Skip to main content

Advertisement

SpringerLink
Log in

An Internally Validated Prognostic Risk-Score Model for Disease-Specific Survival in Clinical Stage I and II Merkel Cell Carcinoma

  • Melanoma
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy for which factors predictive of disease-specific survival (DSS) are poorly defined.

Methods

Patients from six centers (2005–2020) with clinical stage I–II MCC who underwent sentinel lymph node (SLN) biopsy were included. Factors associated with DSS were identified using competing-risks regression analysis. Risk-score modeling was established using competing-risks regression on a training dataset and internally validated by point assignment to variables.

Results

Of 604 patients, 474 (78.5%) and 128 (21.2%) patients had clinical stage I and II disease, respectively, and 189 (31.3%) had SLN metastases. The 5-year DSS rate was 81.8% with a median follow-up of 31 months. Prognostic factors associated with worse DSS included increasing age (hazard ratio [HR] 1.03, p = 0.046), male sex (HR 3.21, p = 0.021), immune compromise (HR 2.46, p = 0.013), presence of microsatellites (HR 2.65, p = 0.041), and regional nodal involvement (1 node: HR 2.48, p = 0.039; ≥2 nodes: HR 2.95, p = 0.026). An internally validated, risk-score model incorporating all of these factors was developed with good performance (AUC 0.738). Patients with ≤ 4.00 and > 4.00 points had 5-year DSS rates of 89.4% and 67.2%, respectively. Five-year DSS for pathologic stage I/II patients with > 4.00 points (n = 49) was 79.8% and for pathologic stage III patients with ≤ 4.00 points (n = 62) was 90.3%.

Conclusions

A risk-score model, including patient and tumor factors, based on DSS improves prognostic assessment of patients with clinically localized MCC. This may inform surveillance strategies and patient selection for adjuvant therapy trials.

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.

Similar content being viewed by others

References

  1. Coggshall K, Tello TL, North JP, Yu SS. Merkel cell carcinoma: an update and review: pathogenesis, diagnosis, and staging. J Am Acad Dermatol. 2018;78(3):433–42. https://doi.org/10.1016/j.jaad.2017.12.001.

    Article  PubMed  Google Scholar 

  2. Paulson KG, Park SY, Vandeven NA, et al. Merkel cell carcinoma: current US incidence and projected increases based on changing demographics. J Am Acad Dermatol. 2018;78(3):457-63.e2. https://doi.org/10.1016/j.jaad.2017.10.028.

    Article  PubMed  Google Scholar 

  3. Sridharan V, Muralidhar V, Margalit DN, et al. Merkel cell carcinoma: a population analysis on survival. J Natl Compr Canc Netw. 2016;14(10):1247–57. https://doi.org/10.6004/jnccn.2016.0134.

    Article  PubMed  Google Scholar 

  4. Farley CR, Perez MC, Soelling SJ, et al. Merkel cell carcinoma outcomes: does ajcc8 underestimate survival? Ann Surg Oncol. 2020;27(6):1978–85. https://doi.org/10.1245/s10434-019-08187-w.

    Article  CAS  PubMed  Google Scholar 

  5. Fitzgerald TL, Dennis S, Kachare SD, Vohra NA, Wong JH, Zervos EE. Dramatic increase in the incidence and mortality from merkel cell carcinoma in the United States. Am Surg. 2015;81(8):802–6. https://doi.org/10.1177/000313481508100819.

    Article  PubMed  Google Scholar 

  6. Harms KL, Healy MA, Nghiem P, et al. Analysis of prognostic factors from 9387 merkel cell carcinoma cases forms the basis for the new 8th edition AJCC staging system. Ann Surg Oncol. 2016;23(11):3564–71. https://doi.org/10.1245/s10434-016-5266-4.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bichakjian C, Nghiem P, Johnson T, Wright C, Sober A. Merkel Cell Carcinoma (Chapter 46). AJCC Cancer Staging Manual. Springer; 2017:549–61.

  8. 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(18):3252–60. https://doi.org/10.1002/cncr.29452.

    Article  PubMed  Google Scholar 

  9. Santamaria-Barria JA, Boland GM, Yeap BY, Nardi V, Dias-Santagata D, Cusack JC. Merkel cell carcinoma: 30-year experience from a single institution. Ann Surg Oncol. 2013;20(4):1365–73. https://doi.org/10.1245/s10434-012-2779-3.

    Article  PubMed  Google Scholar 

  10. Lim CS, Whalley D, Haydu LE, et al. Increasing tumor thickness is associated with recurrence and poorer survival in patients with Merkel cell carcinoma. Ann Surg Oncol. 2012;19(11):3325–34. https://doi.org/10.1245/s10434-012-2509-x.

