Annals of Surgical Oncology

, Volume 23, Issue 11, pp 3564–3571 | Cite as

Analysis of Prognostic Factors from 9387 Merkel Cell Carcinoma Cases Forms the Basis for the New 8th Edition AJCC Staging System

  • Kelly L. HarmsEmail author
  • Mark A. Healy
  • Paul Nghiem
  • Arthur J. Sober
  • Timothy M. Johnson
  • Christopher K. Bichakjian
  • Sandra L. Wong
Medical Oncology



The first consensus Merkel cell carcinoma (MCC) staging system was published in 2010. New information on the clinical course prompts review of MCC staging.


A total of 9387 MCC cases from the National Cancer Data Base Participant User File with follow-up and staging data (1998–2012) were analyzed. Prognostic differences based on clinical and pathological staging were evaluated. Survival estimates were compared by disease extent.


Sixty-five percent of cases presented with local disease, whereas 26 and 8 % presented with nodal and distant disease. Disease extent at presentation was predictive of 5-year overall survival (OS) with estimates of 51, 35, and 14 % for local, nodal, and distant disease. Tumor burden at the regional nodal basin was predictive of 5-year OS with estimates of 40 and 27 % for clinically occult and clinically detected nodal disease. For local disease, we confirm improved prognosis when the regional nodal basin was negative by pathological compared with clinical staging. We identified 336 cases with clinically detected nodal disease and unknown primary tumor and showed improved prognosis over cases presenting with concurrent primary tumor (OS estimates of 42 vs. 27 %).


Analysis of a national dataset of MCC cases validates the predictive value of disease extent at presentation. Separation of clinical and pathological stage groups and regrouping of unknown primary tumors are supported by the analysis. The revised staging system provides more accurate prognostication and has been formally accepted by the AJCC staging committee for inclusion in the 8th edition.


Sentinel Lymph Node Biopsy National Comprehensive Cancer Network Merkel Cell Carcinoma Occult Nodal Metastasis Regional Nodal Basin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



MAH is supported by NIH T32CA009672-24. The data used in the study are from the NCDB PUF. The ACS-CoC has not verified and are not responsible for the analytic/statistical methodology employed or the conclusions drawn by the investigators.


KLH, MAH, TMJ, CKB, and SLW have no conflict of interest disclosures. PN is a consultant for EMD Serono; travel, accommodations, other expenses from EMD Serono; research funding from Brisol Myers Squibb to PN’s institution. AJS has research funding from MELA Sciences; AJS has stock in Merck, Amgen, Teva, and Pfizer.


