Evaluation of the Aggressive-Variant Prostate Cancer Molecular Signature in Clinical Laboratory Improvement Amendments (CLIA) Environments

Authors

Paul V Viscuse
Rebecca S Slack-Tidwell
Miao Zhang
Prih Rohra
Keyi Zhu
F Anthony San Lucas
Eric Konnick
Patrick G Pilie
Bilal Siddiqui
Christopher J Logothetis
Paul Corn
Sumit K Subudhi
Colin C Pritchard
Rama Soundararajan
Ana Aparicio

Publication Date

12-14-2023

Journal

Cancers

Abstract

Aggressive-variant prostate cancers (AVPCs) are a subset of metastatic castrate-resistant prostate cancers (mCRPCs) characterized by defects in ≥ two of three of TP53, RB1, and PTEN (AVPCm), a profile linked to lineage plasticity, androgen indifference, and platinum sensitivity. Men with mCRPC undergoing biopsies for progression were assessed for AVPCm using immunohistochemistry (IHC), next-generation sequencing (NGS) of solid tumor DNA (stDNA), and NGS of circulating tumor DNA (ctDNA) assays in CLIA-certified labs. Biopsy characteristics, turnaround times, inter-reader concordance, and inter-assay concordance were assessed. AVPCm was detected in 13 (27%) patients via IHC, two (6%) based on stDNA, and seven (39%) based on ctDNA. The concordance of the IHC reads between pathologists was variable. IHC had a higher detection rate of AVPCm+ tumors with the shortest turnaround times. stDNA had challenges with copy number loss detection, limiting its detection rate. ctDNA detected the greatest proportion of AVPCm+ tumors but had a low tumor content in two thirds of patients. These data show the operational characteristics of AVPCm detection using various assays, and inform trial design using AVPCm as a criterion for patient selection or stratification.

Keywords

aggressive-variant prostate cancer, immunohistochemistry, molecular biomarker, next-generation sequencing

Comments

Associated Data

PMID: 38136389