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Nomograms Predict Survival Advantages of Gleason Score 3+4 Over 4+3 for Prostate Cancer: A SEER-Based Study.

ABSTRACT: Background: Different proportions of Gleason pattern 3 and Gleason pattern 4 lead to various prognosis of prostate cancer with Gleason score 7. The objective of this study was to compare the survival outcomes of Gleason score 3+4 and 4+3 based on data from the Surveillance, Epidemiology, and End Results cancer registry database, and to investigate independent prognosis-associated factors and develop nomograms for predicting survival in Gleason score 7 prostate cancer patients. Methods: A retrospective study was conducted on 69,116 cases diagnosed as prostate adenocarcinoma with Gleason score 7 between 2004 and 2009. Prognosis-associated factors were evaluated using univariate and multivariate Cox regression analysis, and a 1:1 ratio paired cohort by propensity score matching with the statistical software IBM SPSS, to evaluate prognostic differences between Gleason score 3+4 and 4+3. The primary cohort was randomly divided into training set (n = 48,384) and validation set (n = 20,732). Based on the independent factors of prognosis, nomograms for prognosis were established by the training group and validated by the validation group using R version 3.5.0. Results: After propensity score matching, Cox regression analysis showed that Gleason 4+3 had an increased mortality risk both for overall survival (HR: 1.235, 95% CI: 1.179-1.294, P < 0.001) and cancer-specific survival (HR: 1.606, 95% CI: 1.468-1.762, P < 0.001). Nomograms for overall survival and cancer-specific survival were established with C-index 0.786 and 0.842, respectively. The calibration plot indicated an optimal agreement between the actual observation and nomogram prediction for overall survival and cancer-specific survival probability at 5 or 10 year. Conclusions: Prostate cancer with Gleason score 4+3 had worse overall survival and cancer-specific survival than Gleason score 3+4. Nomograms were formulated to predict 5-year and 10-year OS and CSS in patients with prostate cancer of Gleason score 7.

SUBMITTER: Zhu X

PROVIDER: S-EPMC6646708 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Nomograms Predict Survival Advantages of Gleason Score 3+4 Over 4+3 for Prostate Cancer: A SEER-Based Study.

Zhu Xin X Gou Xin X Zhou Mi M

Frontiers in oncology 20190716

<b>Background:</b> Different proportions of Gleason pattern 3 and Gleason pattern 4 lead to various prognosis of prostate cancer with Gleason score 7. The objective of this study was to compare the survival outcomes of Gleason score 3+4 and 4+3 based on data from the Surveillance, Epidemiology, and End Results cancer registry database, and to investigate independent prognosis-associated factors and develop nomograms for predicting survival in Gleason score 7 prostate cancer patients. <b>Methods: ...[more]

PMID: 31380282

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Project description:BackgroundPatients with newly diagnosed non-metastatic prostate adenocarcinoma are typically classified as at low, intermediate, or high risk of disease progression using blood prostate-specific antigen concentration, tumour T category, and tumour pathological Gleason score. Classification is used to both predict clinical outcome and to inform initial management. However, significant heterogeneity is observed in outcome, particularly within the intermediate risk group, and there is an urgent need for additional markers to more accurately hone risk prediction. Recently developed web-based visualization and analysis tools have facilitated rapid interrogation of large transcriptome datasets, and querying broadly across multiple large datasets should identify predictors that are widely applicable.MethodsWe used camcAPP, cBioPortal, CRN, and NIH NCI GDC Data Portal to data mine publicly available large prostate cancer datasets. A test set of biomarkers was developed by identifying transcripts that had: 1) altered abundance in prostate cancer, 2) altered expression in patients with Gleason score 7 tumours and biochemical recurrence, 3) correlation of expression with time until biochemical recurrence across three datasets (Cambridge, Stockholm, MSKCC). Transcripts that met these criteria were then examined in a validation dataset (TCGA-PRAD) using univariate and multivariable models to predict biochemical recurrence in patients with Gleason score 7 tumours.ResultsTwenty transcripts met the test criteria, and 12 were validated in TCGA-PRAD Gleason score 7 patients. Ten of these transcripts remained prognostic in Gleason score 3 + 4 = 7, a sub-group of Gleason score 7 patients typically considered at a lower risk for poor outcome and often not targeted for aggressive management. All transcripts positively associated with recurrence encode or regulate mitosis and cell cycle-related proteins. The top performer was BUB1, one of four key MIR145-3P microRNA targets upregulated in hormone-sensitive as well as castration-resistant PCa. SRD5A2 converts testosterone to its more active form and was negatively associated with biochemical recurrence.ConclusionsUnbiased mining of large patient datasets identified 12 transcripts that independently predicted disease recurrence risk in Gleason score 7 prostate cancer. The mitosis and cell cycle proteins identified are also implicated in progression to castration-resistant prostate cancer, revealing a pivotal role for loss of cell cycle control in the latter.

Project description:BackgroundProstate tumor volume predicts biochemical recurrence, metastases, and tumor proliferation. A recent study showed that prostate tumor eccentricity (elongation or roundness) correlated with Gleason score. No studies examined the relationship among the prostate tumor's shape, volume, and potential aggressiveness.MethodsOf the 26 patients that were analyzed, 18 had volumes >1 cc for the histology-based study, and 25 took up contrast material for the MRI portion of this study. This retrospective study quantitatively compared tumor eccentricity and volume measurements from pathology assessment sectioned wholemount prostates and multi-parametric MRI to Gleason scores. Multi-parametric MRI (T1, T2, diffusion, dynamic contrast-enhanced images) were resized, translated, and stitched to form spatially registered multi-parametric cubes. Multi-parametric signatures that characterize prostate tumors were inserted into a target detection algorithm (Adaptive Cosine Estimator, ACE). Various detection thresholds were applied to discriminate tumor from normal tissue. Pixel-based blobbing, and labeling were applied to digitized pathology slides and threshold ACE images. Tumor volumes were measured by counting voxels within the blob. Eccentricity calculation used moments of inertia from the blobs.ResultsFrom wholemount prostatectomy slides, fitting two sets of independent variables, prostate tumor eccentricity (largest blob eccentricity, weighted eccentricity, filtered weighted eccentricity) and tumor volume (largest blob volume, average blob volume, filtered average blob volume) to Gleason score in a multivariate analysis, yields correlation coefficient R=0.798 to 0.879 with P<0.01. The eccentricity t-statistic exceeded the volume t-statistic. Fitting histology-based total prostate tumor volume against Gleason score yields R=0.498, P=0.0098. From multi-parametric MRI, the correlation coefficient R between the Gleason score and the largest blob eccentricity for varying thresholds (0.30 to 0.55) ranged from -0.51 to -0.672 (P<0.01). For varying thresholds (0.60 to 0.80) for MRI detection, the R between the largest blob volume eccentricity against the Gleason score ranged from 0.46 to 0.50 (P<0.03). Combining tumor eccentricity and tumor volume in multivariate analysis failed to increase Gleason score prediction.ConclusionsProstate tumor eccentricity, determined by histology or MRI, more accurately predicted Gleason score than prostate tumor volume. Combining tumor eccentricity with volume from histology-based analysis enhanced Gleason score prediction, unlike MRI.

Dataset Information

Nomograms Predict Survival Advantages of Gleason Score 3+4 Over 4+3 for Prostate Cancer: A SEER-Based Study.

Publications

Nomograms Predict Survival Advantages of Gleason Score 3+4 Over 4+3 for Prostate Cancer: A SEER-Based Study.

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