  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.
