The objective of the current study was to determine the clinical role of 18F-FDG PET/CT in the assessment of BTC recurrences when clinicians suspected recurrence during surveillance based on symptoms, laboratory findings (including tumor markers), and CT findings. Our data suggest that 18F-FDG PET/CT alone is not more sensitive or specific than ceCT in the detection of recurrent BTCs. However, these results do not reach statistical significance, probably due to the low number of patients. On the other hand, an additional 18F-FDG PET/CT on ceCT significantly improves the sensitivity in detecting recurrences.
Previous studies have evaluated the utility of 18F-FDG PET or PET/CT in BTCs [11, 13, 16–18]. The study by Kim et al enrolled 123 patients with suspected and potentially operable cholangiocarcinomas, and demonstrated that PET/CT showed no advantage over ceCT in the diagnosis of primary tumors, but was more valuable in the diagnosis of regional lymph node and distant metastases . Petrowsky et al reported that PET/CT and ceCT provided comparable accuracy for primary cholangiocarcinoma, but PET/CT was particularly valuable in detecting unsuspected distant metastases which were not diagnosed by standard imaging in the staging of patients with gallbladder cancer and cholangiocarcinomas (12/12 in PET/CT vs. 3/12 in ceCT; p < 0.001) . In these studies, 18F-FDG PET or PET/CT did not have a statistically significant advantage over ceCT in the diagnosis of primary tumors, but was valuable in identifying occult distant metastases which were not detected by conventional imaging. Only Corvera et al identified the role of 18F-FDG PET in detecting disease recurrences after resection in their analysis and reported that 18F-FDG PET was helpful to clarify recurrences with 76% of sensitivity . Thus, 18F-FDG PET was merely confirmatory because recurrences were also identified on conventional imaging.
Unlike the aforementioned studies, the current analysis documented the complementary role of 18F-FDG PET/CT under a frequently encountered situation in the clinic in which clinicians suspected a recurrence. Of 50 patients, 36 had concordant results between ceCT and subsequent 18F-FDG PET/CT, and 18F-FDG PET/CT was 83% (30/36) consistent with the final recurrence status (Figure 2). Moreover, an additional PET/CT correctly identified six false-negative cases as recurrences which were interpreted as benign or equivocal by ceCT. This resulted in a significant increase in sensitivity (88% vs. 94%, p = 0.03) and suggested a complementary role of 18F-FDG PET/CT beyond ceCT when clinicians suspected a recurrence.
Of these six false-negative cases by ceCT, three were first interpreted as post-operative inflammatory changes. For the other three cases, lymph node metastasis was not confidently interpreted as a recurrence due to the insignificant size. However, the 18F-FDG PET/CT was interpreted as a recurrence in these lesions based on the high 18F-FDG uptake. From this information, five patients could receive palliative chemotherapy, whereas the other patient could not receive chemotherapy because of poor performance status. Moreover, an additional PET/CT showed no 18F-FDG uptake in five false-positive cases by ceCT, which provided decisive information to the clinicians. Among 14 patients with discordant results, 11 patients (11/14, 79%) was treated regarding to the results of PET/CT. In this context, when ceCT is inconclusive for identifying post-operative changes and the lymph nodes are of borderline size, a discernible role for 18F-FDG PET/CT is feasible.
This complementary role of 18F-FDG PET/CT during surveillance has been assessed in other cancers. Specifically, Radan et al described patients with breast cancer and rising tumor markers in which 18F-FDG PET/CT was superior to CT for diagnosis of tumor recurrence, and led to changes in the subsequent clinical management of 51% of the patients . In addition, Guo et al evaluated the role of 18F-FDG PET/CT in patients with possibly recurrent esophageal squamous cell carcinoma who underwent definitive treatment and displayed a remarkable sensitivity and a high specificity and accuracy at regional and distant sites for recurrent esophageal squamous cell carcinoma .
Furukama et al. evaluated the prognostic significance of FDG uptake on PET in patients with biliary tract cancer and demonstrated the SUVmax of 6.3 to be the optimal cutoff point for survival . In addition, their data showed that the SUVmax was one of the significant prognostic factors for overall survival in univariate analysis. However, our data did not show that the SUVmax was the significant prognostic factor for overall survival, probably due to the low number of patients and selection bias.
Our study had limitations other than retrospective design. First of all, the majority of recurrent cases were confirmed clinically. Our standard for non-recurrence required no significant changes in the lesion for a minimum of 3 months; however, such a criterion has not been validated and may be insufficient for confirmation. Second, the validity of 18F-FDG PET/CT may have been overestimated because the nuclear medicine physicians were aware of the findings of the corresponding ceCT. Lastly, the longer time interval between ceCT and PET/CT and the different characteristics of 3 CT scanners between the period of 2003 to 2008 might influence the results. Nevertheless, our study has significance in demonstrating the complementary role of 18F-FDG PET/CT in a commonly encountered clinical situation in which clinicians suspect BTC recurrence by elusive clinical manifestations with equivocal or inconclusive conventional imaging. Additionally, as the most modern PET/CT scanners allow for fully diagnostic ceCT scans, contrast enhanced diagnostic PET/CT could be recommended as the primary modality of choice in case of suspected recurrence.