PET-CT is a powerful radiological tool in different management stages of gastrointestinal malignancies including staging workup and post-treatment follow-up. But as an investigational tool, it has its own limitations. Besides its high cost, false negative and false positive as well as equivocal results are the main limitations. This study done at our institute shows a high rate of non-adherence to the guidelines with almost 60% of PET/CTs ordered for staging purposes, while results of many studies show its lower yield in staging workup.
A systematic review of 12 studies of the staging use of PET scan in esophageal cancer revealed sensitivity of 51% and specificity of 84% in detecting locoregional disease and sensitivity of 67% and specificity of 97% in detecting distant metastasis . And for locoregional N staging, high false-positive results of FDG-PET have been found and most of them related to an inflammatory process .
However, the extra benefit of PET over CT scan in the preoperative staging evaluation of esophageal cancer was tested in a randomized trial conducted by the American College of Surgeons Oncology Group, in which 262 patients with non-metastatic potentially cases after CT of the chest and abdomen were randomly assigned to PET or no PET . With the caveat that 22 percent of eligible patients did not undergo esophagectomy for a variety of reasons, PET after standard clinical staging identified biopsy-confirmed M1b disease in only nine patients (5 %) and unconfirmed evidence of M1b disease (which was accepted by the surgeon as evidence of metastases without biopsy confirmation) in 18 others (10%). An important limitation of the trial was that the integrated PET/CT was not used.
For primary gastric malignancy, PET/CT is associated with a low detection rate (about 55%), especially for early stage, as well as mucinous, signet-ring cell, and poorly differentiated adenocarcinomas, which are typically less metabolically active [9,10,11,12,13,14,15,16,17].
Moreover, it is not uncommon to see variable and occasionally intense physiological uptake within the gastric wall, which may mask FDG uptake by the primary tumor. In addition to that, increased FDG uptake may also correspond to the presence of gastritis. Therefore, PET/CT has a limited role in the detection and T staging of gastric cancer.
In patients with pancreatic cancers, Glucose intolerance is frequently encountered. High serum glucose level can compete with FDG uptake in the pancreatic tumor and can even lead to false-negative PET findings . The performances of PET/CT for detecting malignant pancreatic tumors have been shown to be equivalent to magnetic resonance imaging [19,20,21,22].
In gastrointestinal stromal tumors, PET/CT is now the imaging modality of choice because of its high sensitivity in assessing early therapeutic response to imatinib or other targeted therapies . Thus, PET/CT is beneficial in doubtful cases and when the early prediction of response is of special concern (e.g., preoperative cytoreductive treatments).
Also, PET/CT is not recommended for the detection of hepatocellular carcinoma (HCC), as several studies have demonstrated variable FDG uptake values due to wide range of levels of glucose-6-phosphatase activity and glucose transporters present in HCC [24,25,26,27], with an overall sensitivity of 50–65% [28,29,30].
According to the FFCD, NCCN, and ESMO guidelines, PET/CT is presently not recommended in the diagnosis, staging, and management of HCC.
In gallbladder cancer, there is a lack of evidence supporting the use of PET, and larger studies still needed to determine the potential of this technique in influencing patient outcomes.
In our study, PET/CT changed the stage in 19.6% of cases and changed the management plan in 11.2% only, while in many studies, PET findings led to a significant change in patient management in about one third of the patients in esophageal cancer [31, 32], and in gastric cancer, gastrectomy was shown to be unnecessary in 6–10% of patients .
Our explanation for this lower rate of impact on stage and/or management is the lack of accurate interpretation of PET-CT results that could be due to overuse in non-indicated clinical scenarios, which lead to dilution of clinically significant results.
Early detection of recurrence using imaging techniques is challenging due to tissue changes induced by surgery and/or radiotherapy. However, the available data are insufficient to draw any conclusion and PET/CT cannot be widely recommended in this setting. And our results in this setting was 27% of all requested PET-CT (14.9% in follow-up after the end of treatment, 8.4% in restaging at relapse, assessing response after/during treatment in 3.7%), which present a huge portion in non-indicated setting.
In this study, PET/CT scan reported indeterminate or equivocal results in 32 out of 107 scans (29.9%) which is a relatively high equivocal reporting of lesions. Generally, lesions were considered indeterminate if false-positive or false-negative settings were highly suspected, if they had no or minimal FDG avidity because of small size, or if the clinical settings indicate false-positive results such as inflammatory or post-operative settings. Investigators reviewed the clinical setting of each scan, and as per their best clinical judgment on a retrospective basis, they decided that in 52 scans (out of the total 107), there was a need for pathological pursuit because findings were indeterminate and that could have changed the stage and hence affected the management. However, that was only done after 12 scans of those 52 (23.1%), and that is a low percentage of further confirmation with pathology and could be due to lack of knowledge of PET/CT scan limitations including false-positive results which leads to over trust of PET/CT by some treating physicians.
Therefore, pathology in certain clinical scenarios remains the standard tool to confirm the presence of malignancy and should not be replaced by PET.
The main flaws or limitations of the study were as follows:
The sample selected was from 2007 to 2008 and followed to 2015, which was the time of implementing PET/CT at our institute and time to examine adherence to guidelines and test its limitations. Data collection does not undermine the credibility or validity of these data because the diagnostic approach, as well as clinical settings, has not changed.
The sample size is 77 cases, which underwent 107 scans, which was chosen to fulfill the aim of the study to see the pattern of use of PET/CT scan in GI cancers and to check the adherence to the NCCN guidelines. Sensitivity and specificity PET/CT are completely out of the scope of this study. It is basically an assessment of the use of certain diagnostic tool in certain situations at a certain place and not diagnostic research that should have a certain sample size for a threshold of sensitivity and specificity. Therefore, the sample size was not necessarily large, and in order to see representation from all types of the GI cancers, cases of non-colorectal GI cancers were lumped together because what we are interested in is to see the pattern of use and not the clinical yield of PET/CT scan. Having said that, the cases for colorectal cancer were preplanned to be published in a separate report and we planned to just publish the data on non-colorectal cases in this report.
Last, the study did not dwell on the reasons for not pursuing the pathological diagnosis, because they were either dangerous to perform the biopsy or due to the interventional radiologist refusal or even the patient refused after the risks were explained to him.