Dataset Information

Positive surgical margins in radical prostatectomy patients do not predict long-term oncological outcomes: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.

ABSTRACT:

Objective

To assess the impact of positive surgical margins (PSMs) on long-term outcomes after radical prostatectomy (RP), including metastasis, castrate-resistant prostate cancer (CRPC), and prostate cancer-specific mortality (PCSM).

Patients and methods

Retrospective study of 4,051 men in the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort treated by RP from 1988 to 2013. Proportional hazard models were used to estimate hazard ratios (HRs) of PSMs in predicting biochemical recurrence (BCR), CRPC, metastases, and PCSM. To determine if PSMs were more predictive in certain patients, analyses were stratified by pathological Gleason score, stage, and preoperative prostate-specific antigen (PSA) level.

Results

The median (interquartile range) follow-up was 6.6 (3.2-10.6) years and 1 127 patients had >10 years of follow-up. During this time, 302 (32%) men had BCR, 112 (3%) developed CRPC, 144 (4%) developed metastases, and 83 (2%) died from prostate cancer. There were 1,600 (40%) men with PSMs. In unadjusted models, PSMs were significantly associated with all adverse outcomes: BCR, CRPC, metastases and PCSM (all P ? 0.001). After adjusting for demographic and pathological characteristics, PSMs were associated with increased risk of only BCR (HR 1.98, P < 0.001), and not CRPC, metastases, or PCSM (HR ?1.29, P > 0.18). Similar results were seen when stratified by pathological Gleason score, stage, or PSA level, and when patients who underwent adjuvant radiotherapy were excluded.

Conclusions

PSMs after RP are not an independent risk factor for CRPC, metastasis, or PCSM overall or within any subset. In the absence of other high-risk features, PSMs alone may not be an indication for adjuvant radiotherapy.

SUBMITTER: Mithal P

PROVIDER: S-EPMC4658317 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Positive surgical margins in radical prostatectomy patients do not predict long-term oncological outcomes: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.

Mithal Prabhakar P Howard Lauren E LE Aronson William J WJ Terris Martha K MK Cooperberg Matthew R MR Kane Christopher J CJ Amling Christopher C Freedland Stephen J SJ

BJU international 20150623 2

<h4>Objective</h4>To assess the impact of positive surgical margins (PSMs) on long-term outcomes after radical prostatectomy (RP), including metastasis, castrate-resistant prostate cancer (CRPC), and prostate cancer-specific mortality (PCSM).<h4>Patients and methods</h4>Retrospective study of 4,051 men in the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort treated by RP from 1988 to 2013. Proportional hazard models were used to estimate hazard ratios (HRs) of PSMs in predicting bioc ...[more]

