ASCO GU 2018: Newly Diagnosed High-Risk Disease Treatment: Summarizing Neoadjuvant Trials

San Francisco, CA ( There are approximately 60,000 cases of clinically localized, high risk prostate cancer in the United States yearly.  This number may increase in the future, as prostate cancer screening has declined in recent years.  Men with high risk disease have a Gleason score of 8-10, a PSA of >20, or pT3 disease.  Despite treatment, men with high risk disease have a significant risk of death from prostate cancer, with one study showing a rate of 31% at 15 to 20 years.

Historically, neoadjuvant androgen deprivation therapy (ADT) prior to prostatectomy had not shown a benefit in the treatment of men with high risk disease.  The studies that led to this conclusion, however, had several limitations, including small sample sizes, heterogeneous eligibility criteria, short durations of therapy, and incomplete androgen pathway suppression. 

Dr. Mary-Ellen Taplin, a medical oncologist from the Dana-Farber Cancer Institute, reviewed the historical data regarding neoadjuvant ADT and addressed the need for more effective treatment options in men with high risk disease.  Her research interest is evaluating the impact of intense androgen receptor pathway blockade in men with high risk prostate cancer.  She reviewed her institution's data evaluating combination ADT with an LH-RH agonist (leuprolide) and abiraterone. The studied the effect that these medications have on dihydrotestosterone (DHT) and DHEA.  Men who were given combination therapy had a statistically significant decrease in both of these hormones, as compared with men who were given leuprolide alone. 

Dr. Taplin next discussed ongoing trials evaluating the role of neoadjuvant ADT in men with high risk prostate cancer.  In a trial that continues to accrue patients, unpublished data suggests that a neoadjuvant combination of abiraterone, enzalutamide, and leuprolide leads to an increased likelihood of a patient having no evidence of disease at the time of radical prostatectomy as compared with patients receiving enzalutamide and leuprolide. She also showed data to suggest that a good pathological response may be a surrogate marker of a good clinical response after treatment.  Men in the trial who underwent combination neoadjuvant ADT have a 3-year biochemical recurrence rate of 30%, which is less than what would be predicted by the Memorial Sloan Kettering Cancer Center nomogram. 

She then highlighted the PUNCH Trial, which is scheduled to conclude later this year.  This will be the only phase III clinical trial in the current era which will show the outcomes of neoadjuvant treatment prior to prostatectomy. Patients are randomized to either up-front prostatectomy or to neoadjuvant docetaxel and LH-RH agonists prior to prostatectomy.   The primary endpoint is a 3-year biochemical free recurrence. There is another phase III trial in development comparing neoadjuvant abiraterone, apalutamide, and leuprolide prior to prostatectomy versus prostatectomy alone.

Dr. Taplin concluded that based on the current data, there is a subset of men who will achieve an outstanding pathological response after neoadjuvant ADT, however better biomarkers are needed to determine which men will have a good response.  She believes that there is an emerging role for the use of combination ADT for men with clinically-localized high risk prostate cancer. With the upcoming trials, we will soon have more data to determine the efficacy and outcomes of neoadjuvant ADT.

Presented by: Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute

Written by: Brian Kadow, MD, Fox Chase Cancer Center, Philadelphia, PA at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA

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