Dataset Information

Effect of Clinical Parameters on Risk of Death from Cancer after Radical Prostatectomy in Men with Localized and Locally Advanced Prostate Cancer.

ABSTRACT: Background: The study aimed to assess predictors and to identify patients at increased risk of prostate-cancer-specific mortality (CSM) after radical prostatectomy (RP). Methods: A total of 2421 men with localized and locally advanced PCa who underwent RP in 2001−2017 were included in the study. CSM predictors were assessed using multivariate competing risk analysis. Death from other causes was considered a competing event. Cumulative CSM and other-cause mortality (OCM) were calculated in various combinations of predictors. Results: During the median 8 years (interquartile range 4.4−11.7) follow-up, 56 (2.3%) of registered deaths were due to PCa. Cumulative 10 years CSM and OCM was 3.6% (95% CI 2.7−4.7) and 15.9% (95% CI 14.2−17.9), respectively. The strongest predictors of CSM were Grade Group 5 (GG5) (hazard ratio (HR) 19.9, p < 0.0001), lymph node invasion (HR 3.4, p = 0.001), stage pT3b-4 (HR 3.1, p = 0.009), and age (HR 1.1, p = 0.0007). In groups created regarding age, stage, and GG, cumulative 10 years CSM ranged from 0.4−84.9%, whereas OCM varied from 0−43.2%. Conclusions: CSM after RP is related to GGs, pathological stage, age, and combinations of these factors, whereas other-cause mortality is only associated with age. Created CSM and OCM plots can help clinicians identify patients with the most aggressive PCa who could benefit from more intensive or novel multimodal treatment strategies.

SUBMITTER: Milonas D

PROVIDER: S-EPMC9032251 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Effect of Clinical Parameters on Risk of Death from Cancer after Radical Prostatectomy in Men with Localized and Locally Advanced Prostate Cancer.

Milonas Daimantas D Ruzgas Tomas T Venclovas Zilvinas Z Jonusaite Daniele D Matijosaitis Aivaras Jonas AJ Trumbeckas Darius D Varpiotas Edmundas E Auskalnis Stasys S Skaudickas Darijus D Mickevicius Ramunas R Vaiciunas Kestutis K Mickevicius Jonas J Jievaltas Mindaugas M

Cancers 20220418 8

Background: The study aimed to assess predictors and to identify patients at increased risk of prostate-cancer-specific mortality (CSM) after radical prostatectomy (RP). Methods: A total of 2421 men with localized and locally advanced PCa who underwent RP in 2001−2017 were included in the study. CSM predictors were assessed using multivariate competing risk analysis. Death from other causes was considered a competing event. Cumulative CSM and other-cause mortality (OCM) were calculated in variou ...[more]

PMID: 35454938

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Project description:BackgroundThe effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen (PSA) testing is not known.MethodsFrom November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer (mean age, 67 years; median PSA value, 7.8 ng per milliliter) to radical prostatectomy or observation and followed them through January 2010. The primary outcome was all-cause mortality; the secondary outcome was prostate-cancer mortality.ResultsDuring the median follow-up of 10.0 years, 171 of 364 men (47.0%) assigned to radical prostatectomy died, as compared with 183 of 367 (49.9%) assigned to observation (hazard ratio, 0.88; 95% confidence interval [CI], 0.71 to 1.08; P=0.22; absolute risk reduction, 2.9 percentage points). Among men assigned to radical prostatectomy, 21 (5.8%) died from prostate cancer or treatment, as compared with 31 men (8.4%) assigned to observation (hazard ratio, 0.63; 95% CI, 0.36 to 1.09; P=0.09; absolute risk reduction, 2.6 percentage points). The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age, race, coexisting conditions, self-reported performance status, or histologic features of the tumor. Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter (P=0.04 for interaction) and possibly among those with intermediate-risk or high-risk tumors (P=0.07 for interaction). Adverse events within 30 days after surgery occurred in 21.4% of men, including one death.ConclusionsAmong men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up. Absolute differences were less than 3 percentage points. (Funded by the Department of Veterans Affairs Cooperative Studies Program and others; PIVOT ClinicalTrials.gov number, NCT00007644.).

Project description:BackgroundHomeobox B13 (HOXB13) expression regulates normal prostate development and mutations are associated with prostate cancer (PCa) formation.ObjectiveTo assess the role of HOXB13 mRNA expression in PCa progression following radical prostatectomy.Design, setting, and participantsGenome-wide expression profiles were queried from two retrospective prostatectomy cohorts with follow-up data (Mayo Clinic, n=780; Johns Hopkins Medical Institute [JHMI], n=355), and a prospective genomic registry (n=5239).Outcome measurements and statistical analysisMultivariable Cox regressions were used to analyze metastasis-free survival (MFS).Results and limitationsHOXB13 expression in primary PCa increased with increasing tumor grade and with high metastatic potential based on a genomic signature. The highest quartile of HOXB13 expression was associated with worse MFS compared with the lowest quartile (Mayo Clinic: adjusted hazard ratio [AHR] 1.46, 95% confidence interval [CI] 1.03-2.06, and JHMI: AHR 1.80, 95% CI 1.02-3.19). The combinations of high HOXB13 expression and low expression of its binding partner, MEIS1 (AHR 2.03, 95% CI 1.54-2.66) or MEIS2 (AHR 1.73, 95% CI 1.33-2.26), portended worse MFS. Additionally, high HOXB13 expression in combination with low MEIS1/2 expression correlated with high expression of androgen receptor-mediated genes. The retrospective nature of this study subjects the findings to a bias due to unmeasured variables.ConclusionsPrimary PCa tumors with increased HOXB13 expression have an increased propensity for metastases following prostatectomy, particularly in the setting of low MEIS1/2 expression. High androgen receptor output may account for worse outcomes for these tumors and suggests heightened sensitivity to androgen suppression.Patient summaryUsing genomic data from a large number of prostate cancer (PCa) tumors, we found that increased expression of homeobox B13 (HOXB13), a gene related to normal prostate development, was associated with worse outcomes following surgery for PCa. A biomarker signature suggests that these tumors would be more susceptible to androgen suppression, a common treatment for PCa. Take Home Messagece:: In multiple large cohorts, prostate cancer tumors with high homeobox B13 (HOXB13) expression and low expression of its binding partner MEIS1/2 were enriched with high androgen receptor output and had an increased propensity for metastases following surgery.

