(UroToday.com) The 2023 American Society of Clinical Oncology (ASCO) annual meeting held in Chicago, IL between June 2nd and June 6th was host to a prostate, testicular, and penile cancers poster session. Dr. Ciara McNevin presented the results of an analysis of a large, prospective prostate cancer cohort examining the prevalence of mismatch repair deficiency mutations.
There is currently a paucity of data for the prevalence of mismatch repair deficient (dMMR) prostate cancer. Given the emergence of immunotherapy-based treatment regimens in the advanced prostate cancer disease space and the known prognostic and predictive utility of this biomarker for immunotherapy response, it becomes clear that further evaluation of the prevalence of such mutations is needed to help guide clinical practice and future trial design.
This analysis included patients who underwent a radical prostatectomy and were participants in the Health Professionals Follow-up Study and Physicians’ Health Study. This analysis also included prostate cancer tissue microarrays of patients from the Harvard School of Public Health with primary prostate cancer, across the grade spectrum. Immunohistochemistry was performed to assess MMR proteins expression using tumor tissue available from a biorepository of archival radical prostatectomy tissue. For validation purposes, a polymerase chain reaction-based microsatellite instability assay (Idylla MSI Test, Biocartis) was performed on tumor DNA of MMR-deficient cases and a selection of MMR-intact cases.
This study included 1,016 men with prostate cancer. The majority of patients had disease localized to the prostate (pT1-2: 71%), with 18% having pT3a-b disease. Mismatch repair (MMR) tumor scoring could be performed for:
- MLH1: 75% of cases
- MSH2: 90% of cases
- MSH6: 74% of cases
- PSMS2: 72% of cases
Of the 903 evaluable tumors for MSH2 protein loss, four (0.4%) had MSH2 loss, and 3/708 (0.4%) evaluable tumors had concomitant MSH6 loss. None of the tumors had MLH1 or PMS2 loss. The 4 dMMR tumors had Gleason Scores of 7 (3+4), 8 (n=2), and 9-10. One dMMR tumor and 6 DNA samples from 3 MMR stable cases had repeat scores of 0.
In this nationwide study, MMR deficiency was rare in primary, surgically treated patients. There appears to be a discordance between results from this population-based analysis and those reported previously from hospital-based registries, with a significantly lower proportion of dMMR tumors in this study. This low dMMR prevalence and the need for an internal positive control for reliable scoring calls into question whether immunohistochemistry-based screening for MMR deficiency on limited tissue specimens, such as prostate biopsies, is practical in routine clinical practice.
Presented by: Ciara S. McNevin, MBBCh, MSc, Oncology Specialist Registrar, Department of Hematology and Oncology, St. James Hospital, Dublin, Ireland
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.