Impact of Metastatic Site on the Genomic, Transcriptomic, and Immune Landscape of Prostate Cancer

By: Julia Fiederlein Cipriano, MS
Posted: Tuesday, March 19, 2024

Umang Swami, MD, MS, of the University of Utah, Salt Lake City, and colleagues conducted a real-world data analysis to shed light on the molecular and immunologic mechanisms underlying metastatic tropism in advanced prostate cancer. Their findings, which were presented during the 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium (Abstract 21), may facilitate future drug development.

The investigators performed DNA and RNA sequencing of samples from primary prostate cancers (n = 3,411), as well as those from unpaired visceral (n = 1,029) and nonvisceral (n = 1,634) metastatic sites. Compared with primary prostate cancer, significantly higher mutation rates were reported for multiple genes in visceral and nonvisceral metastases. The investigators noted that RB1, APC, and androgen receptor alterations were more commonly observed, with those in SPOP occurring less frequently, in liver metastases vs primary prostate cancer, whereas SPOP, KRAS, PIK3CA, APC, and BAP1 mutations were more prevalent in lung metastases (P < .05 for all).

Compared with primary prostate cancer, both visceral and nonvisceral metastases showed higher androgen receptor signaling and interferon-γ scores, whereas visceral metastases exhibited higher Neuroendocrine Prostate Cancer scores and were more frequently reported to be PD-L1–positive and tumor mutational burden–high (defined as > 10 mut/Mb; P < .05 for all).

The prevalence of the AR-V7 variant was found to be significantly higher in visceral (36%) and nonvisceral (33%) metastases vs primary prostate cancer (7%). Based on a Gene Set Enrichment Analysis, the E2F, G2M checkpoint, and MYC target pathways were significantly upregulated in both visceral and nonvisceral metastases. Visceral and nonvisceral metastases appeared to be significantly less enriched in macrophage M2, natural killer cells, and regulatory T cells; visceral metastases also seemed to be less enriched in B cells and neutrophils (P < .05).

Disclosure: For full disclosures of the study authors, visit coi.asco.org.

2024 ASCO Genitourinary Cancers Symposium