Neoadjuvant ADT for Asian Patients Undergoing Robotic Radical Prostatectomy Is the Conversation Over?—A Propensity-Matched Comparison

TL;DR

Hormone therapy before prostate cancer surgery reduces cancer spread and recurrence without increasing surgical risks, especially in high-risk patients.

Contribution

Region-specific evidence from Asia shows neoadjuvant ADT benefits high-risk prostate cancer patients without increasing surgical complications.

Findings

Neoadjuvant ADT reduces biochemical recurrence, lymph node involvement, and surgical margins in high-risk prostate cancer.

Patients with PSA density ≥ 0.2 ng/mL², Gleason ≥ 8, and cT3 disease benefit most from neoadjuvant ADT.

No increase in perioperative complications or surgical morbidity was observed with neoadjuvant ADT.

Abstract

This study demonstrates that neoadjuvant ADT prior to radical prostatectomy significantly reduces biochemical recurrence, lymph node involvement, and positive surgical margins in a high-risk prostate cancer population. Importantly, these oncologic benefits are achieved without increasing perioperative complication rates or surgical morbidity. By using a propensity score-matched Asian cohort, the study adds region-specific evidence supporting the reconsideration of neoadjuvant ADT use. The findings highlight patient subgroups (e.g., PSA density ≥ 0.2 ng/mL2, Gleason ≥ 8, cT3) that may derive greater benefit from such intervention. Patient summary: We examined whether hormone therapy given before surgery helps men with prostate cancer. Our findings suggest that it reduces cancer spread and the chance of recurrence without increasing surgical risks. These benefits were especially clear in patients with high-risk disease.

Background: Evidence for neoadjuvant androgen deprivation therapy (ADT) before radical prostatectomy (RP) remains inconclusive, and current guidelines do not endorse its routine use. Objective: We aimed to evaluate the impact of neoadjuvant ADT on surgical and oncologic outcomes in a Singaporean cohort undergoing radical prostatectomy. Design, setting, and participants: In this retrospective study, 1091 men underwent RP between 2013 and 2024; a total of 105 received neoadjuvant ADT and 986 did not. A 1:1 propensity score-matched analysis was performed on age, PSA, PSA density, Gleason score, clinical T-stage, and receipt of adjuvant therapies, yielding 105 matched pairs. Outcome measurements and statistical analysis: The primary outcome was biochemical recurrence (BCR). Secondary surgical outcomes included operative time, estimated blood loss, length of stay, catheter duration, and postoperative complications. Secondary oncologic outcomes included extracapsular extension, margin status, seminal vesicle invasion, lymph node involvement, clinical-to-pathological T-stage downstaging, Gleason score decrease, and PSA decrease. Kaplan–Meier survival and univariable linear and logistic regression analyses were used. Subgroup analysis was performed using stratified odds ratios to identify clinical subgroups that derived the greatest benefit from neoadjuvant ADT in terms of biochemical recurrence reduction. Results and limitations: After matching, neoadjuvant ADT was associated with a lower rate of extracapsular extension (30.8% vs. 51.4%, p = 0.004), positive surgical margins (18.4% vs. 39.4%, p = 0.002), lymph node involvement (1.0% vs. 13.0%, p = 0.002), and biochemical recurrence (4.8% vs. 18.1%, p = 0.005). There were no significant differences in operative time, blood loss, length of stay, or complication rates. Before matching, 2-year biochemical recurrence-free survival (BCR-FS) did not differ significantly (93.0% vs. 88.2%, log-rank p = 0.26), but after matching, BCR-FS favored ADT (93.0% vs. 81.8%, log-rank p = 0.02). Subgroup analysis showed that the reduction in biochemical recurrence with neoadjuvant ADT was more pronounced in patients with PSA density ≥ 0.20 ng/mL2, Gleason score ≥ 8, and clinical T3 disease. Limitations include the retrospective design and potential residual confounding. Conclusions: Neoadjuvant ADT prior to RP significantly reduces locoregional spread and biochemical recurrence without increasing perioperative morbidity. Prospective trials are needed to confirm its benefit in high-risk prostate cancer.

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