Skip to main content

Advertisement

SpringerLink
Log in

Defining the Chance of Statistical Cure Among Patients with Extrahepatic Biliary Tract Cancer

  • Original Scientific Report
  • Published:
World Journal of Surgery Aims and scope Submit manuscript

Abstract

Background

While surgery offers the best curative-intent treatment, many patients with biliary tract malignancies have poor long-term outcomes. We sought to apply a non-mixture cure model to calculate the cure fraction and the time to cure after surgery of patients with peri-hilar cholangiocarcinoma (PHCC) or gallbladder cancer (GBC).

Methods

Using the Extrahepatic Biliary Malignancy Consortium, 576 patients who underwent curative-intent surgery for gallbladder carcinoma or peri-hilar cholangiocarcinoma between 1998 and 2014 at 10 major hepatobiliary institutions were identified and included in the analysis. A non-mixture cure model was adopted to compare mortality after surgery to the mortality expected for the general population matched by sex and age.

Results

The median and 5-year overall survival (OS) were 1.9 years (IQR, 0.9–4.9) and 23.9 % (95 % CI, 19.6–28.6). Among all patients with PHCC or GBC, the probability of being cured after surgery was 14.5 % (95 % CI, 8.7–23.2); the time to cure was 9.7 years and the median survival of uncured patients was 1.8 years. Determinants of cure probabilities included lymph node metastasis and CA 19.9 level (p ≤ 0.05). The cure fraction for patients with a CA 19.9 < 50 U/ml and no lymph nodes metastases were 39.0 % versus only 5.1 % among patients with a CA 19.9 ≥ 50 who also had lymph node metastasis.

Conclusions

Examining an “all comer” cohort, <15 % of patients with PHCC or GBC could be considered cured after surgery. Factors such CA 19.9 level and lymph node metastasis independently predicted long-term outcome. Estimating the odds of statistical cure following surgery for biliary tract cancer can assist in decision-making as well as inform discussions around survivorship.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Valero V 3rd et al (2012) Management of perihilar cholangiocarcinoma in the era of multimodal therapy. Expert Rev Gastroenterol Hepatol 6(4):481–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Kanthan R et al (2015) Gallbladder cancer in the 21st century. J Oncol 2015:967472

    Article  PubMed  PubMed Central  Google Scholar 

  3. Hansel DE et al (2003) Identification of novel cellular targets in biliary tract cancers using global gene expression technology. Am J Pathol 163(1):217–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Tannapfel A et al (2003) Mutations of the BRAF gene in cholangiocarcinoma but not in hepatocellular carcinoma. Gut 52(5):706–712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Valle J et al (2010) Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 362(14):1273–1281

    Article  CAS  PubMed  Google Scholar 

  6. Friend E et al (2011) Development of a questionnaire (EORTC module) to measure quality of life in patients with cholangiocarcinoma and gallbladder cancer, the EORTC QLQ-BIL21. Br J Cancer 104(4):587–592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. El-Khoueiry AB et al (2012) SWOG 0514: a phase II study of sorafenib in patients with unresectable or metastatic gallbladder carcinoma and cholangiocarcinoma. Invest New Drugs 30(4):1646–1651

    Article  CAS  PubMed  Google Scholar 

  8. El-Khoueiry AB et al (2014) S0941: a phase 2 SWOG study of sorafenib and erlotinib in patients with advanced gallbladder carcinoma or cholangiocarcinoma. Br J Cancer 110(4):882–887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ben-Josef E et al (2015) 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 33(24):2617–2622

    Article  CAS  PubMed  Google Scholar 

  10. Jarnagin WR et al (2001) Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg 234(4):507–517 (discussion 517–519)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Akamatsu N, Sugawara Y, Hashimoto D (2011) Surgical strategy for bile duct cancer: advances and current limitations. World J Clin Oncol 2(2):94–107

    Article  PubMed  PubMed Central  Google Scholar 

  12. Mao K et al (2016) Patterns and prognostic value of lymph node dissection for resected perihilar cholangiocarcinoma. J Gastroenterol Hepatol 31(2):417–426

    Article  PubMed  PubMed Central  Google Scholar 

  13. Wang J et al (2015) Evaluation of adjuvant radiation therapy for resected gallbladder carcinoma: a multi-institutional experience. Ann Surg Oncol 22(Suppl 3):1100–1106

