The main growth mode of esophageal cancer is local invasion and lymph node metastasis. Pre-treatment staging, especially lymph node staging, is an important basis for assisting clinicians in choosing reasonable treatment plans and evaluating prognosis. Anatomical images such as gastrointestinal barium meal, CT and transesophageal ultrasound are still commonly used staging methods in clinical practice, but the results of pathological verification are not ideal. There is evidence that 18F-FDG PET/CT can improve the preoperative staging of esophageal cancer, with a sensitivity of 67%-74%, especially for the detection of non-regional lymphoid or blood-borne diseases [10]. Although these results may indicate the important role of 18F-FDG, which is not a tumor-specific tracer, and false positive results may occur. For example, macrophages and neutrophils can show increased 18F-FDG uptake, leading to false positive results. In addition, patients need to have an empty stomach and rest quietly before undergoing 18F-FDG PET/CT examination.
In recent years, 68Ga-FAPI, as a very promising tumor imaging agent, has shown good diagnostic performance for the detection of primary tumors and metastatic tumors. In this study, FAPI showed good detection ability for primary lesions (29/29). In addition, the sensitivity of 68Ga-FAPI PET/CT for detecting lymph node metastasis is equivalent to that reported by previous researchers [4], but relatively low. One possible reason for these relatively low sensitivity values may be related to the inclusion criteria we used. In this study, only patients who underwent esophagectomy and lymph node dissection were included. Exclude patients receiving palliative care, preoperative chemotherapy or radiotherapy. Therefore, more cases of early disease and more patients with metastases under the microscope may be included in the current study. Our research shows that 68Ga-FAPI PET/CT has higher sensitivity, specificity, accuracy, positive predictive value and negative predictive value for lymph node staging than CT.
In this study, 11 metastatic lymph nodes were false-negative in 68Ga-FAPI PET/CT analysis. The reasons may be: (1) there are fewer tumor cells in the metastatic lymph nodes, resulting in less FAPI uptake; (2) the size of the metastatic lymph nodes is small, which is susceptible to the space limitation of PET and is affected by partial volume effects; (3) there is a large area in the metastatic lymph nodes necrosis. In CT scans, false negative results can be obtained, because metastasis may still occur in small or normal-sized lymph nodes; In addition, if there are inflammatory lymph nodes or lymph node swelling caused by granulomatous inflammation, false positive results can also be obtained. In this study, the smallest metastatic lymph node accurately detected by 68Ga-FAPI PET/CT was 3 mm. In CT scans, metastatic lymph nodes are defined as lymph nodes larger than 1 cm. In view of this, we believe that 68Ga-FAPI PET/CT is a more accurate diagnostic tool. In our study, a false positive result was found in 3 lymph nodes in patients with reflux esophagitis due to active inflammation. In addition, some studies have shown that benign lymph nodes may also have increased FAPI uptake, which needs to be differentiated from metastatic lymph nodes[11]. Nevertheless, due to the low incidence of false positive in PET imaging, we believe that it is accurate enough to be used as a basis for esophageal cancer treatment decisions. In view of the high specificity of 68Ga-FAPI PET/CT, it also provides useful information for guiding the choice of surgical methods. If a distant organ shows a positive result, there is no need to surgically remove the metastatic local lymph nodes.
Interestingly, in our study, increased FAPI uptake is also found in rib fractures, osteophytes, inverted papillomas, shoulder arthritis, thyroiditis, and pneumonia. These findings are consistent with some reported literature [12–19]. Therefore, further studies are needed to evaluate the diagnostic value of 68Ga-FAPI PET/CT
Our research has limitations. First of all, the number of patients is relatively small (n = 29), and they are mainly squamous cell carcinoma and males. Therefore, due to the bias of patient distribution, the diagnostic performance of 68Ga-FAPI PET/CT may be exaggerated. Prospective trials of larger patient populations are needed to further study the diagnostic effect of this diagnostic method. In addition, this study excluded patients with advanced esophageal cancer, the sensitivity and accuracy of the two methods for detecting lymph node metastasis may be underestimated. Moreover, the surgeon was instructed in preoperative CT and PET discovery. This fact may increase the verification bias. At the same time, since FAP immunohistochemistry has not been performed in histopathology, further analysis is needed for specific esophageal cancer FAP tissue quantification.