Project description:BackgroundSeveral studies have investigated the relationship between experience measured by caseload and oncological outcomes, economics, and access to care for prostate cancer care. Oncological outcomes have been limited to biochemical failure after radical prostatectomy. Questions remain regarding the more definitive measures of outcomes and their relationship with caseload.MethodsThe National Cancer Database was used to investigate the outcomes of radical prostatectomy in the United States. With overall survival (OS) as the primary outcome, the relationship between the facility annual caseload (FAC) for all prostate cancer encounters and the facility annual surgical caseload (FASC) for those requiring radical prostatectomy was examined with a Cox proportional hazards model. Four volume groups were defined by caseload: <50th percentile (volume group 1 [VG1]), 50th to 74th percentiles (volume group 2 [VG2]), 75th to 89th percentiles (volume group 3 [VG3]), and ≥90th percentile (volume group 4 [VG4]). By FAC/FASC, 11%/8%, 17%/18%, 25%/26%, and 47%/49% of patients were treated in VG1 through VG4, respectively.ResultsBetween 2004 and 2014, 488,389 patients underwent radical prostatectomy. At a median follow-up of 60.75 months, the median OS was not reached. There was a significant OS benefit as the caseload increased. For FAC, the adjusted OS difference between VG1 and VG4 at 90th percentile survivorship reached 13.2 months (hazard ratio [HR], 1.30; 95% CI, 1.23-1.36; P < .0001). For FASC, this was 11.3 months (HR, 1.25; 95% CI, 1.192-1.321; P < .0001).ConclusionsThere is a statistically significant OS advantage from performing radical prostatectomy at a facility with a high annual caseload. Caseload measured by all prostate cancer encounters is a better predictor of favorable outcomes than the number of surgeries performed at a facility.Lay summaryAn in-depth analysis of 488,389 cases of radical prostatectomy performed in more than 1000 facilities over a 10-year period showed better survival when surgery was performed in facilities with more experience and greater caseload. A survival difference of up to 13 months was observed when comparing patients treated at less experienced versus more experienced centers. Experience across all stages of prostate cancer was a stronger predictor of survival outcome than just the number of surgeries performed.

Project description:Accurate estimation of recurrence risk is needed for optimal treatment of clinically localized prostate cancer (PCa) patients. We combined classical clinicopathological predictors of biochemical recurrence (BCR) and molecular markers into a new risk score for predicting BCR after radical prostatectomy (RP). A retrospective study which included 122 PCa patients who attended our department between 2000 and 2007 was conducted. Total RNA was isolated from formalin-fixed paraffin embedded PCa tissue. Gene expression patterns were analyzed in 21 selected samples from 7 localized, 6 locally advanced, and 8 metastatic PCa patients using Illumina microarrays. Expression levels of 41 genes were validated by quantitative PCR in an independent retrospective series of 101 patients with ≥ 10 years follow-up who underwent RP for clinically localized PCa. Univariate and multivariate logistic regression analysis were used to identify individual predictors of BCR. A risk score (RS) for predicting BCR including clinicopathological and gene expression data was developed and Kaplan-Meier curves were generated. Interaction networks between the genes of the model were built by GeneMANIA Cytoscape plugin. In a median follow-up of 120 months (range 3-190), 37 patients developed BCR (36.6%). Expression levels of 7,930 transcripts differed between clinically localized and locally advanced-metastatic PCa groups (FDR<0.1). A set of 41 genes were validated by quantitative PCR. Regression analysis showed that expression of ASF1B and MCL1 as well as Gleason score, extracapsular extension, seminal vesicle invasion and positive margins were independent prognostic factors of BCR. A RS generated using these gene expression and clinicopathological variables was able to discriminate between two groups of patients with a significantly different probability of BCR (HR 6.24; CI 3.23-12.4, p<0.01), improving the individual discriminative performance of each of these variables on their own. Direct interactions between the two genes of the model were not found. In conclusion, identification of new gene expression patterns associated with a high probability of BCR in clinically localized PCa patients treated with RP, and their combination with clinicopathological variables in a robust, easy-to-use and reliable classifier may contribute to improve PCa risk stratification and, consequently, to tailor treatment and surveillance strategies in these patients.

Dataset Information

Effect of Clinical Parameters on Risk of Death from Cancer after Radical Prostatectomy in Men with Localized and Locally Advanced Prostate Cancer.

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Effect of Clinical Parameters on Risk of Death from Cancer after Radical Prostatectomy in Men with Localized and Locally Advanced Prostate Cancer.

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