Skip to main content
SpringerLink
Log in

Surgical Delay Is Associated with Improved Survival in Hepatocellular Carcinoma: Results of the National Cancer Database

  • Original Article
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Hepatocellular carcinoma (HCC) is one of the fastest growing causes of cancer-related death in the USA. Studies that investigated the impact of HCC therapeutic delays are limited to single centers, and no large-scale database research has been conducted. This study investigated the association of surgical delay and survival in HCC patients.

Methods

Patients underwent local tumor destruction and hepatic resection for stages I–III HCC were identified from the 2004 to 2013 Commission on Cancer’s National Cancer Database. Surgical delay was defined as > 60 days from the date of diagnosis to surgery. Generalized linear-mixed model assessed the demographic and clinical factors associated with delay, and frailty Cox proportional hazard analysis examined the prognostic factors for overall survival.

Results

A total of 12,102 HCC patients met the eligibility criteria. Median wait time to surgery was 50 days (interquartile range, 29–86), and 4987 patients (41.2%) had surgical delay. Delayed patients demonstrated better 5-year survival for local tumor destruction (29.1 vs. 27.6%; P = .001) and resection (44.1 vs. 41.0%; P = .007). Risk-adjusted model indicated that delayed patients had a 7% decreased risk of death (HR, 0.93; 95% CI, 0.87–0.99; P = .027). Similar findings were also observed using other wait time cutoffs at 50, 70, 80, 90, and 100 days.

Conclusions

A plausible explanation of this finding may be case prioritization, in which patients with more severe and advanced disease who were at higher risk of death received earlier surgery, while patients with less-aggressive tumors were operated on later and received more comprehensive preoperative evaluation.

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
Fig. 4

Similar content being viewed by others

References

  1. Islami F, Miller KD, Siegel RL, Fedewa SA, Ward EM, Jemal A. Disparities in liver cancer occurrence in the United States by race/ethnicity and state. CA Cancer J Clin. 2017;67(4):273–289.

    Article  PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67:7–30.

    Article  PubMed  Google Scholar 

  3. U.S. Cancer Statistics Working Group. United States Cancer Statistics: 1999–2014 Incidence and Mortality Web-based Report. Atlanta: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute. 2017. Available at: www.cdc.gov/uscs. Accessed 22 December 2017.

  4. Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology, 2011;53(3):1020–1022.

    Article  PubMed  PubMed Central  Google Scholar 

  5. McCormack L, Dutkowski P, El-Badry AM, Clavien PA. Liver transplantation using fatty livers: always feasible? J Hepatol. 2011;54(5):1055–1062.

    Article  PubMed  Google Scholar 

  6. Bhardwaj N, Perera MTPR, Silva MA. Current treatment approaches to HCC with a special consideration to transplantation. J Transplant. 2016;2016:7926264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Giannini EG, Farinati F, Ciccarese F, Pecorelli A, Rapaccini GL, Di Marco M, Benvegnu L, Caturelli E, Zoli M, Borzio F, Chiaramonte M, Trevisani F, Italian Liver Cancer (ITA.LI.CA) Group Prognosis of untreated hepatocellular carcinoma. Hepatology. 2015;61(1):184–190.

    Article  PubMed  Google Scholar 

  8. Singal AG, Tiro JA, Gupta S. Improving hepatocellular carcinoma screening: applying lessons from colorectal cancer screening. Clin Gastroenterol Hepatol. 2013;11(5):472–477.

    Article  PubMed  Google Scholar 

  9. Singal AG, Waljee AK, Patel N, Chen EY, Tiro JA, Marrero JA, Yopp AC. Therapeutic delays lead to worse survival among patients with hepatocellular carcinoma. J Natl Compr Canc Netw. 2013;11(9):1101–1108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Neal RD, Tharmanathan P, France B, Din NU, Cotton S, Fallon-Ferguson J, Hamilton W, Hendry A, Hendry M, Lewis R, Macleod U, Mitchell ED, Pickett M, Rai T, Shaw K, Stuart N, Tørring ML, Wilkinson C, Williams B, Williams N, Emery J. Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes? Systematic review. Br J Cancer. 2015;112 Suppl 1:S92-S107.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Huo TI, Huang YH, Chiang JH, Wu JC, Lee PC, Chi CW, Lee SD. Survival impact of delayed treatment in patients with hepatocellular carcinoma undergoing locoregional therapy: is there a lead-time bias? Scan J Gastroenterol. 2007;42(4):485–492.

    Article  CAS  Google Scholar 

  12. Chen WT, Fernandes ML, Lin CC, Lin SM. Delay in treatment of early-stage hepatocellular carcinoma using radiofrequency ablation may impact survival of cirrhotic patients in a surveillance program. J Surg Oncol. 2011;103(2):133–139.

    Article  PubMed  Google Scholar 

  13. Brahmania M, Ahmed O, Kelley M, Wong D, Kowgier M, Khalili K, Beercroft R, Renner EL, Shah H, Feld J, Janssen HLA, Sherman M. Wait time for curative intent radio frequency ablation is associated with increased mortality in patients with early stage hepatocellular carcinoma. Ann Hepatol. 2017;16(5):765–771.

    Article  PubMed  Google Scholar 

  14. Croome KP, Chudzinski R, Hanto DW. Increasing time delay from presentation until surgical referral for hepatobiliary malignancies. HPB (Oxford). 2010;12(9):644–648.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Lim C, Bhangui P, Salloum C, Gomez-Gavara C, Lahat E, Luciani A, Compagnon P, Calderaro J, Feray C, Azoulay D. Impact of time to surgery in the outcome of patients with liver resection for BCLC 0-A hepatocellular carcinoma. J Hepatol. 2017.

