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      Clinical outcomes of low-dose-rate brachytherapy based radiotherapy for intermediate risk prostate cancer

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          Abstract

          Purpose

          To monitor the outcomes for intermediate-risk prostate cancer patients treated with biologically effective dose (BED) ≥ 200 Gy radiotherapy using low-dose-rate (LDR) brachytherapy.

          Material and methods

          Between 2005 and 2016, a total of 397 patients with intermediate-risk prostate cancer were treated by LDR-based radiotherapy with a BED ≥ 200 Gy. Treatments consisted of LDR brachytherapy alone (177 cases) or LDR and external beam radiotherapy (EBRT) (220 cases). Short-term androgen deprivation therapy (ADT) was used in 186 patients (46.9%). The median follow-up period was 72 months (range 29-165 months). Dosimetric parameters and BED were studied in each case. The numbers of intermediate-risk features were: 163 patients with 1 intermediate-risk feature (41%), 169 patients with 2 intermediate-risk features (43%), and 65 patients with 3 intermediate-risk features (16%). A total of 145 cases were diagnosed as having primary Gleason pattern 4: Gleason score 4 + 3 (36.5%).

          Results

          Three patients developed biochemical failure, thus providing a 7-year actual biochemical failure-free survival (BFFS) rate of 99.1%. Biochemical failure was observed exclusively in cases with distant metastasis: two cases with lymph node metastasis and one case with bone metastasis, thus yielding a 7-year freedom from clinical failure (FFCF) rate of 99.1%. We observed eight deaths, but there was no death from prostate cancer, thus yielding a 7-year cause-specific survival (CSS) rate of 100%, and an overall survival (OS) rate of 98.4%.

          Conclusions

          This study highlights excellent outcomes for intermediate-risk prostate cancer patients, including unfavorable intermediate-risk cases, treated with BED ≥ 200 Gy radiotherapy using LDR brachytherapy. LDR alone with a BED of 200 Gy may be an optimal treatment for both favorable and unfavorable intermediate-risk prostate cancer patients, although a longer follow-up is mandatory to confirm the present findings.

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          Most cited references 10

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          A new risk classification system for therapeutic decision making with intermediate-risk prostate cancer patients undergoing dose-escalated external-beam radiation therapy.

          The management of intermediate-risk prostate cancer (PCa) is controversial, in part due to the heterogeneous nature of patients falling within this classification. We propose a new risk stratification system for intermediate-risk PCa to aid in prognosis and therapeutic decision making. Between 1992 and 2007, 1024 patients with National Comprehensive Cancer Network intermediate-risk PCa and complete biopsy information were treated with definitive external-beam radiation therapy (EBRT) utilizing doses ≥ 81 Gy. Unfavorable intermediate-risk (UIR) PCa was defined as any intermediate-risk patient with a primary Gleason pattern of 4, percentage of positive biopsy cores (PPBC) ≥ 50%, or multiple intermediate-risk factors (IRFs; cT2b-c, prostate-specific antigen [PSA] 10-20, or Gleason score 7). All patients received EBRT with ≥ 81 Gy with or without neoadjuvant and concurrent androgen-deprivation therapy (ADT). Univariate and multivariate analyses were performed using a Cox proportional hazards model for PSA recurrence-free survival (PSA-RFS) and distant metastasis (DM). PCa-specific mortality (PCSM) was analyzed using a competing-risk method. Median follow-up was 71 mo. Primary Gleason pattern 4 (hazard ratio [HR]: 3.26; p<0.0001), PPBC ≥ 50% (HR: 2.72; p=0.0007), and multiple IRFs (HR: 2.20; p=0.008) all were significant predictors of increased DM in multivariate analyses. Primary Gleason pattern 4 (HR: 5.23; p<0.0001) and PPBC ≥ 50% (HR: 4.08; p=0.002) but not multiple IRFs (HR: 1.74; p=0.21) independently predicted for increased PCSM. Patients with UIR disease had inferior PSA-RFS (HR: 2.37; p<0.0001), DM (HR: 4.34; p=0.0003), and PCSM (HR: 7.39; p=0.007) compared with those with favorable intermediate-risk disease, despite being more likely to receive neoadjuvant ADT. Short follow-up and retrospective study design are the primary limitations. Intermediate-risk PCa is a heterogeneous collection of diseases that can be separated into favorable and unfavorable subsets. These groups likely will benefit from divergent therapeutic paradigms. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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            Biologically effective dose values for prostate brachytherapy: effects on PSA failure and posttreatment biopsy results.

