The Usefulness of FDG PET-CT in the Routine Staging of Gastric Cancer: A Retrospective Analysis from the Lead Cancer Center, Pakistan

Introduction

Globally, gastric cancer is one of the primary causes of cancer deaths, particularly in the western population, where unfortunately, patients are present at a later stage, at the time of diagnosis.[1] Early detection and accurate staging of gastric cancer is important for optimal treatment, as surgery is the main curative treatment option for localized disease. Prior to surgical planning, gastric cancer must be staged accurately, which includes lymph node (LN) involvement, degree of local invasion, and presence of distant metastases. Surgical resection together with, either neoadjuvant or adjuvant chemotherapy, is a standard treatment for resectable gastric cancer.[2] Gastric cancer patients with visceral metastases or involvement of LNs outside D2 are usually not considered appropriate for resection due to the risk of early recurrence.[3] As a result, preoperative staging in gastric cancer is essential in identifying patients with locally advanced or metastatic disease, for whom surgery is unlikely to be beneficial.[4] The use of fluorodeoxyglucose positron emission tomography–computed tomography (FDG PET-CT) scans in gastric cancer, particularly in identifying patients with metastasis, is not clear from the literature; however, in esophageal and GOJ/GEJ cancers, FDG PET-CT is widely used in identifying metastatic disease.[5] The lack of use of FDG PET-CT in gastric cancer may be attributed to the observation that gastric cancer, especially the mucinous and diffuse subtypes, is deemed nonavid on FDG PET-CT.[6] Hence, FDG PET-CT is not routinely used in Europe and the United Kingdom for staging of gastric cancer.[7] Surgical resection for gastric cancer carries significant risks, including the possibility of death. Unfortunately, even after what is considered curative surgery, recurrence is not uncommon.[8] Therefore, there is an imminent need to improve the staging process to avoid unnecessary treatment in this group of high-risk patients. In our institution, we have routinely used PET-CT to stage patients with gastric cancer whose staging CT scan did not show metastatic disease.

The rationale of this retrospective review is to evaluate the usefulness of FDG PET-CT in routine staging of gastric cancer patients. We analyzed the FDG PET CT avidity of gastric cancer in our population, with a particular focus on the detection of distant metastases. The goal was not only to improve the staging process but also to avoid unnecessary further investigations and major surgery.

Materials and Methods

After gaining approval from the IRB of our organization, we analyzed the FDG PET-CT data of gastric adenocarcinoma (GA) patients without any obvious metastases on staging CT scan from January 2018 to December 2022. During this time, the medical record numbers of all patients who were discussed in the upper gastrointestinal multidisciplinary team (MDT) meeting at Shaukat Khanum Memorial Cancer Hospital and research Centre (SKMCHandRC), were retrieved and reviewed. Patients who had confirmed histological diagnosis of GA were included. Patients with GOJ/GEJ cancers and metastatic disease on staging CT scans were excluded. Patient demographics, tumor size, site, grade of differentiation, Lauren classification (Intestinal and diffuse types), radiographic information including Tumor, Node, and Metastasis (TNM) staging, and FDG PET scan details were included for data analysis. Signet ring cell carcinoma is included in the diffuse type.[9] We included diffuse types of gastric cancer having signet ring cell histology. FDG PET avidity was assessed as a standardized uptake value (SUV_max) above the hepatic SUV as a reference point. The presence of avid local and regional LNs and visceral metastasis was assessed. Any structure with FDG-PET uptake more intense than liver, were considered FDG-avid tumor.[10]

Results

The demographic and tumor characteristics of the patients are presented in Table 1.

Discussion

Despite the advances in oncological medicine, unfortunately, more than 50% of patients have a disease that has spread beyond loco-regional lymph nodes and unsuitable for curative surgery.[11] Early identification and accurate staging are pivotal for optimal management of gastric cancer, as surgery constitutes the main treatment option for gastric cancer that has not metastasized. FDG PET-CT can help in the accurate diagnosis and staging of cancer, which can avoid unnecessary surgery.[12]

Optimal anatomical delineation of PET findings and FDG negative lesions on CT images can be achieved through PET-CT integration which may contribute to preoperative staging.[13] The utility of PET-CT in routine gastric cancer staging is underutilized; however, it is part of staging workup esophageal and GEJ/GOJ cancers.[5] The lack of utilization of PET-CT in gastric cancers could be attributed to the observation that gastric cancer (especially the mucinous and diffuse subtypes) is usually deemed to be nonavid on PET-CT.[6] Hence, PET-CT is routinely not a part of the staging process in gastric cancer in Europe and the United Kingdom.[7] In contrast to the European and UK practice, in our institution, we have routinely used PET-CT to stage patients with gastric cancer. Hence, we decided to question and evaluated the usefulness of PET-CT scans in detecting metastatic disease. Our study showed that PET-CT does have a place in modern gastric cancer staging and it supplements other imaging modalities used for staging purposes. To the best of our knowledge, this is the first study carried out in Southeast Asia to determine the efficacy of PET-CT scans in routine gastric cancer staging.

