A New Clinically Based Staging System for Perihilar Cholangiocarcinoma

Abstract

OBJECTIVES Current staging systems for perihilar cholangiocarcinoma (pCCA) are inadequate, as they are based on surgical pathology and therefore not relevant to unresectable patients. Clinical trials for potential targeted therapies for pCCA are hampered by the lack of an accurate, nonoperative staging system for predicting survival. We aimed at developing a clinical staging system for pCCA, which would be of prognostic relevance for all pCCA patients and help stratify patients for clinical trials. METHODS Clinical information at the time of pCCA diagnosis of 413 patients seen at Mayo Clinic, Rochester, MN between 2002 and 2010 was retrospectively analyzed. A survival predictive model was developed using Cox proportional hazards analysis. The performance of the staging system was compared with the current AJCC/UICC (the American Joint Committee on Cancer/the Union for International Cancer Control) 7th tumor-node-metastasis (TNM) staging system. RESULTS Eastern Cooperative Oncology Group (ECOG) status, tumor size and number, vascular encasement, lymph node and peritoneal metastasis and CA 19-9 level were grouped into a four-tier staging system. The median survivals of stages I, II, III, and IV patients were 48.6, 21.8, 8.6, and 2.8 months, with hazard ratios (95% confidence interval) of 1.0 (reference), 1.7 (1.1–2.6), 3.1 (2.0–4.7), and 8.7 (5.2–14.5), respectively (P<0.0001). This staging system had greater concordance statistics (standard error) than the TNM staging system (0.725 (0.018) vs. 0.614 (0.017)), indicating better performance in predicting survival. CONCLUSIONS This staging system, based on nonoperative information at the time of pCCA diagnosis, has excellent discriminatory power to classify patients into four prognostic stages. It could be useful to clinicians and for the design of clinical trials.

Outcome and validation of a new clinically based staging system for predicting survival of perihilar cholangiocarcinoma patients

“…However, this factor was not included in the Mayo Clinic clinical staging system as the staging system was aimed to be applicable for all patients regardless of treatment received. Inconsistent with the findings reported in the development cohort,15 we did not observe the association between ECOG status and survival, likely due to the small number of patients with ECOG 2–4.…”

“…This discrepancy was most likely due to the difference in treatment modality given to early stage patients. Specifically, none of the patients in our study received liver transplantation while 43.4% of stage I patients in the previous study15 were treated with liver transplantation. Nonetheless, when comparing survivals of those receiving resection and palliative biliary stenting between the two cohorts, it appears that there was not much difference in survival of the present cohort and the development cohort, that is 17.3 versus 25.3 months for resection and 4.1 versus 5.8 months for stenting.…”

“…Patients who underwent surgical resection or received chemotherapy prior to the first visit at our hospital were excluded. Diagnosis of pCCA was made based on the criteria previously published 15. Briefly, (i) surgical histopathology from resected tumor ( n = 28); (ii) histology from intraluminal endoscopic core biopsy, percutaneous needle biopsy, or intraoperative biopsy ( n = 40); (iii) intraluminal brush cytology ( n = 1); (iv) a CA (cancer antigen) 19‐9 level > 100 U/mL in the setting of a malignant‐appearing biliary tract stricture demonstrated by radiologic imaging and without bacterial cholangitis ( n = 47); or (v) a perihilar mass lesion with a malignant‐appearing biliary tract stricture on cross‐sectional imaging studies with evidence of malignant clinical progression during the follow‐up period ( n = 25).…”

“…Due to the limitations of the three staging systems,14 a new clinical staging system for pCCA was recently proposed and showed promising prognostic value for both unresectable and resectable disease 15. However, the major population of this development cohort was White (87.7%) and the major cause of pCCA in Western countries was primary sclerosing cholangitis (PSC).…”

Low Skeletal Muscle Density Is Associated with Early Death in Patients with Perihilar Cholangiocarcinoma Regardless of Subsequent Treatment

“…Multiple staging systems are available to predict prognosis in patients with (suspected) PHC [4, 8-10]. However, the majority of staging systems, such as the frequently used American Joint Committee on Cancer (AJCC) staging system, are applicable only to a minority of patients who undergo resection [8].…”