Scrotal uptake on PSMA PET in prostate cancer: differentiating metastases from benign and physiologic findings using ultrasound correlation.

[PURPOSE] To identify imaging and clinical features that aid in distinguishing metastatic lesions from benign or physiologic uptake on PSMA PET, using correlation with scrotal ultrasound.

[METHODS] This IRB-approved retrospective study included prostate cancer (PCa) patients who underwent PSMA PET-CT or PET-MRI between July 2021 and May 2025, with a scrotal ultrasound performed within 100 days of the scan. PSMA-avid lesions were assessed for uptake intensity (mild vs. intense), distribution (diffuse vs. focal), laterality (unilateral vs. bilateral), scan indication (initial staging vs. restaging), and SUVmax. Ultrasound findings were reviewed, and metastasis was confirmed by pathology or clinical consensus by three board-certified radiologists. Multivariable logistic regression using LASSO was performed to identify predictors of testicular or paratesticular metastasis.

[RESULTS] Of 114 patients (mean age 70), 24 (21%) demonstrated scrotal PSMA uptake. Focal intense uptake was seen in 6 patients (all unilateral), and mild focal uptake in 17 (13 bilateral, 4 unilateral). One patient showed mild diffuse bilateral uptake; no cases had intense diffuse uptake. Metastasis was confirmed in 5 patients, all of whom showed focal, unilateral, intense uptake. Among the 17 with mild focal uptake, 16 (94%) had no ultrasound abnormalities, consistent with physiologic epididymal uptake. Of 12 patients with ultrasound findings of epididymitis or orchitis, only 2 showed PSMA uptake (1 intense, 1 mild), while 10 had none. LASSO regression identified uptake intensity, SUVmax, PET indication, and laterality as significant predictors of metastasis. PET indication showed the strongest association with metastasis (coefficient = 4.60), followed by uptake intensity (3.97), SUVmax (1.37), and laterality (0.37), indicating a higher likelihood of metastasis in unilateral, intensely avid lesions, particularly in restaging settings.

[CONCLUSION] Focal, unilateral, intense PSMA uptake, especially during restaging, was strongly associated with testicular or paratesticular metastasis. In contrast, mild or bilateral uptake without ultrasound abnormalities was typically physiologic. Combined assessment using PSMA PET and scrotal ultrasound improves diagnostic accuracy in evaluating scrotal findings in PCa patients.