The population included in this study is predominantly younger patients, which is in discordance with western literature, but in concordance with other developing countries.[14] The low age of gastric cancer incidence in developing countries could be partially explained by the lower life expectancy recorded in developing countries.[15] In this study, there were twice as many males as females, consistent with previous reports.[16]

In our population, up to 89% of patients had PET-avid primary disease, and 39% had PET-avid nodal disease. Previous studies showed tumor FDG avidity of up to 81% and nodal avidity of 30% in gastric cancers.[17] According to Lauren’s classification of gastric cancer subtypes, the intestinal type was more FDG avid than the diffuse type, though this was not statistically significant. Interestingly, Findlay et al. did not detect a difference in the rate of primary tumor avidity between the histological subtypes, despite agreeing with our findings on subtype differences in SUV_max.[18] Previous research has also demonstrated that FDG PET-CT is less sensitive in detecting LN metastases in gastric cancer,[19,20] with sensitivity values often <50%, and the current study’s findings are consistent with this. The current investigation identified numerous characteristics that suggest the use of FDG PET-CT in gastric cancer staging. For instance, as 89% of tumors absorb the tracer, staging information is available for these patients. We observed that FDG PET-CT detected occult metastases in an additional 8% of patients, leading to their up-staging and making them unsuitable for curative resection. This prevented substantial expenditure and the morbidity associated with unnecessary surgery, which would have had an uncertain probability of benefiting the patient's long-term survival. Studies have shown that FDG PET-CT can possibly play an additional role in detecting distant metastasis in gastric cancer, with positive results in 6% to 16% of patients.[21,22] The additional expenses associated with PET-CT appear to be low and can be offset by avoiding unnecessary investigations and treatment costs. FDG-PET does not replace staging laparoscopy since it fails to detect peritoneal disease.[23]

The key variables of interest were subjected to multivariate regression analysis to identify factors associated with metastases on PET-CT scan. The FDG-avid nodes and moderate or poorly differentiated tumor remained significant on multivariate analysis. Findlay et al. also reported FDG-avid node as a predictive for the presence of metastatic disease on PET-CT scan.[18] While more invasive than PET-CT, staging laparoscopy allows direct visibility of the liver and peritoneum surface, as well as histology of any suspicious lesion and fluid for cytology analysis. Laparoscopic staging gives clinically substantial utility to the diagnosis of GA. Despite a negative CT scan, up to 30% of patients with disease T2 or above will be found to have peritoneal metastases on staging laparoscopy.[24] The current study also found that 25% of patients had peritoneal metastasis on staging laparoscopy with a negative CT scan. Compared to staging laparoscopy, FDG-PET has lower sensitivity but higher specificity in metastatic disease, which is compatible with the previous studies.[22]

In summary, this study highlights the significance of FDG PET-CT in the routine staging of gastric cancer patients with no apparent metastases on initial staging. Patients eligible for radical curative resection would benefit from additional staging with a PET-CT scan in conjunction with staging laparoscopy. The fact that we can detect occult metastases with a PET-CT is the most useful component because it allows the identification of surgical candidates and prevents futile invasive procedures in patients who have metastatic disease. Gastric cancer has a high avidity, regardless of histological type; FDG PET-CT improves the diagnosis accuracy of stomach cancer. Future prospective large-scale studies are required to investigate the use of FDG PET-CT in gastric cancer staging workup.

The limitations of our study include its retrospective nature and sources of biases, which means that there is a possibility that the group of patients who underwent additional investigations, such as FDG PET-CT, may demonstrate a degree of referral bias, leading to potential overestimating the efficacy of the scans. We have been doing PET-CT as a routine investigation which minimizes the potential for selection bias. Apart from these limitations, initially, FDG PET-CT was reported by multiple members of the team which led to interreporter variation. However, this risk was alleviated by double reporting of FDG.

Conclusions

We concluded that routine FDG PET-CT staging detected metastases in 8% of patients with nonjunctional gastric cancer, most of which would not have been detected by other staging methods. This resulted in improved patient care and avoided unnecessary further investigations and radical therapy.