ORLANDO – A genetic assay for prostate cancer typically used after radical prostatectomy could be used earlier, at the time of diagnostic biopsy testing, to classify patients as low, intermediate, and high risk for metastasis and disease-specific mortality, new research reveals.
Based on an approximately 1-mm biopsy sample, the Decipher Prostate Cancer Classifier assesses the activity of 22 genes relevant to prostate cancer. In a multicenter study of 175 patients, investigators found the 5-year risk for metastatic disease was 5.0% among patients classified as low risk by Decipher, 9.3% in the intermediate-risk group, and 23.4% in the high-risk patients.
Dr. Paul L. Nguyen
“It turns out NCCN [National Comprehensive Cancer Network] risk groups can also provide this kind of risk stratification … so why do we need the extra test?” lead author Paul L. Nguyen, MD, of Dana-Farber Cancer Institute in Boston said here at the Genitourinary Cancers Symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology. Because, he added, Decipher provides “significant prognostic information for distant metastases beyond clinical variables alone,” even after controlling for prostate-specific antigen level, Gleason score, and treatment type, Dr. Nguyen said.
The Decipher RNA–based test also improved the c-index for predicting likelihood of distant metastases, with a 0.75 correlation, compared with 0.66 with NCCN risk stratification and 0.66 based on Cancer of the Prostate Risk Assessment score. “So this adds to what we already know, and it helps us decide which patients are going to develop metastases.”
Decipher’s prognostic value emerged regardless of first line therapy. A total 100 patients received radiation and androgen therapy at Dana-Farber and another 75 underwent radical prostatectomy at the Cleveland Clinic or Johns Hopkins University, Baltimore. Decipher classified 13% of patients as low risk, 51% as intermediate risk, and 34% as high risk. Because prostate tumors can be heterogeneous, researchers chose the highest-grade biopsy sample for each patient.
Local Therapy for High-Risk Patients?
A meeting attendee asked if a patient is “known to be high risk on biopsy, and has a 23% chance of metastasis after treatment, why treat with local treatment in the first place?”
“For these patients, we’re meeting them up front and they have a high risk of disease, a 23% chance of metastasis, I think we’re going to throw everything we can at them,” Dr. Nguyen said. Multiple randomized controlled trials indicate intensifying therapy can improve outcomes and that local therapy contributes to overall survival in these patients, he added. “For these patients who have very high risk disease, we have enough randomized data to show local therapy is still important. The next thing we need to do is work on personalizing their systemic therapy, and figuring out how to integrate these novel systemic therapies based on their genomic scores.”
Disease-Specific Survival
Eleven participants in the study died from prostate cancer. The only variable associated with prostate-specific disease mortality was the Decipher classification, with a hazard ratio of 1.57 for every 10% increase in the score on a univariate model (P = .02).
Dr. Nguyen and his coinvestigators also assessed 5-year prostate cancer specific mortality. They found a 9.4% rate in the Decipher high-risk group, compared with 0% in both the intermediate- and low-risk groups.
“Okay, we have this data. How do we incorporate this test into our practices?” Dr. Nguyen asked. Because the low-risk patients only comprised 13% of the study population, he was unable to state that this group could be directed to active surveillance based on the findings.
What about NCCN intermediate risk? Should these people treated with dose-escalated radiation therapy also be given short-course hormone therapy? “So far we have not seen a survival improvement, and we’re awaiting a definitive trial,” Dr. Nguyen said.
Prognostic, Not Predictive
Could the high-risk classification help physicians decide among prostatectomy, radiation, and long-course hormone therapy versus enrolling patients in a clinical trial to test a novel agent? “Perhaps, and there is some rationale for thinking in that direction,” Dr. Nguyen said. “But it is important to understand the difference between a prognostic and predictive biomarker. We’ve shown Decipher has prognostic value for identifying patients at risk for distant metastases and death.” In contrast, randomized controlled trials would be required to identify a predictive marker that ultimately could guide choice of treatment in an individual, he said.
“Robust markers are needed to see who needs treatment, and which treatment is best for primary and metastatic prostate cancer,” said study discussant Angelo DeMarzo, MD, PhD, of Johns Hopkins University. He asked Dr. Nguyen about the next best step in his research.
“Our paper was mostly intermediate- and high-risk patients; I would personally love to learn more about which patients need long-course, short-course, or no hormone treatment,” Dr. Nguyen said. He would also like to conduct randomized trials to assess any role of Decipher classification for active surveillance, and for guiding treatment intensification versus de-escalation for those patients who receive therapy.