Skip to main content

Reduced Wide Local Excision Margins are Associated with Increased Risk of Relapse and Death from Merkel Cell Carcinoma

Abstract

Introduction

Current recommendations regarding the size of wide local excision (WLE) margins for Merkel cell carcinoma (MCC) are not well established.

Methods

WLE and pathologic margins were respectively reviewed from 79 patients with stage I or II MCC, who underwent WLE at Washington University in St Louis from 2005 to 2019. Outcomes included local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant recurrence-free survival (DRFS), disease-free survival (DFS), and disease-specific survival (DSS).

Results

Thirty-two percent of patients received adjuvant radiotherapy (aRT). At 1 year, DFS was 51.3%, 71.4%, and 87.8% for patients with WLE margins < 1 cm, 1–1.9 cm, and ≥ 2 cm, respectively (p = 0.02). At 3 years, the DSS was 57.7%, 82.6%, and 100% for patients with WLE margins < 1 cm, 1–1.9 cm, and ≥ 2 cm, respectively (p = 0.02). Multivariable Cox analysis demonstrated that every 1-cm increase in WLE margins was associated with improved RRFS [hazard ratio (HR) = 0.28, 95% confidence interval (CI): 0.11–0.75], DRFS (HR 0.30, CI 0.08–0.99), DFS (HR 0.42, CI 0.21–0.86), and DSS (HR 0.16, CI 0.04–0.61). WLE and pathologic margin size were moderately-to-strongly correlated (r = 0.66). Close or positive pathologic margins (< 3 mm) were associated with reduced DRFS (HR 6.83, CI 1.80–25.9), DFS (HR 2.98, CI 1.31–6.75), and DSS (HR 3.52, CI 1.14–10.9).

Conclusion

Reduced WLE and pathologic margins were associated with higher risk of relapse and death from MCC. Larger WLE margins are important in populations with lower rates of adjuvant radiation.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

References

  1. 1.

    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):457-463.

    Article  Google Scholar 

  2. 2.

    National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Merkel Cell Carcinoma (Version I.2020). https://www.nccn.org/professionals/physician_gls/pdf/mcc.pdf. Accessed 20 Jan 2020.

  3. 3.

    Bichakjian CK, Olencki T, Aasi SZ, et al. Merkel cell carcinoma, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw. 2018;16(6):742-774.

    Article  Google Scholar 

  4. 4.

    Bichakjian CK, Olencki T, Alam M, et al. Merkel cell carcinoma, version 1.2014. J Natl Compr Cancer Netw. 2014;12(3):410-424.

    Article  Google Scholar 

  5. 5.

    Miller SJ, Alam M, Andersen J, et al. Merkel cell carcinoma. J Natl Compr Cancer Netw. 2009;7(3):322-332.

    CAS  Article  Google Scholar 

  6. 6.

    Allen PJ, Bowne WB, Jaques DP, Brennan MF, Busam K, Coit DG. Merkel cell carcinoma: prognosis and treatment of patients from a single institution. J Clin Oncol. 2005;23(10):2300-2309.

    Article  Google Scholar 

  7. 7.

    Perez MC, de Pinho FR, Holstein A, et al. Resection margins in Merkel cell carcinoma: is a 1-cm margin wide enough? Ann Surg Oncol. 2018;25(11):3334-3340.

    Article  Google Scholar 

  8. 8.

    Lewis KG, Weinstock MA, Weaver AL, Otley CC. Adjuvant local irradiation for Merkel cell carcinoma. Arch Dermatol. 2006;142(6):693-700.

    Article  Google Scholar 

  9. 9.

    Bhatia S, Storer BE, Iyer JG, et al. Adjuvant radiation therapy and chemotherapy in Merkel cell carcinoma: survival analyses of 6908 cases from the National Cancer Data Base. J Natl Cancer Inst. 2016;108(9):dkw042.

    Article  Google Scholar 

  10. 10.

    Harrington C, Kwan W. Radiotherapy and conservative surgery in the locoregional management of Merkel cell carcinoma: the British Columbia Cancer Agency experience. Ann Surg Oncol. 2016;23(2):573-578.

    Article  Google Scholar 

  11. 11.

    Mojica P, Smith D, Ellenhorn JD. Adjuvant radiation therapy is associated with improved survival in Merkel cell carcinoma of the skin. J Clin Oncol. 2007;25(9):1043-1047.

    Article  Google Scholar 

  12. 12.

