The histopathological evaluation of biopsies by human experts is a gold standard in clinical disease diagnosis. While recent artificial intelligence-based (AI) approaches have reached human expert-level performance, they often display shortcomings caused by variations in sample preparation, limiting clinical applicability. This study investigates the impact of data variation on AI-based histopathological grading and explores algorithmic approaches that confer prediction robustness. To evaluate the impact of data variation in histopathology, we collected a multicentric, retrospective, observational prostate cancer (PCa) trial consisting of six cohorts in 3 countries with 25,591 patients, 83,864 images. This includes a high-variance dataset of 8,157 patients and 28,236 images with variations in section thickness, staining protocol, and scanner. This unique training dataset enabled the development of an AI-based PCa grading framework by training on patient outcome, not subjective grading. It was made robust through several algorithmic adaptations, including domain adversarial training and credibility-guided color adaptation. We named the final grading framework PCAI. We compare PCAI to a BASE model and human experts on three external test cohorts, comprising 2,255 patients and 9,437 images. Variations in sample processing, particularly section thickness and staining time, significantly reduced the performance of AI-based PCa grading by up to 8.6 percentage points in the event-ordered concordance index (EOC-Index) thus highlighting serious risks for AI-based histopathological grading. Algorithmic improvements for model robustness, credibility, and training on high-variance data as well as outcome-based severity prediction give rise to robust models with grading performance surpassing experienced pathologists. We demonstrate how our algorithmic enhancements for greater robustness lead to significantly better performance, surpassing expert grading on EOC-Index and 5-year AUROC by up to 21.2 percentage points.

Background:Prostate cancer (PCa) is among the most common cancers in men and its diagnosis requires the histopathological evaluation of biopsies by human experts. While several recent artificial intelligence-based (AI) approaches have reached human expert-level PCa grading, they often display significantly reduced performance on external datasets. This reduced performance can be caused by variations in sample preparation, for instance the staining protocol, section thickness, or scanner used. Another limiting factor of contemporary AI-based PCa grading is the prediction of ISUP grades, which leads to the perpetuation of human annotation errors. Methods:We developed the prostate cancer aggressiveness index (PCAI), an AI-based PCa detection and grading framework that is trained on objective patient outcome, rather than subjective ISUP grades. We designed PCAI as a clinical application, containing algorithmic modules that offer robustness to data variation, medical interpretability, and a measure of prediction confidence. To train and evaluate PCAI, we generated a multicentric, retrospective, observational trial consisting of six cohorts with 25,591 patients, 83,864 images, and 5 years of median follow-up from 5 different centers and 3 countries. This includes a high-variance dataset of 8,157 patients and 28,236 images with variations in sample thickness, staining protocol, and scanner, allowing for the systematic evaluation and optimization of model robustness to data variation. The performance of PCAI was assessed on three external test cohorts from two countries, comprising 2,255 patients and 9,437 images. Findings:Using our high-variance datasets, we show how differences in sample processing, particularly slide thickness and staining time, significantly reduce the performance of AI-based PCa grading by up to 6.2 percentage points in the concordance index (C-index). We show how a select set of algorithmic improvements, including domain adversarial training, conferred robustness to data variation, interpretability, and a measure of credibility to PCAI. These changes lead to significant prediction improvement across two biopsy cohorts and one TMA cohort, systematically exceeding expert ISUP grading in C-index and AUROC by up to 22 percentage points. Interpretation:Data variation poses serious risks for AI-based histopathological PCa grading, even when models are trained on large datasets. Algorithmic improvements for model robustness, interpretability, credibility, and training on high-variance data as well as outcome-based severity prediction gives rise to robust models with above ISUP-level PCa grading performance.

