Natural History and Prognostic Factors of Advanced Cholangiocarcinoma without Surgery, Chemotherapy, or Radiotherapy: A Large-Scale Observational Study

Jongha Park, Myung-Hwan Kim, Kyu-Pyo Kim, Do Hyun Park, Sung-Hoon Moon, Tae Jun Song, Junbum Eum, Sang Soo Lee, Dong Wan Seo, Sung Koo Lee, Jongha Park, Myung-Hwan Kim, Kyu-Pyo Kim, Do Hyun Park, Sung-Hoon Moon, Tae Jun Song, Junbum Eum, Sang Soo Lee, Dong Wan Seo, Sung Koo Lee

Abstract

Background/aims: We aimed to evaluate survival time and prognostic factors in patients with advanced unresectable cholangiocarcinoma who have not received surgery, chemotherapy, or radiotherapy.

Methods: A total of 1,377 patients, who were diagnosed with primary cholangiocarcinoma between 1996 and 2002, were reviewed retrospectively according to the following inclusion criteria: histologically proven primary adenocarcinoma arising from the bile-duct epithelium, advanced unresectable stages, no severe comorbidity that can affect survival time, and no history of surgery, chemotherapy, or radiotherapy.

Results: Of the 1,377 cases reviewed, 330 patients complied with the inclusion criteria and were thus eligible to participate in this study; 203 had intrahepatic cholangiocarcinoma and 127 had hilar cholangiocarcinoma. The overall survival time of the entire cohort (n=330) was median 3.9 months (range; 0.2 to 67.1). The survival time was significantly shorter in the intrahepatic cholangiocarcinoma group (3.0+/-5.3 months) than in the hilar cholangiocarcinoma group (5.9+/-10.1 months; Kaplan-Meier survival analysis). Multivariate analysis revealed that distant metastasis was a poor prognostic factor for intrahepatic cholangiocarcinoma (p< 0.001), baseline serum albumin >3.0 g/dL was a favorable prognostic factor (p=0.02), and baseline serum carcinoembryonic antigen level >30 ng/mL was a poor prognostic factor for hilar cholangiocarcinoma (p=0.01).

Conclusions: The median survival of advanced unresectable cholangiocarcinoma is dismal.

Keywords: Carcinoembryonic antigen; Cholangiocarcinoma; Natural history.

Figures

Fig. 1
Fig. 1
Study population. Between 1996 and 2002, 1,377 patients were diagnosed with cholangiocarcinoma at our institute; 330 of these patients complied with the inclusion criteria and could thus be included in the study. *Although some cases were clinically operable, surgery was not performed due to the patients' refusal.
Fig. 2
Fig. 2
Survival graphs of advanced unresectable cholangiocarcinoma. The overall median survival time for all cholangiocarcinoma patients (n=330) was 3.9 months. The median survival time was shorter for those with intrahepatic cholangiocarcinoma (3 months) than for those with hilar cholangiocarcinoma (5.9 months; p

