Skip to main content
SpringerLink
Log in

Staging and Treatment

  • Chapter
  • First Online:
Gastrointestinal Cancer

  • 392 Accesses

Abstract

Cholangiocarcinoma (CCA) staging is most commonly classified using the TNM staging systems of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC), which came into effect on January 1, 2018, in its eighth edition. There are separate systems depending on whether the CCA arises primarily from intrahepatic (iCCA), perihilar/hilar (Klatskin) (pCCA), or extrahepatic (distal) bile ducts (dCCA), which all differ in their definitions of tumor stage (T) and in their prognostic stage groupings (Fig. 1a).

Jung Won Chun and Sang Myung Woo are the lead authors of this chapter.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Yamasaki S. Intrahepatic cholangiocarcinoma: macroscopic type and stage classification. J Hepatobiliary Pancreat Surg. 2003;10:288–91.

    Article  PubMed  Google Scholar 

  2. Bagante F, Weiss M, Alexandrescu S, Marques HP, Aldrighetti L, Maithel SK, et al. Long-term outcomes of patients with intraductal growth sub-type of intrahepatic cholangiocarcinoma. HPB (Oxford). 2018;20:1189–97.

    Article  PubMed  Google Scholar 

  3. Mavros MN, Economopoulos KP, Alexiou VG, Pawlik TM. Treatment and prognosis for patients with intrahepatic cholangiocarcinoma: systematic review and meta-analysis. JAMA Surg. 2014;149:565–74.

    Article  PubMed  Google Scholar 

  4. Lee AJ, Chun YS. Intrahepatic cholangiocarcinoma: the AJCC/UICC 8th edition updates. Chin Clin Oncol. 2018;7:6.

    Article  Google Scholar 

  5. Lei H-J, Shyr Y-M, Hsia C-Y, Chen M-H, Huang Y-H, Chau G-Y. Surgical management of intrahepatic cholangiocarcinoma: a narrative review. Dig Med Res. 2021;4:4.

    Article  Google Scholar 

  6. Zhang W, Yan L-N. Perihilar cholangiocarcinoma: current therapy. World J Gastrointest Pathophysiol. 2014;5:344–54.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Klatskin G. Adenocarcinoma of the hepatic duct at its bifurcation within the porta hepatis. An unusual tumor with distinctive clinical and pathological features. Am J Med. 1965;38:241–56.

    Article  CAS  PubMed  Google Scholar 

  8. Bismuth H, Corlette MB. Intrahepatic cholangioenteric anastomosis in carcinoma of the hilus of the liver. Surg Gynecol Obstet. 1975;140:170–8.

    CAS  PubMed  Google Scholar 

  9. Ebata T, Kosuge T, Hirano S, Unno M, Yamamoto M, Miyazaki M, et al. Proposal to modify the International Union against Cancer staging system for perihilar cholangiocarcinomas. Br J Surg. 2014;101:79–88.

    Article  CAS  PubMed  Google Scholar 

  10. Bagante F, Tran T, Spolverato G, Ruzzenente A, Buttner S, Ethun CG, et al. Perihilar cholangiocarcinoma: number of nodes examined and optimal lymph node prognostic scheme. J Am Coll Surg. 2016;222:750–759.e2.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Buettner S, van Vugt JLA, Gaspersz MP, Coelen RJS, Roos E, Labeur TA, et al. Survival after resection of perihilar cholangiocarcinoma in patients with lymph node metastases. HPB. 2017;19:735–40.

    Article  PubMed  Google Scholar 

  12. Jun SY, Sung YN, Lee JH, Park KM, Lee YJ, Hong SM. Validation of the eighth American Joint Committee on cancer staging system for distal bile duct carcinoma. Cancer Res Treat. 2019;51:98–111.

    Article  PubMed  Google Scholar 

  13. Mansour JC, Aloia TA, Crane CH, Heimbach JK, Nagino M, Vauthey JN. Hilar cholangiocarcinoma: expert consensus statement. HPB (Oxford). 2015;17:691–9.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Sano T, Shimizu Y, Senda Y, Kinoshita T, Nimura Y. Assessing resectability in cholangiocarcinoma. Hepat Oncol. 2014;1:39–51.

