Dataset Information

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

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?ConclusionsOur 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.

SUBMITTER: Zhang L

PROVIDER: S-EPMC6029044 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Zhang Lijin L Wu Bin B Zha Zhenlei Z Zhao Hu H Jiang Yuefang Y Yuan Jun J

World journal of surgical oncology 20180703 1

<h4>Background and purpose</h4>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).<h4>Materials and methods</h4>In accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), PubMed, EMBAS ...[more]

PMID: 29970100

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Project description:IntroductionPositive surgical margins (PSM) in cancer patients are commonly associated with worse prognosis and a higher risk of secondary treatment. However, the relevance of this parameter in prostate cancer patients undergoing radical prostatectomy (RP) remains controversial, given the inconsistencies in its ability to predict biochemical recurrence (BCR) and oncological outcomes. Hence, further assessment of the utility of surgical margins for prostate cancer prognosis is required to predict these outcomes more accurately. Over the last decade, studies have used the Gleason score (GS) of positive margins to predict outcomes. Herein, the authors aim to conduct a systematic review investigating the role of GS of PSM after radical prostatectomy in predicting BCR and oncological outcomes.Methods and analysisWe will perform a search using MEDLINE, EMBASE, SCOPUS and COCHRANE databases. The review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will screen titles and abstracts to select articles appropriate for full-text review. Studies discussing GS of PSM after RP will be included. Given the change in reporting of GS, only articles from 2005 to 2019 will be included. The quality of the studies chosen will be assessed using the Newcastle Ottawa tool for non-randomised and Cochrane risk of bias for randomised control studies. We will adopt the grading of recommendations, assessment, development and evaluation framework to comment on quality of cumulative evidence. The primary outcome measure will be time to BCR. Secondary outcome measures include secondary treatment, disease-specific survival, disease progression-free and overall mortality at follow-up period. We aim to perform a meta-analysis if the level of heterogeneity is acceptable (I2 <50%).Ethics and disseminationThe review does not require ethics approval as it is a review of published literature. The findings of the review will be submitted for peer-reviewed publications and presented at scientific meetings.Prospero registration numberCRD42019131800.

Project description:BackgroundTo systematically review and perform a meta-analysis on the predictive value of the primary Gleason grade (PGG) at the positive surgical margin (PSM), length of PSM, number of PSMs, and pathological stage of the primary tumor on biochemical recurrence (BCR) in patients with prostate cancer (PCa) after radical prostatectomy (RP).MethodsA systematic literature search was performed using electronic databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, from January 1, 2005, to October 1, 2023. The protocol was pre-registered in PROSPERO. Subgroup analyses were performed according to the different treatments and study outcomes. Pooled hazard ratios with 95% confidence intervals were extracted from multivariate analyses, and a fixed or random effect model was used to pool the estimates. Subgroup analyses were performed to explore the reasons for the heterogeneity.ResultsThirty-one studies that included 50,028 patients with PCa were eligible for this meta-analysis. The results showed that, compared to PGG3, PGG4/5 was associated with a significantly increased risk of BCR. Compared with PSM ≤3 mm, PSM ≥3 mm was associated with a significantly increased risk of BCR. Compared with unifocal PSM, multifocal PSM (mF-PSM) was associated with a significantly increased risk of BCR. In addition, pT >2 was associated with a significantly increased risk of BCR compared to pT2. Notably, the findings were found to be reliable based on the sensitivity and subgroup analyses.ConclusionsPGG at the PSM, length of PSM, number of PSMs, and pathological stage of the primary tumor in patients with PCa were found to be associated with a significantly increased risk of BCR. Thus, patients with these factors should be treated differently in terms of receiving adjunct treatment and more frequent monitoring. Large-scale, well-designed prospective studies with longer follow-up periods are needed to validate the efficacy of these risk factors and their effects on patient responses to adjuvant and salvage therapies and other oncological outcomes.