  1. 1.
    Moshiri AS, Nghiem P. Milestones in the staging, classification, and biology of Merkel cell carcinoma. J Natl Compr Cancer Netw. 2014;12:1255–62.Google Scholar
  2. 2.
    Lemos BD, Storer BE, Iyer JG, et al. Pathologic nodal evaluation improves prognostic accuracy in Merkel cell carcinoma: analysis of 5823 cases as the basis of the first consensus staging system. J Am Acad Dermatol. 2010;63:751–61.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Iyer JG, Storer BE, Paulson KG, et al. Relationships among primary tumor size, number of involved nodes, and survival for 8044 cases of Merkel cell carcinoma. J Am Acad Dermatol. 2014;70:637–43.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Schwartz JL, Griffith KA, Lowe L, et al. Features predicting sentinel lymph node positivity in Merkel cell carcinoma. J Clin Oncol. 2011;29:1036–41.CrossRefPubMedGoogle Scholar
  5. 5.
    Smith FO, Yue B, Marzban SS, et al. Both tumor depth and diameter are predictive of sentinel lymph node status and survival in Merkel cell carcinoma. Cancer. 2015;121:3252–60.CrossRefPubMedGoogle Scholar
  6. 6.
    Kachare SD, Wong JH, Vohra NA, Zervos EE, Fitzgerald TL. Sentinel lymph node biopsy is associated with improved survival in Merkel cell carcinoma. Ann Surg Oncol. 2014;21:1624–30.CrossRefPubMedGoogle Scholar
  7. 7.
    Tarantola TI, Vallow LA, Halyard MY, et al. Prognostic factors in Merkel cell carcinoma: analysis of 240 cases. J Am Acad Dermatol. 2013;68:425–32.CrossRefPubMedGoogle Scholar
  8. 8.
    Paulson KG, Iyer JG, Byrd DR, Nghiem P. Pathologic nodal evaluation is increasingly commonly performed for patients with Merkel cell carcinoma. J Am Acad Dermatol. 2013;69:653–4.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Bichakjian CK, Olencki T, Alam M, et al. Merkel cell carcinoma, version 1.2014. J Natl Compr Cancer Netw. 2014;12:410–24.PubMedGoogle Scholar
  10. 10.
    Tarantola TI, Vallow LA, Halyard MY, et al. Unknown primary Merkel cell carcinoma: 23 new cases and a review. J Am Acad Dermatol. 2013;68:433–40.CrossRefPubMedGoogle Scholar
  11. 11.
    Chen KT, Papavasiliou P, Edwards K, et al. A better prognosis for Merkel cell carcinoma of unknown primary origin. Am J Surg. 2013;206:752–7.CrossRefPubMedGoogle Scholar
  12. 12.
    Foote M, Veness M, Zarate D, Poulsen M. Merkel cell carcinoma: the prognostic implications of an occult primary in stage IIIB (nodal) disease. J Am Acad Dermatol. 2012;67:395–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Deneve JL, Messina JL, Marzban SS, et al. Merkel cell carcinoma of unknown primary origin. Ann Surg Oncol. 2012;19:2360–6.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Edge SBBD, Compton CC, et al. AJCC cancer staging manual, 7th edn. New York: Springer; 2010.Google Scholar
  15. 15.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29.CrossRefPubMedGoogle Scholar
  16. 16.
    Bilimoria KY, Stewart AK, Winchester DP, Ko CY. The National Cancer Data Base: a powerful initiative to improve cancer care in the United States. Ann Surg Oncol. 2008;15:683–90.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Akhtar S, Oza KK, Wright J. Merkel cell carcinoma: report of 10 cases and review of the literature. J Am Acad Dermatol. 2000;43:755–67.CrossRefPubMedGoogle Scholar
  18. 18.
    Fields RC, Busam KJ, Chou JF, et al. Five hundred patients with Merkel cell carcinoma evaluated at a single institution. Ann Surg. 2011;254:465–73; discussion 473–5.Google Scholar
  19. 19.
    Howle JR, Veness MJ. Outcome of patients with microscopic and macroscopic metastatic nodal Merkel cell carcinoma: an Australian experience. Dermatol Surg. 2014;40:46–51.CrossRefPubMedGoogle Scholar

Copyright information

© Society of Surgical Oncology 2016

Authors and Affiliations

  • Kelly L. Harms
    • 1
    Email author
  • Mark A. Healy
    • 2
    • 3
  • Paul Nghiem
    • 4
    • 5
    • 6
  • Arthur J. Sober
    • 7
  • Timothy M. Johnson
    • 1
    • 2
    • 8
  • Christopher K. Bichakjian
    • 1
  • Sandra L. Wong
    • 2
    • 3
    • 9
  1. 1.Department of DermatologyUniversity of Michigan Health System and Medical SchoolAnn ArborUSA
  2. 2.Department of SurgeryUniversity of Michigan Health System and Medical SchoolAnn ArborUSA
  3. 3.Center for Healthcare Outcomes & PolicyUniversity of MichiganAnn ArborUSA
  4. 4.Department of Medicine/DermatologyUniversity of WashingtonSeattleUSA
  5. 5.Fred Hutchinson Cancer Research CenterSeattleUSA
  6. 6.Seattle Cancer Care AllianceSeattleUSA
  7. 7.Department of DermatologyMassachusetts General Hospital and Harvard Medical SchoolBostonUSA
  8. 8.Department of OtolaryngologyUniversity of Michigan Health System and Medical SchoolAnn ArborUSA
  9. 9.Department of SurgeryDartmouth-Hitchcock Medical Center and Geisel School of Medicine at DartmouthLebanonUSA

Personalised recommendations