Impact of a Genomic Test on Treatment Decision in a Predominantly African American Population With Favorable-Risk Prostate Cancer: A Randomized Trial

Abstract

Purpose: The Genomic Prostate Score (GPS), performed on biopsy tissue, predicts adverse outcome in prostate cancer (PCa) and has shown promise for improving patient selection for active surveillance (AS). However, its impact on treatment choice in high-risk populations of African Americans is largely unknown and, in general, the effect of the GPS on this difficult decision has not been evaluated in randomized trials.

Methods: Two hundred men with National Comprehensive Cancer Network very low to low-intermediate PCa from three Chicago hospitals (70% Black, 16% college graduates) were randomly assigned at diagnosis to standard counseling with or without a 12-gene GPS assay. The primary end point was treatment choice at a second postdiagnosis visit. The proportion of patients choosing AS was compared, and multivariable modeling was used to estimate the effects of various factors on AS acceptance.

Results: AS acceptance was high overall, although marginally lower in the intervention group (77% v 88%; P = .067), and lower still when men with inadequate specimens were excluded (P = .029). Men with lower health literacy who received a GPS were seven-fold less likely to choose AS compared with controls, whereas no difference was seen in men with higher health literacy (P_interaction = .022). Among men with low-intermediate risk, 69% had GPS values consistent with unfavorable intermediate or high-risk cancer. AS choice was also independently associated with a family history of PCa and having health insurance.

Conclusion: In contrast to other studies, the net effect of the GPS was to move patients away from AS, primarily among men with low health literacy. These findings have implications for our understanding of how prognostic molecular assays that generate probabilities of poor outcome can affect treatment decisions in diverse clinical populations.

Trial registration: ClinicalTrials.gov NCT02668276.

FIG 1.

CONSORT diagram for the ENACT trial. ENACT, Engaging Newly Diagnosed Men About Cancer Treatment Options; GPS, Genomic Prostate Score.

FIG 2.

Relationship of GPS to treatment choice within NCCN risk level at baseline: intervention group only. Horizontal lines represent mean GPS: very low = 26.9, low = 27.2, low intermediate = 32.4. GPS, Genomic Prostate Score; NCCN, National Comprehensive Cancer Network.

FIG 3.

Predicted probabilities of choosing AS from the multivariable model showing all combinations of predictors, and modification of the Oncotype DX effect by health literacy. (A) Control group with negative family history of PCa. (B) Intervention group with negative family history of PCa. (C) Control group with positive family history of PCa. (D) Intervention group with positive family history of PCa. Note reversed positions for red and blue curves comparing control versus intervention groups (A v B and C v D). AS, active surveillance; NCCN, National Comprehensive Cancer Network; PCa, prostate cancer.

FIG 4.

Effects of change in GPS-adjusted NCCN risk level on treatment choice from first postdiagnosis visit to the second in the group assigned to Oncotype DX (includes two patients who were undecided). (A) Table depicting treatment decision relative to pre- and post-test NCCN risk level; (B) magnitude of NCCN risk level change versus model estimated likelihood of adverse pathology at surgery. AS, active surveillance; GPS, Genomic Prostate Score; NCCN, National Comprehensive Cancer Network.