    Article  PubMed  Google Scholar 

  11. Morand GB, Madana J, Da Silva SD, Hier MP, Mlynarek AM, Black MJ. Merkel cell carcinoma of the head and neck: poorer prognosis than non-head and neck sites. J Laryngol Otol. 2016;130(4):393–7. https://doi.org/10.1017/S0022215116000153.

    Article  CAS  PubMed  Google Scholar 

  12. Harounian JA, Molin N, Galloway TJ, et al. Effect of sentinel lymph node biopsy and LVI on Merkel cell carcinoma prognosis and treatment. Laryngoscope. 2021;131(3):E828–35. https://doi.org/10.1002/lary.28866.

    Article  PubMed  Google Scholar 

  13. Cook M, Baker K, Redman M, et al. Differential outcomes among immunosuppressed patients with Merkel cell carcinoma: impact of immunosuppression type on cancer-specific and overall survival. Am J Clin Oncol. 2019;42(1):82–8. https://doi.org/10.1097/COC.0000000000000482.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Butala AA, Jain V, Reddy VK, et al. Impact of tumor-infiltrating lymphocytes on overall survival in Merkel cell carcinoma. Oncologist. 2021;26(1):63–9. https://doi.org/10.1634/theoncologist.2020-0070.

    Article  CAS  PubMed  Google Scholar 

  15. Schwartz JL, Griffith KA, Lowe L, et al. Features predicting sentinel lymph node positivity in Merkel cell carcinoma. J Clin Oncol. 2011;29(8):1036–41. https://doi.org/10.1200/JCO.2010.33.4136.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Tarantola TI, Vallow LA, Halyard MY, et al. Prognostic factors in Merkel cell carcinoma: analysis of 240 cases. J Am Acad Dermatol. 2013;68(3):425–32. https://doi.org/10.1016/j.jaad.2012.09.036.

    Article  PubMed  Google Scholar 

  17. Conic RRZ, Ko J, Saridakis S, et al. Sentinel lymph node biopsy in Merkel cell carcinoma: predictors of sentinel lymph node positivity and association with overall survival. J Am Acad Dermatol. 2019;81(2):364–72. https://doi.org/10.1016/j.jaad.2019.03.027.

    Article  PubMed  Google Scholar 

  18. 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(5):1624–30. https://doi.org/10.1245/s10434-013-3434-3.

    Article  PubMed  Google Scholar 

  19. Paulson KG, Iyer JG, Blom A, et al. Systemic immune suppression predicts diminished Merkel cell carcinoma-specific survival independent of stage. J Invest Dermatol. 2013;133(3):642–6. https://doi.org/10.1038/jid.2012.388.

    Article  CAS  PubMed  Google Scholar 

  20. Asgari MM, Sokil MM, Warton EM, Iyer J, Paulson KG, Nghiem P. Effect of host, tumor, diagnostic, and treatment variables on outcomes in a large cohort with Merkel cell carcinoma. JAMA Dermatol. 2014;150(7):716–23. https://doi.org/10.1001/jamadermatol.2013.8116.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 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(4):637–43. https://doi.org/10.1016/j.jaad.2013.11.031.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Hastie T, Tibshirani R, Friedman J. The elements of statistical learning: data mining, inference, and prediction. 2nd edn. Berlin: Springer; 2009. p. 219–59.

    Book  Google Scholar 

  23. Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94(446):496–509. https://doi.org/10.1080/01621459.1999.10474144.

    Article  Google Scholar 

  24. StataCorp. Competing-risks regression. STATA. Accessed March 21, 2022, https://www.stata.com/manuals/ststcrreg.pdf

  25. Rufibach K. Use of Brier score to assess binary predictions. J Clin Epidemiol. 2010;63(8):938–9. https://doi.org/10.1016/j.jclinepi.2009.11.009.

    Article  PubMed  Google Scholar 

  26. Hajian-Tilaki K. Receiver operating characteristic (ROC) Curve analysis for medical diagnostic test evaluation. Caspian J Int Med. 2013;4(2):627–35.

    Google Scholar 

  27. Liu X. Classification accuracy and cut point selection. Stat Med. 2012;31(23):2676–86. https://doi.org/10.1002/sim.4509.

    Article  PubMed  Google Scholar 

  28. Schemper M, Smith TL. A note on quantifying follow-up in studies of failure time. Control Clin Trials. 1996;17(4):343–6. https://doi.org/10.1016/0197-2456(96)00075-x.

    Article  CAS  PubMed  Google Scholar 

  29. StataCorp. Stata Statistical Software: Release 17. College Station, TX: StataCorp LLC; 2021.

  30. Frohm ML, Griffith KA, Harms KL, et al. Recurrence and survival in patients with Merkel cell carcinoma undergoing surgery without adjuvant radiation therapy to the primary site. JAMA Dermatol. 2016;152(9):1001–7. https://doi.org/10.1001/jamadermatol.2016.1428.