    Article  Google Scholar 

  14. Hueman MT, Vollmer CM Jr, Pawlik TM (2009) Evolving treatment strategies for gallbladder cancer. Ann Surg Oncol 16(8):2101–2115

    Article  PubMed  Google Scholar 

  15. Amini N et al (2015) Lymph node status after resection for gallbladder adenocarcinoma: prognostic implications of different nodal staging/scoring systems. J Surg Oncol 111(3):299–305

    Article  PubMed  Google Scholar 

  16. Weiss MJ et al (2014) Multimodal treatment strategies for advanced hilar cholangiocarcinoma. Langenbecks Arch Surg 399(6):679–692

    Article  PubMed  Google Scholar 

  17. Poruk KE, Pawlik TM, Weiss MJ (2015) Perioperative management of hilar cholangiocarcinoma. J Gastrointest Surg 19(10):1889–1899

    Article  PubMed  PubMed Central  Google Scholar 

  18. Maetani S, Gamel JW (2010) Evolution of cancer survival analysis. Surg Oncol 19(2):49–51 (discussion 61)

    Article  PubMed  Google Scholar 

  19. Lambert PC et al (2007) Estimating and modeling the cure fraction in population-based cancer survival analysis. Biostatistics 8(3):576–594

    Article  PubMed  Google Scholar 

  20. Cvancarova M et al (2013) Proportion cured models applied to 23 cancer sites in Norway. Int J Cancer 132(7):1700–1710

    Article  CAS  PubMed  Google Scholar 

  21. Dal Maso L et al (2014) Long-term survival, prevalence, and cure of cancer: a population-based estimation for 818 902 Italian patients and 26 cancer types. Ann Oncol 25(11):2251–2260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Spolverato G et al (2015) Can hepatic resection provide a long-term cure for patients with intrahepatic cholangiocarcinoma? Cancer 121(22):3998–4006

    Article  PubMed  Google Scholar 

  23. Edge SB, Byrd D, Compton CC, Fritz AG, Greene FL, Trotti A (2010) AJCC cancer staging manual, 7th edn. Springer, New York

  24. Mayo SC et al (2011) Refining the definition of perioperative mortality following hepatectomy using death within 90 days as the standard criterion. HPB (Oxford) 13(7):473–482

    Article  Google Scholar 

  25. Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240(2):205–213

    Article  PubMed  PubMed Central  Google Scholar 

  26. Othus M et al (2012) Cure models as a useful statistical tool for analyzing survival. Clin Cancer Res 18(14):3731–3736

    Article  PubMed  PubMed Central  Google Scholar 

  27. Tsodikov AD, Ibrahim JG, Yakovlev AY (2003) Estimating cure rates from survival data: an alternative to two-component mixture models. J Am Stat Assoc 98(464):1063–1078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. ftp.cdc.gov/pub/Health_Statistics/NCHS/Publications/NVSR/62_07/

  29. Miyazaki M et al (2015) Clinical practice guidelines for the management of biliary tract cancers 2015: the 2nd English edition. J Hepatobiliary Pancreat Sci 22(4):249–273

    Article  PubMed  Google Scholar 

  30. Chan E, Berlin J (2015) Biliary tract cancers: understudied and poorly understood. J Clin Oncol 33(16):1845–1848

    Article  CAS  PubMed  Google Scholar 

  31. Park JO et al (2015) Gemcitabine plus cisplatin for advanced biliary tract cancer: a systematic review. Cancer Res Treat 47(3):343–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kim Y et al (2015) Patient perceptions regarding the likelihood of cure after surgical resection of lung and colorectal cancer. Cancer 121(20):3564–3573

    Article  PubMed  PubMed Central  Google Scholar 

  33. Pawlik TM et al (2014) What are patients’ expectations about the effects of chemotherapy for advanced cancer? J Am Coll Surg 219(3):588–590

    Article  PubMed  Google Scholar 

  34. Cai C et al (2012) smcure: an R-package for estimating semiparametric mixture cure models. Comput Methods Progr Biomed 108(3):1255–1260

    Article  Google Scholar 

  35. De Angelis R et al (1999) Mixture models for cancer survival analysis: application to population-based data with covariates. Stat Med 18(4):441–454

