ESMO 2017: Prostate Cancer Poster Discussion: Invited Discussant

Madrid, Spain (UroToday.com) Dr. David Olmos from Madrid, Spain provided a discussion regarding two high-level posters at this morning’s prostate cancer session at ESMO 2017. The two studies included “DNA repair gene panel mutations in young onset and aggressive v non-aggressive prostate cancer cases in the UK” [1] by Dr. Eeles and colleagues and “Prognostic Associations of PSA Decline with Survival, Radiographic Response and Progression in Chemotherapy-Naïve Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Enzalutamide” [2] by Dr. Armstrong and colleagues.

Dr. Eeles’ study found that there is a higher percentage of DNA damage response and repair gene germline mutations in prostate cancer cases occurring among men < 65 years, and among those with aggressive and lethal disease. Based on these findings, the goal should be to develop a testing panel for use in clinical care in the near future. Dr. Olmos questions why a cutoff of 65 years was selected? Is there a recommended cut-off to suspect germline deleterious mutations? As he notes, there have been four prior studies that have germline deleterious mutations between carriers and non-carriers based on various median ages with no statistical significance noted for these studies based on age cut-off.

Dr. Armstrong’s study found that PSA declines after 3 months of enzalutamide therapy are strongly associated with soft-tissue response and improvements in rPFS and OS, particularly for PSA responses >50%. These outcomes are predictive of multiple endpoints, including time to PSA progression, time to radiographic progression, and time to death. Dr. Olmos notes that similar results for PSA decline have been previously reported for patients undergoing docetaxel and abiraterone therapy. Furthermore, he notes that PSA declines as early as 4 weeks post-treatment may predict treatment benefit, however 10% of non-responders at week 4 have 90% PSA decline by 12 weeks [3].

Speaker: David Olmos, Hospital Universitario, HM Monteprincipe, Madrid, Spain

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain

References:

1. Eeles R, Saunders E, Wakerell S, et al. DNA repair gene panel mutations in young onset and aggressive v non-aggressive prostate cancer cases in the UK. ESMO 2017 abstr 786.
2. Armstrong AJ, Lin P, Higano CS, et al. Prognostic Associations of PSA Decline with Survival, Radiographic Response and Progression in Chemotherapy-Naïve Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Enzalutamide. ESMO 2017 abstr 787.
3. Rescigno P, Lorente D, Biancini D, et al. Prostate-specific antigen decline after 4 weeks of treatment with abiraterone acetate and overall survival in patients with metastatic castration-resistant prostate cancer. Eur Urol 2016;70(5):724-731.