Dr. Klotz began with a discussion of germline DNA analysis in men on AS. A study of 1,211 men on AS underwent germline analysis for ATM, BRCA1, and BRCA2. Only 2.1% of men had a germline mutation in one of these genes, but those who did had a significantly higher rate (hazard ratio [HR] = 2.0) for Gleason score being upgraded. The rate was even higher in men with germline BRCA2 alterations (HR = 2.7). He highlighted that germline testing is now widely available and inexpensive and should be considered especially in men with a strong family history of prostate cancer and AS avoided for those with a pathogenic BRCA2 alteration. The Prostate Genetic Score (PGS) incorporates 30 prostate cancer risk loci and has a negative predictive value of 97% for aggressive prostate cancer.
Online risk calculators utilizing easily-obtainable clinical factors can be helpful. The PASS Risk Calculator (https://canarypass.org/calculators/) incorporates age, BMI, PSA, prostate volume, and the number of positive and negative biopsies. A benefit of this tool is that it is dynamic (it can be repeated as patient data changes) and it provides patient-centered results.
Prostate MRI is widely being used in AS of men with low-risk prostate cancer. Dr. Klotz described prostate MRI as “a game-changer, but with important limitations.” He summarized the test performance of MRI in AS, highlighting the NPC for clinically significant cancers ranging from 76-100%.
However, data from multiple studies suggests that there is an incremental improvement in detection of Gleason grade 2 prostate cancer when template prostate biopsy is added to MRI-guided biopsy.
Limitations of prostate MRI in AS include that it’s not real-time, it requires a radiologist with experience in reading MRIs, it may miss small satellite lesions and underestimate lesion volume, it’s expensive, and certain patients are not good candidates due to claustrophobia, hip implants, pacemakers, etc. Further, one study reported that 31% of men who had a stable MRI progressed from Gleason grade 1 to 2 and performing a biopsy only for an increased MRI score would miss Gleason grade 2 disease in 17% of men.
High-resolution micro-ultrasound is an emerging imaging modality for risk-stratification of localized prostate cancer. Prostate Risk Identification using Micro-Ultrasound (PRIMUS) score has been shown to correlate with the risk of high-risk cancer. Additional benefits include the ability to perform real-time biopsy of high-risk lesions. Multi-institutional data suggests that the sensitivity is similar to, if not better than, prostate MRI. While promising, Dr. Klotz cautioned that this is early data and needs further validation before incorporation into clinical practice.
Many biomarkers have been developed for risk-stratification in men undergoing AS. The benefits of biomarkers over MRI are that they are widely available, cheaper, standardized, validated, and not reliant on interpretation. The slide below highlights differences in the biomarker utility, input, cost, and test characteristics.
Dr. Klotz did not discuss any of the biomarkers in detail but focused on a discussion of how to incorporate biomarkers into clinical practice. He cautioned that an adverse genomic profile should prompt reassessment and/or close follow-up, not immediate treatment.
Given the availability of imaging and biomarkers in AS, Dr. Klotz raised the question of whether there is incremental value of combining imagining and biomarkers. The study below of biomarkers and MRI performed in the same patients found overlapping performance of the biomarkers and MRI with no incremental improvement in performance when combined.
He concluded with a summary of the ASCO guidelines on molecular biomarkers in localized prostate cancer:
Commercially available molecular biomarkers (i.e. Oncotype DX, Prolaris, Decipher, ProMark) may be offered in situations in which the assay result… is likely to affect management. Rounding ordering… is not recommended.” Evidence quality intermediate.
Additional molecular biomarkers do not have sufficient data to be clinically actionable or are not commercially available and should not be offered. Evidence quality insufficient.
Presented by: Laurence Klotz, MD, Professor of Surgery at Sunnybrook Health Sciences Centre, Odette Cancer Centre, University of Toronto
Written by: Jacob Berchuck, MD, Medical Oncology Fellow at the Dana-Farber Cancer Institute (Twitter: @jberchuck) at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California