Surgical margin status and its impact on prostate cancer prognosis after radical prostatectomy: a meta-analysis

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Abstract

Background and purpose

Positive surgical margins (PSMs) correlate with adverse outcomes in numerous solid tumours. However, the prognostic value of PSMs in prostate cancer (PCa) patients who underwent radical prostatectomy remains unclear. Herein, we performed a meta-analysis to evaluate the association between PSMs and the prognostic value for biochemical recurrence-free survival (BRFS), cancer-specific survival (CSS), overall survival (OS), cancer-specific mortality (CSM) and overall mortality (OM) in PCa patients.

Materials and methods

According to the PRISMA statement, online databases PubMed, EMBASE and Web of Science were searched to identify relevant studies published prior to February 2018. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to evaluate the relationship between PSMs and PCa.

Results

Ultimately, 32 cohort studies that met the eligibility criteria and involved 141,222 patients (51–65,633 per study) were included in this meta-analysis. The results showed that PSMs were significantly predictive of poorer BRFS (HR = 1.35, 95% CI 1.28–1.48, p < 0.001), CSS (HR = 1.49, 95% CI 1.16–1.90, p = 0.001) and OS (HR = 1.11, 95% CI 1.02–1.20, p = 0.014). In addition, PSMs were significantly associated with higher risk of CSM (HR = 1.23, 95% CI 1.16–1.30, p < 0.001) and OM (HR = 1.09, 95% CI 1.02–1.16, p = 0.009) in patients with PCa.

Conclusions

Our study suggests that the presence of a histopathologic PSM is associated with the clinical outcomes BRFS, CSS, OS, CSM and OM in patients with PCa, and PSMs could serve as a poor prognostic factor for patients with PCa.

Electronic supplementary material

The online version of this article (10.1007/s00345-018-2333-4) contains supplementary material, which is available to authorized users.

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Most cited references 46

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Annual Report to the Nation on the status of cancer, 1975-2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer.

Brenda Edwards, Anne-Michelle Noone, Angela Mariotto … (2014)

The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updates on cancer incidence and death rates and trends in these outcomes for the United States. This year's report includes the prevalence of comorbidity at the time of first cancer diagnosis among patients with lung, colorectal, breast, or prostate cancer and survival among cancer patients based on comorbidity level. Data on cancer incidence were obtained from the NCI, the CDC, and the NAACCR; and data on mortality were obtained from the CDC. Long-term (1975/1992-2010) and short-term (2001-2010) trends in age-adjusted incidence and death rates for all cancers combined and for the leading cancers among men and women were examined by joinpoint analysis. Through linkage with Medicare claims, the prevalence of comorbidity among cancer patients who were diagnosed between 1992 through 2005 residing in 11 Surveillance, Epidemiology, and End Results (SEER) areas were estimated and compared with the prevalence in a 5% random sample of cancer-free Medicare beneficiaries. Among cancer patients, survival and the probabilities of dying of their cancer and of other causes by comorbidity level, age, and stage were calculated. Death rates continued to decline for all cancers combined for men and women of all major racial and ethnic groups and for most major cancer sites; rates for both sexes combined decreased by 1.5% per year from 2001 through 2010. Overall incidence rates decreased in men and stabilized in women. The prevalence of comorbidity was similar among cancer-free Medicare beneficiaries (31.8%), breast cancer patients (32.2%), and prostate cancer patients (30.5%); highest among lung cancer patients (52.9%); and intermediate among colorectal cancer patients (40.7%). Among all cancer patients and especially for patients diagnosed with local and regional disease, age and comorbidity level were important influences on the probability of dying of other causes and, consequently, on overall survival. For patients diagnosed with distant disease, the probability of dying of cancer was much higher than the probability of dying of other causes, and age and comorbidity had a smaller effect on overall survival. Cancer death rates in the United States continue to decline. Estimates of survival that include the probability of dying of cancer and other causes stratified by comorbidity level, age, and stage can provide important information to facilitate treatment decisions. © 2013 American Cancer Society.

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Positive surgical margins after radical prostatectomy: a systematic review and contemporary update.

James Eastham, Alberto Briganti, Jonathan H. Epstein … (2014)

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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Prostate cancer-specific mortality after radical prostatectomy for patients treated in the prostate-specific antigen era.

F Bianco, Peter T. Scardino, Ofer Yossepowitch … (2009)

The long-term risk of prostate cancer-specific mortality (PCSM) after radical prostatectomy is poorly defined for patients treated in the era of widespread prostate-specific antigen (PSA) screening. Models that predict the risk of PCSM are needed for patient counseling and clinical trial design. A multi-institutional cohort of 12,677 patients treated with radical prostatectomy between 1987 and 2005 was analyzed for the risk of PCSM. Patient clinical information and treatment outcome was modeled using Fine and Gray competing risk regression analysis to predict PCSM. Fifteen-year PCSM and all-cause mortality were 12% and 38%, respectively. The estimated PCSM ranged from 5% to 38% for patients in the lowest and highest quartiles of predicted risk of PSA-defined recurrence, based on a popular nomogram. Biopsy Gleason grade, PSA, and year of surgery were associated with PCSM. A nomogram predicting the 15-year risk of PCSM was developed, and the externally validated concordance index was 0.82. Neither preoperative PSA velocity nor body mass index improved the model's accuracy. Only 4% of contemporary patients had a predicted 15-year PCSM of greater than 5%. Few patients will die from prostate cancer within 15 years of radical prostatectomy, despite the presence of adverse clinical features. This favorable prognosis may be related to the effectiveness of radical prostatectomy (with or without secondary therapy) or the low lethality of screen-detected cancers. Given the limited ability to identify contemporary patients at substantially elevated risk of PCSM on the basis of clinical features alone, the need for novel markers specifically associated with the biology of lethal prostate cancer is evident.

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Author and article information

Contributors

Bin Wu: +86 188-0069-8626 , jyrmyywb@163.com

Journal

Journal ID (nlm-ta): World J Urol

Journal ID (iso-abbrev): World J Urol

Title: World Journal of Urology

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0724-4983

ISSN (Electronic): 1433-8726

Publication date (Electronic): 15 May 2018

Publication date PMC-release: 15 May 2018

Publication date (Print): 2018

Volume: 36

Issue: 11

Pages: 1803-1815

Affiliations

Department of Urology, Affiliated Jiang-yin Hospital of the Southeast University Medical College, 163 Shou-shan Road, Jiangyin, 214400 Jiangsu People’s Republic of China

Article

Publisher ID: 2333

DOI: 10.1007/s00345-018-2333-4

PMC ID: 6208659

PubMed ID: 29766319

SO-VID: b3f407f0-4adc-45a0-9771-a4d6236ac549

License:

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.

History

Date received : 6 March 2018

Date accepted : 8 May 2018

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ScienceOpen disciplines: Urology

Keywords: prostate cancer,radical prostatectomy,positive surgical margin,prognosis,meta-analysis

Data availability:

ScienceOpen disciplines: Urology

Keywords: prostate cancer, radical prostatectomy, positive surgical margin, prognosis, meta-analysis

Surgical margin status and its impact on prostate cancer prognosis after radical prostatectomy: a meta-analysis

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Materials and methods

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Electronic supplementary material

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Most cited references 46

Annual Report to the Nation on the status of cancer, 1975-2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer.

Positive surgical margins after radical prostatectomy: a systematic review and contemporary update.

Prostate cancer-specific mortality after radical prostatectomy for patients treated in the prostate-specific antigen era.

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