EAU PCa 17: Diagnosis: What to do and not to do?

Vienna, Austria (UroToday.com) Dr. Henk Van Der Poel from The Netherlands provided an in depth discussion about what to and what not to do after a diagnosis of prostate cancer at this morning’s General Update on Diagnosis and Staging at the EAU Update on Prostate Cancer in Vienna, Austria. Dr. Van Der Poel started by highlighting the known risk factors of prostate cancer, namely age, family history (2.1-2.5x), race (2.3x higher for black men), and inherited genetic traits (2-6x) such as BRCA-2, HOXB13 mutations and Lynch syndrome.

Dr. Van Der Poel notes that men at elevated risk of prostate cancer include (i) > 50 years of age or age >45 years with a family history of prostate cancer, (ii) PSA >1 ng/mL at 40 years of age, and (iii) PSA >2 ng/mL at 60 years of age. Men requesting an early diagnosis should be given a PSA test, as well as a digital rectal examination. Certainly, family history can play a important role in risk of diagnosis and death from prostate cancer. The hazard ratio of death from prostate cancer among men with relatives who died of prostate cancer is 2.08 (father), 2.30 (brother), and 6.86 (father and brother) [1]. The EAU guidelines [2] further delineate prostate cancer risk, recommending (prior to biopsy to decrease risk/harm) the use of a prostate cancer risk calculator, and/or an additional serum or urine based test (ie. PHI, PCA3, 4Kscore, etc), and/or imaging. As Dr. Van Der Poel notes, large multicenter studies (MRI-FIRST, PRECISION) are currently ongoing to define the added value of a pre-biopsy MRI in biopsy-naïve patients, although at this time it is too early to make recommendations on the routine use of pre-biopsy mpMRI in these patients.

Several studies have delineated the approximate risk of significant prostate cancer based on mpMRI PIRADS score: (i) 1-2: 22% risk of significant prostate cancer, (ii) 3: 31% risk of significant prostate cancer, (iii) 4: 48% risk of significant prostate cancer, (iv) 5: 78% risk of significant prostate cancer. The much anticipated PROMIS clinical trial provided further information regarding mpMRI prior to a prostate biopsy [3]. From this study, the NPV of mpMRI was noted to be 89% compared to 74% for TRUS biopsy; the sensitivity for clinically significant prostate cancer (GS ≥ 4+3 or 6mm of cancer) was 93% for mpMRI and 48% for TRUS biopsy. Dr. Van Der Poel makes several other observations from the PROMIS study: (i) “significant disease” remains open for discussion, (ii) there were no MRI targeted biopsies in PROMIS, (iii) only 27% of men did not have PIRADs 3-5 lesions, and (iv) there were significant differences in MRI scanners and radiologist’s experience. A recent systematic review of the NPV for mpMRI detection of prostate cancer noted a median NPV of 82.4% (IQR 68.7-91.9%) for overall cancer detection, and 88.1% (IQR 82.2-94.7%) for clinically significant prostate cancer [4]. In Dr. Van Der Poel’s opinion, the impact of cancer prevalence on NPV makes it necessary to risk-stratify patients referred for pre-biopsy mpMRI before mpMRI’s NPV can be fully assessed. Furthermore, based on this review, he notes that an unsatisfactory 12% of significant prostate cancer were missed by MRI.

Following a negative prostate biopsy, there are several tests that may be implemented prior to repeating a prostate biopsy, namely Progensa, PHI, 4Kscore test, and ConfirmMDX. Dr. Van Der Poel made several important remarks regarding repeat biopsy: (i) suspicious DRE results in a 5-30% cancer risk, (ii) atypical small acinar proliferation results in a 40% cancer risk, (iii) extensive (>3 biopsies) of high-grade PIN results in a 30% cancer risk, (iv) a few atypical glands immediately adjacent to HGPIN results in a ~50% cancer risk, and (v) intraductal carcinoma as a solitary finding results in >90% risk of associated high-grade prostate cancer. Furthermore, the EAU guidelines [2] notes that for repeat biopsy it recommends a mpMRI and subsequent targeting and systematic biopsies if MRI lesions are present.

Finally, Dr. Van Der Poel discussed the implications and indications for 68Ga-PSMA-PET scanning in prostate cancer staging. A recent systematic review of 16 studies and 1,309 patients demonstrated a sensitivity/specificity per patient of 86%/86% and sensitivity/specificity per lesion of 80%/97% [5]. Furthermore, PSMA-PET’s ability to detect lesions based on PSA level included: 42% at <0.2 ng/mL, 58% at 0.2-1 ng/mL, 76% at 1-2 ng/mL, 95% at >2 ng/mL. According to Dr. Van Der Poel, because of choline PET’s low sensitivity (<20%) for detecting nodal metastasis, it has no role for up front imaging, albeit in this space PSMA-PET remains investigational.

Dr. Van Der Poel concludes with several take-home messages, notably (i) don’t underestimate lethal prostate cancer in the family history, (ii) perform an mpMRI prior to repeat biopsy, (iii) primary mpMRI prior to prostate biopsy is not currently standard of care, and (iv) although interesting and with exciting initial results, PSMA-PET is still investigational.

Speaker: Henk Van Der Poel, Netherlands Cancer Institute, Amsterdam, The Netherlands

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the EAU - Update on Prostate Cancer, September 15-16, 2017- Vienna, Austria

References:

1. Brandt A, Bermejo JL, Sundquist J, et al. Age-specific risk of incident prostate cancer and risk of death from prostate cancer defined by the number of affected family members. Eur Urol 2010;58(2):275-280.
2. Mottet N, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening Diagnosis, and Local Treatment with Curative Intent. Eur Urol 2017;71(4):618-629.
3. Ahmed HU, El-Shater Bosaily A, Brown LC, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): A paired validating confirmatory study. Lancet 2017;389(10071):815-822.
4. Moldovan PC, Van Den Broeck T, et al. What is the negative predictive value of multiparametric magnetic resonance imaging in excluding prostate cancer at biopsy? A systematic review and meta-analysis from the European Association of Urology Prostate Cancer Guidelines Panel. Eur Urol 2017;72(2):250-266.
5. Perera M, Papa N, Christidis D, et al. Sensitivity, specificity, and predictors of positive 68Ga-Prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: A systematic review and meta-analysis. Eur Urol 2016;70(6):926-937.