The clinical course of prostate cancer is highly variable. Current prognostic variables, stage, and Gleason score have limitations in assessing treatment regimens for individual patients, especially in the intermediate-risk group of Gleason score 7. ERG:TMPRSS2 fusion and loss of PTEN are some of the most common genetic alterations in prostate cancer. Immunohistochemistry of PTEN and ERG has generated interest as a promising method for more precise outcome prediction but requires further validation in population-based cohorts. We studied the predictive value of ERG and PTEN expression by immunohistochemistry in two large radical prostatectomy cohorts comprising 815 patients with extensive follow-up information. Clinical end points were initiation of secondary therapy, overall survival, and disease-specific survival. Predictions of clinical outcomes were also assessed according to androgen receptor (AR) activity. PTEN loss, especially in ERG-negative cancers, predicted initiation of secondary treatments and shortened disease-specific survival time, as well as stratifying Gleason score 7 patients into different prognostic groups with regard to secondary treatments and disease-specific survival. High AR immunoreactivity in ERG-negative cancers with PTEN loss predicted worse disease-specific survival. We also observed that in Gleason score 7 ERG-negative cases with PTEN loss and high AR expression have significantly shorter disease-specific survival time compared with ERG-positive cases. Our conclusion is that loss of PTEN is a strong determining factor for shorter disease-specific survival time and initiation of secondary therapies after radical prostatectomy. The predictive value of PTEN immunoreactivity is further accentuated in ERG-negative cancers with high AR expression. Negative PTEN expression, accompanied by ERG status, can be used to stratify patients with Gleason score 7 into different survival groups. Assessment of PTEN and ERG status could provide an additional tool for initial diagnostics when determining the prognosis and subsequent follow-up regimen for patients treated by radical prostatectomy.
Localized low-grade prostate cancer is challenging to visualize in DW-MRI, and this imaging technique provides no additional prognostic benefit compared to PSA and repeat biopsies.
Histological Gleason grading of prostate cancer has been through modifications and conjoined into a Grade Grouping system recently. The aim of this study was to determine whether the new Grade Grouping system predicts disease-specific and all-cause mortality after radical prostatectomy. We constructed a clinical database consisting of all consecutively radical prostatectomy-treated men between 1983 and 1998 and between 2000 and 2005 at the Helsinki University Hospital and at the Turku University Hospital, respectively. Patients' all-cause and prostate cancer-specific mortality information was updated in November 2015 from the Finnish Cancer Registry. Secondary therapy information was also available from the patients' records at Helsinki. Univariate and multivariate statistical analyses were performed to assess predictive significance of the Grade Grouping system. Grade Grouping associated independently with increased risk of prostate cancer-specific mortality within 15 years of follow-up in a multivariable model containing age at operation, diagnostic prostate-specific antigen, pathological stage and lymph node status at operation. Additionally, the all-cause mortality-free survival time and time to secondary therapies were different between the Grade Groups, emphasized in the subanalysis of Grade Groups 1-2 versus Grade Groups 3-5. We can conclude that the new Grade Grouping system is feasible in predicting prostate cancer-specific survival after radical surgical treatment. Grade Grouping offers a simpler way to interpret the predicted course of the disease to individual patients and thus may help in justifying more conservative follow-up approaches, especially in the lower Grade Group patients.
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