2337P - Feasibility of mutation detection in cytological samples from metastasis in patients with metastatic prostate cancer

Background

Mutations in homologous recombination repair (HRR) genes are actionable targets for poly (ADP-ribose) polymerase inhibitors in cancer. Extraction of DNA from archival paraffin-embedded tissue is challenging. In addition, somatic mutations in HRR genes are more frequent in metastases than in primary tumours. Fine needle aspiration (FNA) of metastases is an alternative method to surgical, core needle and circulating tumour DNA-based liquid biopsy and may provide sufficient DNA for genomic analysis.

Methods

We performed a retrospective analysis on our clinical, cytological and next-generation sequencing (NGS) data based on ultrasound-guided FNA samples of metastases in prostate cancer patients. The aims were to evaluate the success rate of FNA for NGS, identify possible obstacles and optimise it.

Results

From Jan. 2021 to Dec. 2022, 27 FNAs of metastases from 21 patients with metastatic castrate-resistant prostate cancer have been undertaken at the Institute of Oncology Ljubljana. The samples were retrieved from lymph node, liver and bone metastases in 59% (16/27), 30% (8/27) and 11% (3/27) patients, respectively. Six out of 27 (22%) samples were unsuccessful according to cytologists. Of undiagnostic samples, 4/6 were obtained from liver and 2/6 from lymph nodes. A high percentage of liver samples, 75% (3/4), contained less than 10% of tumour cells. All samples from bones (3/3) and 56% (9/16) from lymph nodes had more than 50% of tumour cells. Median percentage of tumour cells per sample was 80% (range 5-100). Altogether, 21/27 (78%) samples were adequate for DNA extraction and successful NGS. BRCA 2 pathogenic mutation were detected in two patients (2/21); of these two, one had an adjacent mutation in CDK12 and the other in FANCL together with a high tumor mutational burden. In three patients (3/21) ATM pathogenic mutations were found, one being adjacent to mutation in CHECK1 and the other in BARD1.

Conclusions

Ultrasound-guided FNA of metastases is a feasible method to obtain good quality DNA for NGS in patients with metastatic prostate cancer when searching for potential molecular targets. Close collaboration between dedicated radiologists and cytopathologists could further improve the success rate of this method.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Mencinger: Financial Interests, Personal, Invited Speaker: Astellas, Johnson, Pfizer, AstraZeneca, Roche; Financial Interests, Institutional, Local PI, IMVIGOR 130 trial: Roche. V. Kloboves Prevodnik: Financial Interests, Institutional, Research Funding: BD Biosciences; Other, Institutional, Research Funding: Hologic. B. Seruga: Financial Interests, Personal, Advisory Board, Honorarium: Astellas, Pfizer, Janssen. All other authors have declared no conflicts of interest.