PSMA PET/CT Improves Outcomes in Prostate Cancer Recurrence

Published: March 16, 2026

Prostate-specific membrane androgen (PSMA) PET/CT imaging is significantly impacting the management of men with prostate cancer who experience biochemical recurrence following radical prostatectomy, allowing for more precise treatment decisions and improved outcomes. A retrospective evaluation conducted at UCLA demonstrated a strong association between staging from PSMA PET/CT and progression-free survival (PFS), with specific therapies proving more beneficial for patients with certain staging characteristics.

The Evolution of Recurrence Detection

Between 20% and 40% of men undergoing radical prostatectomy for localized prostate cancer experience a biochemical recurrence within 10 years. Traditionally, salvage radiotherapy has been the standard of care for patients with rising prostate-specific antigen (PSA) levels, even as low as 0.1 ng/mL. However, conventional imaging modalities like CT, MRI, and bone scans often lack the sensitivity to accurately pinpoint the location of recurrence at these low PSA levels.

“You were just measuring size of lymph nodes, size of abnormality, if any, that you could see on a CT scan,” explains Jeremie Calais, MD, PhD, director of clinical research in the Ahmanson Translational Theranostics division, vice chair of the department of nuclear medicine and theranostics, and associate professor at David Geffen School of Medicine at UCLA. “We treated blindly. We gave salvage radiation therapy to the whole prostate fossa and pelvis lymph nodes area due to the fact that most of the recurrences were located there.”

The advent of PSMA PET/CT has revolutionized this approach. This imaging technique utilizes radioactive molecules that bind specifically to PSMA, a protein highly expressed on prostate cancer cells. This allows for the detection of previously undetectable lesions, enabling more targeted treatment strategies.

UCLA Study Findings

Researchers at UCLA retrospectively analyzed data from five prospective investigations conducted between January 2016 and May 2021, encompassing 113 men who had undergone radical prostatectomy, experienced biochemical recurrence, and subsequently received salvage radiotherapy after PSMA PET/CT imaging. The median age of patients was 67 years, with a median PSA of 0.4 ng/mL and a median time of 19.9 months from radical prostatectomy to PSMA PET/CT.

The study revealed that 40.7% of patients had no visible lesions on PSMA PET/CT, whereas 38.9% had one lesion, 16.8% had two or three, and 1.8% had between four and eight lesions. The most common sites of detected lesions were pelvic lymph node metastasis (34.5%), prostatic bed recurrence (18.6%), osseous metastasis (10.6%), and extrapelvic lymph node metastasis (3.5%).

After a median follow-up of 59.4 months, the cohort exhibited a median PFS of 49.2 months, with 2-year and 5-year PFS rates of 72.6% and 48.7%, respectively. Staging from PSMA PET/CT demonstrated a significant association with PFS (P = .006).

Patients with T0N0M0 disease (no visible disease) had the lowest risk of death compared to those with M1b-M1C disease (distant metastasis) (adjusted HR = 0.25; 95% CI, 0.11-0.57). N1/M1a disease (regional or distant lymph node metastasis) had an adjusted HR of 0.39 (95% CI, 0.18-0.89), and TrN0M0 disease (local recurrence) had an adjusted HR of 0.39 (95% CI, 0.16-0.96).

“Because this was a new technique, people tended to think that if you have nothing, you should do nothing. We can de-escalate treatment management,” Calais said. “We found out that’s not the case. People are doing better when we irradiate the area where we are supposed to irradiate— even when there is no visible disease there.”

Freedom from distant metastasis reached a median of 76.4 months, with 2-year and 5-year rates of 85.8% and 72.4%, respectively. The 2- and 5-year rates of freedom from initiation of new treatment were 92.9% and 82.7%, respectively. The cohort had a 2-year overall survival (OS) of 100% and a 5-year OS of 97.1%.

Treatment Optimization Based on PSMA PET/CT Findings

The study also highlighted the benefits of tailoring treatment based on PSMA PET/CT results. Whole pelvis radiotherapy significantly improved PFS for men with TrN0M0 disease (adjusted HR = 0.12; 95% CI, 0.01-0.76), but not for those with T0N0M0 disease. Prostate bed irradiation improved PFS for men with N1/M1 disease who had no PSMA-avid disease visible in the prostate bed (aHR = 0.25; 95% CI, 0.1-0.67). Androgen deprivation therapy improved PFS for men with nodal or distant metastasis (aHR = 0.37; 95% CI, 0.16-0.9), but not for those with TrN0M0 or T0N0M0 disease.

Ongoing Research

Calais and colleagues are currently conducting a prospective phase 3 trial comparing outcomes in men who received PSMA PET/CT imaging versus those who did not. The trial includes 103 patients in the investigation arm and 90 in the control arm, with data analysis expected by the end of 2026. The primary endpoints are success rates of salvage radiation therapy, measured by PSA levels 5 years after initiation of treatment.

Source: Nikitas J, et al. J Natl Compr Canc Netw. 2026; doi:10.6004/jnccn.2025.7102.

Disclosure: Calais reports consulting for Astellas, Blue Earth Diagnostics, Curium Pharma, DS Pharma, Exini Diagnostics, GE Healthcare, IBA RadioPharma, Isoray, Janssen, Lantheus, Lightpoint Medical, Monrol, Novartis, Point Biopharma, Progenics, RadioMedix, Sanofi and Telix Pharmaceuticals; serving on a data safety monitoring board for Curium Pharma; and serving as a scientific advisor for Curium Pharma, Lantheus, Novartis and Telix Pharmaceuticals.