Prostate cancer is among the most common cancers in men with around 1.4 million new cases each year world-wide. A vital part in the diagnosis of prostate cancer is the evaluation of its severity using biopsies and histopathology. Recent progress in artificial intelligence-based image analysis has led to a flurry of algorithms for the automated analysis of prostate cancer histopathological data focusing on the detection of cancerous areas, the grading of cancer severity, and patient outcome. Some of these approaches have reached human expert-level performance and digital models trained directly on patient outcomes might surpass human performance in the future. Although these results hold great promise for the future usage of digital pathology in clinical settings, several bottlenecks remain to be addressed. Especially the robustness, reliability and trustworthiness of predictions must be guaranteed across a wide range of variation in protocols and instrumentation. While human experts are relatively robust to technical and biological variation in biopsies, artificial intelligence-based systems tend to struggle with differences in staining intensity, color, scanner type, and image resolution, impeding the clinical usage of digital models. In this work we highlight salient problems and minimal requirements of computational pathology for future use in clinical settings, while focusing on prostate cancer as a use case. In particular, we highlight data and model problems and solutions that include data variability, dataset size, and data annotations, as well as model robustness to data heterogeneity, model prediction confidence, and the explainability of model decisions. While model and data requirements for successful computational pathology in clinics will be highlighted, legal, ethical, and deployment requirements will not be addressed in this review. In summary, we provide a short overview of the field, salient problems, and potential solutions to harvest the full potential of digital pathology for prostate cancer in clinical practice.

In order to plan the best treatment for prostate cancer patients, the aggressiveness of the tumor is graded based on visual assessment of tissue biopsies according to the Gleason scale. Recently, a number of AI models have been developed that can be trained to do this grading as well as human pathologists. But the accuracy of the AI grading will be limited by the accuracy of the subjective “ground truth” Gleason grades used for the training. We have trained an AI to predict patient outcome directly based on image analysis of a large biobank of tissue samples with known outcome without input of any human knowledge about cancer grading. The model has shown similar and in some cases better ability to predict patient outcome on an independent test-set than expert pathologists doing the conventional grading.

Einleitung Bilaterale Lungeninfiltrate und eine Anämie führten die Patientin in unsere Abteilung. Nebenbefundlich bestanden echokardiographisch Hinweise für eine hochgradige pulmonale Hypertonie mit einem PAPsys von 70 mmHg. Nach antibiotischer Therapie, bei Haemophilus influenzae Nachweis, persistierten CT- morphologisch bipulmonale Herdinfiltrate und Milchglasinfiltrationen.

BACKGROUND Radical prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from randomized trials with long‐term follow‐up is sparse. METHODS We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow‐up data through 2017. Cumulative incidence and relative risks with 95% confidence intervals for death from any cause, death from prostate cancer, and metastasis were estimated in intention‐to‐treat and per‐protocol analyses, and numbers of years of life gained were estimated. We evaluated the prognostic value of histopathological measures with a Cox proportional‐hazards model. RESULTS By December 31, 2017, a total of 261 of the 347 men in the radical‐prostatectomy group and 292 of the 348 men in the watchful‐waiting group had died; 71 deaths in the radical‐prostatectomy group and 110 in the watchful‐waiting group were due to prostate cancer (relative risk, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001; absolute difference in risk, 11.7 percentage points; 95% CI, 5.2 to 18.2). The number needed to treat to avert one death from any cause was 8.4. At 23 years, a mean of 2.9 extra years of life were gained with radical prostatectomy. Among the men who underwent radical prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension, and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower (scores range from 2 to 10, with higher scores indicating more aggressive cancer). CONCLUSIONS Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer. (Funded by the Swedish Cancer Society and others.)

Erworbene Resistenzen gegenüber Tyrosinkinaseinhibitoren (TKI's) stellen die Schwachstelle der Targettherapien beim Nicht-Kleinzelligen Bronchialkarzinom (NSCLC) dar. Epidermal Growth Factor Receptor (EGFR)-TKI's sind die etablierte first-line Therapie bei Patienten mit fortgeschrittenem NSCLC und nachgewiesener EGFR-Mutation. Durchschnittlich entwickeln sich jedoch nach etwa 9 – 12 Monaten erworbene Resistenzen gegenüber den TKI's. Die Resistenzentwicklung wird in etwa 60% der Fälle durch eine sekundäre EGFR-T790 M Mutation vermittelt. Verschiedene andere Mechanismen der sekundären Resistenzentwicklung wurden bereits beschrieben. Unter anderem waren dies sekundäre Mutationen in verschiedenen Onkogenen oder die Transformation des Phänotyps, jedoch mit einer sehr viel geringeren Inzidenz.

