AUA 2022: When is Neoadjuvant Androgen Deprivation Therapy Beneficial for Highly Aggressive Prostate Cancer Candidates to Radical Prostatectomy? Implications for Multi-modal Tailored Approaches and Trials Design

( The 2022 American Urological Association (AUA) Annual Meeting included a session on advanced prostate cancer and a presentation by Dr. Giorgio Gandaglia discussing when neoadjuvant ADT is beneficial for aggressive prostate cancer in candidates for radical prostatectomy. A revitalized interest in neoadjuvant ADT in prostate cancer has been raised by the introduction of novel androgen receptor targeting agents. Identifying men who might benefit from neoadjuvant hormonal manipulation is key for both tailored approaches and for selecting the proper population to include in trials testing new neoadjuvant therapies.

This study evaluated 411 patients with biopsy GG5 prostate cancer treated with radical prostatectomy with an extended pelvic lymph node dissection between 1995 and 2021. Neoadjuvant or adjuvant treatments (namely, ADT and/or radiotherapy) were administered according to the treating physician’s preference. Biochemical recurrence was defined as two PSA values >0.2 ng/ml, and clinical recurrence was the onset of metastases at conventional imaging. An interaction test assessed whether the impact of the neoadjuvant ADT varied according to a risk score based on preoperative features and developed in men who received radical prostatectomy alone. The observed versus predicted clinical recurrence-free survival was plotted for neoadjuvant ADT versus no neoadjuvant ADT.

In this study, median PSA was 10 ng/ml, 149 (36%) patients had cT3 at DRE, and 55 (14%) patients had cN1 at conventional imaging. Overall, 95 (23%), 161 (40%), and 219 (53%) men received neoadjuvant, adjuvant ADT and/or radiotherapy, respectively. A total of 140 (34%) patients received radical prostatectomy alone and the median number of nodes removed was 21. 

Overall, 238 (58%), 210 (51%) and 179 (44%) patients had pT3b, pN1 and positive margins, respectively. Neoadjuvant ADT was associated with lower risk of positive surgical margins (33 vs. 48%, p=0.001). 

Median follow-up was 61 months, 106 men experienced clinical recurrence, and the 7-year clinical recurrence-free survival rate was 61%. A cT3 (HR 2.22; p=0.01) and higher PSA (HR 1.01; p=0.01) predicted clinical recurrence on multivariable analyses. The impact of neoadjuvant ADT on clinical recurrence-free survival varied according to a risk score based on cT3, PSA and cN status. Men with a risk of clinical recurrence higher than 40% at 8-years according to the risk score are those who may benefit most from upfront ADT:


Dr. Gandaglia concluded his presentation discussing when neoadjuvant ADT is beneficial for aggressive prostate cancer in candidates for radical prostatectomy with the following take-home messages:

  • Neoadjuvant ADT may be highly beneficial in patients with biopsy GG5 prostate cancer with aggressive disease characteristics to reduce the long-term risk of clinical recurrence
  • These results could guide the design of novel clinical trials aimed at assessing the role of neoadjuvant therapies in prostate cancer

Presented by: Giorgio Gandaglia, San Raffaele, Milan, Italy

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.

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