FAPI-Guided Surgery In Medullary Thyroid Carcinoma Shows Promising Results

Key Takeaways

• PET-CT findings were associated with operative-plan changes in 46% of patients, and 91% of those changes were later supported by histopathology.
• Biochemical cure at 1 month was observed in the two R0 resection arms, at 84.2% in newly diagnosed disease and 46.7% in recurrent disease.
• Lesion-level accuracy was 96.5% with the tracer study versus 72.7% with conventional imaging, with higher sensitivity and specificity as well.

The cohort included newly diagnosed disease, recurrent disease, and unresectable disease or distant metastasis. All participants underwent [68Ga]Ga-CTR-FAPI-30 PET-CT-guided surgery to assess whether the tracer could improve preoperative lesion localization. Main findings included postoperative biochemical cure, lesion-level diagnostic performance, and operative-plan changes.

The prospective, open-label phase II trial enrolled 50 patients with medullary thyroid carcinoma. All patients underwent [68Ga]Ga-CTR-FAPI-30 PET-CT-guided surgery using a PET tracer, a covalent targeted radioligand fibroblast activation protein inhibitor. The prespecified analysis separated patients into newly diagnosed MTC with R0 resection, recurrent MTC with R0 resection, and unresectable disease or distant metastasis. The primary endpoint was biochemical cure at 1 month postoperatively, and secondary endpoints were event-free survival, diagnostic accuracy, and surgical plan modification rate. Results centered on postoperative biochemical cure, lesion localization, and operative planning.

At 1 month, biochemical cure was 84.2% in arm 1 (95% CI, 60.4% to 96.6%) and 46.7% in arm 2 (95% CI, 21.3% to 73.4%). Arm 1 included newly diagnosed disease after R0 resection, and arm 2 included recurrent disease after R0 resection. Investigators reported that both rates exceeded historical benchmarks, with P values ranging from 0.007 to 0.049. These findings were limited to the two R0 resection arms.

In lesion analysis, researchers evaluated 231 lesions with gold-standard pathology and compared [68Ga]Ga-CTR-FAPI-30 PET-CT with conventional imaging. Diagnostic accuracy was 96.5% with the tracer study and 72.7% with conventional imaging. Sensitivity was 98.5% versus 81.7%, and specificity was 85.3% versus 20.6%, with all comparisons reaching P < 0.0001. These results showed closer agreement with pathology across this surgically verified lesion set. The performance difference was consistent with improved lesion localization accuracy.

Compared with investigator-determined approaches, PET-CT findings altered surgical planning for nearly half of patients. Among those imaging-driven changes, 91% were supported by histopathology.