Disease staging is one of the fundamental steps in the development of a treatment plan for patients with mesothelioma. Effective measurement of tumor spread and the identification of distant metastases are important indications of long-term prognosis and, therefore, are determinate conditions in deciding which patients are eligible for radical surgery and which patients will be treated less invasively. Generally speaking, patients who are considered Stage I-III for pleural mesothelioma may be acceptable for “curative” surgeries such as extrapleural pneumonectomy, while patients with Stage IV disease are excluded from these procedures and will be treated palliatively. Staging is designed to separate out patients so those in the disease’s later stages do not undergo operations that are associated with significant surgical complications and extended recovery time when their long-term prognosis is not hopeful.

Historically, however, there have been difficulties in the accurate determination of stage because of mesothelioma’s unique behavior and morphological form. Unlike most other cancers which present as an individualized tumor with clear boundaries (even if there are multiple tumors, they generally fit this same individualized pattern), pleural mesothelioma presents as a diffuse malignancy that grows along tissue surfaces, with little distinction between malignant and non-malignant areas. This can make determining the full extent of tumor infiltration difficult to properly image. CT is the standard technology in diagnostic imaging for mesothelioma and MRI can be used to supplement its results, but these technologies have known limitations in determining a number of important tumor states, including tumor involvement of the chest wall and diaphragm, as well as a fundamental inability to identify distant metastatic events or to determine lymph node status. PET can be used to identify distant metastases, but it has poor spatial resolution, so precise localization is difficult. Mediastinoscopy is used to determine the status of the mediastinal lymph nodes, but it is an invasive procedure and is limited in its ability to target all of the important lymph nodes.

Because of these difficulties, some of which are common to all cancers and some of which are specific to pleural mesothelioma, researchers have developed a number of new technologies to aid physicians in their ability to accurately diagnose and stage malignant events. One of these new systems is integrated PET/CT, which combines PET’s ability to identify distant metastases with CT’s high resolution imaging of internal anatomic structures. A number of studies on this technology’s use for mesothelioma have been published and the results have been quite promising. Continuing this researching, researchers in Denmark have recently published an article on their use of PET/CT in the preoperative staging of patients with pleural mesothelioma. In their article, “Preoperative Staging of Mesothelioma by 18F-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography/Computed Tomography Fused Imaging and Mediastinoscopy Compared to Pathological Findings After Extrapleural Pneumonectomy,” the authors demonstrate PET/CT’s advancements over CT for pre-operative staging and they recommend its greater use in the staging of mesothelioma, but they also show that it cannot replace mediastinoscopy for the analysis of nodal status.

Overview of the Study

42 patients were enrolled in the study between October 2003 and October 2006. All patients had histologically-confirmed mesothelioma, epitheloid subtype. All patients received neoadjuvant chemotherapy prior to their staging assessments, which were conducted by CT and PET/CT. The results of the scans were interpreted separately and blinded from the other. Patients whose PET/CT results indicated any non-resectable tumor infiltration of the chest wall or of structures in the mediastinum, or any evidence of distant metastases, were not given surgery, although patients whose results indicated possible N2 or N3 metastases were still referred for mediastinoscopy for histological determination of stage. If these results also showed positive N2 or N3 metastatic status, the patients did not undergo surgery.

All other patients were referred for extrapleural pneumonectomy.

The study was interested in two major topics:

1. The ability of PET/CT compared to CT to detect inoperative stages of mesothelioma; and,
2. The validity of PET/CT's results for staging, when compared against mediastinoscopy and final staging determined at EPP

Results

CT vs. PET/CT for Preoperative Staging

The results of the CT vs. PET/CT analysis showed a clear benefit to PET/CT. Of the 42 patients who were screened, PET/CT discovered: T4 disease in 7 patients, while CT did not show any; 14 patients with N2 or N3 disease, while CT only showed 7 patients; and 7 cases of distant metastases, while CT, again, did not show any. These findings resulted in an “upstage migration” of 8 cases: CT disclosed only one case as Stage IV disease, while PET/CT identified nine Stage IV cases (including the one identified by CT). In total, PET/CT excluded 12 of the 42 cases as non-resectable due to T4/M1 status, while CT did not exclude any.

PET/CT vs. Mediastinoscopy

PET/CT identified 30 patients with potentially-resectable disease. Of these patients, 14 indicated possible N2/N3 status, but they were not excluded from surgical consideration without histological confirmation of the findings. All 30 patients were then referred for mediastinoscopy. 6 patients demonstrated histologically-confirmed N2 metastases, which reduced the number of patients eligible for extrapleural pneumonectomy to 24.

All of these patients then received an EPP.

PET/CT vs. Final EPP Staging Results

Of the 24 patients who underwent EPP, 2 had undiagnosed T4 disease that PET/CT missed. T-stage was lower in 1 patient, equal in 13 and higher in 10. These results led to the following stage migration: percentage of patients identified as Stage I was reduced from 63% to 21%, while Stage IV patients increased from 4% to 12%. When compared to both mediastinoscopy and EPP staging, PET/CT correctly identified a number of N-stage cases, but it was also less accurate then both: it under-staged 3 patients when compared to mediastinoscopy and 7 when compared to final staging completed during EPP.

Conclusion

Mesothelioma remains a very difficult disease to treat effectively, and only a subset of patients are eligible for the invasive procedures that are necessary to possibly extend survival times for the disease. The need for accurate staging technologies is not unique to the treatment of pleural mesothelioma, but the difficulties of the disease complicate it. CT has been used, but it has well-known limitations for mesothelioma staging. PET/CT has showed great promise in other studies and the authors of the article describing the present study conclude that PET/CT is an important advancement in the surgical staging of pleural mesothelioma, but that it doesn’t alleviate the need for invasive, yet more accurate, diagnostic techniques such as mediastinoscopy. PET/CT can improve the selection of patients for EPP, especially when compared with CT, but the authors state that more work needs to be done to develop more accurate, non-invasive techniques.

Labels: mesothelioma, pleuralmesothelioma, staging