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Intensified Neoadjuvant Therapy Improves Outcomes in Very High-Risk Prostate Cancer

In patients with very high-risk prostate cancer undergoing radical prostatectomy, intensifying neoadjuvant therapy by adding abiraterone or docetaxel to androgen deprivation therapy (ADT) may improve pathologic response compared with ADT alone.

Hongqian Guo, MD, of Affiliated Drum Tower Hospital, Medical School of Nanjing University in Nanjing, China, and colleagues pooled data from 2 randomized, controlled, phase 2 clinical trials ( NCT04356430 and NCT04869371). Among 137 patients, 132 men (96.4%) had very-high-risk prostate cancer, including 78.8% with locally advanced disease, defined as cT3b-4. All patients received 24 weeks of neoadjuvant therapy followed by robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND) within 2 weeks.

The rate of complete pathologic response or minimal residual disease was significantly higher for the groups receiving abiraterone plus ADT (31%) or docetaxel plus ADT (28%) compared with ADT alone (2%), the investigators reported in Frontiers in Pharmacology. The combination neoadjuvant therapies were both significantly associated with more than 16-fold increased odds of this outcome compared with ADT alone. To lesser degrees, pre-operative PSA levels of 0.1 ng/mL or less and Gleason score were also predictive.

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The 3-year biochemical progression-free survival rate was 61.2%, 51.1%, and 41.9% for abiraterone plus ADT, docetaxel plus ADT, and ADT alone, respectively, the investigators reported.

Adverse events occurred at a greater frequency in the abiraterone plus ADT group (81%) and docetaxel plus ADT group (89%), compared with the ADT only group (68%). Grade 3 or higher adverse events were most common in the docetaxel plus ADT group: 14%, 36%, and 6%, respectively. Perioperative events were comparable.

There is currently no consensus on the optimal treatment for men with high-risk prostate cancer, Dr Guo’s team noted. Neoadjuvant ADT plus abiraterone or docetaxel may permit better pathologic response in these patients, they suggested. Although non-surgical treatment remains the first-line strategy, therapeutic advances have provided “impetus” for researchers to consider surgery as part of multimodal therapy.


Zhuang J, Wang Y, Zhang S, et al. Androgen deprivation therapy plus abiraterone or docetaxel as neoadjuvant therapy for very-high-risk prostate cancer: a pooled analysis of two phase II trials. Front Pharmacol. 14:1217303. Published online June 26, 2023. doi:10.3389/fphar.2023.1217303