GENETIC SCORE FOR PROSTATE CANCER

A biopsy-based Genomic Prostate Score predicts outcomes in men with clinically localized prostate cancer, according to a retrospective study.

"Higher scores were associated with increased risk of metastasis or death in intermediate-risk patients, 10 years after undergoing radical prostatectomy,” Dr. Stephen K. Van Den Eeden from Kaiser Permanente Northern California, in Oakland, told Reuters Health by email. “These results were statistically significant even after adjusting for criteria from the risk-stratification systems of the National Comprehensive Cancer Network (NCCN) or the American Urological Association, which are two commonly used to determine clinical risk.”

The Genomic Prostate Score, based on the OncotypeDX Prostate Cancer assay, ranges from 0 to 100, with increasing scores indicating more biologically aggressive disease. Previous studies have validated it as a predictor of adverse pathology and biochemical recurrence (BCR) after radical prostatectomy.

Dr. Van Den Eeden and colleagues retrospectively assessed how well the Genomic Prostate Score predicts distant metastases and prostate cancer-specific death in 259 men with localized prostate cancer treated with radical prostatectomy between 1995 and 2010.

During a median follow-up of 9.8 years, 64 prostate cancer-specific deaths, 79 metastatic events, and 117 BCRs occurred, according to the October 6 European Urology online report.

Each 20-point increase in Genomic Prostate Score was associated with a 2.34-fold increased risk of distant metastases, a 2.69-fold increased risk of prostate cancer-specific death, and a 2.11-fold increased risk of BCR, after adjustment for other variables.

Among the four biological pathways represented in the Genomic Prostate Score, downregulation of androgen signaling and upregulation of stromal-response gene groups were most strongly associated with each outcome, although all four gene groups contributed to the prediction.

The score predicted all three outcomes within clinically relevant subsets of patients by NCCN risk groups, age, race, and central biopsy Gleason score.

Coauthor Dr. Joseph C. Presti from Kaiser Oakland Medical Center told Reuters Health by email, “It is unclear which subset of patients might benefit most from the test, because men with low-risk prostate cancer have very high 10-year survival, and those with high-risk cancer are usually recommended for treatment. The test that we looked at is one of several similar tests currently in development to determine long-term outcomes for prostate cancer patients.”

“The limitations of this study point to the need for additional research before any conclusions can be drawn about the clinical implications of this test,” Dr. Van Den Eeden said. “While the overall results were statistically significant, prediction was imperfect; some patients with high scores did not experience disease progression, while some with low scores later developed metastases or died of prostate cancer.”

“Furthermore, our study was limited to patients who had undergone radical prostatectomy, and it is unknown how the test may perform for those treated with radiotherapy or who undergo active surveillance,” he said. “Also, by necessity, the tissue samples we tested were from an era when diagnostic biopsies were less comprehensive (limited biopsy scheme), so it is unclear whether our results would hold for men diagnosed today by extended biopsy schemes.”

Dr. Michael S. Leapman from Yale University School of Medicine, New Haven, Connecticut, recently compared Genomic Prostate Score results with prostate MRI findings. He told Reuters Health by email, "It is intriguing to note a wide distribution of Genomic Prostate Score results within standard clinical risk groups. These findings underscore that the heterogeneity in outcome even among high-risk patients might be explained, in part, by genomic features that can be quantified and used to more precisely assign prognosis.”

“Given the varied management options available (including active surveillance), a better understanding of a patient’s risk of harboring aggressive disease can allow for tailored treatments,” he said. “These may include an expanding role for active surveillance in individuals with outside of standard inclusion criteria but with favorable genomic scores. Conversely, those with comparatively higher genomic profiles might be offered earlier treatment and closer monitoring.”

“Several other genomic assays exist and have been validated to predict the risk of death from prostate cancer,” Dr. Leapman said. “In addition, the landscape of refined risk prediction tools includes advanced imaging, such as multi-parametric MRI, that allows for more accurate clinical staging. Comparative studies are currently lacking, and may be increasingly important as we seek to understand how best to evaluate patients with newly diagnosed prostate cancer.”

Dr. Pierre-Jean Lamy from Institut Medical d'Analyse Genomique (“imagenome”), Clinique Beau Soleil, Montpellier, France, who recently reviewed prognostic biomarkers in localized prostate cancer, told Reuters Health by email, "Many publications have already shown that mRNA signatures for patients after radical prostatectomy could have a prognostic value, usually based on the prediction of Gleason score, biochemical relapse, and even metastasis. Only a few of them are based on the prediction of cancer-specific mortality.”

“But the main interest of the study is to show that the association between Genomic Prostate Score and time to metastasis or prostate cancer death remained significant after adjusting for American Urological Association, and Cancer of the Prostate Risk Assessment (CAPRA) risks,” he said. “This independent prognostic value shows the clinical added value of the test that could provide prognostic information beyond NCCN risk stratification.”

Genomic Health, Inc. sponsored the study, employed four of the 11 authors, and had various relationships with the other seven.

SOURCE: http://bit.ly/2kEOqy7

Eur Urol 2017.