Project description:ImportanceStratifying patients with biochemical recurrence (BCR) after primary treatment for prostate cancer based on the risk of prostate cancer-specific mortality (PCSM) is essential for determining the need for further testing and treatments.ObjectiveTo evaluate the association of BCR after radical prostatectomy or radiotherapy and its current risk stratification with PCSM.Design, setting, and participantsThis population-based cohort study included a total of 16 311 male patients with 10 364 (64%) undergoing radical prostatectomy and 5947 (36%) undergoing radiotherapy with curative intent (cT1-3, cM0) and PSA follow-up in Stockholm, Sweden, between 2003 and 2019. Follow-up for all patients was until death, emigration, or end of the study (ie, December 31, 2018). Data were analyzed between September 2022 and March 2023.Main outcomes and measuresPrimary outcomes of the study were the cumulative incidence of BCR and PCSM. Patients with BCR were stratified in low- and high-risk according to European Association of Urology (EAU) criteria.ExposuresRadical prostatectomy or radiotherapy.ResultsA total of 16 311 patients were included. Median (IQR) age was 64 (59-68) years in the radical prostatectomy cohort (10 364 patients) and 69 (64-73) years in the radiotherapy cohort (5947 patients). Median (IQR) follow-up for survivors was 88 (55-138) months and 89 (53-134) months, respectively. Following radical prostatectomy, the 15-year cumulative incidences of BCR were 16% (95% CI, 15%-18%) for the 4024 patients in the low D'Amico risk group, 30% (95% CI, 27%-32%) for the 5239 patients in the intermediate D'Amico risk group, and 46% (95% CI, 42%-51%) for 1101 patients in the high D'Amico risk group. Following radiotherapy, the 15-year cumulative incidences of BCR were 18% (95% CI, 15%-21%) for the 1230 patients in the low-risk group, 24% (95% CI, 21%-26%) for the 2355 patients in the intermediate-risk group, and 36% (95% CI, 33%-39%) for the 2362 patients in the high-risk group. The 10-year cumulative incidences of PCSM after radical prostatectomy were 4% (95% CI, 2%-6%) for the 1101 patients who developed low-risk EAU-BCR and 9% (95% CI, 5%-13%) for 649 patients who developed high-risk EAU-BCR. After radiotherapy, the 10-year PCSM cumulative incidences were 24% (95% CI, 19%-29%) for the 591 patients in the low-risk EAU-BCR category and 46% (95% CI, 40%-51%) for the 600 patients in the high-risk EAU-BCR category.Conclusions and relevanceThese findings suggest the validity of EAU-BCR stratification system. However, while the risk of dying from prostate cancer in low-risk EAU-BCR after radical prostatectomy was very low, patients who developed low-risk EAU-BCR after radiotherapy had a nonnegligible risk of prostate cancer mortality. Improving risk stratification of patients with BCR is pivotal to guide salvage treatment decisions, reduce overtreatment, and limit the number of staging tests in the event of PSA elevations after primary treatment.

Project description:BACKGROUND:A positive surgical margin (PSM) following radical prostatectomy (RP) for prostate cancer is associated with increased risk of biochemical recurrence. We sought to examine whether the pathologist is an independent predictor of PSMs. METHODS:We performed a retrospective review of 3,557 men who underwent RP for localized prostate cancer at our institution from 2003 to 2015. We evaluated 29 separate pathologists. Univariate and multivariable logistic regression were used to test variables previously shown to influence PSM rates. RESULTS:Overall rate of PSM was 18.9%. Compared with patients without PSM, patients with PSM had higher body mass index (mean: 28.8 vs. 28.3), Gleason score?7 (84% vs. 66%), extracapsular extension (51% vs. 20%), and median prostate-specific antigen (5.9 vs. 5.1ng/ml) (all P<0.05). Univariate logistic regression showed that surgeon experience, pathologist experience, and pathologist genitourinary fellowship training were all predictors of PSMs (all P<0.05). Multivariable regression analysis confirmed that decreased surgeon experience, increased pathologist experience, higher pathologic Gleason score, higher pathologic stage, and higher prostate-specific antigen were significant predictors of PSMs. Increasing surgeon experience was associated with decreased odds of PSM (odds ratio = 0.79 per 1 standard deviation increase, 95% CI [0.70-0.89]). In contrast, increasing pathologist experience was associated with increased odds of PSM (odds ratio = 1.11 per 1 standard deviation increase, 95% CI [1.03-1.19]). The relationship between pathologist experience and PSM appeared to be nonlinear (Fig. 2). CONCLUSIONS:Greater pathologist experience appears to be associated with greater odds of PSMs following radical prostatectomy, even after controlling for case mix, pathologist fellowship training, and surgeon experience. Based on these findings, pathologists with less experience reviewing RP specimens may consider requesting rereview by a dedicated genitourinary pathologist.

