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      Positive surgical margin is associated with biochemical recurrence risk following radical prostatectomy: a meta-analysis from high-quality retrospective cohort studies

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          Abstract

          Background and purpose

          Although numerous studies have shown that positive surgical margin (PSM) is linked to biochemical recurrence (BCR) in prostate cancer (PCa), the research results have been inconsistent. This study aimed to explore the association between PSM and BCR in patients with PCa following radical prostatectomy (RP).

          Materials and methods

          In accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), PubMed, EMBASE and Wan Fang databases were searched for eligible studies from inception to November 2017. The Newcastle–Ottawa Scale was used to assess the risk of bias of the included studies. Meta-analysis was performed by using Stata 12.0. Combined hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models.

          Results

          Ultimately, 41 retrospective cohort studies of high quality that met the eligibility criteria, comprising 37,928 patients (94–3294 per study), were included in this meta-analysis. The results showed that PSM was associated with higher BCR risk in both univariate analysis (pooled HR = 1.56; 95% CI 1.46, 1.66; p < 0.001) and multivariate analysis (pooled HR = 1.35; 95% CI 1.27, 1.43; p < 0.001). Moreover, no potential publication bias was observed among the included studies in univariate analysis (p-Begg = 0.971) and multivariate analysis (p-Begg = 0.401).

          Conclusions

          Our meta-analysis demonstrated that PSM is associated with a higher risk of BCR in PCa following RP and could serve as an independent prognostic factor in patients with PCa.

          Electronic supplementary material

          The online version of this article (10.1186/s12957-018-1433-3) contains supplementary material, which is available to authorized users.

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          Most cited references54

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          The University of California, San Francisco Cancer of the Prostate Risk Assessment score: a straightforward and reliable preoperative predictor of disease recurrence after radical prostatectomy.

          Multivariate prognostic instruments aim to predict risk of recurrence among patients with localized prostate cancer. We devised a novel risk assessment tool which would be a strong predictor of outcome across various levels of risk, and which could be easily applied and intuitively understood. We studied 1,439 men diagnosed between 1992 and 2001 who had undergone radical prostatectomy and were followed in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database, a longitudinal, community based disease registry of patients with prostate cancer. Disease recurrence was defined as prostate specific antigen (PSA) 0.2 ng/ml or greater on 2 consecutive occasions following prostatectomy or a second cancer treatment more than 6 months after surgery. The University of California, San Francisco-Cancer of the Prostate Risk Assessment (UCSF-CAPRA) score was developed using preoperative PSA, Gleason score, clinical T stage, biopsy results and age. The index was developed and validated using Cox proportional hazards and life table analyses. A total of 210 patients (15%) had recurrence, 145 by PSA criteria and 65 by second treatment. Based on the results of the Cox analysis, points were assigned based on PSA (0 to 4 points), Gleason score (0 to 3), T stage (0 to 1), age (0 to 1) and percent of biopsy positive cores (0 to 1). The UCSF-CAPRA score range is 0 to 10, with roughly double the risk of recurrence for each 2-point increase in score. Recurrence-free survival at 5 years ranged from 85% for a UCSF-CAPRA score of 0 to 1 (95% CI 73%-92%) to 8% for a score of 7 to 10 (95% CI 0%-28%). The concordance index for the UCSF-CAPRA score was 0.66. The UCSF-CAPRA score is a straightforward yet powerful preoperative risk assessment tool. It must be externally validated in future studies.
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            Positive surgical margins after radical prostatectomy: a systematic review and contemporary update.

