Their retrospective study was of 100 patients with prostate cancer, including 53 African American men, evaluated for the frequency of MSI and correlated with clinical response data to pembrolizumab treatment. Among the cohort were subjects with locally-advanced, biochemically recurrent, or metastatic disease at the Ben Taub Hospital (BTH) in Houston. The authors observed MSI-high in 4% (4/100 subjects) and 3% (662/2090) within a de-identified nationwide cohort of metastatic PC from Tempus. The African American population at BTH and in the large Tempus cohort displayed similar frequency of MSI (3.7%, 2/53; 3.6%, 8/225, respectively). In keeping with other reports evaluating the reliably of genomic assessments from the circulating (blood) compartment, concordance was 100% between the two assays among MSI-high cases.
Beyond demonstrating similar frequencies of MSI-high between African American and non-African American patients with prostate cancer, the authors highlight the potential clinical value of a reliable method for determining high microsatellite instability. Of the four African American patients with MSI-high status, two received immune checkpoint inhibition with an anti-PD1 agent, pembrolizumab, and each had a robust response, including prostate-specific antigen (PSA) responses below the limits of detection, complete radiographic resolution of lymphadenopathy, and an absence of progression of visceral disease (via PCWG3 criteria). Additionally, longitudinal assessment of ctDNA demonstrated the absence of evidence of prostate cancer (Figure).
Notably, the second case study presented by Dr. Tamer Khasab was in a patient with platinum-resistant, poorly-differentiated carcinoma of prostatic origin, highlighting response in MSI-high patients with aggressive variant prostate cancer – a space with a clear unmet clinical need.
While it remains incompletely understood why African American men experience higher rates and worse outcomes than non-African American men with prostate cancer, Khashab et al. demonstrate similar rates of MSI-high in prostate cancer, both from a cohort from their “safety net” hospital in Houston and more broadly from de-identified data from Tempus. These data do not support MSI-high explaining higher immune activity in African American prostate cancers. However, they do support the use of MSI-high in therapy decision-making in African American men with metastatic prostate cancer.
Presented by: Tamer Khashab, MD, Fellow, Department of Medicine, Division of Hematology and Oncology, Harris Health/Ben Taub Hospital and Baylor College of Medicine, Houston, Texas
Written by: Jones Nauseef, MD, Ph.D., Fellow, Division of Hematology and Oncology, Weill Cornell Medicine/New York Presbyterian Hospital, New York, New York, Twitter: @DrJonesNauseef during the 2021 ASCO Genitourinary Cancers Symposium (ASCO GU), February 11th to 13th, 2021
1. Sartor, Oliver, Andrew J. Armstrong, Chiledum Ahaghotu, David G. McLeod, Matthew R. Cooperberg, David F. Penson, Philip W. Kantoff, et al. "Survival of African-American and Caucasian men after sipuleucel-T immunotherapy: outcomes from the PROCEED registry." Prostate cancer and prostatic diseases 23, no. 3 (2020): 517-526.