[¹⁸F]F-FAPI PET/CT and LAparoscopy in STagIng advanced gastric Cancer: a multicenter prospective study (PLASTIC-3...

Treatment decisions for locally advanced gastric adenocarcinoma rely on staging with gastroscopy, computed tomography (CT), and staging laparoscopy (SL). However, CT often fails to detect peritoneal and other distant metastases, and SL is an invasive procedure with complication risks and costs. Therefore, an accurate non-invasive imaging biomarker to detect such metastases could improve the care for gastric cancer patients. Radiolabeled fibroblast-activating protein inhibitors (FAPI), targeting stromal cancer-associated fibroblasts, are promising radiotracers. Preliminary Asian studies indicate that FAPI PET/CT outperforms [¹⁸F]FDG PET/CT in tracer uptake, tumor-to-background ratio and diagnostic sensitivity in gastric cancer. However, larger studies using FAPI PET/CT in homogeneous, representative cohorts are needed to validate and translate these findings to Western populations. This study evaluates the clinical impact and diagnostic accuracy of [¹⁸F]AlF-FAPI-74 PET/CT for optimizing patient staging, aiming to reduce futile toxic neoadjuvant and surgical treatments. This may help optimize treatment pathways, enhance quality of life (QoL), and reduce patient burden and healthcare costs.

This Dutch multicenter prospective clinical trial will recruit 250 patients with resectable, locally advanced gastric adenocarcinoma (cT3-4N0-3M0) as determined by gastroscopy and CT, planned for curative treatment. The modality under investigation is [¹⁸F]AlF-FAPI-74 PET/CT. The primary outcome is the proportion of patients in whom [¹⁸F]AlF-FAPI-74 PET/CT leads to a change in treatment intent. Secondary outcomes include diagnostic performance, patient burden from incidental or false-positive PET/CT findings, diagnostic delay, and clinicopathological correlation between [¹⁸F]AlF-FAPI-74 PET/CT and intra-operative findings during SL. The composite reference standard for 'true' (intraperitoneal) tumor burden includes SL-based peritoneal cancer index scores, biopsy, imaging and intra-operative findings. If [¹⁸F]AlF-FAPI-74 PET/CT proves reliable, its cost-effectiveness will be compared to the PLASTIC-study. Recruitment started July 3rd 2025 and will continue for 36 months.

This study hypothesizes that [¹⁸F]AlF-FAPI-74 PET/CT can detect two-thirds of all gastric cancer patients with M1-disease according to the reference standard. Additionally, an [¹⁸F]AlF-FAPI-74 PET/CT scan may reduce healthcare costs, optimize treatment pathways and patients' QoL. The study findings will be relevant for countries with similar treatment algorithms and healthcare systems.

ClinicalTrials.gov, NCT07018661. This trial was registered prospectively on June 12th, 2025.