ASCO GU 2017: Genomic Tests in Active Surveillance and the Role of Hereditary Testing - Session Highlights

Orlando, Florida USA ( Dr. Mucci presented an overview of the use of genetic biomarkers in the active surveillance (AS) cohort for prostate cancer (PCa) patients. To be specific, biomarker utility for AS exists only in the window after diagnostic biopsy, when important decisions regarding treatment vs. surveillance for diagnosed PCa are being made.

Clinical factors such as PSA and DRE, which have been the mainstay of current AS protocols, have good sensitivity but lower specificity. Also, Gleason scoring has some variability across institutions, indicating a need for a more objective measurement of disease risk. Important questions persist, such as what is the best way to manage a patient with low-volume Gleason 3+4 disease? Molecular biomarkers may hold the key to understanding how to understand these tumors and their appropriateness for AS vs. treatment.

There are 3 important principals for a successful biomarker development:
  • Biomarkers should perform better than clinical factors at predicting disease charactersitics.
  • Biomarker tests should have high specificity.
  • We must identify optimal patient cohorts for biomarker validation.
There are 3 important genomic tests for localized PCa: Oncotype Dx, Prolaris, and Decipher:
  • Oncotype Dx: 12 genes + 5 reference: Predicting risk of adverse pathology on RP.
  • Prolaris: 31 genes +15 housekeeping: Predicting risk of progression post-RP and in untreated cohorts.
  • Decipher: 22 genes: Predicting risk of recurrence and metastasis post-RP. This test has high specificity.

Only Oncotype Dx and Prolaris can be used in the post-biopsy setting to determine the appropriateness of AS selection. For Prolaris, every 1 unit increase in score has demonstrated a 2-2.5x increase in cancer death in untreated patients. In treated cohorts when evaluating for metastatic disease and cancer death, the increased risk per 1 unit score increase was 3-5x. For Oncotype Dx, every 20 unit increase in GPS score = 2-2.7x increase in adverse pathology (Gleason 4+3 or higher and/or pT3 disease) at treatment.

Hereditary markers for prostate cancer have not yet shown to be of any prognostic significance. No SNPs have been specifically identified that track with disease characteristics, and genetic variants in other known pathways are currently not known to play a large role in prostate cancer progression.

Several outstanding issues still exist in this space. Do genomic tests have sufficient specificity to predict long-term good outcomes? Prolaris may have this specificity, but evidence suggests it may be a better predictor of aggressive disease at diagnosis. For Oncotype Dx, it is unclear what the specificity is for adverse pathology and the test has not been studied for metastasis and mortality outcomes. Furthermore, we do not have any good data on whether these tests perform similarly in non-white men, which continues to be a glaring deficit of most prostate cancer outcomes studies.
Overall, further validation of biomarkers in select cohorts with respect to outcomes such as metastasis and mortality are needed. Early identification of aggressive disease is paramount, and growing evidence suggests that molecular biomarkers will play an ever-larger role in the future of AS.

Presented By: Lorelei A. Mucci, MPH, ScD, Harvard T.H. Chan School of Public Health

Written By: Shreyas Joshi, MD, Fox Chase Cancer Center

at the 2017 Genitourinary Cancers Symposium - February 16 - 18, 2017 – Orlando, Florida USA