Preoperative characteristics of high-Gleason disease predictive of favourable pathological and clinical outcomes at radical prostatectomy
ABSTRACT Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Men with high-risk prostate cancer experience recurrence, metastases and death at the highest rate in the prostate cancer population. Pathological stage at radical prostatectomy (RP) is the greatest predictor of recurrence and mortality in men with high-grade disease. Preoperative models predicting outcome after RP are skewed by the large proportion of men with low- and intermediate-risk features; there is a paucity of data about preoperative criteria to identify men with high-grade cancer who may benefit from RP. The present study adds comprehensive biopsy data from a large cohort of men with high-grade prostate cancer at biopsy. By adding biopsy parameters, e.g. number of high-grade cores and >50% involvement of any core, to traditional predictors of outcome (prostate-specific antigen concentration, clinical stage and Gleason sum), we can better inform men who present with high-grade prostate cancer as to their risk of favourable or unfavourable disease at RP.
• To investigate preoperative characteristics that distinguish favourable and unfavourable pathological and clinical outcomes in men with high biopsy Gleason sum (8-10) prostate cancer to better select men who will most benefit from radical prostatectomy (RP).
• The Institutional Review Board-approved institutional RP database (1982-2010) was analysed for men with high-Gleason prostate cancer on biopsy; 842 men were identified. • The 10-year biochemical-free (BFS), metastasis-free (MFS) and prostate cancer-specific survival (CSS) were calculated using the Kaplan-Meier method to verify favourable pathology as men with Gleason <8 at RP or ≤ pT3a compared with men with unfavourable pathology with Gleason 8-10 and pT3b or N1. • Preoperative characteristics were compared using appropriate comparative tests. • Logistic regression determined preoperative predictors of unfavourable pathology.
• There was favourable pathology in 656 (77.9%) men. The 10-year BFS, MFS and CSS were 31.0%, 60.9% and 74.8%, respectively. • In contrast, men with unfavourable pathological findings had significantly worse 10-year BFS, MFS and CSS, at 4.3%, 29.1% and 52.3%, respectively (all P < 0.001). • In multivariable logistic regression, a prostate-specific antigen (PSA) concentration of >10 ng/mL (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.38-3.62, P= 0.001), advanced clinical stage (≥ cT2b; OR 2.55, 95% CI 1.55-4.21, P < 0.001), Gleason pattern 9 or 10 at biopsy (OR 2.55, 95% CI 1.59-4.09, P < 0.001), increasing number of cores positive with high-grade cancer (OR 1.16, 95% CI 1.01-1.34, P= 0.04) and >50% positive core involvement (OR 2.25, 95% CI 1.17-4.35, P= 0.015) were predictive of unfavourable pathology.
• Men with high-Gleason sum at biopsy are at high risk for biochemical recurrence, metastasis and death after RP; men with high Gleason sum and advanced pathological stage (pT3b or N1) have the worst prognosis. • Among men with high-Gleason sum at biopsy, a PSA concentration of >10 ng/mL, clinical stage ≥ T2b, Gleason pattern 9 or 10, increasing number of cores with high-grade cancer and >50% core involvement are predictive of unfavourable pathology.
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ABSTRACT: Prostate cancer is diverse in clinical presentation, histopathological tumor growth patterns, and survival. Therefore, individual assessment of a tumor's aggressive potential is crucial for clinical decision-making in men with prostate cancer. To date a large number of prognostic markers for prostate cancer have been described, most of them based on radical prostatectomy specimens. However, in order to affect clinical decision-making, validation of respective markers in pretreatment diagnostic needle-biopsies is essential. Here, we discuss established and promising histopathological and molecular parameters in diagnostic needle-biopsies.BioMed Research International 08/2014; 2014:12. DOI:10.1155/2014/341324 · 2.71 Impact Factor
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ABSTRACT: Even if limited to one biopsy core, most urologists and radiation oncologists use the highest Gleason score (GS) to guide therapy. To evaluate the suitability of using biopsy characteristics to predict tumor characteristics at radical prostatectomy (RP) in men with high biopsy GS (BGS) cancer to better select men who will most benefit from various local therapies, we retrospectively reviewed the biopsy and RP findings of 144 men with a BGS 8-10. 106 and 38 patients with a BGS 8 and 9-10 respectively were included. 48% of cases were downgraded to a final GS of 7 at RP, including 54% of BGS 8, and 32% of BGS 9 – 10 group. Overall, 31% had pT2 disease at RP. Multiple biopsy features, including the GS, the number of positive cores, the number of cores with high GS cancer, and the maximum volume of high-grade cancer per core (MVPC) consistently predicted final GS and RP tumor stage. Multivariate analysis showed that biopsy GS and MVPC were independent predictors of final GS, while MVPC was also an independent predictor for final pT stage. Patients with high BGS are not a homogeneous group in terms of local tumor characteristics. In addition to BGS (9-10 being worse than 8), other biopsy findings, especially the number of involved cores, number of cores with high BGS cancer, and MVPC are important predictors of findings at RP that should be incorporated in the decision treatment-planning. Most patients with only one core BGS 8 cancer harbor GS7 cancer.Human pathology 10/2014; 45(10). DOI:10.1016/j.humpath.2014.06.014 · 2.81 Impact Factor
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ABSTRACT: Background:Outcomes in men with National Comprehensive Cancer Network (NCCN) high-risk prostate cancer (PCa) can vary substantially-some will have excellent cancer-specific survival, whereas others will experience early metastasis even after aggressive local treatments. Current nomograms, which yield continuous risk probabilities, do not separate high-risk PCa into distinct sub-strata. Here, we derive a binary definition of very-high-risk (VHR) localized PCa to aid in risk stratification at diagnosis and selection of therapy.Methods:We queried the Johns Hopkins radical prostatectomy database to identify 753 men with NCCN high-risk localized PCa (Gleason sum 8-10, PSA >20 ng ml(-1), or clinical stage T3). Twenty-eight alternate permutations of adverse grade, stage and cancer volume were compared by their hazard ratios for metastasis and cancer-specific mortality. VHR criteria with top-ranking hazard ratios were further evaluated by multivariable analyses and inclusion of a clinically meaningful proportion of the high-risk cohort.Results:The VHR cohort was best defined by primary pattern 5 present on biopsy, or 5 cores with Gleason sum 8-10, or multiple NCCN high-risk features. These criteria encompassed 15.1% of the NCCN high-risk cohort. Compared with other high-risk men, VHR men were at significantly higher risk for metastasis (hazard ratio 2.75) and cancer-specific mortality (hazard ratio 3.44) (P<0.001 for both). Among high-risk men, VHR men also had significantly worse 10-year metastasis-free survival (37% vs 78%) and cancer-specific survival (62% vs 90%).Conclusions:Men who meet VHR criteria form a subgroup within the current NCCN high-risk classification who have particularly poor oncological outcomes. Use of these characteristics to distinguish VHR localized PCa may help in counseling and selection optimal candidates for multimodal treatments or clinical trials.Prostate Cancer and Prostatic Disease advance online publication, 5 November 2013; doi:10.1038/pcan.2013.46.Prostate Cancer and Prostatic Diseases 11/2013; DOI:10.1038/pcan.2013.46 · 2.83 Impact Factor