Fibroblast-activating protein (FAP) expression and first clinical utility of ⁶⁸ Ga-FAPI-PET-CT in testicular cancer patients.

Abstract

e17019 Background: The fibroblast activation protein (FAP) is usually expressed on the surface of fibroblasts within the tumor and overexpression is associated with worse oncological outcome in several cancer entities. As a novel imaging modality, 68 Ga-FAPI-PET-CT showed promising results with high sensitivity and specificity in detecting cancer infiltrated lymph nodes (LN). As of today, FAP expression as well as 68 Ga-FAPI-PET-CT has not been investigated in LN metastases in TC patients. Methods: We performed a retrospective analysis of metastatic TC patients who received retroperitoneal lymph node dissection as a primary treatment (pRPLND) as well as in patients who received RPLND after chemotherapy (cxRPLND) with residual LN mass. Tumor tissue in the testis and the LN of patients were immunohistochemically (IHC) stained with a FAP-inhibitor antibody and categorized as negative (0), medium (1) and high (2). A t-test was performed for statistical analysis between pRPLND and cxRPLND and stratified for malignancy vs. no malignancy. Furthermore, three patients with metastatic TC received 68 Ga-FAPI-PET-CT. Results: A total of 46 patients with a mean age of 43 (standard deviation (SD) ± 11.9) and 33 years (SD ± 10.9) at initial diagnosis, were identified with 10 seminomas and 36 non-seminomas. Twenty-one patients received pRPLND and 25 patients cxRPLND. Overall, malignancy in RPLND was present in 50% (pRPLND 42.9% (=9), cxRPLND 56% (n=14)). IHC expression of FAP in the testis was negative, medium and high in 12.5%, 46.9% and 40.6%. In 21 LN with malignancy (seminoma n=6, non-seminoma n=14) IHC was negative, medium and high in 22.75%, 36.35%, 40.9%, respectively. In 21 LN with no malignancy, there were 52.4% negative, 19% medium and 28.6% with high FAP expression. There was no statistically significant difference in FAP IHC between pRPLND vs. cxRPLND as well as LN malignancy vs. no malignancy (p=0.56, p=0.08). Three TC patients received a 68 Ga-FAPI-PET-CT showing a SUV max of 11.9, 4.9, one patient showed no avid lesion. FAP expression in two patients with avid LN lesions were considered high. The patient with a SUV max of 11,9 showed malignancy in an initial biopsy (seminoma), the one with the SUV max of 4,9 received RPLND without malignancy. The latter patient did not receive a LN biopsy. Conclusions: Expression of FAP in patients with TC showed high expression in both testis as well as metastatic LN. 68 Ga-FAPI-PET-CT results were heterogenous with varying avidity of FAP in retroperitoneal lymph nodes and requires further validation.