The 8th edition of the American Joint Committee on Cancer (AJCC) staging system has recently made changes in the staging of hilar and intrahepatic cholangiocarcinoma (CCA).
Flavio Rocha, MD, Hepatopancreatobiliary Surgeon, Virginia Mason Medical Center, Director of Research, Digestive Disease Institute, and Associate Medical Director of the Floyd and Delores Jones Cancer Institute, Seattle, WA, provided an overview of the changes made in the 8th edition of the AJCC’s tumor, node, metastasis (TNM) staging system at the 2020 Annual Cholangiocarcinoma Summit. These changes have direct implications for the management of patients with hilar or intrahepatic CCA.
In the AJCC 8th edition, regional lymph node metastasis was downstaged from stage TIVA to stage IIIB. In the setting of hilar CCA, the TIV tumor category is now defined as tumor involving local extrahepatic structures by direct invasion and is categorized as stage IIIB, which was downstaged from stage IVA. The reason is that the prognosis in such tumors is not affected by periductal invasion. “These tumors can be resectable in certain centers,” said Dr Rocha.
In addition, the nodal classification has changed from the AJCC 7th edition to the 8th edition. “The N category has been changed from a location‑based system to a number‑based system so that N1 is now 1 to 3 nodes, and N2 is 4 or more nodes,” he said.
Gaspersz and colleagues from the Netherlands evaluated the accuracy of survival and prognostic parameters across the TNM staging system, comparing the difference between the AJCC 8th edition and 7th edition in patients with perihilar CCA.1 Of 248 patients with CCA, 53 patients were reclassified when considering substages IIIA and IIIB, and 35 were reclassified when considering only the major stages (stages I/II, III, and IV). The survival curves were stratified according to the major stage based on either edition.1
In both editions, the AJCC staging system performed better in the subgroup of patients with CCA who underwent a curative-intent resection compared with the entire cohort. The 8th edition had a slightly better prognostic value compared with the 7th edition in this subgroup.
Until 2014, the management of intrahepatic CCA was stratified according to TNM stage, with early stage (stage I or stage II), which constituted approximately 30% to 40% of intrahepatic CCA cases, considered to be resectable. TNM stage III, defined by visceral peritoneum perforation and local hepatic invasion, and stage IV, defined by periductal invasion, were considered unresectable and were managed with locoregional therapy or gemcitabine plus cisplatin chemotherapy.
In the AJCC 8th edition, the TI stage of intrahepatic CCA has been separated into “A” and “B,” depending on tumor size, “because we know this is a prognostic factor,” he said. TIA tumors are categorized as ≤5 cm, and TIB tumors are categorized as >5 cm, without vascular invasion.
Stage T2 CCA is now defined as a solitary tumor with intrahepatic vascular invasion, or as multiple tumors with or without vascular invasion.
At the 2019 European Society for Medical Oncology Congress, Lamarca and colleagues presented their study results in a poster showing that patients with intrahepatic CCA and liver metastases in the absence of extrahepatic metastases had a worse prognosis compared with patients with other stages of disease. The overall survival in the group with liver metastases was similar to that of patients with stage IVB according to the AJCC 7th edition staging criteria. Lamarca and colleagues concluded that new staging criteria should be considered for patients diagnosed with liver metastases only.
This concept was later confirmed in a retrospective analysis by Italian researchers Conci and colleagues, who examined outcomes among a multi-institutional series of 259 patients with resected intrahepatic CCA based on whether the patient had a single tumor, satellites, or multifocal disease.2
“The patients with a single tumor had the best prognosis followed by those who had satellites near the primary tumor,” but the difference in the cumulative survival rate was significantly better in the patients with a single tumor versus those with satellites (P = .001), said Dr Rocha. “Certainly, the ones who had multifocal disease or intrahepatic metastases did not do as well…almost as poor as those who were not resected at all.”
Another important change in the setting of intrahepatic CCA is in the staging of regional node disease. As noted earlier, in the edition, regional lymph node metastasis was downstaged from TIVA to IIIB. In the staging of intrahepatic CCA, harvesting of at least 6 lymph nodes is recommended for complete nodal staging.
“This can be challenging, because it’s hard to predict preoperatively how many nodes you’re going to get in your lymphadenectomy,” said Dr Rocha. “Keep in mind that the lymph nodes still considered in the field are the hilar, the cystic duct, the common bile duct, hepatic artery, and portal vein lymph nodes, and not the aorta and vena cava lymph nodes.”
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