    Article  PubMed  Google Scholar 

  36. Cai WK et al (2014) Preoperative serum CA19-9 levels is an independent prognostic factor in patients with resected hilar cholangiocarcinoma. Int J Clin Exp Pathol 7(11):7890–7898

    PubMed  PubMed Central  Google Scholar 

  37. Goetze TO (2015) Gallbladder carcinoma: prognostic factors and therapeutic options. World J Gastroenterol 21(43):12211–12217

    Article  PubMed  PubMed Central  Google Scholar 

  38. Goere D et al (2013) Is there a possibility of a cure in patients with colorectal peritoneal carcinomatosis amenable to complete cytoreductive surgery and intraperitoneal chemotherapy? Ann Surg 257(6):1065–1071

    Article  PubMed  Google Scholar 

  39. Hosokawa I et al (2016) Long-term survival benefit and potential for cure after R1 resection for colorectal liver metastases. Ann Surg Oncol 23(6):1897–1905

    Article  PubMed  Google Scholar 

  40. Rama R, Swaminathan R, Venkatesan P (2010) Cure models for estimating hospital-based breast cancer survival. Asian Pac J Cancer Prev 11(2):387–391

    PubMed  Google Scholar 

Download references

Author information

Author notes

    Authors and Affiliations

    1. Professor and Chair Department of Surgery, The Urban Meyer III and Shelley Meyer Chair in Cancer Research, The Ohio State University Wexner Medical Center, 395 W. 12th Ave., Suite 670, Columbus, OH, 43210, USA

      Gaya Spolverato, Fabio Bagante & Timothy M. Pawlik

    2. Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA, USA

      Cecilia G. Ethun & Shishir K. Maithel

    3. Department of Surgery, Stanford University Medical Center, Stanford, CA, USA

      George Poultsides & Thuy Tran

    4. Division of Surgical Oncology, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

      Kamran Idrees & Chelsea A. Isom

    5. Department of Surgery, Washington University School of Medicine, St Louis, MO, USA

      Ryan C. Fields & Bradley Krasnick

    6. Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

      Emily Winslow & Clifford Cho

    7. Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, KY, USA

      Robert C. G. Martin & Charles R. Scoggins

    8. Department of Surgery, Wake Forest University, Winston-Salem, NC, USA

      Perry Shen & Harveshp D. Mogal

    9. Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

      Carl Schmidt, Eliza Beal & Timothy M. Pawlik

    10. Department of Surgery, New York University, New York, NY, USA

      Ioannis Hatzaras & Rivfka Shenoy

    Authors
    1. Gaya Spolverato
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Fabio Bagante
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Cecilia G. Ethun
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. George Poultsides
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Thuy Tran
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Kamran Idrees
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Chelsea A. Isom
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Ryan C. Fields
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Bradley Krasnick
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Emily Winslow
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Clifford Cho
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Robert C. G. Martin
      View author publications

      You can also search for this author in PubMed Google Scholar

    13. Charles R. Scoggins
      View author publications

      You can also search for this author in PubMed Google Scholar

    14. Perry Shen
      View author publications

      You can also search for this author in PubMed Google Scholar

    15. Harveshp D. Mogal
      View author publications

      You can also search for this author in PubMed Google Scholar

    16. Carl Schmidt
      View author publications

      You can also search for this author in PubMed Google Scholar

    17. Eliza Beal
      View author publications

      You can also search for this author in PubMed Google Scholar

    18. Ioannis Hatzaras
      View author publications

      You can also search for this author in PubMed Google Scholar

    19. Rivfka Shenoy
      View author publications

      You can also search for this author in PubMed Google Scholar

    20. Shishir K. Maithel
      View author publications

      You can also search for this author in PubMed Google Scholar

    21. Timothy M. Pawlik
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Timothy M. Pawlik.

    Ethics declarations

    Conflict of interest

    None.

    Additional information

    Gaya Spolverato and Fabio Bagante contributed equally to this manuscript.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    Supplementary material 1 (DOCX 13 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Spolverato, G., Bagante, F., Ethun, C.G. et al. Defining the Chance of Statistical Cure Among Patients with Extrahepatic Biliary Tract Cancer. World J Surg 41, 224–231 (2017). https://doi.org/10.1007/s00268-016-3691-y

    Download citation

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00268-016-3691-y

    Keywords

    Search

    Navigation