To better understand prostate function and disease, it is important to define and explore the molecular constituents that signify the prostate gland. The aim of this study was to define the prostate specific transcriptome and proteome, in comparison to 26 other human tissues. Deep sequencing of mRNA (RNA-seq) and immunohistochemistry-based protein profiling were combined to identify prostate specific gene expression patterns and to explore tissue biomarkers for potential clinical use in prostate cancer diagnostics. We identified 203 genes with elevated expression in the prostate, 22 of which showed more than five-fold higher expression levels compared to all other tissue types. In addition to previously well-known proteins we identified two poorly characterized proteins, TMEM79 and ACOXL, with potential to differentiate between benign and cancerous prostatic glands in tissue biopsies. In conclusion, we have applied a genome-wide analysis to identify the prostate specific proteome using transcriptomics and antibody-based protein profiling to identify genes with elevated expression in the prostate. Our data provides a starting point for further functional studies to explore the molecular repertoire of normal and diseased prostate including potential prostate cancer markers such as TMEM79 and ACOXL.

Survival after invasive bladder cancer has improved less than that of other common non-skin cancers. In many types of malignancy, treatment failure has been attributed to therapy-resistant stem-like cancer cells. Our aim was therefore to determine identities of stem cell marker-positive cells in bladder cancer tissue and to investigate possible associations between these cells and different forms of bladder neoplasia. We investigated tissue from 52 patients with bladder neoplasia and 18 patients with benign bladder conditions, from a cohort that had been previously described with regard to diagnosis and outcome. The samples were analysed immunohistologically for the stem cell markers aldehyde dehydrogenase 1 A1 (ALDH1) and CD44, and markers of cell differentiation. The majority of stem cell marker-positive cells were located in connective tissue, and a smaller fraction in epithelial tissue. Stem cell marker-positive cells exhibiting possible stem cell characteristics included cells in deeper locations of benign and malignant epithelium, and sub-endothelial cells in patients with or without neoplasia. Stem cell marker-positive cells with non-stem cell character included stellate cells, mast cells, endothelial cells, foamy histiocytes, and neurons. Significantly, ALDH1+ stellate cells and ALDH1+ mast cells were reduced in number in stroma of benign-appearing mucosa of bladder cancer patients. The stem cell markers ALDH1 and CD44 label several types of differentiated cells in bladder tissue. ALDH1+ stellate cells and mast cells appear to be reduced in stroma of normal-appearing mucosa of bladder cancer patients, and may be part of a "field effect" in cancer-near areas.

ZusammenfassungIm phlebologischen Alltag ist die CVI aufgrund der sie typischerweise begleitenden Stadien-abhängigen Hautveränderungen häufig eine Blickdiagnose, die für die therapeutische Entscheidungsfindung durch apparative Diagnostik bestätigt und spezifiziert wird. Gerade im Hinblick auf die beiden häufigsten Stadieneinteilungen der CVI (nach Widmer bzw. der CEAP-Klassifikation) spielt die klinische Erscheinung eine wesentliche Rolle. Dieser Artikel gibt einen Überblick über die charakteristischen Hautveränderungen der unterschiedlichen Stadien der CVI und soll den klinischen Blick für die Diagnose der CVI schulen.

What's known on the subject? and What does the study add? The current basis for diagnosis and prognosis in urinary bladder cancer is based on the pathologists' assessment of a biopsy of the tumour. Urinary biomarkers are preferable as they can be non‐invasively sampled. Urinary cytology is the only test with widespread use but is hampered by poor reproducibility and low sensitivity. By studying the protein expression in bladder tumour tissue samples of proteins previously found in elevated levels in the urine of patients with bladder cancer, we have been able to show that these proteins originate from the tumour. The immunoreactivity of three of the investigated proteins increased with higher stage. Also a serine peptidase inhibitor was found to be predictive of progression from non‐muscle‐invasive to muscle‐invasive tumours. Objectives To analyse the expression of five bladder cancer‐associated urinary proteins and investigate if expression is related to the malignant phenotype of the tumour. To explore the possible prognostic value of these proteins. Patients and Methods Urine samples, 16 from patients with bladder cancer and 26 from controls, were used in Western Blotting experiments. Tissue microarrays with bladder tissue from 344 patients diagnosed with bladder cancer between 1984 and 2005 was used in immunohistochemistry experiments. The proteins apolipoprotein E (APOE), fibrinogen β chain precursor (FGB), leucine‐rich α2‐glycoprotein (LRG1), polymerase (RNA) I polypeptide E (POLR1E), α1‐antitrypsin (SERPINA1) and topoisomerase 2A (TOP2A) were probed with antibodies validated by the Human Protein Atlas. Results Increased expressions of APOE, FGB and POLR1E were correlated with increased tumour stage (P < 0.001). Expression of SERPINA1 in Ta and T1 tumours was found to increase the risk of tumour progression (hazard ratio 2.57, 95% confidence interval 1.13–5.87; P = 0.025) Conclusions All proteins previously detected in urine from patients with bladder cancer were also expressed in bladder cancer tissue. The expression of APOE, FGB and POLR1E increased with stage and they are potential diagnostic markers. SERPINA1 was identified as a prognostic marker candidate.

