Malignant field signature analysis in biopsy samples at diagnosis identifies lethal disease in patients with localized Gleason 6 and 7 prostate cancer

TL;DR

This study develops a 98-gene expression signature that predicts lethal prostate cancer in biopsy samples at diagnosis, enabling better risk stratification and treatment decisions for patients with Gleason 6 and 7 tumors.

Contribution

The paper introduces a novel 98-gene signature that accurately predicts lethal prostate cancer from biopsy samples at diagnosis, capturing malignant field effects even with minimal cancer cell presence.

Findings

98-gene signature predicts 89-100% of death events within 4-6 years.

Signature performs well with as little as 2% cancer cells in biopsy.

Effective in stratifying patients by age and risk, aiding clinical decision-making.

Abstract

Overtreatment of early-stage low-risk prostate cancer (PC) patients represents a significant problem in disease management and has socio-economic implications. Development of genetic and molecular markers of clinically significant disease in patients diagnosed with low grade localized PC would have a major impact in disease management. A gene expression signature (GES) is reported for lethal PC in biopsy specimens obtained at the time of diagnosis from patients with Gleason 6 and Gleason 7 tumors in a Swedish watchful waiting cohort with up to 30 years follow-up. A 98-genes GES identified 89 and 100 percent of all death events 4 years after diagnosis in G7 and G6 patients, respectively; at 6 years follow-up, 83 and 100 percent of all deaths events were captured. Remarkably, the 98-genes GES appears to perform successfully in patients stratification with as little as 2% of cancer cells in a specimen, strongly indicating that it captures a malignant field effect in prostates harboring cancer cells of different degrees of aggressiveness. In G6 and G7 tumors from PC patients of age 65 or younger, GES identified 86 percent of all death events during the entire follow-up period. In G6 and G7 tumors from PC patients of age 70 or younger, GES identified 90 percent of all death events 6 years after diagnosis. Classification performance of the reported in this study 98-genes GES of lethal PC appeared suitable to meet design and feasibility requirements of a prospective 4 to 6 years clinical trial, which is essential for regulatory approval of diagnostic and prognostic tests in clinical setting. Prospectively validated GES of lethal PC in biopsy specimens of G6 and G7 tumors will help physicians to identify, at the time of diagnosis, patients who should be considered for exclusion from active surveillance programs and who would most likely benefit from immediate curative interventions.