Effect of neoadjuvant androgen deprivation therapy on prostate and tumor morphology prior to MRI-guided transurethral ultrasound ablation of prostate cancer.

Thermal ablation is a minimally invasive treatment for localized prostate cancer (PCa). MRI-guided transurethral ultrasound ablation (TULSA) enables precise, temperature-controlled therapy, but its 3 cm ablation radius may limit coverage in large prostates or capsule-adjacent tumors. Neoadjuvant androgen deprivation therapy (nADT) may improve treatment feasibility by reducing prostate and tumor size. In this prospective, single-arm pilot study (NCT05917860), 15 treatment-naïve patients with organ-confined, intermediate-risk ISUP 2-3 PCa and at least one biopsy-concordant PI-RADS ≥ 3 lesion received 3-month nADT with degarelix before whole-gland TULSA. Multiparametric MRI was performed at baseline and monthly thereafter to assess prostate and lesion volumes, tumor-capsule relationship, and urethra-capsule distance. All patients completed nADT. Across 27 PI-RADS ≥ 3 lesions, four patients had unifocal disease, and 11 had multifocal disease (2-3 lesions). Twenty lesions were ISUP Grade Group 2 and three were Grade Group 3. PSA declined by 87% (-7.6 ng/mL; 95% CI. -9.7 to -5.7; p < 0.001), and all patients achieved castrate testosterone levels. Prostate volume decreased by 26% (-15 mL; 95% CI. -20 to -12; p < 0.001), index lesion volume by 69% (-0.8 mL; 95% CI. -1.2 to -0.5; p < 0.001), and index-lesion capsule contact length by 40% (-5 mm; 95% CI. -7 to -4; p < 0.001). Capsule bulging resolved in four of seven patients, and urethra-capsule distance decreased to ≤ 30 mm in all six patients with a baseline distance > 30 mm. Short-term nADT with degarelix was associated with significant changes in prostate and tumor morphology. Future studies should determine whether these changes improve TULSA outcomes.