References

    1. de Groen PC, Gores GJ, LaRusso NF, Gunderson LL, Nagorney DM. Biliary tract cancers. N Engl J Med. 1999;341:1368–1378.
    1. Lazaridis KN, Gores GJ. Cholangiocarcinoma. Gastroenterology. 2005;128:1655–1667.
    1. Nair S, Shiv Kumar K, Thuluvath PJ. Mortality from hepatocellular and biliary cancers: changing epidemiological trends. Am J Gastroenterol. 2002;97:167–171.
    1. Patel T. Increasing incidence and mortality of primary intrahepatic cholangiocarcinoma in the United States. Hepatology. 2001;33:1353–1357.
    1. Olnes MJ, Erlich R. A review and update on cholangiocarcinoma. Oncology. 2004;66:167–179.
    1. Jarnagin WR, Fong Y, DeMatteo RP, et al. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg. 2001;234:507–517. discussion 517-519.
    1. Witzigmann H, Berr F, Ringel U, et al. Surgical and palliative management and outcome in 184 patients with hilar cholangiocarcinoma: palliative photodynamic therapy plus stenting is comparable to r1/r2 resection. Ann Surg. 2006;244:230–239.
    1. Sasaki A, Aramaki M, Kawano K, et al. Intrahepatic peripheral cholangiocarcinoma: mode of spread and choice of surgical treatment. Br J Surg. 1998;85:1206–1209.
    1. Nakeeb A, Pitt HA, Sohn TA, et al. Cholangiocarcinoma: a spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg. 1996;224:463–473. discussion 473-475.
    1. Washburn WK, Lewis WD, Jenkins RL. Aggressive surgical resection for cholangiocarcinoma. Arch Surg. 1995;130:270–276.
    1. Patel T, Singh P. Cholangiocarcinoma: emerging approaches to a challenging cancer. Curr Opin Gastroenterol. 2007;23:317–323.
    1. Reddy SB, Patel T. Current approaches to the diagnosis and treatment of cholangiocarcinoma. Curr Gastroenterol Rep. 2006;8:30–37.
    1. Mansfield SD, Barakat O, Charnley RM, et al. Management of hilar cholangiocarcinoma in the North of England: pathology, treatment, and outcome. World J Gastroenterol. 2005;11:7625–7630.
    1. Ortner ME, Caca K, Berr F, et al. Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study. Gastroenterology. 2003;125:1355–1363.
    1. Lee HY, Kim SH, Lee JM, et al. Preoperative assessment of resectability of hepatic hilar cholangiocarcinoma: combined CT and cholangiography with revised criteria. Radiology. 2006;239:113–121.
    1. Weber SM, DeMatteo RP, Fong Y, Blumgart LH, Jarnagin WR. Staging laparoscopy in patients with extrahepatic biliary carcinoma: analysis of 100 patients. Ann Surg. 2002;235:392–399.
    1. Burke EC, Jarnagin WR, Hochwald SN, Pisters PW, Fong Y, Blumgart LH. Hilar cholangiocarcinoma: patterns of spread, the importance of hepatic resection for curative operation, and a presurgical clinical staging system. Ann Surg. 1998;228:385–394.
    1. D'Angelica MI, Jarnagin WR, Blumgart LH. Resectable hilar cholangiocarcinoma: surgical treatment and long-term outcome. Surg Today. 2004;34:885–890.
    1. Isaji S, Kawarada Y, Taoka H, Tabata M, Suzuki H, Yokoi H. Clinicopathological features and outcome of hepatic resection for intrahepatic cholangiocarcinoma in Japan. J Hepatobiliary Pancreat Surg. 1999;6:108–116.
    1. Sano T, Kamiya J, Nagino M, et al. Macroscopic classification and preoperative diagnosis of intrahepatic cholangiocarcinoma in Japan. J Hepatobiliary Pancreat Surg. 1999;6:101–107.
    1. Bismuth H, Castaing D, Traynor O. Resection or palliation: priority of surgery in the treatment of hilar cancer. World J Surg. 1988;12:39–47.
    1. Smith AC, Dowsett JF, Russell RC, Hatfield AR, Cotton PB. Randomised trial of endoscopic stenting versus surgical bypass in malignant low bileduct obstruction. Lancet. 1994;344:1655–1660.
    1. Miyakawa S, Ishihara S, Takada T, et al. Results from the Biliary Tract Cancer Statistics Registry in Japan based on general rules for surgical and pathological studies on cancer of the biliary tract: hilar cholangiocarcinoma. Kan Tan Sui. 2005;50:415–424.
    1. Connor S, Barron E, Redhead DN, et al. Palliation for suspected unresectable hilar cholangiocarcinoma. Eur J Surg Oncol. 2007;33:341–345.
    1. Shaib YH, Davila JA, Henderson L, McGlynn KA, El-Serag HB. Endoscopic and surgical therapy for intrahepatic cholangiocarcinoma in the united states: a population-based study. J Clin Gastroenterol. 2007;41:911–917.
    1. Paik WH, Park YS, Hwang JH, et al. Palliative treatment with self-expandable metallic stents in patients with advanced type III or IV hilar cholangiocarcinoma: a percutaneous versus endoscopic approach. Gastrointest Endosc. 2009;69:55–62.
    1. Broome U, Olsson R, Loof L, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut. 1996;38:610–615.
    1. Kaplan GG, Laupland KB, Butzner D, Urbanski SJ, Lee SS. The burden of large and small duct primary sclerosing cholangitis in adults and children: a population-based analysis. Am J Gastroenterol. 2007;102:1042–1049.
    1. Weber A, Landrock S, Schneider J, et al. Long-term outcome and prognostic factors of patients with hilar cholangiocarcinoma. World J Gastroenterol. 2007;13:1422–1426.
    1. Su CH, Tsay SH, Wu CC, et al. Factors influencing postoperative morbidity, mortality, and survival after resection for hilar cholangiocarcinoma. Ann Surg. 1996;223:384–394.
    1. Su WC, Chan KK, Lin XZ, et al. A clinical study of 130 patients with biliary tract cancers and periampullary tumors. Oncology. 1996;53:488–493.
    1. Kuusela P, Haglund C, Roberts PJ. Comparison of a new tumour marker CA 242 with CA 19-9, CA 50 and carcinoembryonic antigen (CEA) in digestive tract diseases. Br J Cancer. 1991;63:636–640.
    1. Gores GJ. Early detection and treatment of cholangiocarcinoma. Liver Transpl. 2000;6:S30–S34.
    1. Charatcharoenwitthaya P, Enders FB, Halling KC, Lindor KD. Utility of serum tumor markers, imaging, and biliary cytology for detecting cholangiocarcinoma in primary sclerosing cholangitis. Hepatology. 2008;48:1106–1117.
    1. Kim HJ, Kim MH, Myung SJ, et al. A new strategy for the application of CA19-9 in the differentiation of pancreaticobiliary cancer: analysis using a receiver operating characteristic curve. Am J Gastroenterol. 1999;94:1941–1946.
    1. Miwa S, Miyagawa S, Kobayashi A, et al. Predictive factors for intrahepatic cholangiocarcinoma recurrence in the liver following surgery. J Gastroenterol. 2006;41:893–900.
    1. Heimbach JK, Gores GJ, Haddock MG, et al. Predictors of disease recurrence following neoadjuvant chemoradiotherapy and liver transplantation for unresectable perihilar cholangiocarcinoma. Transplantation. 2006;82:1703–1707.
    1. Ohtsuka M, Ito H, Kimura F, et al. Results of surgical treatment for intrahepatic cholangiocarcinoma and clinicopathological factors influencing survival. Br J Surg. 2002;89:1525–1531.
    1. Ghazale A, Chari ST, Zhang L, et al. Immunoglobulin G4-associated cholangitis: clinical profile and response to therapy. Gastroenterology. 2008;134:706–715.
    1. Kim MH, Sekijima J, Lee SP. Primary intrahepatic stones. Am J Gastroenterol. 1995;90:540–548.
    1. Cha JM, Kim MH, Lee SK, et al. Clinicopathological review of 61 patients with early bile duct cancer. Clin Oncol (R Coll Radiol) 2006;18:669–677.

Source: PubMed

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