Dr. van Moorselaar then highlighted the Messing trial assessing immediate versus deferred ADT in patients with node-positive prostate cancer after radical prostatectomy and lymphadenectomy.3 This trial had 98 patients randomized to receive immediate ADT (n=47) or to be observed (n=51), with ADT to be given on detection of distant metastases or symptomatic recurrences. At median follow-up of 11.9 years (range 9.7-14.5), men assigned immediate ADT had a significant improvement in overall survival (HR 1.84, 95% CI 1.01-3.35), prostate-cancer-specific survival (HR 4.09, 95% CI 1.76-9.49), and progression-free survival (HR 3.42, 95% CI 1.96-5.98). Dr. van Moorselaar notes that issues for this trial were that there was no central pathology review and that there were 220 patients planned, but only 98 in the trial. Furthermore, there was lower cancer-specific survival in the observation group compared to two other series (78% after 5 years versus 91%). Additionally, there was no baseline prostate-specific antigen (PSA) testing and recruitment was at 36 institutions, potentially leading to heterogeneity in management.
Dr. van Moorselaar also highlighted the EORTC 30846 trial which evaluated the effect of early versus delayed hormone treatment in pN1-3 prostate cancer.4 There were 254 men randomized and in the ITT analysis, there was a 22% increase in the hazard of death of those randomized to delayed treatment (HR 1.22, 95% CI 0.92, 1.62). Additionally, the median overall survival (OS) in the immediate treatment group was 7.6 years (95% CI, 6.3-8.3 years) versus 6.1 years (95% CI, 5.7-7.3 years) in the delayed treatment group.
Data from the CHAARTED trial has recently been extracted to outcomes by volume of disease.5 For patients with the high-volume disease (n = 513), the median OS was 51.2 months with chemohormonal therapy versus 34.4 months with ADT alone (HR 0.63, 95% CI 0.50-0.79). For patients with low-volume disease (n = 277), there was no OS benefit was observed (HR 1.04, 95% CI 0.70-1.55):
In the ARCHES trial, patients with predominately high-volume disease were randomized to enzalutamide + ADT or ADT alone. Notably, 17% of the cohort had previously received docetaxel. While OS data from this cohort is immature, the addition of enzalutamide was found to reduce the risk of radiographic progression versus ADT plus placebo by 61% (HR 0.39, 95% CI 0.30-0.50) . The ENZAMET trial also utilized enzalutamide but had ~50% of patients with high-volume disease. Interim analysis after a median follow up of 34 months from this trial showed a significant survival benefit in the enzalutamide group versus those receiving standard nonsteroidal anti-androgens (HR 0.67 95% CI 0.52-0.86) .
Dr. van Moorselaar concluded highlighting the EAU guidelines that there is strong evidence to suggest that men should be offered ADT in combination with docetaxel for men that present with M1 disease who are fit for chemotherapy. Additionally, men may also consider the option of abiraterone or apalutamide or enzalutamide for those that are fit for these regimens.
Presented by: Jeroen van Moorselaar, MD, PhD, VU University Medical Centre, Amsterdam, The Netherlands
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Augusta, GA, USA, Twitter: @zklaassen_md, at the Virtual 2020 EAU Annual Meeting #EAU20, July 17-19, 2020.
- Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373(8):737-746.
- Fizazi K, Tran N, Fein L, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2017;377(4):352-360.
- Messing EM, Manola J, Yao J, et al. Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Lancet Oncol 2006 Jun;7(6):472-479.
- Schroder FH, Kurth KH, Fossa SD, et al. Early versus delayed endocrine treatment of T2-T3 pN1-N3 M0 prostate cancer without local treatment of the primary tumour: Final results of European Organization for the Research and Treatment of Cancer protocol 30846 after 13 years of follow-up (a randomized controlled trial). Eur Urol 2009 Jan;55(1):14-22.
- Kyriakopoulos CE, Chen YH, Carducci MA, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: Long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol 2018 Apr 10;36(11):1080-1087.
- Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy with Enzalutamide or Placebo in Men with Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2019 Nov 10;37(32):2974-2986.
- Davis ID, Martin AJ, Stockler MR, et al. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N Engl J Med 2019 Jul 11;381(2):121-131.