Prostate-specific membrane antigen (PSMA)-targeted PET/CT may help detect and localise recurrent prostate cancer after minimally invasive focal therapy, while offering a different diagnostic profile from multiparametric MRI (mpMRI). A single-centre retrospective analysis at the University of California Los Angeles included patients assessed for suspected recurrence after focal treatment, a setting in which post-treatment changes can make imaging difficult to interpret. PSMA PET/CT identified local, nodal and distant abnormalities, and biopsy-validated comparisons showed higher sensitivity than MRI, although MRI retained higher specificity in segment-level analysis. The findings remain limited by the selected patient population, modest validation cohort and reader variability.
Detection Across the Prostate and Beyond
The main cohort included 112 patients who had previously received focal therapy and later underwent PSMA PET/CT because recurrence was suspected on the basis of prostate-specific antigen levels. No intervening treatment occurred between focal therapy and imaging. Treatment types included high-intensity focused ultrasound, cryoablation, laser ablation and electroporation. The median interval between focal therapy and PSMA PET/CT was 27 months. Clinical data came from electronic medical records, and PET positivity was assessed on both per-patient and per-region bases.
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Using the majority assessment of 3 masked readers, PSMA PET/CT was positive for intraprostatic uptake in 82% of patients. Pelvic lymph node involvement was identified in 15%, while distant metastases were suspected in 9%. Regional interpretation covered the prostate, pelvic nodes and distant metastatic sites using a per-region approach. Suspected seminal vesicle invasion and extracapsular extension were also recorded. Reader agreement was only moderate, showing that interpretation after focal therapy remains challenging.
Most disagreements occurred in patients with no more than 1 prostate lesion and lower PRIMARY scores, with discordant interpretations mainly involving low-volume or equivocal intraprostatic findings. Urinary tracer activity, inflammation, benign prostatic hyperplasia, tissue remodelling and treatment-related cavities can all create nonspecific uptake and mimic local recurrence. False-positive PSMA PET findings also remained a challenge, supporting multimodal assessment and careful correlation with pathology.
PET and MRI Show Different Diagnostic Strengths
A biopsy-validated subgroup of 39 patients had both mpMRI and prostate biopsy available close to the PSMA PET/CT examination. Biopsy histopathology served as the reference standard, with clinically significant prostate cancer defined as International Society of Urological Pathology (ISUP) grade group 2 or greater. Within this subgroup, 34 patients had clinically significant disease confirmed on biopsy. Diagnostic performance was assessed both per patient and across matched prostate segments.
On a per-patient basis, PSMA PET/CT sensitivity was 85%, compared with 82% for MRI. The statistical comparison did not show a significant difference between the modalities. At the segment level, standard PSMA PET sensitivity was 59%, compared with 25% for MRI. MRI, however, had higher segment-level specificity than PSMA PET, at 93% versus 82%.
Positive predictive values were similar between the 2 modalities in the segment analysis, while negative predictive value favoured PSMA PET. Delayed pelvic PET imaging at 90 minutes showed no significant differences in specificity, positive predictive value or negative predictive value compared with standard acquisition. The delayed acquisition was assessed alongside standard imaging to determine whether a later pelvic scan added value in the prostate bed. Expert readers considered it potentially helpful in equivocal cases complicated by urinary activity or post-treatment changes, although larger prospective studies are needed to confirm its clinical value.
Interpretation Challenges Limit Certainty
Post-treatment anatomy remains a central difficulty in using PSMA PET/CT after focal therapy. Visual interpretation considered the focality, asymmetry and intensity of uptake together with corresponding CT findings. Delayed pelvic imaging and contrast-enhanced CT were often helpful when findings were equivocal, particularly where urinary tracer activity or treatment-related tissue changes complicated assessment. Precise knowledge of the location and extent of previous focal treatment was also considered important when interpreting remodelling and treatment-related cavities.
The retrospective design places important limits on the findings. Patients were referred for biochemical recurrence rather than undergoing systematic surveillance, creating selection bias towards those with concerning clinical, biochemical or imaging findings. The biopsy subgroup was therefore enriched for recurrent disease and contained a limited number of true-negative cases. This limits the robustness and generalisability of specificity estimates.
The diagnostic comparison was further restricted by the limited overall availability of contemporaneous MRI and biopsy results. MRI examinations were interpreted by a single reader, and the standard and delayed pelvic PET acquisitions in the validation subgroup were also assessed by 1 PET reader because of resource constraints. Moderate interreader agreement for PSMA PET highlighted the need for more standardised interpretation frameworks and reader training. Larger prospective, multireader studies are needed to validate the results and clarify the value of delayed pelvic imaging.
PSMA PET/CT showed potential for detecting and localising recurrent prostate cancer after focal therapy, including disease within the prostate, pelvic nodes and distant sites. In the biopsy-validated subgroup, PET showed higher sensitivity than MRI, particularly at the segment level, while MRI was more specific.
Interpretation remained difficult in some post-treatment settings, and reader agreement was only moderate. The retrospective, single-centre design, selected recurrence population and limited validation cohort restrict how broadly the results can be applied. Prospective studies with larger cohorts and multireader assessment are needed to define the optimal role of PSMA PET/CT after focal therapy.
Source: Journal of Nuclear Medicine
Image Credit: iStock
References:
Jafarvand M, Farolfi A, Mei R et al. (2026) PSMA PET Imaging for Prostate Cancer Recurrence After Minimally Invasive Focal Therapy: A Single-Center Retrospective Study. Journal of Nuclear Medicine: jnumed.125.271556.
