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At 23 years of follow-up in the SPCG-4 trial, mortality among men who underwent radical prostatectomy was 11.7 percentage points lower than that among men whose condition was managed by watchful waiting. Radical prostatectomy was associated with a mean of nearly 3 years of extra life.

The randomized Swedish trial of prostatectomy versus watchful waiting in disease detected mainly clinically (not by PSA screening) continues to show a benefit for early prostatectomy. The number of men younger than 65 needed to treat to prevent one death is now four. The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a randomized trial of radical prostatectomy versus watchful waiting in men with localized prostate cancer diagnosed before the era of prostate-specific antigen (PSA) testing, showed a survival benefit of radical prostatectomy as compared with observation at 15 years of follow-up. 1 By contrast, the Prostate Cancer Intervention versus Observation Trial (PIVOT), initiated in the early era of PSA testing, showed that radical prostatectomy did not significantly reduce prostate cancer–specific or overall mortality after 12 years. 2 PSA screening profoundly changes the clinical domain of study. Among other considerations, the substantial additional lead time . . .

After about 13 years of follow-up, men <65 years of age with prostate cancer diagnosed on the basis of obstructive urinary symptoms (rather than elevated prostate-specific antigen levels) and assigned to radical prostatectomy, as compared with watchful waiting, have improved survival. The randomized Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) showed that radical prostatectomy decreased the risk of metastases, the rate of death from prostate cancer, and the rate of death from any cause. 1 – 3 Although the participants in SPCG-4 were predominantly men whose cancers were detected on the basis of symptoms, rather than by elevated prostate-specific antigen (PSA) levels, prostate-cancer events have also accumulated during an extended follow-up period in a subgroup of men with low-risk disease. Determining whether there is a survival benefit for men with low-risk disease is relevant in light of the risk of overdiagnosis resulting . . .

Men with early prostate cancer were randomly assigned to undergo radical prostatectomy or watchful waiting. Ten-year estimates of the risks of death from prostate cancer, of distant metastasis, and of local progression all favored radical prostatectomy over watchful waiting for men younger than 65 years. Ten-year estimates of the risks of death from prostate cancer, of distant metastasis, and of local progression all favored radical prostatectomy over watchful waiting for men younger than 65 years. Radical prostatectomy is becoming one of the most common major surgical procedures in many Western countries. In the United States alone, an estimated 60,000 men undergo this operation each year. However, to our knowledge, only one randomized trial quantified the benefit of radical prostatectomy. 1 In 2002, we presented the results of a clinical trial in which radical prostatectomy was compared with watchful waiting in the management of early prostate cancer. 1 Our analysis was based on a mean follow-up time of 6.2 years, a relatively short period in relation to the often long natural history of early prostate cancer. 2 We found . . .

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.

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.

In this randomized trial, conducted between 1989 and 2022 to compare radical prostatectomy with watchful waiting, radical prostatectomy led to a 48% lower risk of death from prostate cancer and to 2.2 life-years gained.

Background: The Par complex – comprising partition-defective 6 (Par6), Par3, and atypical protein kinase C (aPKC) – is crucial for cell polarisation, the loss of which contributes to cancer progression. Transforming growth factor β (TGF β )-induced phosphorylation of Par6 on the conserved serine 345 is implicated in epithelial-to-mesenchymal transition (EMT) in breast cancer. Here we investigated the importance of phosphorylated Par6 in prostate cancer. Methods: We generated a p-Par6 345 -specific antibody and verified its specificity in vitro . Endogenous p-Par6 345 was analysed by immunoblotting in normal human prostate RWPE1 and prostate cancer (PC-3U) cells. Subcellular localisation of p-Par6 345 in migrating TGF β -treated PC-3U cells was analysed by confocal imaging. Invasion assays of TGF β -treated PC-3U cells were performed. p-Par6 expression was immunohistochemically analysed in prostate cancer tissues. Results: TGF β induced Par6 phosphorylation on Ser345 and its recruitment to the leading edge of the membrane ruffle in migrating PC-3U cells, where it colocalised with aPKC ζ . The p-Par6–aPKC ζ complex is important for cell migration and invasion, as interference with this complex prevented prostate cancer cell invasion. High levels of activated Par6 correlated with aggressive prostate cancer. Conclusions: Increased p-Par6Ser 345 levels in aggressive prostate cancer tissues and cells suggest that it could be a useful novel biomarker for predicting prostate cancer progression.

Aims: A methodology for quantitative comparison of histological stains based on their classification and clustering performance, which may facilitate the choice of histological stains for automatic pattern and image analysis. Background: Machine learning and image analysis are becoming increasingly important in pathology applications for automatic analysis of histological tissue samples. Pathologists rely on multiple, contrasting stains to analyze tissue samples, but histological stains are developed for visual analysis and are not always ideal for automatic analysis. Materials and Methods: Thirteen different histological stains were used to stain adjacent prostate tissue sections from radical prostatectomies. We evaluate the stains for both supervised and unsupervised classification of stain/tissue combinations. For supervised classification we measure the error rate of nonlinear support vector machines, and for unsupervised classification we use the Rand index and the F-measure to assess the clustering results of a Gaussian mixture model based on expectation–maximization. Finally, we investigate class separability measures based on scatter criteria. Results: A methodology for quantitative evaluation of histological stains in terms of their classification and clustering efficacy that aims at improving segmentation and color decomposition. We demonstrate that for a specific tissue type, certain stains perform consistently better than others according to objective error criteria. Conclusions: The choice of histological stain for automatic analysis must be based on its classification and clustering performance, which are indicators of the performance of automatic segmentation of tissue into morphological components, which in turn may be the basis for diagnosis.

Insulin-like growth factor binding protein 2 (IGFBP2) has been shown to be overexpressed in prostatic intraepithelial neoplasia (PIN) and invasive cancer and the serum level to parallel that of prostate-specific antigen (PSA) in prostate cancer. A combination of cDNA and tissue microarray results recently demonstrated overexpression of IGFBP2 in hormone refractory prostate cancer, indicating that the IGF system may be part of a key growth regulatory pathway in prostate cancer. The present study reexamines the immunohistochemical expression of IGFBP2 and its relationship to grade in tissue from 193 radical prostatectomy specimens from patients with localized prostate adenocarcinoma. We found a significant overexpression of IGFBP2 in all instances of PIN and in more than 90% of cancers regardless of the grade. An intense overexpression was noted in the neuroendocrine cells in normal glands as well as in cancer. The IGFBP2 expression was also analyzed in 18 cases of biopsy diagnosed prostate cancer. In all these cases, the glands interpreted as invasive cancer in hematoxylin-eosin stained sections overexpressed IGFBP2, without a significant correlation to grade. We conclude that overexpression of IGFBP2 is a powerful marker for malignant transformation in the prostate epithelium and suggest that optimized immunohistochemical detection of IGFBP2 expression may be an adjunct tool in the diagnosis of prostate cancer.