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  • Evaluation of ERG and PTEN protein expression in cribriform architecture prostate carcinomas.

    ERG and PTEN have been suggested as potential prognostic markers in prostatic adenocarcinoma. We assessed the relationship between ERG and PTEN protein expression in cribriform architecture prostatic carcinomas and adjacent acinar non-cribriform carcinoma and determined the interobserver variability in assessment of these markers.

    Published December 9, 2016

  • Improving the Rotterdam European Randomized Study of Screening for Prostate Cancer Risk Calculator for Initial Prostate Biopsy by Incorporating the 2014 ISUP Gleason Grading and Cribriform growth: Beyond the Abstract

    Population-wide screening with PSA reduces the mortality of prostate cancer (PCa) but with the downside of overdiagnosis and overtreatment [1, 2]. Men considering a PSA test would like to be informed about their benefits, possibilities and extent of overdiagnosis and overtreatment [3]. However, candidates for testing are only willing to accept a small increase of their chance of dying from PCa when considering reducing their chance on overdiagnosis and potential overtreatment [4]. Multivariable risk-based stratification for screening, as put forward by the European Randomized Study of Screening for Prostate Cancer section Rotterdam Risk Calculator (ERSPC-RC), has the potential for informed decision making [5]. But, as stated by Pruthi et al., risk assessment tools do have some shortcomings, which reinforces the need for continuous updating and adaptations of the devices [6]. Within the current study we aimed to improve our ERSPC-RC by incorporating contemporary pathologic biopsy classifications that better reflect disease burden [7].

    Especially the course of disease of Gleason score 7 prostate cancer is heterogeneous. Kweldam et al.  found that the presence of a cribriform pattern (CR) and intraductal carcinoma (IDC) in Gleason 7 radical prostatectomy specimen are major predictive factors for the occurrence of distant metastases and also are related to prostate cancer-specific death [8]. This observation was confirmed when looking at this growth patterns in biopsy specimen. There it was shown that men with Gleason 7 on biopsy without the presence of CR and IDC had similar 15-year biochemical recurrence-free survival rates as compared with low-risk prostate cancer patients (Gleason 6) [9]. More accurate disease classification based on biopsy specimen is indispensable for treatment decision making. 

    We therefore decided to update the ERSPC-RC with these new insights. While improvement in risk prediction is mostly sought by adding new potentially relevant predictors to the model, we attempted to refine our predictions by including the in 2014 updated International Society of Urological Pathology Gleason Grading (ISUP) system and info on CR/IDC presence into the original calculator ERSPC-RC3. By doing so, we aim to better distinguish (lethal) clinically relevant PCa from indolent PCa (Figure 1). 

    Screen Shot 2017 07 25 at 1.28.25 PM
    Figure 1.     The original risk calculator in comparison with the improved ERSPC-Cribriform-RC including cribriform pathological findings. The improved RC distinguishes better clinically relevant PCa and reduces the number of missed diagnosis of clinical relevant. PSA: Prostate Specific Antigen, DRE: Digital Rectal Exam, PV: Prostate Volume measured by DRE, ISUP: International Society of Urological Pathology. 

    The ERSPC-Cribriform-RC is a practical and easy-to-use risk calculator (Figure 2). The urologist only has to know the patient’s age, PSA result and findings of the digital rectal examination (DRE). DRE provides information whenever a node is present and gives an estimate of prostate volume, which is sufficient to be of aid in better predicting biopsy outcome. 

    Screen Shot 2017 07 25 at 1.28.54 PM
    Figure 2. Prostate cancer risk calculators can be found at www.prostatecancer-riskcalculator.com or as an app for your smartphone at the Appstore “Prostate cancer risk calculators”. There you can fill in the patient’s information. The risk calculator will provide for the probability of having clinical significant PCa and advice about biopsy.

    With the use of the ERSPC-Cribriform-RC, the urologist can substantially reduce the number of patients undergoing biopsy and at the same time minimize overdiagnosis. The current study shows that the use of the improved ERSPC-Cribriform-RC diminishes overdiagnosis with 34% while the percentage of missed diagnosis of clinically relevant PCa is 2%, which is a considerable improvement as compared to the original ERSPC-RC. Since this RC requires relatively easy retrieving information, general practitioners should also be able to use this tool and as such reduce the number of referrals. 

    To answer the patient’s question if he has a life-threatening PCa or not, just a simple PSA test is not enough. Combining relevant clinical characteristics and new pathological insights increases predictive ability. Most likely new developments like magnetic resonance imaging techniques, proteomics and/or genomics will provide more relevant pre-biopsy information that needs to be incorporated in future prediction tools. 

    Written by: Jan FM Verbeek, MD, Department of Urology, Erasmus Medical Center, Rotterdam, The Netherlands 

    Read the Abstract

    Reference

    [1] Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. The Lancet. 2014;384:2027-35.
    [2] Loeb S, Bjurlin MA, Nicholson J, et al. Overdiagnosis and overtreatment of prostate cancer. European urology. 2014;65:1046-55.
    [3] Moynihan R, Nickel B, Hersch J, et al. Public opinions about overdiagnosis: A national community survey. PLoS One. 2015;10:e0125165.
    [4] Howard K, Salkeld GP, Patel MI, Mann GJ, Pignone MP. Men's preferences and trade-offs for prostate cancer screening: a discrete choice experiment. Health Expect. 2015;18:3123-35.
    [5] Roobol MJ, Verbeek JF, van der Kwast T, Kümmerlin IP, Kweldam CF, van Leenders GJ. Improving the ERSPC risk calculator for initial prostate biopsy incorporating the 2014 International Society of Urological Pathology Gleason grading and cribriform growth. European urology. 2017.
    [6] Pruthi DK, Ankerst DP, Liss MA. Novel definitions of low-risk and high-risk prostate cancer: Implications for the European Randomized Study of Screening for Prostate Cancer Risk Assessment Tool. European urology. 2017.
    [7] Kweldam CF, Kümmerlin IP, Nieboer D, et al. Prostate cancer outcomes of men with biopsy Gleason score 6 and 7 without cribriform or intraductal carcinoma. European ournal of cancer. 2016;66:26-33
    [8] Kweldam CF, Wildhagen MF, Steyerberg EW, Bangma CH, van der Kwast TH, van Leenders GJ. Cribriform growth is highly predictive for postoperative metastasis and disease-specific death in Gleason score 7 prostate cancer. Modern pathology. 2015;28:457-64.
    [9] Kweldam CF, Kümmerlin IP, Nieboer D, et al. Disease-specific survival of patients with invasive cribriform and intraductal prostate cancer at diagnostic biopsy. Modern pathology. 2016;29:630-6.
    Published July 25, 2017
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