    Article  PubMed  Google Scholar 

  15. Khan AS, Dageforde LA. Cholangiocarcinoma. Surg Clin North Am. 2019;99:315–35.

    Article  PubMed  Google Scholar 

  16. Rahbari NN, Garden OJ, Padbury R, Brooke-Smith M, Crawford M, Adam R, et al. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery. 2011;149:713–24.

    Article  PubMed  Google Scholar 

  17. Meyer CG, Penn I, James L. Liver transplantation for cholangiocarcinoma: results in 207 patients. Transplantation. 2000;69:1633–7.

    Article  CAS  PubMed  Google Scholar 

  18. Rea DJ, Heimbach JK, Rosen CB, Haddock MG, Alberts SR, Kremers WK, et al. Liver transplantation with neoadjuvant chemoradiation is more effective than resection for hilar cholangiocarcinoma. Ann Surg. 2005;242:451–61.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Rosen CB, Heimbach JK, Gores GJ. Liver transplantation for cholangiocarcinoma. Transpl Int. 2010;23:692–7.

    Article  PubMed  Google Scholar 

  20. Abou-Alfa GK, Sahai V, Hollebecque A, Vaccaro G, Melisi D, Al-Rajabi R, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020;21:671–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Primrose JN, Fox RP, Palmer DH, Malik HZ, Prasad R, Mirza D, et al. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019;20:663–73.

    Article  CAS  PubMed  Google Scholar 

  22. Shroff RT, Kennedy EB, Bachini M, Bekaii-Saab T, Crane C, Edeline J, et al. Adjuvant therapy for resected biliary tract cancer: ASCO clinical practice guideline. J Clin Oncol. 2019;37:1015–27.

    Article  PubMed  Google Scholar 

  23. Ben-Josef E, Guthrie KA, El-Khoueiry AB, Corless CL, Zalupski MM, Lowy AM, et al. SWOG S0809: a phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and gallbladder carcinoma. J Clin Oncol. 2015;33:2617–22.

    Article  CAS  PubMed  Google Scholar 

  24. Eckel F, Schmid RM. Chemotherapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials. Br J Cancer. 2007;96:896–902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273–81.

    Article  CAS  PubMed  Google Scholar 

  26. Okusaka T, Nakachi K, Fukutomi A, Mizuno N, Ohkawa S, Funakoshi A, et al. Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer. 2010;103:469–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Mizusawa J, Morizane C, Okusaka T, Katayama H, Ishii H, Fukuda H, et al. Randomized phase III study of gemcitabine plus S-1 versus gemcitabine plus cisplatin in advanced biliary tract cancer: Japan Clinical Oncology Group Study (JCOG1113, FUGA-BT). Jpn J Clin Oncol. 2016;46:385–8.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kim ST, Kang JH, Lee J, Lee HW, Oh SY, Jang JS, et al. Capecitabine plus oxaliplatin versus gemcitabine plus oxaliplatin as first-line therapy for advanced biliary tract cancers: a multicenter, open-label, randomized, phase III, noninferiority trial. Ann Oncol. 2019;30:788–95.

    Article  CAS  PubMed  Google Scholar 

  29. Sahai V, Catalano PJ, Zalupski MM, Lubner SJ, Menge MR, Nimeiri HS, et al. Nab-paclitaxel and gemcitabine as first-line treatment of advanced or metastatic cholangiocarcinoma: a phase 2 clinical trial. JAMA Oncol. 2018;4:1707–12.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Shroff RT, Javle MM, Xiao L, Kaseb AO, Varadhachary GR, Wolff RA, et al. Gemcitabine, cisplatin, and nab-paclitaxel for the treatment of advanced biliary tract cancers: a phase 2 clinical trial. JAMA Oncol. 2019;5:824–30.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Chen JS, Jan YY, Lin YC, Wang HM, Chang WC, Liau CT. Weekly 24 h infusion of high-dose 5-fluorouracil and leucovorin in patients with biliary tract carcinomas. Anticancer Drugs. 1998;9:393–7.

    Article  CAS  PubMed  Google Scholar 

  32. Choi CW, Choi IK, Seo JH, Kim BS, Kim JS, Kim CD, et al. Effects of 5-fluorouracil and leucovorin in the treatment of pancreatic-biliary tract adenocarcinomas. Am J Clin Oncol. 2000;23:425–8.