Einleitung: Die Tuberkulose ist eine der häufigsten Infektionskrankheiten weltweit. Jährlich wird von 8 bis 10 Millionen Fällen berichtet. Obwohl der Erreger Mycobacterium tuberculosis seit über 100 Jahren bekannt ist, gestaltet sich die Diagnosestellung einer akuten Erkrankung schwierig. Insbesondere dann, wenn sich keine säurefesten Stäbchen im Sputum nachweisen lassen, wird die Unterscheidung zwischen aktiver und latenter Tuberkulose problematisch.

OBJECTIVE To determine interobserver variation in histopathologic diagnosis of carcinoma in situ (CIS) and dysplasia (collectively intraurothelial neoplasia [IUN]) of the bladder and identify histomorphologic features important for diagnosis. STUDY DESIGN A total of 272 consecutive bladder tissue samples were re-evaluated blindly by two general pathologists and one uropathologist for IUN. Discrepancies were resolved jointly. Fifteen histopathologic attributes were evaluated for prediction of diagnosis. Followup revealed recurrence and progression rates for each diagnostic category. RESULTS Thirty-six percent of specimens contained no evaluable flat mucosa; 51% percent of specimens from papillary urothelial neoplasia (PUN) cases showed CIS. General pathologists detected 56-69% of CIS and 8-42% of dysplasia. Histopathologic features most predictive for CIS were nuclear size, variation in nuclear shape, loss of maturation, loss of polarity, and architectural disorder. None of these individually or in combination exceeded general pathologists' diagnostic accuracy. IUN was not predictive of recurrence or progress. CONCLUSION Using material mostly consisting of flat mucosa gratuitously provided in PUN resection specimens, IUN carries no prognostic value. General histopathologists detect IUN poorly to moderately, and the five most discriminatory histomorphologic features are insufficient for diagnosis. Interobserver agreement for dysplasia is dismal. Absent flat mucosa in PUN resections predicts recurrence.

OBJECTIVE To determine whether a reduced set of the histopathologic features used in internationally accepted classifications is capable of accurately grading papillary urothelial neoplasms (PUN). STUDY DESIGN All surgical specimens from urinary bladders received during a 2-year period were reexamined by an expert uropathologist for assessing the accuracy of original nonexpert PUN grading and staging. Thirteen histopathologic features entailing 32 attributes were evaluated with regard to prediction of expert grade. Patients were followed for 35-59 months (mean, 47). RESULTS A total of 88 PUN specimens could be analyzed completely including follow-up specimens. Agreement between original and expert grade was 71% for low-grade and 87% for high-grade PUN, with overall kappa = 0.53. The histomorphologic features most predictive of expert grade were architectural disorder, variability of nuclear enlargement, and absence of umbrella cells. Neither individual histomorphologic attributes nor their combinations were as predictive of expert pathologist grade as original diagnoses. CONCLUSION Improvements in PUN grading and prognostication are not likely to be accomplished by only reducing the number of histomorphologic features currently recommended by the World Health Organization and International Society of Urological Pathology.

