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).
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.
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
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Reference
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