    Article  CAS  PubMed  Google Scholar 

  33. Takada T, Kato H, Matsushiro T, Nimura Y, Nagakawa T, Nakayama T. Comparison of 5-fluorouracil, doxorubicin and mitomycin C with 5-fluorouracil alone in the treatment of pancreatic-biliary carcinomas. Oncology. 1994;51:396–400.

    Article  CAS  PubMed  Google Scholar 

  34. Lamarca A, Hubner RA, David Ryder W, Valle JW. Second-line chemotherapy in advanced biliary cancer: a systematic review. Ann Oncol. 2014;25:2328–38.

    Article  CAS  PubMed  Google Scholar 

  35. Lamarca A, Palmer DH, Wasan HS, Ross PJ, Ma YT, Arora A, et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2021;22:690–701.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yoo C, Kim K-P, Kim I, Kang MJ, Cheon J, Kang BW, et al. Liposomal irinotecan (nal-IRI) in combination with fluorouracil (5-FU) and leucovorin (LV) for patients with metastatic biliary tract cancer (BTC) after progression on gemcitabine plus cisplatin (GemCis): multicenter comparative randomized phase 2b study (NIFTY). J Clin Oncol. 2021;39:4006.

    Article  Google Scholar 

  37. Lamarca A, Ross P, Wasan HS, Hubner RA, McNamara MG, Lopes A, et al. Advanced intrahepatic cholangiocarcinoma: post hoc analysis of the ABC-01, -02, and -03 clinical trials. J Natl Cancer Inst. 2020;112:200–10.

    PubMed  Google Scholar 

  38. Valle JW, Borbath I, Khan SA, Huguet F, Gruenberger T, Arnold D. Biliary cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27:v28–37.

    Article  CAS  PubMed  Google Scholar 

  39. Gkika E, Hawkins MA, Grosu A-L, Brunner TB. The evolving role of radiation therapy in the treatment of biliary tract cancer. Front Oncol. 2020;10:604387.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Tao R, Krishnan S, Bhosale PR, Javle MM, Aloia TA, Shroff RT, et al. Ablative radiotherapy doses lead to a substantial prolongation of survival in patients with inoperable intrahepatic cholangiocarcinoma: a retrospective dose response analysis. J Clin Oncol. 2016;34:219–26.

    Article  CAS  PubMed  Google Scholar 

  41. Gkika E, Hallauer L, Kirste S, Adebahr S, Bartl N, Neeff HP, et al. Stereotactic body radiotherapy (SBRT) for locally advanced intrahepatic and extrahepatic cholangiocarcinoma. BMC Cancer. 2017;17:781.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Brunner TB, Blanck O, Lewitzki V, Abbasi-Senger N, Momm F, Riesterer O, et al. Stereotactic body radiotherapy dose and its impact on local control and overall survival of patients for locally advanced intrahepatic and extrahepatic cholangiocarcinoma. Radiother Oncol. 2019;132:42–7.

    Article  PubMed  Google Scholar 

  43. Frakulli R, Buwenge M, Macchia G, Cammelli S, Deodato F, Cilla S, et al. Stereotactic body radiation therapy in cholangiocarcinoma: a systematic review. Br J Radiol. 2019;92:20180688.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Valle JW, Lamarca A, Goyal L, Barriuso J, Zhu AX. New horizons for precision medicine in biliary tract cancers. Cancer Discov. 2017;7:943–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Jusakul A, Cutcutache I, Yong CH, Lim JQ, Huang MN, Padmanabhan N, et al. Whole-genome and epigenomic landscapes of etiologically distinct subtypes of cholangiocarcinoma. Cancer Discov. 2017;7:1116–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Abou-Alfa GK, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:796–807.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Zhu AX, Macarulla T, Javle MM, Kelley RK, Lubner SJ, Adeva J, et al. Final results from ClarIDHy, a global, phase III, randomized, double-blind study of ivosidenib (IVO) versus placebo (PBO) in patients (pts) with previously treated cholangiocarcinoma (CCA) and an isocitrate dehydrogenase 1 (IDH1) mutation. J Clin Oncol. 2021;39:266.

    Article  Google Scholar 

  48. Javle M, Lowery M, Shroff RT, Weiss KH, Springfeld C, Borad MJ, et al. Phase II study of BGJ398 in patients with FGFR-altered advanced cholangiocarcinoma. J Clin Oncol. 2018;36:276–82.

