Genomic test score linked with increased risk of adverse pathology

San Francisco-A higher OncotypeDX Genomic Prostate Score (GPS) is associated with an increased risk of adverse pathology in patients who undergo delayed radical prostatectomy (RP) after a period of active surveillance.

In examining a database of men enrolled on AS at the University of California, San Francisco (UCSF), researchers led by Peter R. Carroll, MD, found that each five-unit increase in GPS was associated with a significantly increased risk of adverse pathology and a significantly increased risk of biochemical recurrence following surgery.

The data were presented at the Genitourinary Cancers Symposium in San Francisco by Zachary Kornberg, fourth-year medical student at UCSF, working under Dr. Carroll.

Also see: Enzalutamide plus ADT improves rPFS in hormone-sensitive PCa

“The GPS was developed for patients with low- to intermediate-risk prostate cancer who would have otherwise qualified for AS but went on to have RP, as a predictor for adverse pathology,” said Kornberg. “We studied a very similar cohort who elected for AS and then went on to have a delayed RP after a short period of AS.”

The GPS is derived from the RNA expression of 17 genes that are associated with a likelihood of having high grade (Gleason pattern 4) and/or high stage (pathologic T-stage 3) if the prostate is removed and examined. The assay can be performed on core needle biopsies.

Of 1,662 men enrolled on AS at UCSF from 1997 to 2016, the investigators evaluated 215 with Gleason score 3+3 or low-volume disease (≤33% positive cores) Gleason score 3+4 prostate cancer on diagnostic or confirmatory biopsy. All 215 men had a PSA level <20 ng/mL, clinical stage T1/2, and Cancer of the Prostate Risk Assessment (CAPRA) score <6, and all underwent GPS testing at diagnostic or confirmatory biopsy (within 24 months).

The primary outcome was adverse pathology at delayed RP, defined as Gleason score ≥4+3, stage ≥pT3a or pN1.

Continue to the next page for more.Mean age of the cohort at diagnosis was 60.7 years and their median PSA was 5.3 ng/mL. Two-thirds (67%) had clinical stage T1c and 33% had stage T2 prostate cancer. Some 72% had biopsy Gleason 3+3 and 28% had Gleason 3+4 disease. CAPRA clinical risk was low (0-2) in 83% and intermediate (3-5) in 17%. The median GPS was 26.4. GPS was performed at diagnostic biopsy in 68% and at confirmatory biopsy in 32%.

The median time from diagnosis to RP was 23 months. A total of 121 men had adverse pathology at a median time of 27 months to RP.

Read: Patients on AS still undergo unnecessary biopsies

When adjusted for CAPRA, each five-unit increase in GPS was associated with a 16% increased risk (p<.01) of adverse pathology and a 10% increased risk (p=.04) of biochemical recurrence at delayed RP. Clinical CAPRA score at diagnosis was not associated with adverse pathology (p=.60).

“I think for patients with low to intermediate prostate cancer who are diagnosed on needle core biopsy, it’s very reasonable to use GPS in conjunction with clinical factors such as PSA density and clinical CAPRA score to guide patients as to whether they may or may not be suitable for AS,” Kornberg said. “You can tell patients with a very high GPS that they have a higher risk of having adverse pathology at delayed RP.”

Dr. Carroll has received honoraria from Intuitive Surgical and is a consultant/adviser for Nutcracker Therapeutics. Several study authors have disclosures related to Genomic Health and/or other pharmaceutical companies. For full disclosures, click here.