            To analyze the effect of biologically effective dose (BED) values on prostate-specific antigen (PSA) failure and posttreatment biopsy. From 1990 to 2003, 1,377 patients had prostate brachytherapy alone (I-125 or Pd-103) (571), hormonal and brachytherapy (371), and trimodality therapy (hormonal, implant, and external beam) (435). Dose was defined as the D90 (dose delivered to 90% of the gland from the dose-volume histogram). Freedom from PSA failure (FFPF) at 10 years was 87%. The 10-year FFPF for BED 100-120, >120-140, >140-160, 180-200, and >200 were 46%, 68%, 81%, 85.5%, 90%, 90%, and 92%, respectively (p 100-120, >120-140, >140-160, >160-180, >180-200, and >200 were 24% (8/33), 15% (3/20), 6% (2/33), 6% (3/52), 7% (6/82), 1% (1/72), and 3% (4/131), respectively (p<0.0001). BED was the most significant predictor of biopsy outcome in multivariate analysis (p=0.006). Biologically effective dose equations provide a method of comparing different isotopes and combined therapies in the brachytherapy management of prostate cancer. The effects of BED on FFPF and posttreatment biopsy demonstrate a strong dose-response relationship.
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              Contemporary evaluation of the National Comprehensive Cancer Network prostate cancer risk classification system.

              To analyze the National Comprehensive Cancer Network prostate cancer guidelines pretreatment risk groups in a contemporary series of patients treated with radical prostatectomy. We analyzed our institutional radical prostatectomy database, including all patients with clinically localized disease treated from 2000 to 2010. Using the National Comprehensive Cancer Network guidelines, the patients were classified into low-, intermediate-, or high-risk groups. The pathologic outcomes were assessed, and the biochemical recurrence (BCR)-free survival rates were calculated and compared using the log-rank test and Cox proportional hazards analysis. A total of 12 821 men met the inclusion criteria. The pathologic and 10-year BCR-free survival rates differed significantly by risk group (low risk, 92.1%; intermediate risk, 71.0%; and high risk, 38.8%; P < .01). Among the intermediate-risk men, the 10-year BCR-free survival was significantly greater for men assigned to the intermediate-risk group by clinical stage (88.8%) than for those deemed intermediate risk by the Gleason score (73.6%) or prostate-specific antigen (PSA) level (79.5%; P = .01). Likewise, in the high-risk men, a trend was seen toward improved 5-year BCR-free survival for patients with clinical stage T3a tumors (77.8%) compared with those considered high risk because of the Gleason score (53.7%) or PSA level (41.0%; P = .13). On multivariate analysis, clinical stage, Gleason score, and PSA level were all significantly associated with BCR. We observed heterogeneous outcomes among patients within the National Comprehensive Cancer Network intermediate- and high-risk groups. The BCR-free survival rates were superior for men with an advanced clinical stage compared with those with an advanced Gleason score or elevated PSA level. This within-group heterogeneity must be considered when choosing the treatment modality and predicting an individual patient's prognosis. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Role: Prof.
                Journal
                J Contemp Brachytherapy
                J Contemp Brachytherapy
                JCB
                Journal of Contemporary Brachytherapy
                Termedia Publishing House
                1689-832X
                2081-2841
                28 February 2020
                February 2020
                : 12
                : 1
                : 6-11
                Affiliations
                [1 ]Department of Brachytherapy for Prostate Cancer, Shiga University of Medical Science, Shiga, Japan,
                [2 ]Department of Radiology, Shiga University of Medical Science, Shiga, Japan
                Author notes
                Address for correspondence: Prof. Keisei Okamoto, MD, PhD, Department of Brachytherapy for Prostate Cancer, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan, phone: +81 77 548 2993, fax: +81 77 548 2993, e-mail: keiseiok814@ 123456gmail.com
                Article
                39632
                10.5114/jcb.2020.92405
                7073334
                Copyright © 2020 Termedia

                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 ( http://creativecommons.org/licenses/by-nc-sa/4.0/)

                Categories
                Original Paper

                Oncology & Radiotherapy

                intermediate risk, low-dose-rate, brachytherapy, prostate cancer

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