    Fields RC, Busam KJ, Chou JF, et al. Five hundred patients with Merkel cell carcinoma evaluated at a single institution. Ann Surg. 2011;254(3):465-473; discussion 473-465.

  13. 13.

    Andea AA, Coit DG, Amin B, Busam KJ. Merkel cell carcinoma: histologic features and prognosis. Cancer. 2008;113(9):2549-2558.

    Article  Google Scholar 

  14. 14.

    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):642-646.

    CAS  Article  Google Scholar 

  15. 15.

    Boorjian SA, Karnes RJ, Crispen PL, et al. The impact of positive surgical margins on mortality following radical prostatectomy during the prostate specific antigen era. J Urol. 2010;183(3):1003-1009.

    Article  Google Scholar 

  16. 16.

    Houssami N, Macaskill P, Marinovich ML, Morrow M. The association of surgical margins and local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy: a meta-analysis. Ann Surg Oncol. 2014;21(3):717-730.

    Article  Google Scholar 

  17. 17.

    Van Zee KJ, Subhedar P, Olcese C, Patil S, Morrow M. Relationship between margin width and recurrence of ductal carcinoma in situ: analysis of 2996 women treated with breast-conserving surgery for 30 years. Ann Surg. 2015;262(4):623-631.

    Article  Google Scholar 

  18. 18.

    Nghiem P, Park SY. Less toxic, more effective treatment—a win-win for patients with Merkel cell carcinoma. JAMA Dermatol. 2019;55(11):1223–1224.

    Article  Google Scholar 

  19. 19.

    Chen MM, Roman SA, Sosa JA, Judson BL. The role of adjuvant therapy in the management of head and neck merkel cell carcinoma: an analysis of 4815 patients. JAMA Otolaryngol Head Neck Surg. 2015;141(2):137-141.

    Article  Google Scholar 

  20. 20.

    Eich HT, Eich D, Staar S, et al. Role of postoperative radiotherapy in the management of Merkel cell carcinoma. Am J Clin Oncol. 2002;25(1):50-56.

    Article  Google Scholar 

  21. 21.

    Servy A, Maubec E, Sugier PE, et al. Merkel cell carcinoma: value of sentinel lymph-node status and adjuvant radiation therapy. Ann Oncol. 2016;27(5):914-919.

    CAS  Article  Google Scholar 

  22. 22.

    Vargo JA, Ghareeb ER, Balasubramani GK, Beriwal S. RE: adjuvant radiation therapy and chemotherapy in Merkel Cell carcinoma: survival analyses of 6908 cases from the National Cancer Data Base. J Natl Cancer Inst. 2017;109(10):djx052.

    Article  Google Scholar 

  23. 23.

    Tsang G, O’Brien P, Robertson R, Hamilton C, Wratten C, Denham J. All delays before radiotherapy risk progression of Merkel cell carcinoma. Aust. Radiol. 2004;48(3):371-375.

    CAS  Article  Google Scholar 

  24. 24.

    Yusuf M, Gaskins J, Tennant P, Bumpous J, Dunlap N. Survival impact of time to initiation of adjuvant radiation for Merkel cell carcinoma: an analysis of the National Cancer Database. Pract Radiat Oncol. 2019;9(4):e372-e385.

    Article  Google Scholar 

  25. 25.

    Graboyes EM, Garrett-Mayer E, Ellis MA, et al. Effect of time to initiation of postoperative radiation therapy on survival in surgically managed head and neck cancer. Cancer. 2017;123(24):4841-4850.

    Article  Google Scholar 

  26. 26.

    Perez CA, Grigsby PW, Castro-Vita H, Lockett MA. Carcinoma of the uterine cervix. I. Impact of prolongation of overall treatment time and timing of brachytherapy on outcome of radiation therapy. Int J Radiat Oncol Biol Phys. 1995;32(5):1275-1288.

    CAS  Article  Google Scholar 

Download references

Acknowledgments

This work was supported in part by institutional funds from the Departments of Radiation Oncology and Pathology & Immunology, and the Siteman Cancer Center at Washington University in St Louis School of Medicine.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Mackenzie D. Daly MD.

Ethics declarations

Disclosure

The authors do not have any significant conflicts of interest to report.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Andruska, N., Mahapatra, L., Brenneman, R.J. et al. Reduced Wide Local Excision Margins are Associated with Increased Risk of Relapse and Death from Merkel Cell Carcinoma. Ann Surg Oncol 28, 3312–3319 (2021). https://doi.org/10.1245/s10434-020-09145-7

Download citation