BACKGROUND:The immune modulating molecules cyclooxygenase-2 (COX-2), transforming growth factor-beta (TGF-beta) and interleukin-10 (IL-10) have regulatory roles in cancer progression. There are conflicting data regarding the roles of these molecules in prostate cancer. To elucidate the prognostic impact of these proteins and provide information on prognosis and treatment, we compared the expression of COX-2, TGF-beta, and IL-10 in prostate cancer specimens with or without metastases. Ki67 was included as a measure of growth fraction of tumor cells. METHODS:Digital video analysis images from tumor cell areas and tumor stromal areas were analyzed on formalin fixed, paraffin-embedded and immunohistochemical stained cancer specimens from 59 patients: 32 patients with metastases and 27 patients without clinical, biochemical, or radiological evidence of metastases within 10 years after diagnosis. The expression of COX-2 was scored as negative, weak, moderate, or strong. The expressions of TGF-beta and IL-10 were assessed as proportions of moderately or strongly stained cells. Ki67 was detected as strong nuclear staining in proliferating cells. RESULTS:In primary cancers in the metastatic group, COX-2, TGF-beta and Ki67 were stronger expressed in epithelial tumor cell and tumor stromal areas compared with non-metastatic cancers (for all markers, p<0.0001). High intensity of COX-2 staining in tumor areas was strongly associated with death from prostate cancer in univariate analyses (hazard ratio [HR] 95% CI, 4.0 (1.1-14.5)). In multivariate analyses, the risk estimate was strengthened but did not reach significance. No associations to death were found for the other markers. CONCLUSION:High expression of COX-2, TGF-beta and Ki67 were in metastatic primary prostate carcinoma compared to non-metastatic cancers. High expression of COX-2 was associated to death from prostate carcinoma.

Background: Bacillus Calmette-Guerin (BCG) is the intravesical treatment of choice for carcinoma in situ (CIS).Objective: Our aim was to assess if sequential mitomycin C (MMC) plus BCG after transurethral resection (TUR) is worthy of further study in non-muscle-invasive bladder cancer patients with CIS.Design, setting, and participants: In a noncomparative phase 2 study, 96 patients with primary/secondary/concurrent CIS of the urinary bladder were randomized to sequential MMC plus BCG or to BCG alone after TUR.Intervention: Patients received six weekly instillations of MMC followed by six weekly instillations of BCG or six weekly instillations of BCG, 3 wk rest, and three further weekly instillations of BCG. Complete responders received three weekly maintenance instillations at 6, 12, 18, 24, 30, and 36 mo in accordance with the initial randomization.Measurements: End points were complete response (CR) rate at the first control cystoscopy 16-18 wk after start of treatment, disease-free interval, overall survival, and side effects.Results and limitations: Ninety-six patients were randomized, 48 to each treatment group. Ten patients were ineligible, and three did not start treatment. In all random-ized patients, CR rates on MMC plus BCG and BCG alone were 70.8% and 66.7%, respectively. In 83 eligible patients who started treatment, CR rates were 75.6% and 73.8%, respectively. Based on a median follow-up of 4.7 yr, 25 patients (52.1%) on MMC plus BCG and 22 patients (45.8%) on BCG alone were disease free. Twelve patients stopped treatment due to toxicity: three during induction (two MMC plus BCG, one BCG) and nine during maintenance (three MMC plus BCG, six BCG).Conclusions: In the treatment of patients with CIS, sequential chemoimmunotherapy with MMC plus BCG had acceptable toxicity. CR and disease-free rates were similar to those on BCG alone and to previous publications on sequential chemoimmunotherapy.

