Annals of Surgical Oncology

, Volume 25, Issue 5, pp 1193–1201 | Cite as

Adjuvant Therapy Is Associated With Improved Survival in Resected Perihilar Cholangiocarcinoma: A Propensity Matched Study

  • Ibrahim Nassour
  • Ali A. Mokdad
  • Matthew R. Porembka
  • Michael A. Choti
  • Patricio M. Polanco
  • John C. Mansour
  • Rebecca M. Minter
  • Sam C. Wang
  • Adam C. Yopp
Gastrointestinal Oncology



There are limited well-controlled studies that conclusively demonstrate a benefit of adjuvant therapy in resected perihilar cholangiocarcinoma. Most studies include all biliary tract tumors as one entity despite the heterogeneity of these diseases.


We identified patients with resected perihilar cholangiocarcinoma from the National Cancer Database between 2006 and 2013. Patients who received adjuvant therapy (AT) were compared to an observation (OB) cohort by propensity score matching.


We identified 1846 patients: 1053 patients (57%) in the OB group, and 793 (43%) in the AT group. Patients who received adjuvant therapy were more likely to be younger, have a higher rate of private insurance, have higher T and N stage tumors, and were more likely to have positive resection margins. After 1:1 propensity score matching, 577 OB group patients were compared with 577 AT group patients. The AT cohort was associated with better overall survival compared with the OB cohort (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.64–0.83). The median survival was 29.5 and 23.3 months for the AT and OB groups, respectively (P < 0.01). Subgroup analysis demonstrated a survival advantage for adjuvant therapy in disease with positive resection margins (HR 0.53; 95% CI 0.42–0.67).


Adjuvant therapy is associated with improved survival in resected perihilar cholangiocarcinoma, especially in disease with positive resection margins. This study supports the use of adjuvant therapy in high-risk patients.



Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001105. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. RMM is the Alvin Baldwin, Jr. Chair in Surgery. MRP is the Dedman Family Scholar in clinical care. SCW is a UT Southwestern Disease-Oriented Clinical Scholar. The authors would like to thank Helen Mayo from the UT Southwestern Health Sciences Digital Library and Learning Center for assistance with literature searches, and Dave Primm for help in editing this manuscript.


The National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001105.


All authors have no disclosures.

Supplementary material

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Supplementary material 1 (DOCX 89 kb)


