The following is a summary of “Clinical and Genomic Factors Associated with Greater Tumor Mutational Burden in Prostate Cancer,” published in the August 2023 issue of Oncology by Hougen et al.
Tumor mutational burden(TMB) is a biomarker for immune checkpoint inhibitor therapy, but the association of genomic and clinical factor with TMB are not fully understood. Researchers aimed to identify independent predictors of TMB levels using a clinicogenomic database.
The study involved 2,740 prostate cancer specimens from the prostate gland (51.6%), lymph nodes (14.6%), and bone (10.4%). Prolonged androgen deprivation therapy use beyond 24 months weakly correlated with higher TMB (fold-change estimate [FCE] 1.14, 95% CI 1.03-1.26; P= 0.009). Metastases in the bladder (FCE 1.20, 95% CI 1.02-1.42; P= 0.029), liver (FCE 1.26, 95% CI 1.10-1.43; P< 0.001), and other locations (FCE 1.26, 95% CI 1.11-1.43; P< 0.001) were associated with high TMB compared to the prostate gland. High (FCE 8.46, 95% CI 6.42-11.15; P< 0.001) and intermediate (FCE 1.77, 95% CI 1.46-2.14; P < 0.001) microsatellite instability status were linked to increased TMB. Genes such as MLH1, MSH2, MSH6, BRCA2, CDK12, MRE11, and PALB2 were altered and associated with higher TMB.
The study found TMB can potentially predict immunotherapy response in advanced prostate cancer. They assessed factors influencing TMB, discovering that bladder and liver metastases exhibit higher TMB than the primary tumor. Specific genes were linked to elevated TMB. Prior treatment type showed no strong association with TMB, indicating that TMB can guide treatment decisions at any stage.