You have accessJournal of UrologyBladder Cancer: Superficial II1 Apr 20101474 SEQUENTIAL CHEMO-IMMUNOTHERAPY WITH MITOMYCIN C (MMC) AND BACILLUS CALMETTE-GUERIN (BCG) VERSUS BCG ALONE IN PATIENTS WITH CARCINOMA IN SITU (CIS) OF THE URINARY BLADDER. RESULTS OF EORTC GU GROUP RANDOMIZED PHASE II STUDY 30993 Ziya Kirkali, Willem Oosterlinck, Richard Sylvester, Fernando Calais Da Silva, Christer Busch, Ferran Algaba, Sandra Collette, and Aldo Bono Ziya KirkaliZiya Kirkali Izmir, Turkey More articles by this author , Willem OosterlinckWillem Oosterlinck Ghent, Belgium More articles by this author , Richard SylvesterRichard Sylvester Brussels, Belgium More articles by this author , Fernando Calais Da SilvaFernando Calais Da Silva Lisbon, Portugal More articles by this author , Christer BuschChrister Busch Uppsala, Sweden More articles by this author , Ferran AlgabaFerran Algaba Barcelona, Spain More articles by this author , Sandra ColletteSandra Collette Brussels, Belgium More articles by this author , and Aldo BonoAldo Bono Varese, Italy More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1189AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES BCG is the intravesical treatment of choice according to American and European guidelines for the treatment of non muscle invasive bladder cancer (NMIBC) patients with CIS. Complete response (CR) rates of 65 to 70% can be expected on BCG. MMC is widely used in the chemotherapeutic treatment of NMIBC, especially in patients with only papillary disease. As a possible synergistic effect between MMC and BCG may be expected, this study was undertaken to assess the activity of sequential MMC-BCG versus BCG alone in the post transurethral resection (TUR) treatment of NMIBC patients with CIS. METHODS NMIBC patients with biopsy proven primary, secondary or concurrent CIS were randomized within 28 days after TUR of all visible tumor to either weekly MMC (6 instillations) followed by weekly BCG (6 instillations) or weekly BCG (6 instillations, 3 weeks rest, 3 instillations). Complete responders also received 3 weekly maintenance instillations at 6, 12, 18, 24, 30 and 36 months in accordance with the initial randomisation. Patients with muscle invasive tumors or tumors in the upper urinary tract were ineligible. The primary endpoint was the CR rate at the first control cystoscopy 16 to 18 weeks after start of treatment. RESULTS From June 2001 to February 2005, 96 patients were randomized, 48 to each treatment. 10 of 96 patients were ineligible: CIS was not confirmed by central pathology review in 8 patients. 3 patients did not start treatment. In the intent to treat population of all randomized patients, the CR rates on MMC + BCG and BCG alone were 70.8% and 66.7%, respectively. In the 83 eligible patients who started treatment, the CR rates were 75.6% and 73.8%, respectively. Based on a median follow up of 4.7 years, 23 patients (47.9%) on MMC + BCG and 26 patients (54.2%) on BCG alone have failed treatment, including 9 and 10 of the CRs, respectively. Seven patients (7.3%) progressed to muscle invasive disease, 6 (6.3%) developed distant metastases, 13 (13.5%) had a cystectomy and 18 (18.8%) died, 6 (6.3%) due to bladder cancer. Treatment was relatively well tolerated, 12 patients stopped treatment due to toxicity: 3 during induction (2 MMC + BCG, 1 BCG) and 9 during maintenance (3 MMC + BCG, 6 BCG). CONCLUSIONS Sequential chemo-immunotherapy with MMC + BCG is feasible, but there was no suggestion of a possible synergistic effect. Both treatment groups had acceptable toxicity and yielded similar complete response rates in the treatment of patients with CIS of the urinary bladder. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e568 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ziya Kirkali Izmir, Turkey More articles by this author Willem Oosterlinck Ghent, Belgium More articles by this author Richard Sylvester Brussels, Belgium More articles by this author Fernando Calais Da Silva Lisbon, Portugal More articles by this author Christer Busch Uppsala, Sweden More articles by this author Ferran Algaba Barcelona, Spain More articles by this author Sandra Collette Brussels, Belgium More articles by this author Aldo Bono Varese, Italy More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Background: Associations between metabolic syndrome (MetS) components and prostate cancer development have not been studied comprehensively; results have been divergent. Using the National Cholesterol Education Program Adult Treatment panel III (NCEP) and International Diabetes Federation (IDF) definitions of the MetS, we investigated such associations taking competing risks of death into consideration. Methods: In the prospective Uppsala Longitudinal Study of Adult Men of 2,322 Caucasian men with 34 years of follow-up baseline, MetS measurements at age 50 years were used. Cumulative incidence of prostate cancer and death with/without the MetS were calculated. Competing risk of dying was taken into account by calculating the conditional probability of prostate cancer with/without the MetS. Results: Two hundred and thirty-seven prostate cancers were identified. Prostate cancer probability by age 80 years with baseline MetS compared with without MetS was nonsignificantly higher [5.2 percent units (confidence interval (CI), −0.8% to 11.3%; NCEP); 2.7 percent units (CI, −2.7% to 8.0%; IDF)]; cumulative incidence proportions of death was significantly higher [19.3 percent units (CI, 13.4-25.3%; NCEP); 15.3 percent units (CI, 9.5-21.1%; IDF)]; and conditional probability of prostate cancer considering death from other causes was significantly higher [7.3 percent-units (CI, 0.2-14.5%); odds ratio of 1.64 (CI, 1.03-2.23; NCEP)] and nonsignificantly higher [5.0 percent-units (CI, −1.6% to 11.6%); odds ratio of 1.43 (CI, 0.89-1.90; IDF]. Conclusions: The MetS by the NCEP definition is associated with prostate cancer, taking the competing risk of early death from other causes into account. Impact: The results further highlight the public health effect of the increasing prevalence of MetS and the importance of considering competing risks when studying risk factors for cancer. Cancer Epidemiol Biomarkers Prev; 19(8); 2088–96. ©2010 AACR.

