Cancer-associated fibroblast activation protein in Appalachian women with uterine cervix cancer

[²¹²Pb]Pb-PSV-359 is a radiopharmaceutical utilizing an alpha particle-emitting radionuclide lead-212 (²¹²Pb) and a fibroblast activation protein (FAPα)-targeted antagonist being assessed as anticancer treatment. Prior nuclear imaging studies have shown that almost all cancer-associated fibroblasts within uterine cervix cancer tumors express the radiopharmaceutical target FAP when assessed by radiotracer uptake criteria. It is unknown whether immunohistopathology supports this claim. Therapeutic response to [²¹²Pb]Pb-PSV-359 likely associates with FAP expression, and thus, it seems sensible to evaluate FAP immunoreactivity as a triage biomarker when intending to use this agent against persistent, recurrent or metastatic uterine cervix cancer.

We examined a series of 37 uterine cervix cancer paraffin-embedded tumors to determine whether this tumor type expresses FAP at a sufficient cell proportion and staining intensity for an immunoreactive score (IRS) of six or higher, as [²¹²Pb]Pb-PSV-359 is currently being evaluated in clinical trials only against tumors demonstrating radiotracer uptake criteria rather than also by immunoreactivity criteria.

The results show that 28 of 34 (82%) uterine cervix cancer tumors with evaluable desmoplastic stroma had cancer-associated fibroblasts expressing FAP. Twenty (59%) tumors scored at an IRS six or higher. Primary tumors from patients with stage IVB disease at diagnosis (n=11) or metastatic tumors (n=6) had cancer-associated fibroblasts expressing FAP most often (76%).

Cancer-associated fibroblast FAP immunoreactivity in this series indicates that [²¹²Pb]Pb-PSV-359 radiopharmaceutical therapy might have usefulness in women with persistent, recurrent or metastatic uterine cervix cancer. A phase I clinical trial inclusive of metastatic uterine cervix cancer patients is underway (NCT06710756).