ASCO GU 2023: Genomic Alterations in Patients with Prostate Cancer with Liver Metastases

(UroToday.com) Among patients with metastatic castration resistant prostate cancer (mCRPC), it is often those with visceral metastases to the liver that experience the worst prognosis. The authors previously reported preliminary ctDNA data in a manuscript evaluating serum markers and tumor volume of patients with liver metastasis1. Here, Ms. Crystal Casado (BS) and colleagues at Tulane University sought to describe the DNA alterations detected in circulation from patients with CRPC metastatic to liver.

A retrospective review was conducted of patients from Tulane Cancer Center with CRPC and found 158 who had Guardant360 ctDNA and germline assays for evaluation. Analysis was limited to those identified alterations with a minimum variant allele fraction of 0.1%. Among these, 12 (8%) had known liver metastases, as judged by imaging modalities. Paired clinicopathologic data was collected and analyses were performed using Fisher’s Exact and Wilcoxon Rank Sum tests, where appropriate.

The most commonly observed somatic mutations in the group of patients with liver metastases were in AR (50%, 6/12) and PIK3CA (25%, 3/12), although these alterations were not observed at a frequency different from those patients without detectable liver metastases. In contrast, amplifications in FGFR1 were more commonly detected in patients with liver metastasis (16.7%, 2/12 v 1.37%, 2/146; OR 14.40, p=0.03)(Table 1).

In analysis of germline sequencing, the authors report a higher collective rate of pathogenic (P) and likely pathogenic (LP) alterations in the liver metastasis group. In this collection of 158 patients with mCRPC, 40% of those in the liver metastasis group harbored P/LP alterations whereas only 11% in those patients without liver metastasis (OR 5.38 [1.38-21.25], p=0.023). Rates of VUS (variants of unknown significance) and negative tests were not different. The authors provide a list of the genes with detected P/LP alterations (Table 2)

In conclusion, the authors demonstrated a disproportionate number of germline P/LP mutations in the patients with CPRC metastatic to liver, as opposed to those without liver metastases. In the somatic compartment, the patients with liver metastases were enriched in FGFR1 amplifications, which the authors note have been associated with poor prognosis in non-prostate cancer types. Expansion of this work into larger cohorts may produce a valuable set of ctDNA markers that are associated with development of aggressive forms of mCRPC with proclivity for metastasis to the liver.

Written by: Jones Nauseef, MD, PhD, Assistant Professor of Medicine within the Division of Hematology and Medical Oncology, Sandra and Edward Meyer Cancer Center, and Englander Institute for Precision Medicine Weill Cornell Medicine and Assistant Attending physician at NewYork-Presbyterian Hospital. @DrJonesNauseef on Twitter during the 2023 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 16 – Saturday Feb 18, 20223

1. Ranasinghe L, Cotogno P, Ledet E, Bordlee B, Degeyter K, Nguyen N, Steinberger A, Manogue C, Barata P, Lewis BE, Sartor AO. Relationship between serum markers and volume of liver metastases in castration-resistant prostate cancer. Cancer Treat Res Commun. 2019;20:100151. doi: 10.1016/j.ctarc.2019.100151. Epub 2019 May 14. PMID: 31128516.