Neoadjuvant androgen deprivation therapy with bicalutamide compared to hormonal agents in treating high-risk prostate...

High-risk and locally advanced prostate cancer (HRPC/LAPC) continues to present significant therapeutic challenges. Although conventional neoadjuvant therapy combining androgen deprivation therapy (ADT) with first-generation antiandrogens [e.g., bicalutamide (BICA)] has been widely adopted, this approach's limited efficacy in achieving durable pathological responses and improving long-term survival underscores the need for more effective strategies. The emergence of novel hormonal therapies (NHTs), such as abiraterone and next-generation androgen receptor inhibitors (e.g., darolutamide), has revolutionized the treatment for patients with advanced disease by enabling marked suppression of the androgen signaling pathway. However, evidence regarding the perioperative benefits of ADT plus NHT relative to those of conventional ADT + BICA remains scarce, particularly in terms of pathological outcomes [e.g., complete response and minimal residual disease (MRD)] and early efficacy indicators. This study thus aimed to compare these treatment approaches through a retrospective analysis of real-world data in order to better inform the optimization of neoadjuvant strategies for this high-risk population. The objective of this study was to compare the pathological and early oncological outcomes of neoadjuvant ADT plus NHT to those of conventional ADT plus BICA in patients with high-risk or LAPC undergoing radical prostatectomy (RP).

A retrospective cohort study was conducted that included 87 patients who received neoadjuvant therapy followed by RP. Patients were stratified into two groups: an ADT + BICA group (n=35) and an ADT + NHT group (n=52). The primary endpoints included the pathological complete response (pCR) rate, incidence of MRD, the pathological downstaging rate (based on American Joint Committee on Cancer eighth edition staging), and positive surgical margin (PSM) rate. The secondary endpoints included the rate of ≥50% decline in prostate-specific antigen level (PSA50 response rate), PSA90 response rate, and biochemical recurrence (BCR) rate.

The ADT + NHT group, compared to the ADT + BICA group, demonstrated significantly higher rates of pCR (15.4% vs. 0%, P=0.04), MRD (30.8% vs. 8.6%; P=0.01), and pathological downstaging (44.2% vs. 22.9%; P=0.04). Although both groups achieved 100% PSA50 and high PSA90 response rates (97.1% vs. 94.2%), no significant differences were observed in PSM rates (32.7% vs. 48.6%; P=0.14) or BCR-free survival (log-rank P=0.90). Among NHT agents, darolutamide showed the most favorable performance. All regimens were well-tolerated, with no grade 3-4 adverse events being reported.

Neoadjuvant ADT + NHT was associated with improved pathological responses compared to ADT + BICA, although this advantage did not translate into significant differences in surgical margins or short-term survival outcomes. These findings support the superior pathological efficacy of NHT-containing regimens and underscore the need for longer-term follow-up to evaluate their survival benefits.