Neoadjuvant therapy prior to prostatectomy can improve both oncologic and quality-of-life outcomes in selected high-risk patients, according to new research presented at the American Urological Association's (AUA) 2026 Annual Meeting.
Men who received combination neoadjuvant therapy with apalutamide plus abiraterone/prednisone and gonadotropin-releasing hormone (GnRH) agonist had the best outcome as far as preservation of sexual function and fewer positive surgical margins, with comparable oncologic outcomes. Rates of early recurrence were similar across all treatment groups.
“For men who have undergone a prostatectomy, one of the biggest concerns is what life looks afterwards,” said study author Anthony Zhang, MD, Clinical Research Fellow, Yale School of Medicine, who presented the findings at the meeting. “For a full cancer removal, surgeons may hypothetically take a wider margin around the prostate, which may come at the cost of erectile dysfunction and urinary incontinence.”
Men with high-risk localized prostate cancer often require wider excision for oncologic control. This may come at the cost of erectile function and urinary continency.
Zhang explained that even though the use of neoadjuvant hormone has been studied for years, with earlier studies demonstrating that tumors can be shrunk and positive surgical margins reduced, they remained inconclusive. “No clear long-term improvement in cancer out comes has been clearly delineated,” he said.
In the current study, Zhang and colleagues evaluated the use of apalutamide, a next generation androgen receptor inhibitor, both alone and in combination with abiraterone/prednisone and GnRH agonist before surgery, or immediate surgery without pre-treatment.
“The goal was to intensify the androgen suppression, hypothetically reducing the tumor size and ultimately making the nerve sparing prostatectomy more feasible, leading to improved functional recovery after surgery,” said Zhang.
In this phase II trial, 73 men were randomized to one of three treatment arms: Arm 1 received neoadjuvant apalutamide for 3 months prior to radical prostatectomy;. Arm 2 received intensified neoadjuvant therapy consisting of apalutamide combined with abiraterone acetate, prednisone, and a GnRH agonist for 3 months before surgery; and. Arm 3 proceeded directly to surgery without any type of neoadjuvant systemic therapy.
Participants had high-risk localized prostate cancer with Gleason ≥8 or PSA>20 ng/mL. The primary endpoint of the study was potency recovery at 12 months following surgery and key secondary endpoints were continence, post-surgical margins, prostate volume change, biochemical recurrence, testosterone recovery, operative complications and adverse events (AE).
At 12 months, potency recovery was highest in the combination neoadjuvant therapy arm, reaching 50%, versus 37.5% for apalutamide alone and 17.4% in the surgery-only arm (p=0.017). Surgical margin rates were also lower in the combination therapy arm (15.4%) versus apalutamide alone (29.2%) and surgery alone (47.8%). The difference reached statistical significance (p=0.047). Biochemical recurrence rates (BCR) at 12 months were similar across groups (p=0.58), with BCR-free survival 75-81%. Testosterone recovery occurred in 95.8% of neoadjuvant patients, with a median of 3 months.
Apalutamide monotherapy was also associated with improved early continence recovery at 3 months post-prostectomy.
These results are encouraging, explained Zhang. “One of the largest challenges with prostatectomy in high risk localized diseases is tht the surgeon may take a wider margin which may involve nerves responsible for erection and urinary control,” he said. “And what our study shows is that giving a short 3 months course of apalutamide therapy can potentially change that with suppression of engine signaling and shrinkage or tumor downstaging prior to surgery.”
This could translate into urologists potentially being able to better preserve neurovascular bundles, resulting in improved functional recovery.
As for AEs, Zhang noted that there were some tradeoffs with intensified hormone suppression prior to surgery, as compared to the prostatectomy only arm. Howecer,most ofthese adverse events are manageable, and low grade. They were generally low grade and manageable with only one grade 4 adverse event of hot flashes
“Overall these findings suggest that a short course of apalutamide based therapy prior to prostatectomy may offer a meaningful way to improve the functional recovery without compromising early cancer control,” he concluded.
Supported by Rutgers Cancer Institute of New Jersey and Janssen
Abstract IP38-02
Neoadjuvant Apalutamide Therapy Enhances Potency Preservation Following Radical Prostatectomy by Downstaging the Disease in Men with High-Risk Prostate Cancer: Results of a Randomized Three-Arm Phase II Trial. Presented at the American Urological Association (AUA) 2026 Annual Meeting, Washington, DC, May 15 –May 18, 2026.
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