  1. 1.
    Nakeeb A, Pitt HA, Sohn TA, et al. Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg. 1996;224(4):463–73 discussion 473–5.
  2. 2.
    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(2):241–56.CrossRefPubMedGoogle Scholar
  3. 3.
    Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273–81. Scholar
  4. 4.
    Anderson CD, Pinson CW, Berlin J, Chari RS. Diagnosis and treatment of cholangiocarcinoma. Oncologist. 2004;9(1):43–57. Scholar
  5. 5.
    Nakeeb A, Tran KQ, Black MJ, et al. Improved survival in resected biliary malignancies. Surgery. 2002;132(4):555–64. Scholar
  6. 6.
    Pichlmayr R, Weimann A, Klempnauer J, et al. Surgical treatment in proximal bile duct cancer. A single-center experience. Ann Surg. 1996;224(5):628–38.PubMedGoogle Scholar
  7. 7.
    Mansour JC, Aloia TA, Crane CH, Heimbach JK, Nagino M, Vauthey J-N. Hilar Cholangiocarcinoma: expert consensus statement. HPB. 2015;17(8):691–9. Scholar
  8. 8.
    Jarnagin WR, Fong Y, DeMatteo RP, et al. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg. 2001;234(4):507.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Hasegawa S, Ikai I, Fujii H, Hatano E, Shimahara Y. Surgical resection of hilar cholangiocarcinoma: analysis of survival and postoperative complications. World J Surg. 2007;31(6):1258–65. Scholar
  10. 10.
    Hemming AW, Reed AI, Fujita S, Foley DP, Howard RJ. Surgical management of hilar cholangiocarcinoma. Ann Surg. 2005;241(5):693.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Nishio H, Nagino M, Nimura Y. Surgical management of hilar cholangiocarcinoma: the Nagoya experience. HPB (Oxford). 2005;7(4):259–62. Scholar
  12. 12.
    Jarnagin WR, Ruo L, Little SA, et al. Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma. Cancer. 2003;98(8):1689–700. Scholar
  13. 13.
    Vern-Gross TZ, Shivnani AT, Chen K, et al. Survival outcomes in resected extrahepatic cholangiocarcinoma: effect of adjuvant radiotherapy in a surveillance, epidemiology, and end results Analysis. Int J Radiat Oncol Biol Phys. 2011;81(1):189–98.CrossRefPubMedGoogle Scholar
  14. 14.
    Pitt HA, Nakeeb A, Abrams RA, et al. Perihilar cholangiocarcinoma. postoperative radiotherapy does not improve survival. Ann Surg. 1995;221(6):788–97; discussion 797–8.Google Scholar
  15. 15.
    Cameron JL, Pitt HA, Zinner MJ, Kaufman SL, Coleman J. Management of proximal cholangiocarcinomas by surgical resection and radiotherapy. Am J Surg. 1990;159(1):91–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Horgan AM, Amir E, Walter T, Knox JJ. Adjuvant therapy in the treatment of biliary tract cancer: a systematic review and meta-analysis. J Clin Oncol. 2012;30(16):1934–40. Scholar
  17. 17.
    Sagawa N, Kondo S, Morikawa T, Okushiba S, Katoh H. Effectiveness of radiation therapy after surgery for hilar cholangiocarcinoma. Surg Today. 2005;35(7):548–52. Scholar
  18. 18.
    Cheng Q, Luo X, Zhang B, Jiang X, Yi B, Wu M. Predictive factors for prognosis of hilar cholangiocarcinoma: postresection radiotherapy improves survival. Eur J Surg Oncol (EJSO). 2007;33(2):202–7.CrossRefPubMedGoogle Scholar
  19. 19.
    Kim TH, Han S-S, Park S-J, et al. Role of adjuvant chemoradiotherapy for resected extrahepatic biliary tract cancer. Int J Radiat Oncol Biol Phys. 2011;81(5):e853–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Ben-Josef E, Guthrie KA, El-Khoueiry AB, 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(24):2617–22. Scholar
  21. 21.
    Kang MJ, Jang J-Y, Chang J, et al. Actual long-term survival outcome of 403 consecutive patients with hilar cholangiocarcinoma. World J Surg. 2016;40(10):2451–9. Scholar
  22. 22.
    Leng KM, Liu YP, Wang ZD, et al. Results of adjuvant radiation therapy for locoregional perihilar cholangiocarcinoma after curative intent resection. Onco Targets Ther. 2017;10:2257–66. Scholar
  23. 23.
    Mizuno T, Ebata T, Yokoyama Y, et al. Adjuvant gemcitabine monotherapy for resectable perihilar cholangiocarcinoma with lymph node involvement: a propensity score matching analysis. Surg Today. 2017;47(2):182–92. Scholar
  24. 24.
    Kim S-W, Noh OK, Kim JH, et al. Adjuvant concurrent chemoradiotherapy with low-dose daily cisplatin for extrahepatic bile duct cancer. Cancer Chemother Pharmacol. 2017;79(6):1161–7. Scholar
  25. 25.
    NCCN Clinical Practice Guidlines in Oncology. Hepatobiliary cancers. Accessed 6 Feb 2017.
  26. 26.
    National Cancer Data Base. Published July 4, 2016. Accessed 4 July 2016.
  27. 27.
    Mattei A. Estimating and using propensity score in presence of missing background data: an application to assess the impact of childbearing on wellbeing. Stat Methods Appl. 2008;18(2):257–73. Scholar
  28. 28.
    Austin PC. The use of propensity score methods with survival or time-to-event outcomes: reporting measures of effect similar to those used in randomized experiments. Stat Med. 2014;33(7):1242–58. Scholar
  29. 29.
    Giobbie-Hurder A, Gelber RD, Regan MM. Challenges of guarantee-time bias. J Clin Oncol. 2013;31(23):2963–9. Scholar
  30. 30.
    Damhuis RAM, Wijnhoven BPL, Plaisier PW, Kirkels WJ, Kranse R, van Lanschot JJ. Comparison of 30-day, 90-day and in-hospital postoperative mortality for eight different cancer types. Br J Surg. 2012;99(8):1149–54. Scholar
  31. 31.
    Talsma AK, Lingsma HF, Steyerberg EW, Wijnhoven BPL, Van Lanschot JJB. The 30-day versus in-hospital and 90-day mortality after esophagectomy as indicators for quality of care. Ann Surg. 2014;260(2):267–73. Scholar
  32. 32.
    Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med. 2009;28(25):3083–107. Scholar
  33. 33.
    R Core Team: R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. [Internet], 2015.; Ref2 Sekhon J: Multivariate and Propensity Score Matching Software with Automated Balance Optimization: The Matching Package for R. J Stat Softw 42:1–52.
  34. 34.
    Wang R, Lagakos SW, Ware JH, Hunter DJ, Drazen JM. Statistics in medicine–reporting of subgroup analyses in clinical trials. N Engl J Med. 2007;357(21):2189–94. Scholar
  35. 35.
    Brookhart MA, Wyss R, Layton JB, Stürmer T. Propensity score methods for confounding control in nonexperimental research. Circ Cardiovasc Qual Outcomes. 2013;6(5):604–11. Scholar
  36. 36.
    Takada T, Amano H, Yasuda H, et al. Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? Cancer. 2002;95(8):1685–95. Scholar
  37. 37.
    Gemox versus surveillance following surgery of localized biliary tract cancer: Results of the PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial.| 2017 Gastrointestinal Cancers Symposium Abstracts.Google Scholar
  38. 38.
    Primrose JN, Fox R, Palmer DH, et al. Adjuvant capecitabine for biliary tract cancer: the BILCAP randomized study. J Clin Oncol. 2017. Scholar

Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  • Ibrahim Nassour
    • 1
  • Ali A. Mokdad
    • 1
  • Matthew R. Porembka
    • 1
  • Michael A. Choti
    • 1
  • Patricio M. Polanco
    • 1
    • 2
  • John C. Mansour
    • 1
  • Rebecca M. Minter
    • 1
  • Sam C. Wang
    • 1
  • Adam C. Yopp
    • 1
  1. 1.Division of Surgical Oncology, Department of SurgeryUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Department of Veterans AffairsNorth Texas Health Care SystemDallasUSA

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