Genomic Decipher Score Predicts Prostate Cancer Metastasis, Mortality

The Decipher prostate cancer gene-expression classifier can predict patients’ risk of metastasis and prostate cancer-specific mortality (PCSM) using biopsy specimens prior to radical prostatectomy or radiotherapy plus androgen deprivation, according to a mixed-cohort study presented (abstract 4) at the 2017 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, held February 16–18 in Orlando, Florida.

“It provided significant prognostic information beyond clinical variables alone,” said Paul L. Nguyen, MD, vice chair for clinical research at Brigham and Women’s Hospital and the Dana-Farber Cancer Institute in Boston. “Those 20% of patients with genomic high risk actually had a very high 23.4% metastasis and a very high risk, almost 10%, of dying from prostate cancer. For these patients we have to think, could there be a role for treatment intensification or enrolling these patients in a clinical trial?”

Decipher is a 22-gene metastasis risk-predicting RNA gene expression signature designed for use after radical prostatectomy, using surgical specimens, to inform adjuvant or salvage treatment decision making. The Decipher signature includes gene markers for cell cycle proliferation, adhesion and motility, immune modulation, and androgen signaling pathways.

Previous studies have evaluated the use of Decipher after radical prostatectomy. The authors of the new study sought to assess the Decipher classifier’s prognostic utility when used earlier, with biopsy specimens, in order to inform initial treatment decisions.

The team studied PCSM and metastasis among 175 patients treated with radical prostatectomy (n = 75) at the Cleveland Clinic or Johns Hopkins or radiation plus androgen deprivation therapy (ADT; n = 100) at Dana-Farber. Just over half of the patients’ cancers were deemed to be intermediate-risk using the National Comprehensive Cancer Network (NCCN) classification system; 33.7% were NCCN high-risk. Only 13% of cohort patients had NCCN low-risk prostate cancer.

At a follow-up of 6 years, 32 patients had developed metastatic disease and 11 had died of prostate cancer, Nguyen reported.

“The classifier scores did stratify the risk of metastasis,” Nguyen said. “The 5-year distant metastasis risk by Decipher score showed that the high-risk patients had a 23.4% risk of 5-year metastasis, the intermediate-risk patients had a 9.3% risk of metastasis, and the low-risk patients had a 5% risk of metastasis at 5 years.”

The team’s multivariate model “shows that the classifier does add valuable prognostic information to clinical variables when predicting for distant metastasis even when you adjust for PSA, Gleason score, T category, and treatment type,” Nguyen said. Indeed, in a multivariate analysis, the Decipher score was the only significant correlate of distant metastasis (hazard ratio [HR], 1.39; 95% CI, 1.09–1.77; P = .0069).

“It trumped all of the other variables,” he said.

There was no difference in outcomes between patients treated with radical prostatectomy and those treated with radiotherapy and androgen inhibition.

The Decipher classifier also improved the Harrell's concordance index (C-index) for prediction of distant metastasis, Nguyen said. “If you look at the NCCN risk groups, the C-index is 0.66, but if you look at NCCN added to the Decipher score, it goes all the way up to 0.75. So this adds to what we already know and enhances our ability to decide which patients are going to develop metastases.”

Decipher also predicted PCSM (HR, 1.57 per 10% increase in Decipher score; 95% CI, 1.07–2.40; P = .02). Because the number of these deaths were low, multivariate analysis was not possible. Patients with a high-risk Decipher score had a 5% (5-year) PCSM, whereas no patients with intermediate-risk and low-risk Decipher scores died during the study period.

For NCCN low- and intermediate-risk patients (n = 112), the Decipher score also stratifies the risk of distant metastasis and “in fact, identifies a very high-risk group for distant metastasis that developed a 33.1% risk of metastasis at 5 years,” Nguyen said.

The Decipher test has prognostic value, but more work is needed to demonstrate its predictive value. That will require randomized clinical trials comparing different treatments.