The following is a summary of “Determinants of widespread metastases and of metastatic tropism in patients with prostate cancer: A genomic analysis of primary and metastatic tumors,” published in the May 2023 issue of the Urologic Oncology by Alshalalfa et al.

Emerging evidence suggests metastasis is more accurately characterized as a disease spectrum than a binary state. A greater comprehension of the genomic characteristics that determine the extent and location of metastasis can aid in risk stratification and surveillance. Here, we identify genomic alterations in primary prostate cancers that predict the disease’s ability to metastasize widely. Through cBioPortal, genomic and clinical data on 1,312 patients with primary prostate cancer were extracted from the MSK-MET cohort. Publicly accessible data on metastatic site counts and overall survival (OS) were the primary outcomes. The MSK-IMPACT targeted sequencing platform was used to profile primary tumor samples. Researchers concentrated on 58 frequently altered genes in prostate cancer. 

Cox proportional hazard analyses determined hazard ratios (HRs) and 95% CIs for overall mortality among patients with various metastatic outcomes. About 939 (71%) of the 1,312 patients in their cohort developed metastases, and 113 (8.6%) of these patients had metastases to five or more different anatomical sites (defining widespread metastases, WSM). The most prevalent site of metastasis was bone (36%), and 80% of patients with liver metastases had four or more additional metastatic sites. Among patients with metastasis, an increasing number of metastatic sites was associated with elevated mortality risk (HR: 1.8, 95%CI: 1.63–1.99, P<0.001). TP53 (40% vs 20%, P< 0.0001), FOXA1-amplification (8% vs 3%, P = 0.02), AR-amplification (4.4% vs 1%, P = 0.01), RB1-deletion (5.3% vs 0.7%, P = 0.001), and BRCA2-deletion (4.4% vs 0.7%, P = 0.01). 

A univariable survival analysis revealed that all these alterations were predictive of OS. Only TP53 mutations, FOXA1, and AR amplifications were independent prognostic factors upon multivariable analysis. FOXA1 (n = 37) and AR (n = 13) amplifications were mutually exclusive, and patients with both had a very poor OS (HR: 3.57, 95% CI:2.26–5.6, P< 0.001). They identified genomic alterations in primary prostate carcinomas (TP53 mutations, FOX1/AR amplification, and RB1/BRCA2 deletion) that predict widespread metastases and poor prognosis.

Source: sciencedirect.com/science/article/abs/pii/S1078143923000790