Neovascular prostate specific membrane antigen (PSMA) expression in bone and soft tissue sarcoma: a systematic analysis

Bone and soft tissue sarcomas are a highly heterogeneous group of rare cancers of mesenchymal origin. Treatment options other than surgery have limited efficacy due to low response rates with some exceptions. Radioligand therapy targeting prostate-specific membrane antigen (PSMA) may provide a novel treatment option, as it was recently suggested that soft tissue sarcomas express PSMA in the neovasculature, and on PET/CT imaging, multiple sarcomas have shown intense PSMA-tracer accumulation. Moreover, in prostate cancer patients, incidental PSMA uptake was seen in hemangiomas. In addition to confirming previous results in soft tissue sarcoma, the current study aims to systematically explore the expression of PSMA in bone tumors and in vascular tumors. Immunohistochemistry for PSMA was performed on a total of 706 tumors. High PSMA expression in the neovasculature was seen in 29% of the soft tissue sarcomas and 33% of the bone sarcomas. Malignant tumors showed a higher frequency of PSMA expression (score 2) as compared to benign tumors, with a high frequency in rhabdomyosarcoma (2 of 2, 100%), mesenchymal chondrosarcoma (14 of 20, 70%), undifferentiated sarcoma of bone (4 of 6, 67%) and of soft tissue (13 of 20, 65%), and osteosarcoma (46 of 81, 57%). In addition, giant cell tumor of bone displayed a high PSMA labelling in 67% of the cases. In contrast, high PSMA expression was seen in only 0-40% of the non-neoplastic vessels in vascular tumors, while 8% of them expressed PSMA in the tumor cells. Thus, with variable frequency among the different subtypes, a subset of bone and soft tissue tumors, both malignant and intermediate behavior, express PSMA and these patients may benefit from PSMA-targeting PET/CT scans or PSMA targeted radioligand therapy.