearly if results were positive or if the prostate-specific antigen (PSA) level increased. Short-term hormone therapy was used with 280 (47.9%) patients. Radiation doses were converted to biologically effective doses (BED) (using alpha/beta = 2). Comparisons were made by chi-square analysis and linear regression. Survival was determined by the Kaplan-Meier method. The median PSA concentration was 7.1 ng/ml, and the median follow-up period was 7.1 years. PB results were positive for 48/584 (8.2%) patients. Positive biopsy results by BED group were as follows: 22/121 (18.2%) patients received a BED of 150 to 200 Gy; and 6/193 (3.1%; p 200 Gy. Significant associations of positive PB results by risk group were low-risk group BED (p = 0.019), intermediate-risk group hormone therapy (p = 0.011) and BED (p = 0.040), and high-risk group BED (p = 0.004). Biochemical freedom from failure rate at 7 years was 82.7%. Biochemical freedom from failure rate by PB result was 84.7% for negative results vs. 59.2% for positive results (p 200 Gy with an alpha/beta ratio of 2 yields 96.9% local control rate. Failure to establish local control impacts survival. Copyright 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                J Contemp Brachytherapy
                J Contemp Brachytherapy
                JCB
                Journal of Contemporary Brachytherapy
                Termedia Publishing House
                1689-832X
                2081-2841
                19 October 2017
                October 2017
                : 9
                : 5
                : 403-409
                Affiliations
                [1 ]Schiffler Cancer Center, Wheeling Jesuit, University Wheeling, WV
                [2 ]Department of Urology, Wheeling Hospital, Wheeling, WV
                [3 ]Puget Sound Healthcare Corporation Group, Health Cooperative University of Washington, Seattle, WA
                [4 ]Ohio University, Eastern St. Clairsville, OH
                [5 ]Department of Pathology, Wheeling Hospital, Wheeling, WV, USA
                Author notes
                Address for correspondence: Gregory S. Merrick, MD, Schiffler Cancer Center, Wheeling Hospital, 1 Medical Park, Wheeling, WV 26003, USA. phone: +1 304-243-3490, fax: +1 304-243-5047. e-mail: gmerrick@ 123456urologicresearchinstitute.org
                Article
                30825
                10.5114/jcb.2017.70763
                5705829
                Copyright: © 2017 Termedia Sp. z o. o.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.

                Categories
                Original Paper

                Oncology & Radiotherapy

                prostate cancer, brachytherapy, quality of life, morbidity

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