  16. Akce M, Sansgiry S, Temple SL, Davila J, Sada Y. The effect of treatment delay on survival in patients with hepatocellular cancer. J Clin Oncol. 2017;35:15_Suppl.e15645.

    Article  Google Scholar 

  17. Boffa DJ, Rosen JE, Mallin K, Loomis A, Gay G, Palis B, Thoburn K, Gress D, McKellar DP, Shulman LN, Facktor MA, Winchester DP. Using the National Cancer Database for outcomes research: a review. JAMA Oncol. 2017;3(12):1722–1728.

    Article  PubMed  Google Scholar 

  18. Chidi AP, Bryce CL, Han K, Dong ZM, Geller DA, Tsung A. Predictors of delay of surgical intervention in patients with hepatocellular carcinoma. J Surg Res. 2014;186:610–611.

    Article  Google Scholar 

  19. Myrdal G, Lambe M, Hillerdal G, Lamberg K, Agustsson T, Stahle E. Effect of delays on prognosis in patients with non-small cell lung cancer. Thorax. 2004;59(1):45–49.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Diaconescu R, Lafond C, Whittom R. Treatment delays in non-small cell lung cancer and their prognostic implications. J Thorac Oncol. 2011;6(7):1254–1259.

    Article  PubMed  Google Scholar 

  21. González-Barcala FJ, García-Prim JM, Álvarez-Dobaño JM, Moldes-Rodriguez M, Garcia-Sanz MT, Pose-Reino A, Valdes-Cuadrado L. Effects of delays on survival in patients with lung cancer. Clin Transl Oncol. 2010(12);12:836.

    Article  PubMed  Google Scholar 

  22. Amri R, Bordeianou LG, Sylla P, Berger DL. Treatment delay in surgically-treated colon cancer: does it affect outcomes? Ann Surg Oncol. 2014;21(12):3909–3016.

    Article  PubMed  Google Scholar 

  23. Crawford SC, Davis JA, Siddiqui NA, de Caestecker L, Gills CR, Hole D, Penney G. The wait time paradox: population based retrospective study of treatment delay and survival of women with endometrial cancer in Scotland. BMJ. 2002;325(7357):196.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Wallace DM, Bryan RT, Dunn JA, Begum G, Bathers S, West Midlands Urological Research Group Delay and survival in bladder cancer. BJU Int. 2002;89(9):868–878.

    Article  CAS  PubMed  Google Scholar 

  25. Hoehn RS, Hanseman DJ, Jernigan PL, Wima K, Ertel AE, Abbott DE, Shah SA. Disparities in care for patients with curable hepatocellular carcinoma. HPB (Oxford). 2015;17(9):747–752.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Bilimoria KY, Ko CY, Tomlinson JS, Stewart AK, Talamonti MS, Hynes DL, Winchester DP, Bentrem DJ. Wait times for cancer surgery in the United States: trends and predictors of delays. Ann Surg. 2011;253(4):779–785.

    Article  PubMed  Google Scholar 

  27. Jindal M, Zheng C, Quadri HS, Ihemelandu CU, Hong YK, Smith AK, Dudeja V, Shara NM, Johnson LB, Al-Refaie WB. Why do long-distance travelers have improved pancreatectomy outcomes? J Am Coll Surg. 2017;225(2):216–225.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Haddad AQ, Hutchinson R, Wood EL, Miranda G, Gershman B, Messer J, Svatek R, Black PC, Boorjian SA, Shah J, Daneshmand S, Lotan Y. Association of distance to treatment facility with survival and quality outcomes after radical cystectomy: a multi-institutional study. Clin Genitourin Cancer. 2017;15(6):689–695.e2.

    Article  PubMed  Google Scholar 

Download references

Funding Source

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Wisconsin Surgical Outcomes Research Program, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, 53726, USA

    Kerui Xu

  2. Department of Epidemiology, College of Public Health, University of Nebraska Medical Center, Omaha, NE, 68198-4395, USA

    Kerui Xu, Shinobu Watanabe-Galloway, Paraskevi A. Farazi & K. M. Monirul Islam

  3. Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-2000, USA

    Fedja A. Rochling

  4. Department of Health Services Research and Administration, College of Public Health, University of Nebraska Medical Center, Omaha, NE, 68198-4350, USA

    Hongmei Wang

  5. Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, 68198-4375, USA

    Jiangtao Luo

Authors
  1. Kerui Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shinobu Watanabe-Galloway
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fedja A. Rochling
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paraskevi A. Farazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. M. Monirul Islam
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hongmei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jiangtao Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

KX contributed to the study design, conceptualization, statistical analysis, and drafted the original paper. KMMI was responsible for data acquisition. SWG and FR also contributed to the study design and conceptualization, and JL assisted with statistical analysis. FR, PF, HW, and KMMI critically reviewed and edited the paper for important intellectual content. SWG supervised research activities.

Corresponding author

Correspondence to Kerui Xu.

Ethics declarations

The data used in the study are derived from a de-identified NCDB file. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methodology employed, or the conclusions drawn from these data by the investigator.

Ethics Committee Approval

The study was exempted from review by the University of Nebraska Medical Center Institutional Review Board.

Conflict of Interest

The authors declare that they have no conflict of interest.

Electronic Supplementary Material

ESM 1

(DOCX 45 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, K., Watanabe-Galloway, S., Rochling, F.A. et al. Surgical Delay Is Associated with Improved Survival in Hepatocellular Carcinoma: Results of the National Cancer Database. J Gastrointest Surg 23, 933–943 (2019). https://doi.org/10.1007/s11605-018-3925-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-018-3925-4

Keywords

Search

Navigation