PMID: 26010160

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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:Importance:Prostate cancer is the most common malignant neoplasm among men and is the one with the highest positive surgical margin (PSM) rate. This high rate is due to the difficulty in balancing the risk of extraprostatic disease and excising periprostatic structures, which ultimately affects patients' quality of life. In the case of a PSM, the appropriateness of adjuvant radiation therapy (aRT) should be discussed. The financial burden of PSMs on health systems has not been investigated. Objective:To estimate the financial costs associated with a PSM during radical prostatectomy on the basis of the odds of undergoing aRT. Design, Setting, and Participants:This cohort study used data on men with prostate cancer from the US National Cancer Database (January 1, 2010, through December 31, 2015). Data were requested in March 2019, accessed in April 2019, and analyzed in August 2019. Exposure:Treatment with radical prostatectomy followed by aRT, if indicated. Main Outcomes and Measures:The attributable risk fraction of PSMs on undergoing aRT was estimated from a logistic regression with aRT administration as the outcome. The analysis was adjusted for patients' socioeconomic and demographic characteristics and tumor characteristics. The aRT cost for the year 2019 was calculated using the Medicare Physician Fee Schedule and the Hospital Outpatient Prospective Payment System. The fraction of this cost attributable to a PSM was estimated according to its attributable risk fraction. Results:In total, 230?175 men were identified (median [interquartile range] age at diagnosis, 62.0 [56.0-67.0] years). Overall, 22.8% of the patients had a PSM. Patients with PSMs were more likely than those without PSMs to be older (median [interquartile range] age, 62.0 [56.0-66.0] years vs 62.0 [57.0-67.0] years) and nonwhite (9320 patients [17.8%] vs 29?872 patients [16.8%]), to have higher comorbidity scores (1604 patients [3.1%] vs 4884 patients [2.7%] with a Charlson-Deyo Comorbidity Index score ?2) and worse tumor characteristics (category T3 and T4 disease, 26?394 patients [50.3%] vs 36?040 patients [20.3%]), and to have lower socioeconomic indicators (median annual income <$30?000, 5708 patients [10.9%] vs 17?874 patients [10.1%]; proportion of individuals without a high school degree in the area ?29%, 6925 patients [13.2%] vs 22?648 patients [12.7%]). In addition, PSMs were documented more frequently at nonacademic institutions than academic ones (31?702 patients [60.5%] vs 20?714 patients [39.5%]). A total of 11?585 patients (5.0%) underwent aRT, and 7698 of them (3.3%) had a PSM at the final pathology examination. When controlling for patients' socioeconomic and demographic characteristics and tumor characteristics, men with PSMs were more likely than those with negative margins to undergo aRT, with an odds ratio of 3.79 (95% CI, 3.63-3.96; P?<?.001). The attributable risk fraction of the presence of a PSM on aRT was 44% (95% CI, 42%-45%). The attributable cost of a PSM was calculated as $17?356 (95% CI, $16?567-$17?751). Assuming 60?000 prostatectomies in 2019 and similar trends of PSM and aRT, the overall health burden attributable to PSMs was calculated to be $52?068?000 (95% CI, $49?701?000-$53?253?000). Conclusions and Relevance:The estimated aRT cost attributable to the presence of a PSM was $17?356, resulting in $52?068?000 in spending on aRT in 2019. Strategies to reduce PSMs could be associated with a reduction in the overall health costs of surgically treated PCa.

Project description:Background and objectivesPrevious studies have demonstrated that positive surgical margins (PSMs) were independent predictive factors for biochemical and oncologic outcomes in patients with prostate cancer (PCa). This study aimed to conduct a meta-analysis to identify the predictive factors for PSMs after radical prostatectomy (RP).MethodsWe selected eligible studies via the electronic databases, such as PubMed, Web of Science, and EMBASE, from inception to December 2020. The risk factors for PSMs following RP were identified. The pooled estimates of standardized mean differences (SMDs)/odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. A fixed effect or random effect was used to pool the estimates. Subgroup analyses were performed to explore the reasons for heterogeneity.ResultsTwenty-seven studies including 50,014 patients with PCa were eligible for further analysis. The results showed that PSMs were significantly associated with preoperative prostate-specific antigen (PSA) (pooled SMD = 0.37; 95% CI: 0.31-0.43; P < 0.001), biopsy Gleason Score (<6/≥7) (pooled OR = 1.53; 95% CI:1.31-1.79; P < 0.001), pathological Gleason Score (<6/≥7) (pooled OR = 2.49; 95% CI: 2.19-2.83; P < 0.001), pathological stage (<T2/≥T3) (pooled OR = 3.90; 95% CI: 3.18-4.79; P < 0.001), positive lymph node (PLN) (pooled OR = 3.12; 95% CI: 2.28-4.27; P < 0.001), extraprostatic extension (EPE) (pooled OR = 4.44; 95% CI: 3.25-6.09; P < 0.001), and seminal vesicle invasion (SVI) (pooled OR = 4.19; 95% CI: 2,87-6.13; P < 0.001). However, we found that age (pooled SMD = 0.01; 95% CI: -0.07-0.10; P = 0.735), body mass index (BMI) (pooled SMD = 0.12; 95% CI: -0.05-0.30; P = 0.162), prostate volume (pooled SMD = -0.28; 95% CI: -0.62-0.05; P = 0.097), and nerve sparing (pooled OR = 0.90; 95% CI: 0.71-1.14; P = 0.388) had no effect on PSMs after RP. Besides, the findings in this study were found to be reliable by our sensitivity and subgroup analyses.ConclusionsPreoperative PSA, biopsy Gleason Score, pathological Gleason Score, pathological stage, positive lymph node, extraprostatic extension, and seminal vesicle invasion are independent predictors of PSMs after RP. These results may helpful for risk stratification and individualized therapy in PCa patients.

