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Background: The International Society of Urological Pathology (ISUP) revised the Gleason system in 2005 and 2014. The impact of these changes on prostate cancer (PCa) prognostication remains unclear. Objective: To evaluate if the ISUP 2014 Gleason score (GS) predicts PCa death better than the pre-2005 GS, and if additional histopathological information can further improve PCa death prediction. Patients and Methods: We conducted a case–control study nested among men in the National Prostate Cancer Register of Sweden diagnosed with non-metastatic PCa 1998– 2015. We included 369 men who died from PCa (cases) and 369 men who did not (controls). Two uro-pathologists centrally re-reviewed biopsy ISUP 2014 Gleason grading, poorly formed glands, cribriform pattern, comedonecrosis, perineural invasion, intraductal, ductal and mucinous carcinoma, percentage Gleason 4, inflammation, high-grade prostatic intraepithelial neoplasia (HGPIN) and post-atrophic hyperplasia. Pre-2005 GS was back-transformed using i) information on cribriform pattern and/or poorly formed glands and ii) the diagnostic GS from the registry. Models were developed using Firth logistic regression and compared in terms of discrimination (AUC). Results: The ISUP 2014 GS (AUC = 0.808) performed better than the pre-2005 GS when back-transformed using only cribriform pattern (AUC = 0.785) or both cribriform and poorly formed glands (AUC = 0.792), but not when back-transformed using only poorly formed glands (AUC = 0.800). Similarly, the ISUP 2014 GS performed better than the diagnostic GS (AUC = 0.808 vs 0.781). Comedonecrosis (AUC = 0.811), HGPIN (AUC = 0.810) and number of cores with ? 50% cancer (AUC = 0.810) predicted PCa death independently of the ISUP 2014 GS. Conclusion: The Gleason Grading revisions have improved PCa death prediction, likely due to classifying cribriform patterns, rather than poorly formed glands, as Gleason 4. Comedonecrosis, HGPIN and number of cores with ? 50% cancer further improve PCa death discrimination slightly. [ABSTRACT FROM AUTHOR]

In this paper, we describe the Prognostic Factors for Mortality in Prostate Cancer (ProMort) study and use it to demonstrate how the weighted likelihood method can be used in nested case-control studies to estimate both relative and absolute risks in the competing-risks setting. ProMort is a case-control study nested within the National Prostate Cancer Register (NPCR) of Sweden, comprising 1,710 men diagnosed with low- or intermediate-risk prostate cancer between 1998 and 2011 who died from prostate cancer (cases) and 1,710 matched controls. Cause-specific hazard ratios and cumulative incidence functions (CIFs) for prostate cancer death were estimated in ProMort using weighted flexible parametric models and compared with the corresponding estimates from the NPCR cohort. We further drew 1,500 random nested case-control subsamples of the NPCR cohort and quantified the bias in the hazard ratio and CIF estimates. Finally, we compared the ProMort estimates with those obtained by augmenting competing-risks cases and by augmenting both competing-risks cases and controls. The hazard ratios for prostate cancer death estimated in ProMort were comparable to those in the NPCR. The hazard ratios for dying from other causes were biased, which introduced bias in the CIFs estimated in the competing-risks setting. When augmenting both competing-risks cases and controls, the bias was reduced. [ABSTRACT FROM AUTHOR]

