SUO 2017: Using Genomic Biomarkers to Select Patients for Postoperative Therapies for Prostate Cancer

Washington, DC (UroToday.com) Over the last 10 years, several genomic biomarkers have become available to help in the management of prostate cancer patients treated with prostatectomy. It is important to note that most of these biomarkers are prognostic in nature. Prognostic biomarkers provide information on outcomes independent on treatment received whereas predictive biomarkers specifically identify response and resistance to a particular therapy. In order to be able to provide a more personalized approach to the adjuvant care of these patients we need predictive biomarkers.

Dr. Feng, an associated professor of radiation oncology from UCSF, discussed the development of several genomic predictive biomarkers for the selection of adjuvant therapies in high risk patients following radical prostatectomy. Dr. Feng, points out that the use of adjuvant radiation in post-prostatectomy patients remains low; although, there is level 1 evidence that points to its survival benefit. The main hesitation is related to the risk overtreatment, given that only 30% of patients have been found to benefit from added radiation therapy. Dr. Feng’s group has developed a predictive biomarker, PORTOS (Post Operative Radiation Therapy Outcomes) Score, which is a 24-gene tool based on several DNA damage repair genes which aims to predict the benefit of adjuvant radiation therapy.  The PORTOS score was developed by using a historical cohort of 545 patients with high risk prostate cancer who where match 1:1 for those receiving adjuvant therapy and does who did not.  On the discovery cohort the PORTOS score was not found be associated with any clinic-pathological factors which adds to its independent predictive ability. In the both the discovery and validation cohorts patients with high PORTOS scores were found to benefit from the adjuvant XRT while those with low PORTOS score did not.

Hormonal therapy is another adjuvant therapy that has been proven to improve survival in patients with node positive disease; but, again it is rarely used. As with adjuvant radiation there is significant concern with the risk of overtreatment in this population given the significant effect hormonal therapy can have in quality of life measures and the potential for bone and cardiovascular complications. Borrowing a test from breast cancer, Dr. Feng has shown how the PAM50 signature can identify patients at greatest benefit for adjuvant hormonal therapy. The PAM50 signature, measure the expression of 50 classifier genes which then categorizes breast cancer into three subtypes (Luminal A, Luminal B, and Basal). The test is currently utilized in breast cancer patients to identify those who benefit from aromatase therapy. The test was applied to 1567 patients with a high-risk prostate cancer which showed similar genomic signature clustering into the three subtype categories. On retrospective analysis 780 patients, matched 2:1 on the receipt of ADT, patients with a luminal type B signature were noted to have the most significant response to hormonal therapy. A prospective trial, NRG GU006, has recently been open to further asses the use of the predictive biomarkers in patient with high risk features who don’t achieve an undetectable PSA.

In summary, two predictive biomarkers have been developed for the post-operative setting which show promise for the goal of individualized therapy. It is important to note that these biomarkers have been validated only in retrospective cohorts and further prospective validation is necessary.

Presented by: Felix Feng MD, Associate Professor of Radiation Oncology, University of California San Francisco

Written by: Andres F. Correa, Society of Urologic Oncology Fellow, Fox Chase Cancer Center, Philadelphia, PA, at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC

 

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