            The clinical significance of positive surgical margins (PSMs) in radical prostatectomy (RP) specimens and the management of affected patients remain unclear. To address pitfalls in the pathologic interpretation of margin status; provide an update on the incidence, predictors, and long-term oncologic implications of PSMs in the era of robot-assisted laparoscopic RP (RALRP); and suggest a practical evidence-based approach to patient management. A systematic review of the literature was performed in April 2013 using Medline/PubMed, Web of Science, and Scopus databases and the Cochrane Database of Systematic Reviews. Studies focusing on PSMs in RP pertinent to the objectives of this review were included. Particular attention was paid to publications within the last 5 yr and those concerning RALRP. A total of 74 publications were retrieved. Standardized measures to overcome variability in the pathologic interpretation of surgical margins have recently been established by the International Society of Urological Pathology. The average rate of PSMs in contemporary RALRP series is 15% (range: 6.5-32%), which is higher in men with a more advanced pathologic stage and equivalent to the rate reported in prior open and laparoscopic prostatectomy series. The likelihood of PSMs is strongly influenced by the surgeon's experience irrespective of the surgical approach. Technical modifications using the robotic platform and the role of frozen-section analysis to reduce the margin positivity rate continue to evolve. Positive margins are associated with a twofold increased hazard of biochemical relapse, but their association with more robust clinical end points is controversial. Level 1 evidence suggests that adjuvant radiation therapy (RT) may favorably affect prostate-specific antigen recurrence rates, but whether the therapy also affects systemic progression, prostate cancer-specific mortality, and overall survival remains debatable. Although positive margins in prostate cancer are considered an adverse oncologic outcome, their long-term impact on survival is highly variable and largely influenced by other risk modifiers. Adjuvant RT appears to be effective, but further study is required to determine whether early salvage RT is an equivalent alternative. Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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              Adjuvant and salvage radiotherapy after prostatectomy: AUA/ASTRO Guideline.

              The purpose of this guideline is to provide a clinical framework for the use of radiotherapy after radical prostatectomy as adjuvant or salvage therapy. A systematic literature review using the PubMed®, Embase, and Cochrane databases was conducted to identify peer-reviewed publications relevant to the use of radiotherapy after prostatectomy. The review yielded 294 articles; these publications were used to create the evidence-based guideline statements. Additional guidance is provided as Clinical Principles when insufficient evidence existed. Guideline statements are provided for patient counseling, the use of radiotherapy in the adjuvant and salvage contexts, defining biochemical recurrence, and conducting a re-staging evaluation. Physicians should offer adjuvant radiotherapy to patients with adverse pathologic findings at prostatectomy (i.e., seminal vesicle invasion, positive surgical margins, extraprostatic extension) and should offer salvage radiotherapy to patients with prostatic specific antigen or local recurrence after prostatectomy in whom there is no evidence of distant metastatic disease. The offer of radiotherapy should be made in the context of a thoughtful discussion of possible short- and long-term side effects of radiotherapy as well as the potential benefits of preventing recurrence. The decision to administer radiotherapy should be made by the patient and the multi-disciplinary treatment team with full consideration of the patient's history, values, preferences, quality of life, and functional status. Please visit the ASTRO and AUA websites (http://www.redjournal.org/webfiles/images/journals/rob/RAP%20Guideline.pdf and http://www.auanet.org/education/guidelines/radiation-after-prostatectomy.cfm) to view this guideline in its entirety, including the full literature review. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                stzlj913729553@163.com
                jyrmyywb@163.com
                zhazhenl@sohu.com
                phdzhaoh@sina.com
                1957jiangyf@sina.com
                6.1229231679@qq.com
                Journal
                World J Surg Oncol
                World J Surg Oncol
                World Journal of Surgical Oncology
                BioMed Central (London )
                1477-7819
                3 July 2018
                3 July 2018
                2018
                : 16
                : 124
                Affiliations
                Departments of Urology, Affiliated Jiang-yin Hospital of the Southeast University Medical College, Jiang-yin, 214400 China
                Article
                1433
                10.1186/s12957-018-1433-3
                6029044
                29970100
                0b485d9a-168f-46ed-aac8-b3f4e900f54d
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 30 January 2018
                : 26 June 2018
                Categories
                Review
                Custom metadata
                © The Author(s) 2018

                Surgery
                positive surgical margin,prostate cancer,radical prostatectomy,biochemical recurrence,meta-analysis

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