Comparison of PET imaging of [18F]F-FAPI and [18F]F-FDG for diagnosis of suspected lymph node metastases in penile squamous cell carcinoma: a prospective pilot study.

PURPOSE: To evaluate the potential value of [18F]F-FAPI PET/CT for detecting inguinal lymph node (ILN) metastases in locally advanced penile squamous cell carcinoma (PSCC) and to compare the results with those of [18F]F-FDG PET/CT.

METHODS

In this prospective pilot study, 25 patients with histologically confirmed PSCC underwent both [18F]F-FAPI and [18F]F-FDG PET/CT followed by radical ILN dissection within 30 days. Diagnostic performance was assessed using postoperative histopathology as the reference. Semi-quantitative parameters (SUVmax, SUVmean, tumor-to-background ratio (TBR)) were analyzed, and immunohistochemical staining for FAP and GLUT1 was performed on resected lymph nodes to assess correlations with PET-derived metrics.

RESULTS

Among 25 evaluable patients, 12 (48%) had pathologically confirmed lymph node metastases. On a patient-based analysis showed [18F]F-FAPI PET/CT achieved 100% accuracy in N-staging, compared to 72% for [18F]F-FDG PET/CT. On a lesion-based analysis, a total of 447 lymph nodes were dissected, of which 27 were confirmed as metastases. The sensitivity, specificity, positive predictive value, and accuracy for [18F]F-FDG vs. [18F]F-FAPI PET/CT were as follows: sensitivity, 0.89 (95% CI: 0.71-0.97) vs. 0.96 (95% CI: 0.81-1.00); specificity, 0.93 (95% CI: 0.90-0.95) vs. 1.00 (95% CI: 0.99-1.00); PPV, 0.44 (95% CI: 0.35-0.53) vs. 1.00 (95%CI: 0.87-1.00); and accuracy, 92.2% vs. 99.8%, respectively. Metastatic lymph nodes exhibited significantly higher SUVmax, SUVmean, and TBR than benign nodes, with [18F]F-FAPI demonstrating superior discriminative ability. Immunohistochemical analysis revealed markedly elevated expression of both FAP and GLUT1 in metastatic nodes than in benign nodes, with FAP upregulation being more pronounced. FAPI uptake correlated positively with FAP expression, whereas FDG uptake correlated positively with GLUT1 expression.

CONCLUSION

[18F]F-FAPI PET/CT demonstrates promising diagnostic performance in detecting ILN metastases in patients with PSCC compared to [18F]F-FDG. This modality holds potential value in refining patient selection for inguinal lymph node dissection and reducing unnecessary surgical morbidity.

TRIAL REGISTRATION: ChiCTR2400085605. https://www.chictr.org.cn .