The utility of next-generation sequencing in metastatic prostate cancer FNA biopsies.

BACKGROUND

Current American Society of Clinical Oncology guidelines state that patients with metastatic prostate cancer (MPC) should undergo germline and somatic DNA sequencing. The authors examined the utility of next-generation sequencing (NGS) on fine-needle aspiration (FNA) biopsies in which NGS was performed on cell block (CB) and/or smears.

METHODS

A retrospective review was performed of cytology cases with diagnosis of MPC either before and/or after NGS on FNA material. Clinical and NGS data were obtained from the medical record. Androgen receptor, NKX3.1, INSM1, synaptophysin, chromogranin, Rb, PTEN, and Ki67 immunohistochemical stains were performed on CB if not originally done.

RESULTS

Slides and NGS data were available for 46 MPC FNA biopsies from 45 patients from 2015 to 2024. Metastatic sites included 20 lymph node, 12 liver, five lung, four soft tissue, two pleura, two bone, and one adrenal gland. Ten patients (22%) had change or potential change in therapy based on NGS results. For one patient with poorly differentiated carcinoma previously thought to be urothelial, a TMPRSS2:ERG fusion confirmed prostatic origin. NGS confirmed lung origin for one patient diagnosed initially as metastatic prostatic adenocarcinoma. For one patient, NGS demonstrated TP53 and RB1 mutations, supporting transformation to high-grade neuroendocrine carcinoma. Change or potential change in therapy was planned for two patients with CDK12 mutations, one with IDH1 mutation, three with BRCA2 mutations, and one with PTEN and TP53 mutations.

CONCLUSIONS

NGS on cytology material showed diagnostic and therapeutic utility in a subset of patients, with 10 of 46 patients (22%) having a change or potential in therapy based on NGS results.