SUO 2017: Genomics and Molecular Testing after Radical Prostatectomy

Washington, DC (UroToday.com) Dr. Ross gave a synopsis of the genomic testing available after radical prostatectomy.  Over the last century, our understanding of both histologic implications has grown to genomics and proteomics and transformed our ability to evaluate prostate malignancies.  Clinically available genomic tests in localized prostate cancer include Prolaris, Oncotype Dx, and Decipher.  Prolaris measures a cell cycle progression score of 31 genes.  Oncotype DX utilizes 12 genes involved in stromal response, androgen signaling, cellular organization, and proliferation.

Focusing on Decipher, a 22 RNA expression based genomic marker, outputs a genomic classifier score ranging from 0-1.  This is a validated marker that has been an independent predictor of biochemical recurrence, metastasis, and prostate cancer specific recurrence after radical prostatectomy.  The test is available for men with adverse pathology (>pT3a or positive margin) or those who develop biochemical recurrence.  Initial validation of the Decipher signature was performed at the Mayo clinic in 219 high risk men.  Low, intermediate, and high categorical cut-offs for genomic scores stratified patients into risk groups of clinical metastasis with hazard ratios of 1.0, 2.4, and 7.3, respectively.  Subsequent validation at both Johns Hopkins, Cleveland Clinic, and Mayo Clinic found similar results.  Furthermore, a 2017 Journal of Clinical Oncology meta-analysis of 855 patients from 5 cohorts demonstrated that Decipher was a significant predictor of metastasis across all clinical subgroups based on clinicopathologic, treatment and demographic factors. 

However, genomic risk should not be considered in isolation.  Clinical genomic low risk Decipher patients demonstrated no difference in 10-year metastasis between patients who were treated with adjuvant radiation and observation.  High genomic risk patients demonstrated improved outcomes with earlier radiotherapy compared to late or no radiotherapy.  Minimal differences in survival were seen in this cohort in patients who were treated with late salvage versus observation.

Finally, Dr. Ross discussed the pathway that he uses in the clinic with his prostate cancer patients.   In all patients with adverse prostatectomy pathology, a Decipher test is ordered. PSA is first performed 2 months following surgery.  Patients with undetectable PSA and 2 or more risk factors (genomic score > 0.8, pT3b, N+, or Gleason 8-10 disease) may be prioritized to adjuvant therapy.  Fully informed decision making regarding adjuvant therapy or active monitoring can then be decided.  The number needed to treat with adjuvant therapy to prevent metastasis is 3.  Dr. Ross hypothesizes that genomic risk may also be able to guide intensification of adjuvant and salvage therapies (ie +/- ADT).  The current use of these tests is to better determine prognostic risk; however, the future tests will hopefully be able to predict therapeutic risk. 

Presented by: Ashley Ross, MD, PhD, Texas Urology Specialists

Written by: David B. Cahn, DO, MBS, Fox Chase Cancer Center, Philadelphia, PA, Twitter: @dbcahn at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC
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