Project description:The objective of this study was to utilize a microarray platform to determine the microRNA (miRNA) expression profile in prostate cancer tissue from patients who underwent radical prostatectomy and were followed for an average of 47 months. The GeneChip® miRNA Array (Affymetrix) contains more than 46,000 probes, and more than 1,100 mature human miRNAs and transcripts. An expression level higher or lower than 1.1 with a p<0.05 were considered to be differentially expressed. When tumors with a GS<7 were compared with those with a GS≥7, five miRNAs were down-regulated and nine were up-regulated. In comparing tumors from patients with PSA <10 ng/mL vs. those with PSA ≥10 ng/mL, 21 miRNAs were down-regulated and 29 were overexpressed. There was decreased expression of 21 miRNAs and increased expression of 22 miRNAs when pT2 and pT3 tumors were compared. The comparison of the expression profiles of men with vs. without recurrent disease (PSA>0.2 ng/mL) revealed that 14 miRNAs were down-regulated and 17 were up-regulated. Considering the three prognostic factors and biochemical recurrence, miR-335 was overexpressed in pT3 tumors in patients with PSA>10 ng/mL, miR-1202 was overexpressed in recurrent tumors in which PSA >10 ng/mL, and miR-885 and miR-1226 were overexpressed in recurrent pT3 tumors. Six miRNAs (miR- 361, 378, 548, 574, 652 and 892) had decreased expression in pT3 tumors in patients with PSA >10 ng/mL. miR-16 was down-regulated in recurrent pT3 tumors. miR-92 and miR-450 exhibited decreased expression in recurrent tumors in patients with PSA > 10 ng/mL. miR-28 was down-regulated in pT3 adenocarcinomas with a GS ≥ 7. The differentially expressed miRNAs in recurrent tumors were validated using qRT-PCR in 74 additional specimens. miR-21 was overexpressed in recurrent tumors, and in the Cox model, expression levels higher than 0.64 were indicative of biochemical recurrence with a risk of 2.4. These results, which were based on clinical specimens from patients treated in a standardized way and followed for an average of 47 months, provide an initial understanding of the role of miRNAs in prostatecancer progression; the foremost representative is miR-21, which has been implicated in the progression of various human cancers.

Project description:The objective of this study was to utilize a microarray platform to determine the microRNA (miRNA) expression profile in prostate cancer tissue from patients who underwent radical prostatectomy and were followed for an average of 47 months. The GeneChipM-BM-. miRNA Array (Affymetrix) contains more than 46,000 probes, and more than 1,100 mature human miRNAs and transcripts. An expression level higher or lower than 1.1 with a p<0.05 were considered to be differentially expressed. When tumors with a GS<7 were compared with those with a GSM-bM-^IM-%7, five miRNAs were down-regulated and nine were up-regulated. In comparing tumors from patients with PSA <10 ng/mL vs. those with PSA M-bM-^IM-%10 ng/mL, 21 miRNAs were down-regulated and 29 were overexpressed. There was decreased expression of 21 miRNAs and increased expression of 22 miRNAs when pT2 and pT3 tumors were compared. The comparison of the expression profiles of men with vs. without recurrent disease (PSA>0.2 ng/mL) revealed that 14 miRNAs were down-regulated and 17 were up-regulated. Considering the three prognostic factors and biochemical recurrence, miR-335 was overexpressed in pT3 tumors in patients with PSA>10 ng/mL, miR-1202 was overexpressed in recurrent tumors in which PSA >10 ng/mL, and miR-885 and miR-1226 were overexpressed in recurrent pT3 tumors. Six miRNAs (miR- 361, 378, 548, 574, 652 and 892) had decreased expression in pT3 tumors in patients with PSA >10 ng/mL. miR-16 was down-regulated in recurrent pT3 tumors. miR-92 and miR-450 exhibited decreased expression in recurrent tumors in patients with PSA > 10 ng/mL. miR-28 was down-regulated in pT3 adenocarcinomas with a GS M-bM-^IM-% 7. The differentially expressed miRNAs in recurrent tumors were validated using qRT-PCR in 74 additional specimens. miR-21 was overexpressed in recurrent tumors, and in the Cox model, expression levels higher than 0.64 were indicative of biochemical recurrence with a risk of 2.4. These results, which were based on clinical specimens from patients treated in a standardized way and followed for an average of 47 months, provide an initial understanding of the role of miRNAs in prostatecancer progression; the foremost representative is miR-21, which has been implicated in the progression of various human cancers. Fifty-three patients underwent a radical prostatectomy performed by the same surgeon (MS) to treat localized PC between August 2000 and June 2002. The mean age was 65 years (SD: 7.5, range: 49 - 77). The mean Gleason score was 7 (SD: 1.1, range: 5 - 10); 15 tumors had a score of 5 or 6, and 38 had a score between 7 and 10. Twenty-four (45.3%) of the patients had pT2 tumors, and 29 (54.7%) had pT3 tumors. The control group consisted of three patients with lower urinary tract symptoms, a mean age of 55.3 years and a diagnosis of benign prostatic hyperplasia (BPH) who consented to open surgery.

Dataset Information

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

Background and purpose

Materials and methods

Results

Publications

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

Similar Datasets

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