    Article  PubMed  Google Scholar 

  31. Kubica AW, Brewer JD. Melanoma in immunosuppressed patients. Mayo Clin Proc. 2012;87(10):991–1003. https://doi.org/10.1016/j.mayocp.2012.04.018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Nguyen AT, Luu M, Lu DJ, et al. Quantitative metastatic lymph node burden and survival in Merkel cell carcinoma. J Am Acad Dermatol. 2021;84(2):312–20. https://doi.org/10.1016/j.jaad.2019.12.072.

    Article  PubMed  Google Scholar 

  33. Lee JS, Durham AB, Bichakjian CK, et al. Completion lymph node dissection or radiation therapy for sentinel node metastasis in Merkel cell carcinoma. Ann Surg Oncol. 2019;26(2):386–94. https://doi.org/10.1245/s10434-018-7072-7.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors did not receive funding for the completion of this work. All authors have read and acknowledged the contents of this manuscript. C. Slingluff reports research funding to his University from Merck, Celldex, and GlaxoSmithKline; research support in kind to his University from Theraclion and 3M; Scientific Advisory Board role with Immatics (prior), and Curevac (planned); PI role for Polynoma with compensation to his University; and patent royalties as co-inventor of peptides for use in cancer vaccines (patents held by the UVA Licensing and Ventures Group), all outside the submitted work.

Author information

Author notes

  1. Adrienne B. Shannon and Richard J. Straker have contributed equally to this work.

Authors and Affiliations

  1. Division of Endocrine and Oncologic Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

    Adrienne B. Shannon MD, Richard J. Straker III MD, Luke J. Keele PhD, Giorgos C. Karakousis MD & John T. Miura MD

  2. Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA

    Michael J. Carr MD, MS, Vernon K. Sondak MD & Jonathan S. Zager MD

  3. Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, FL, USA

    Michael J. Carr MD, MS, Robyn Panchaud BA, Kenneth Y. Tsai MD, PhD, Vernon K. Sondak MD & Jonathan S. Zager MD

  4. Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, OH, USA

    James Sun MD

  5. Division of Surgical Oncology, Department of Surgery, Duke University Medical Center, Durham, NC, USA

    Karenia Landa MD & Georgia M. Beasley MD, MHS

  6. Division of Surgical Oncology, Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA

    Kirsten Baecher MD & Michael C. Lowe MD, MA

  7. Division of Breast and Melanoma Surgery, Department of Surgery, University of Virginia, Charlottesville, VA, USA

    Kevin Lynch MD & Craig L. Slingluff Jr., MD

  8. Division of Head and Neck Surgical Oncology, Department of Otolaryngology, University of Virginia, Charlottesville, VA, USA

    Harrison G. Bartels MD & Mark J. Jameson MD, PhD

  9. Department of Pathology, Moffitt Cancer Center, Tampa, FL, USA

    Robyn Panchaud BA & Kenneth Y. Tsai MD, PhD

  10. Division of Surgical Oncology, Cedars-Sinai Medical Center, The Angeles Clinic and Research Institute, Los Angeles, CA, USA

    Mark B. Faries MD

Authors
  1. Adrienne B. Shannon MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard J. Straker III MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael J. Carr MD, MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. James Sun MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Karenia Landa MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kirsten Baecher MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kevin Lynch MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Harrison G. Bartels MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Robyn Panchaud BA
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Luke J. Keele PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Michael C. Lowe MD, MA
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Craig L. Slingluff Jr., MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Mark J. Jameson MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Kenneth Y. Tsai MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Mark B. Faries MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Georgia M. Beasley MD, MHS
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Vernon K. Sondak MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Giorgos C. Karakousis MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Jonathan S. Zager MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. John T. Miura MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

MBF reports advisory board participation with Merck, Bristol Myers Squibb, Novartis, Array, Pulse Bioscience, and Sanofi, all outside the submitted work. G.M. Beasley reports relevant financial activities outside the submitted work as a member of the 2020 Regeneron Sanofi advisory board. V. Sondak reports personal fees from Array, Bristol Myers Squibb, Genentech, Merck, Novartis, Pfizer, Regeneron, Replimune, and research funding to his institution from Neogene Therapeutics, outside the submitted work. J.S. Zager reports advisory board participation with Merck, Amgen, and Sanofi Regeneron; speakers bureau participation with Array Biopharma and Sun Pharma; and research work with Amgen, Provectus, Castle Biosciences, and Delcath Systems, all outside the submitted work.

Corresponding author

Correspondence to Adrienne B. Shannon MD.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shannon, A.B., Straker, R.J., Carr, M.J. et al. An Internally Validated Prognostic Risk-Score Model for Disease-Specific Survival in Clinical Stage I and II Merkel Cell Carcinoma. Ann Surg Oncol 29, 7033–7044 (2022). https://doi.org/10.1245/s10434-022-12201-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-022-12201-z

Search

Navigation