EAU 2020: Salvage Lymph Node Dissection in Prostate Cancer: Primary Treatment of Pelvic Lymph Node Metastatic Prostate Cancer - Systemic Only

(UroToday.com) To conclude the session on primary treatment of pelvic lymph node metastatic prostate cancer at the 2020 European Association of Urology Virtual Annual Meeting, Jeroen van Moorselaar, MD, PhD, discussed the use of systemic therapy only. Dr. van Moorselaar notes that all prospective data on the definition of M1 disease are currently based on computed tomography (CT) scan and bone scan, and that primary androgen deprivation therapy (ADT) has been the standard of care for over 50 years. The definition of high and low-volume metastatic disease has evolved over the last several years, primarily based on data from CHAARTED1 and LATITUDE:2


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) [6]. 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) [7].
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

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