(UroToday.com) The 2022 EAU annual meeting featured a game-changing session, including a discussant presentation by Dr. Alexandre De La Taille discussing results of ARNEO, a randomized phase II trial of neoadjuvant degarelix with or without apalutamide prior to radical prostatectomy for high-risk prostate cancer. Dr. De La Taille notes that the EAU guidelines provide a strong recommendation that we should not offer neoadjuvant androgen deprivation therapy before surgery. Although neoadjuvant hormonal therapy decreases the pT3, positive surgical margin, and lymph node positivity rates, there has yet to be definitive evidence for an effect on PSA or cancer-specific survival. Furthermore, these benefits appear to be greater with an increased treatment duration of up to 8 months.
There is rationale for combination neoadjuvant hormonal therapy. Efstathiou and colleagues1 previously tested 3 months of abiraterone acetate + prednisone + luteinizing hormone-releasing hormone (LHRH) agonist versus 3 months of LHRH agonist alone followed by radical prostatectomy in 65 men. This trial did not see a significant difference of organ-confined carcinoma (p = 0.27). However, tumor volume measures were significantly lower for abiraterone acetate + prednisone + LHRH agonist treatment (pā¤0.001):
As follows is a table summarizing the data on neoadjuvant hormonal therapy to date:
Dr. De La Taille notes that there are several important phase 3 trials in this disease space that will soon be reporting results. PROTEU is a phase 3 trial randomizing men with high-risk localized prostate cancer to 6 months of apalutamide + ADT versus placebo + ADT, followed by radical prostatectomy, followed by 6 months of additional therapy. The primary endpoints are percentage of patients with pathologic complete response and metastasis free survival. The trial design for PROTEUS is as follows:
ERADICATE is a phase 3 double blinded study of early intervention after radical prostatectomy with ADT with or without darolutamide versus placebo in men at highest risk of prostate cancer metastasis by genomic (Decipher > 0.6) stratification. The primary endpoint for this trial is metastasis free survival:
With regards to ARNEO, Dr. De La Taille notes that the positives are as follows:
- The trial utilized PSMA imaging
- Transcriptome analysis was included
- Utilization of degarelix, which is proven to rapidly decrease testosterone, have no testosterone increase, and may be superior to leuprolide
Two negatives of ARNEO according to Dr. De La Taille are that hormonal therapy was only used for 3 months and we are still awaiting survival data from this trial. Dr. De La Taille concluded this discussant presentation of the ARNEO trial by emphasizing that for surgeons who trust in surgery and a multimodal approach for high-risk prostate cancer patients, data from ARNEO, PROTEUS, and ERADICATE will provide additional clarity for how to manage these patients.
Presented by: Alexandre De La Taille, MD, PhD, Univ Paris Est Creteil, Creteil, France
Written by: Zachary Klaassen, MD, MSc ā Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 European Association of Urology (EAU) Annual Hybrid Meeting, Amsterdam, NL, Fri, July 1 ā Mon, July 4, 2022.
References:
- Efstathiou E, Davis JW, Pisters L, et al. Clinical and biological characterization of localized high-risk prostate cancer: Results of a randomized preoperative study of luteinizing hormone-releasing hormone agonist with or without abiraterone acetate plus prednisone. Eur Urol. 2019 Oct;76(4):418-424.