You have accessJournal of Urology1 Apr 2009PREDICTION OF DISEASE PROGRESSION INCLUDING DURABLE RESPONSE TO HORMONAL THERAPY AT DIAGNOSIS, USING THE PROSTATE NEEDLE BIOPSY AND PRETREATMENT CLINICAL VARIABLES Michael J. Donovan, Faisal Khan, Gerardo Fernandez, Ricardo Mesa-Tejada, Marina Sapir, Valentina Bayer-Zubek, Stephen Fogarsi, Yevgen Vengrenyuk, Mikhail Teverovskiy, R. Jeffrey Karnes, Thomas Gaffey, Christer Busch, Stephen J Freedland, Peter Albertsen, Jose Costa, and Carlos Cordon-Cardo Michael J. DonovanMichael J. Donovan More articles by this author , Faisal KhanFaisal Khan More articles by this author , Gerardo FernandezGerardo Fernandez More articles by this author , Ricardo Mesa-TejadaRicardo Mesa-Tejada More articles by this author , Marina SapirMarina Sapir More articles by this author , Valentina Bayer-ZubekValentina Bayer-Zubek More articles by this author , Stephen FogarsiStephen Fogarsi More articles by this author , Yevgen VengrenyukYevgen Vengrenyuk More articles by this author , Mikhail TeverovskiyMikhail Teverovskiy More articles by this author , R. Jeffrey KarnesR. Jeffrey Karnes More articles by this author , Thomas GaffeyThomas Gaffey More articles by this author , Christer BuschChrister Busch More articles by this author , Stephen J FreedlandStephen J Freedland More articles by this author , Peter AlbertsenPeter Albertsen More articles by this author , Jose CostaJose Costa More articles by this author , and Carlos Cordon-CardoCarlos Cordon-Cardo More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(09)62147-9AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "PREDICTION OF DISEASE PROGRESSION INCLUDING DURABLE RESPONSE TO HORMONAL THERAPY AT DIAGNOSIS, USING THE PROSTATE NEEDLE BIOPSY AND PRETREATMENT CLINICAL VARIABLES." The Journal of Urology, 181(4S), p. 771 © 2009 by American Urological AssociationFiguresReferencesRelatedDetails Volume 181Issue 4SApril 2009Page: 771 Advertisement Copyright & Permissions© 2009 by American Urological AssociationMetricsAuthor Information Michael J. Donovan More articles by this author Faisal Khan More articles by this author Gerardo Fernandez More articles by this author Ricardo Mesa-Tejada More articles by this author Marina Sapir More articles by this author Valentina Bayer-Zubek More articles by this author Stephen Fogarsi More articles by this author Yevgen Vengrenyuk More articles by this author Mikhail Teverovskiy More articles by this author R. Jeffrey Karnes More articles by this author Thomas Gaffey More articles by this author Christer Busch More articles by this author Stephen J Freedland More articles by this author Peter Albertsen More articles by this author Jose Costa More articles by this author Carlos Cordon-Cardo More articles by this author Expand All Advertisement PDF downloadLoading ...