    Article  CAS  PubMed  Google Scholar 

  49. Javle MM, Roychowdhury S, Kelley RK, Sadeghi S, Macarulla T, Waldschmidt DT, et al. Final results from a phase II study of infigratinib (BGJ398), an FGFR-selective tyrosine kinase inhibitor, in patients with previously treated advanced cholangiocarcinoma harboring an FGFR2 gene fusion or rearrangement. J Clin Oncol. 2021;39:265.

    Article  Google Scholar 

  50. Westphalen CB, Krebs MG, Le Tourneau C, Sokol ES, Maund SL, Wilson TR, et al. Genomic context of NTRK1/2/3 fusion-positive tumours from a large real-world population. NPJ Precis Oncol. 2021;5(1):69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med. 2018;378(8):731–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Menichincheri M, Ardini E, Magnaghi P, Avanzi N, Banfi P, Bossi R, et al. Discovery of entrectinib: a new 3-aminoindazole as a potent anaplastic lymphoma kinase (ALK), c-ROS oncogene 1 kinase (ROS1), and Pan-tropomyosin receptor kinases (Pan-TRKs) inhibitor. J Med Chem. 2016;59(7):3392–408.

    Article  CAS  PubMed  Google Scholar 

  53. Bang Y-J, Ueno M, Malka D, Chung HC, Nagrial A, Kelley RK, et al. Pembrolizumab (pembro) for advanced biliary adenocarcinoma: results from the KEYNOTE-028 (KN028) and KEYNOTE-158 (KN158) basket studies. J Clin Oncol. 2019;37:4079.

    Article  Google Scholar 

  54. Piha-Paul SA, Oh DY, Ueno M, Malka D, Chung HC, Nagrial A, et al. Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: results from the KEYNOTE-158 and KEYNOTE-028 studies. Int J Cancer. 2020;147:2190–8.

    Article  CAS  PubMed  Google Scholar 

  55. Ueno M, Chung HC, Nagrial A, Marabelle A, Kelley RK, Xu L, et al. Pembrolizumab for advanced biliary adenocarcinoma: results from the multicohort, phase II KEYNOTE-158 study. Ann Oncol. 2018;29:viii210.

    Article  Google Scholar 

  56. Kim RD, Kim DW, Alese OB, Li D, Shah N, Schell MJ, et al. A phase II study of nivolumab in patients with advanced refractory biliary tract cancers (BTC). J Clin Oncol. 2019;37:4097.

    Article  Google Scholar 

  57. Klein O, Kee D, Nagrial A, Markman B, Underhill C, Michael M, et al. Evaluation of combination nivolumab and ipilimumab immunotherapy in patients with advanced biliary tract cancers: subgroup analysis of a phase 2 nonrandomized clinical trial. JAMA Oncol. 2020;6:1405–9.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Sahai V, Griffith KA, Beg MS, Shaib WL, Mahalingam D, Zhen DB, et al. A multicenter randomized phase II study of nivolumab in combination with gemcitabine/cisplatin or ipilimumab as first-line therapy for patients with advanced unresectable biliary tract cancer (BilT-01). J Clin Oncol. 2020;38:4582.

    Article  Google Scholar 

  59. Oh D-Y, Lee K-H, Lee D-W, Kim TY, Bang J-H, Nam A-R, et al. Phase II study assessing tolerability, efficacy, and biomarkers for durvalumab (D) ± tremelimumab (T) and gemcitabine/cisplatin (GemCis) in chemo-naïve advanced biliary tract cancer (aBTC). J Clin Oncol. 2020;38:4520.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea (Republic of)

    Hoon Jai Chun

  2. Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Korea (Republic of)

    Seun Ja Park

  3. Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Kyonggi-do, Korea (Republic of)

    Yun Jeong Lim

  4. Department of Internal Medicine, Yonsei University Severance Hospital, Seoul, Korea (Republic of)

    Si Young Song

Authors
  1. Hoon Jai Chun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seun Ja Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yun Jeong Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Si Young Song
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chun, H.J., Park, S.J., Lim, Y.J., Song, S.Y. (2023). Staging and Treatment. In: Gastrointestinal Cancer. Springer, Singapore. https://doi.org/10.1007/978-981-99-0815-8_54

Download citation

  • DOI: https://doi.org/10.1007/978-981-99-0815-8_54

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-99-0814-1

  • Online ISBN: 978-981-99-0815-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation