Staging Invasive Lobular Carcinoma: A Prospective Study on the Efficacy of 18F-Fluoroestradiol (FES)-PET/CT

Invasive lobular carcinoma (ILC) often presents diagnostic challenges on conventional imaging, necessitating advanced imaging strategies for accurate staging. [18F]Fluoroestradiol (FES), a PET radiopharmaceutical, targets estrogen receptor-positive (ER+) lesions, which are prevalent in ILC. This study evaluates the utility of FES-PET/CT compared to standard-of-care (SOC) imaging for staging ER+ ILC.

This IRB-approved prospective trial (October 2022-October 2024) enrolled adults with histologically confirmed ER+ ILC at a National Cancer Institute-designated Comprehensive Cancer Center. Participants underwent FES-PET/CT, with optional [18F]Fluorodeoxyglucose (FDG)-PET/CT. The primary endpoint was the percentage of stage changes post-FES-PET/CT compared to SOC imaging, analyzed using a 1-sided binomial proportions test. Imaging was interpreted by a blinded nuclear and breast radiology specialist, with staging per AJCC eighth edition guidelines.

Of 27 enrolled participants, 25 underwent FES-PET/CT (2 excluded due to synthesis failure). Mean age was 60.3 years. Pre-FES-PET/CT staging was stage I (16%), II (60%), III (20%), and IV (4%). FES-PET/CT altered clinical staging in 32% of cases (P = .036), identifying occult stage IV disease in 12.5% and histologically confirmed axillary lymph node metastases in 8%. However, it missed axillary metastases in 28% compared to surgical staging. FDG-PET/CT, performed in 15 participants, showed 40% discordance with FES-PET/CT.

FES-PET/CT significantly enhances staging accuracy for ER+ ILC, detecting occult metastases that impact clinical management. Its limitations in axillary nodal detection suggest it complements, rather than replaces, surgical staging. Larger trials are needed to validate these findings.