Maxwell KN, Cheng HH, Powers J, et al. - Findings demonstrate that gTP53 (germline TP53 pathogenic and likely pathogenic variants) predisposes to aggressive prostate cancer. Considering prostate cancer as part of Li-Fraumeni syndrome (LFS) screening protocols and TP53 in germline prostate cancer susceptibility testing is recommended.

• In this multi-institutional retrospective study, prostate cancer incidence in a cohort of LFS males and gTP53 prevalence in a prostate cancer cohort was assessed to know if gTP53 predisposes to prostate cancer.

• Among 163 adult LFS males, 31 prostate cancer cases were found.

• Of LFS males without prostate cancer (n=117) at the time of genetic testing, six received a diagnosis of prostate cancer over a median of 3.0 yr of follow-up, a 25-fold elevated risk.

• In the prostate cancer cohort, 0.6% had gTP53, a relative risk 9.1-fold higher than that of population controls.

• Experts noted hotspots at the sites of attenuated variants not related to classic LFS.

• Somatic inactivation of the second TP53 allele was found in two-thirds of available gTP53 prostate tumors.

• In gTP53 prostate cancer cases, median age at diagnosis was 56 yr, Gleason ≥8 tumors were present in 44%, and advanced disease at diagnosis in 29%.