SAN FRANCISCO, CA USA (UroToday.com) - Dr. Sandler’s presentation was focused on review of past and “newer” androgen deprivation therapies (ADT) in a neoadjuvant and adjuvant setting, after external beam radiation therapy (EBRT) and/or radical prostatectomy (RP).
He reviewed clinical trial, RTOG 9408, showing that in low-risk prostate cancer, no benefit has been shown with adjuvant ADT after EBRT. In regards to intermediate risk, although benefit with short term ADT has been shown, secondary analysis from RTOG 9202 study showed no benefit in overall survival and cancer specific survival with long term ADT. He went on discussing the benefits of ADT in men with high-risk prostate cancer. He presented the randomized study by Bolla and colleagues in which men with locally advanced prostate cancer were randomly assigned to either external-beam radiotherapy plus 6-months of androgen suppression to 2 groups, one who received no further treatment and the other who received 2.5 years of further treatment with a luteinizing hormone-releasing hormone agonist. The 5-year overall mortality for short-term and long-term suppression was 19.0% and 15.2%, respectively.
In regards to use of ADT as an adjuvant treatment after RP, he presented studies which have shown survival benefits for men who do experience biochemical relapse after surgery. Randomized trial RTOG 0534, with accrual of 1 485 men so far, will shine more light on this subject by the end of this year. Dr. Sandler went on showing results of institutional series which have shown no cancer specific or overall survival benefit with neoadjuvant ADT prior to RP. He mentioned that historically ADT appears to have more synergic effect with EBRT compared to RP. He showed that ligand-mediated activation of the androgen receptor (AR) is critical for prostate cancer survival, and failure to completely ablate tissue androgens may limit suppression of cancer growth. In regards to this topic, he presented results of randomized study of 35 men with intermediate- or high-risk localized prostate cancer who were either assigned to goserelin combined with dutasteride, bicalutamide and dutasteride, or bicalutamide, dutasteride, and ketoconazole for 3 months prior to RP. In the controlled arm, patients received combined androgen blockade with luteinizing hormone-releasing hormone agonist and bicalutamide. Findings of this clinical trial were that addition of androgen synthesis inhibitors lowers prostate androgens below that achieved with standard therapy, however the significant AR signaling remains intact.
Dr. Sandler finally discussed the preliminary results of abiraterone acetate in neoadjuvant setting, showing that rough early results have indicated a pathologic complete response rate of 24% vs 11% in control arm. Results from randomized phase III trial of enzulatimide (ENZARAD) in neoadjuvant setting (160mg daily for 24 months and LHRH for 24 months + EBRT vs no enzulatimide) is currently pending. He concluded his presentation acknowledging that while EBRT and conventional ADT are beneficial for intermediate- and high-risk prostate cancer patients, results of conventional ADT and RP are not too encouraging. Perhaps studies looking at novel ADT and EBRT/RP will be more promising, with better toxicity profile.
Highlights of a presentation by Howard M. Sandler, MD, MS, FASTRO at the 2014 Genitourinary Cancers Symposium - January 30 - February 1, 2014 - San Francisco Marriott Marquis - San Francisco, California USA
Cedars-Sinai, Los Angeles, CA USA