Darolutamide Boosts PSMA Expression in a Subset of Patients With Localized Prostate Cancer

Short-course darolutamide (Nubeqa) was found to increase prostate-specific membrane antigen (PSMA) expression in patients with high-risk localized prostate cancer, according to findings from the single-arm, phase 2 Daro-PET study (NCT05900973) presented during the 2026 Genitourinary Cancers Symposium.¹

In the intention-to-treat (ITT) population (n = 16), 31% of patients (n = 5) experienced any maximum standardized uptake value (SUV_max) increase following 7 days of treatment with darolutamide, with 18.8% (90% CI, 5.3%-41.7%) of patients experiencing at least a 20% increase (range, 36.5%-62%), meeting the study’s primary end point. The per-protocol population (n = 14) had comparable results, with 36% (n = 5) of patients experiencing any SUV_max increase and 21% (n = 3; 90% CI, 6.1%-46.6%) achieving an increase of 20% or more.

Half of patients (90% CI, 26.4%-73.6%; n = 7/14) experienced increased tumor volume (range, 6.2%-98.6%); 21.4% of patients (n = 3) had increased SUV_mean and total lesion PSMA. Moreover, no new pelvic or extrapelvic metastases were found following darolutamide.

“A 7-day course of darolutamide increased PSMA expression in a subset of men with high-risk localized prostate cancer,” Jéssica Vasconcellos, MD, of Instituto D’Or de Pesquisa e Ensino in São Paulo, Brazil, and co-authors wrote in the abstract. “These findings support further evaluation of androgen receptor pathway inhibitors to improve the performance of PSMA PET/CT and PSMA-targeted therapies.”

What is the design of the Daro-PET study? What inspired this research?

It is hypothesized that androgen suppression could transiently boost PSMA expression, with implications for PSMA PET detection and therapies designed to target this marker. However, authors noted that most available information comes from studies that have been performed in metastatic castration-resistant prostate cancer, with limited insights into localized, castration-sensitive disease.

The single-arm Daro-PET study was launched to examine whether 1 week of darolutamide given at a twice-daily dose of 600 mg after baseline PSMA PET/CT would result in increased PSMA expression in patients with high-risk localized prostate cancer.^1,2 The study utilizes a two-stage Simon design with 80% power and a one-sided α of 0.05; this required 12 patients for stage 1, an expansion to 16 patients after 1 event was reported, and 3 or more events signifying a positive trial.

The primary end point of the study was the proportion of patients with an increase in SUV_max from baseline PSMA PET/CT to repeat PSMA PET/CT following darolutamide treatment. Important secondary end points comprised tumor volume, SUV_mean, total lesion PSMA, new metastases, safety, and per-protocol analyses.

A total of 16 patients were enrolled onto the study between July 2023 and March 2025.¹ In these patients, the median age was 61 years (range, 55.5-70.5). More than half of patients (56%) had an International Society of Urological Pathology grade of 4 or higher. Moreover, 37.5% of patients had clinical T stage 2 disease, and 62.5% had cT3 disease. The total median prostate-specific antigen level was 10.01 ng/mL (interquartile range [IQR], 6.41-11.24) and the total median testosterone was 314 ng/dL (IQR, 258.3-392.9). One fourth of patients had baseline lymph node involvement, and 27% of patients had multifocal prostate uptake at baseline PET/CT scan.

What additional information was reported from the study at the meeting?

“All patients completed the protocol with full treatment adherence with no adverse [effects],” the study authors wrote. “Two patients did not undergo prostatectomy by shared decision-making.”

The authors also noted that 3 patients had 2 prostatic uptake foci, with heterogenous changes in PSMA uptake following exposure to short-course darolutamide.

They concluded that “translational studies are planned to investigate the mechanisms involved.”

Disclosures: Dr Vasconcellos disclosed serving on a Speakers’ Bureau for MSD and Servier, receipt of research funding from Bayer, and receipt of travel, accommodations, or expenses from MSD and Servier.

References

1. Vasconcellos J, Mosci C, Queiroz M, et al. A phase 2 trial of darolutamide to enhance prostate-specific membrane antigen expression in patients with localized prostate cancer (Daro-PET). J Clin Oncol. 2026;44(suppl 7):310. doi:10.1200/JCO.2026.44.7_suppl.310
2. A phase 2 trial of darolutamide as a prostate-specific membrane antigen (PSMA) expression enhancer in patients with localized prostate cancer. Clinicaltrials.gov. August 7, 2023. Accessed February 26, 2026. https://clinicaltrials.gov/study/NCT05900973