Differences in residual lesion detection after treatment of metastatic prostate cancer based on dual-tracer PET/CT

Background 18 F-fluorodeoxyglucose ( 18 F-FDG) positron-emission tomography/computed tomography (PET/CT) and 68 Ga-prostate-specific membrane antigen ( 68 Ga-PSMA) PET/CT are widely used imaging modalities for the diagnosis and management of prostate cancer. However, comparative data on their performance in evaluating residual disease in treated metastatic prostate cancer remain limited. This study aimed to compare the efficacy of 68 Ga-PSMA-11 and 18 F-FDG PET/CT in detecting residual lesions after therapy in patients with metastatic prostate cancer. Methods We retrospectively analyzed 26 metastatic prostate cancer patients who underwent both 68 Ga-PSMA-11 PET/CT and 18 F-FDG PET/CT at Nanyang Central Hospital between January 2023 and June 2025. A composite reference standard incorporating histopathology (when available) and follow-up contrast-enhanced CT or MRI was used to confirm metastatic lesions. Lesion-based detection rates and tumor-to-background ratios (TBR) were compared between the two tracers. Results In post-treatment primary tumors, detection rates were 92% for 18 F-FDG and 100% for 68 Ga-PSMA-11. 68 Ga-PSMA-11 demonstrated significantly higher SUVmax (median 17.08 vs 5.05, IQR 10.76-24.67 vs 3.90-6.38; P < 0.001, r = 0.81) and TBR (median 26.98 vs 4.81, IQR 17.00-38.97 vs 3.72-6.08; P < 0.001, r = 0.85) than 18 F-FDG. For bone metastases, detection rates were 95% and 100%, respectively, with 68 Ga-PSMA-11 again exhibiting superior SUVmax and TBR (8.29 ± 5.02 vs 33.77 ± 23.51, P < 0.001, d = 0.95; 6.56 ± 3.97 vs 33.08 ± 23.03, P < 0.001, d = 1.03). The per-lesion detection rate for lymph node metastases was 91% for 18 F-FDG PET/CT and 96% for 68 Ga-PSMA-11 PET/CT. SUVmax and TBR were significantly higher with 68 Ga-PSMA-11 (17.02 (9.40-27.07) vs 4.17 (3.55-5.17), P = 0.005, r = 0.80; 26.88 (14.85-42.77) vs 3.96 (3.38-4.93), P = 0.002, r = 0.85). Conclusions 68 Ga-PSMA-11 PET/CT shows higher tracer avidity and tumor-to-background contrast than 18 F-FDG PET/CT for detecting residual primary tumors, lymph node, and bone metastases after therapy in metastatic prostate cancer. 18 F-FDG PET/CT may serve as a complementary modality, and combined use of both tracers could enhance the detection of residual disease in treated patients.