The addition of the Oncotype DX Genomic Prostate Score (GPS) assay to standard risk counseling did not increase the selection of active surveillance (AS) among a predominantly African-American population of men with favorable-risk prostate cancer, according to findings from the ENACT trial published in the Journal of Clinical Oncology.1
The ENACT trial randomized patients to standard NCCN-based risk counseling alone (control) or in combination with GPS. Across the entire population, AS selection was high; however, the choice of AS was slightly lower among patients receiving GPS, at 77% compared with 88% in the control arm. Further, in the GPS arm, patients with lower health literacy were 7 times less likely to select AS versus the control arm. In contrast, no difference in choice was observed in those patients with higher health literacy.
Adoption of AS was also independently associated with having health insurance and having a family history of prostate cancer; however, there was no independent association between race and selecting AS.
“In this trial, acceptance of AS for management of relatively favorable-risk prostate cancer was remarkably high, regardless of race, both among men who received the GPS prognostic assay and those who received only conventional risk counseling. Thus, we found that the GPS assay did not increase AS acceptance, and there was no apparent difference in its effect associated with race,” the authors wrote.
“The GPS effect was highly dependent on health literacy, with essentially no effect among men with higher literacy, but much lower adoption of AS among men with low health literacy,” the authors added.
The ENACT trial included 200 patients with very low to low-intermediate prostate cancer as defined by the NCCN guidelines. The study was conducted at 3 hospitals in Chicago: the University of Illinois at Chicago, John H. Stroger Jr. Hospital of Cook County, and the Jesse Brown VA Medical Center.
In general, patient characteristics were well balanced between the study arms. Across all patients, the median age was 63.6 years, 70% of patients were African American, 16.5% were European American, 12.5% were Hispanic/Latino, and 1% were Asian. About 56% of patients had at least some college, 16% were college graduates, 16% were self-pay/uninsured, and 29% had a family history of prostate cancer.
Disease risk level was very low for 40% of patients, low for 35% of patients, and low-intermediate for 25% of patients. The median PSA level was 5.98 ng/mL, 81% were Gleason grade group 1 (GG1; 3 + 3), and 19% were GG2 (3 + 4). IPSS (urinary function) was 9.7 and Sexual Health Inventory for Men (SHIM) score (sexual function) was 6.4.
In their manuscript, the authors noted, “Random assignment evenly balanced key variables at baseline, except for prostate cancer in a first- degree relative and Sexual Health Inventory for Men score indicating severe erectile dysfunction, which were less common in the intervention group and thus were given particular attention as potential confounders in the analysis.”
At their first visit to the hospital (V1), all patients received their diagnosis and identical counseling describing their treatment options. Also at V1, the investigators randomized the patients to standard counseling alone or standard counseling with GPS. The GPS test examines biopsy tissue and, using a model that examines expression levels of 12 genes plus clinical features, predicts outcomes.
Visit 2 (V2) took place 2 to 3 weeks later. At V2, all patients received reinforced NCCN-based risk counseling, those assigned to GPS discussed their GPS report, and all patients made a treatment decision with their clinician. Four weeks after V2, visit 3 was held to collect patient surveys and find out whether a change in choice of treatment had occurred. The fourth visit was held at the initial clinical interaction following recovery from surgery, completion of radiation treatment, or the first clinical visit for AS monitoring.
Treatment selection at V2 was the primary end point of the study. Additionally, “The proportion of patients choosing AS was compared, and multivariable modeling was used to estimate the effects of various factors on AS acceptance,” the authors explained.
Overall, there were 191 evaluable patients, comprising 99 patients in the intervention arm and 92 patients in the control arm. There were 76 patients (77%) in the GPS arm who chose AS, compared with 81 patients (88%) in the control arm. Twenty-one patients (21%) in the GPS arm and 11 patients (12%) in the control arm selected surgery or radiation. There were 2 patients in the control arm categorized as “undecided.”
“As more biomarkers yielding probability estimates enter the clinic, it is important to understand their impact on cancer treatment choice and decision quality in diverse patient populations. Any reasonable strategy for attacking the racial disparity in prostate cancer outcomes should include AS, provided patients are judiciously selected for this option,” the authors wrote in their conclusion. “However, this strategy must also emphasize improved early detection, as highlighted by the fact that nearly three quarters of the newly diagnosed men screened for this trial were ineligible because of an excessive NCCN risk level.”
1. Murphy AB, Abern MR, Liu L, et al. Impact of a genomic test on treatment decision in a predominantly African American population with favorable-risk prostate cancer: a randomized trial [published online April 9, 2021]. J Clin Oncol. doi: 10.1200/JCO.20.02997