Background: In Sweden, human tissue samples obtained from diagnostic and surgical procedures have for decades been routinely stored in a formalin-fixed, paraffin-embedded, form. Through linkage with nationwide registers, these samples are available for molecular studies to identify biomarkers predicting mortality even in slow-progressing prostate cancer. However, tissue fixation causes modifications of nucleic acids, making it challenging to extract high-quality nucleic acids from formalin fixated tissues., Methods: In this study, the efficiency of five commercial nucleic acid extraction kits was compared on 30 prostate biopsies with normal histology, and the quantity and quality of the products were compared using spectrophotometry and Agilent's BioAnalyzer. Student's t-test's and Bland-Altman analyses were performed in order to investigate differences in nucleic acid quantity and quality between the five kits. The best performing extraction kits were subsequently tested on an additional 84 prostate tumor tissues. A Spearman's correlation test and linear regression analyses were performed in order to investigate the impact of tissue age and amount of tissue on nucleic acid quantity and quality., Results: Nucleic acids extracted with RNeasy® FFPE and QIAamp® DNA FFPE Tissue kit had the highest quantity and quality, and was used for extraction from 84 tumor tissues. Nucleic acids were successfully extracted from all biopsies, and the amount of tumor (in millimeter) was found to have the strongest association with quantity and quality of nucleic acids., Conclusions: To conclude, this study shows that the choice of nucleic acid extraction kit affects the quantity and quality of extracted products. Furthermore, we show that extraction of nucleic acids from archival formalin-fixed prostate biopsies is possible, allowing molecular studies to be performed on this valuable sample collection.

Objective: The aims of this study were to create a cohort of retrospectively collected renal cell carcinoma (RCC) specimens to be used a basis for prognostic molecular studies, and to investigate the outcome and time trends in patients surgically treated for RCC in a single-centre cohort., Materials and Methods: Patients undergoing surgery for RCC between 1986 and 2010 were included in the study. Medical records were reviewed, and the diagnostic tissue was re-evaluated according to a modern classification. The change in patient and tumour characteristics over time was analysed., Results: The study included 345 patients. Smaller tumours, as indicated by primary tumour diameter, tumour (T) stage and American Joint Committee on Cancer (AJCC) stage, were found more frequently in later years compared to the early 1990s. No changes in the clinical outcome for the patients were seen among the time periods investigated. Increasing T stage, AJCC stage, primary tumour diameter and decreasing haemoglobin levels were associated with cancer-specific mortality in univariate analysis. A high calcium level was significantly associated with increased cancer-specific mortality (hazard ratio = 4.25, 95% confidence interval 1.36-13.28) in multivariate analysis., Conclusions: This study on patients who underwent surgery for RCC from 1986 to 2010 at a single institution in Sweden indicates that there has been a change in tumour characteristics of patients diagnosed with RCC over time. It was also shown that calcium levels were an independent prognostic factor for cancer-specific mortality in this cohort. This cohort could provide a valuable basis for further molecular studies.

Background: A challenge in prostate cancer (PCa) management is identifying potentially lethal disease at diagnosis. Inflammation, focal prostatic atrophy, and prostatic intraepithelial neoplasia (PIN) are common in prostate tumor specimens, but it is not clear whether these lesions have prognostic significance., Methods: We conducted a case-control study nested in a cohort of men diagnosed with stage T1a-b PCa through transurethral resection of the prostate in Sweden. Cases are men who died of PCa (n = 228). Controls are men who survived more than 10 years after PCa diagnosis without metastases (n = 387). Slides were assessed for Gleason grade, inflammation, PIN, and four subtypes of focal prostatic atrophy: simple atrophy (SA), postatrophic hyperplasia (PAH), simple atrophy with cyst formation, and partial atrophy. We estimated OR and 95% CI for odds of lethal PCa with multivariable logistic regression., Results: Chronic inflammation and PIN were more frequently observed in tumors with PAH, but not SA. No specific type of atrophy or inflammation was significantly associated with lethal PCa overall, but there was a suggestion of a positive association for chronic inflammation. Independent of age, Gleason score, year of diagnosis, inflammation, and atrophy type, men with PIN were 89% more likely to die of PCa (95% CI: 1.04-3.42)., Conclusion: Our data show that PIN, and perhaps presence of moderate or severe chronic inflammation, may have prognostic significance for PCa., Impact: Lesions in tumor adjacent tissue, and not just the tumor itself, may aid in identification of clinically relevant disease., (©2011 AACR)