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:Preservation of continence and sexual function continues to be a formidable quality-of-life issue regarding outcomes after radical prostatectomy. There is little argument that physical preservation of the nerves and sphincters is a critical component to achieving success in these domains. Previously demonstrated factors such as advancing age, deteriorating physical health status, and subnormal baseline potency negatively impact outcomes. Our hypothesis, however, has been that inflammatory response to surgery has a large impact on surgical outcomes of prostatectomy. Trauma-induced inflammation could account for variation in recovery despite nearly identical surgery on many patients, especially in high-volume surgeons. In other words, we suggest and maintain that younger and healthier patients tolerate and/or recover better from the trauma/inflammation of surgery. Those who do not recover as well may have altered inflammatory response to injury. A common response to decrease inflammation in response to physical injury would be as simple as to cool the injury with ice. Previous neurologic studies have suggested that using ice during surgical intervention can reduce the inflammatory damage. Therefore, we applied this concept that preemptive hypothermia could reduce inflammation to the robot-assisted prostatectomy procedure to potentially lead to improved continence and potency outcomes. In 2009, we introduced the concept of regional hypothermia via an endorectal cooling balloon during robot-assisted radical prostatectomy (RARP). We have published our single institution data demonstrating a significant reduction of overall incontinence. Defining continence as zero-pads, our overall 1-year incontinence has been reduced by 70% (from 13% to 4%). Severe incontinence, defined as two or more pads, was likewise reduced by 70% (from 2.9% to 0.9%). Regional hypothermia used during the time of surgery represents a novel strategy for minimizing inflammation and subsequent muscle and nerve damage in RARP.

Project description:Several retrospective and a few prospective studies have shown that metastasis-directed therapy (MDT) could delay clinical progression and postpone the initiation of systemic treatment in oligorecurrent prostate cancer (PCa) patients. However, these endpoints are strongly influenced by variables such as concomitant use of androgen deprivation therapy (ADT) and follow-up imaging protocols. The aim of this manuscript was to assess palliative ADT- and metastatic castration-resistant prostate cancer (mCRPC)-free survival as long-term oncological outcomes in oligorecurrent PCa treated by MDT. We retrospectively identified consecutive post-prostatectomy oligorecurrent PCa patients treated by MDT (salvage lymphadenectomy, radiotherapy, or metastasectomy) at our tertiary referral center. Patients were eligible for inclusion if they developed recurrence following radical prostatectomy, had ?5 metastatic lesions on imaging and had a serum testosterone >50 ng/dL or a testosterone suppression therapy-free interval of >2 years prior to the first MDT as an assumption of recovered serum testosterone (if no testosterone measurement available). Patients with castration-resistant or synchronous oligometastatic PCa at the time of first MDT were excluded. Repeated MDTs were allowed, as well as a period of concomitant ADT. Kaplan-Meier analyses were performed to assess palliative ADT-free and mCRPC-free survival. We identified 191 eligible patients who underwent MDT. Median follow-up from first MDT until last follow-up or death was 45 months (IQR 27-70; mean 51 months). Estimated median palliative-ADT free survival was 66 months (95% CI 58-164) and estimated median mCRPC-free survival was not reached (mean 117 months, 95% CI 103-132). In total, 314 MDTs were performed and 25 patients (13%) received ?3 MDTs. This study demonstrated that (repeated) MDT is feasible and holds promise in terms of palliative ADT-free and mCRPC-free survival for patients with oligorecurrent PCa. However, these findings should be confirmed in prospective randomized controlled trials.

Dataset Information

Positive surgical margins in radical prostatectomy patients do not predict long-term oncological outcomes: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.

Objective

Patients and methods

Results

Conclusions

Publications

Positive surgical margins in radical prostatectomy patients do not predict long-term oncological outcomes: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.

Similar Datasets

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