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Merkel Cell Carcinoma: Assessing the Effect of Wide Local Excision, Lymph Node Dissection, and Radiotherapy on Recurrence and Survival in Early-Stage Disease—Results From a Review of 82 Consecutive Cases Diagnosed Between 1992 and 2004

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Abstract

Background

Wide surgical excision, lymph node dissection, and radiotherapy have been used with varying efficacy in the management of early-stage Merkel cell carcinoma.

Methods

Records of 82 patients with early-stage Merkel cell carcinoma between 1992 and 2004 were reviewed.

Results

Forty-two patients developed a recurrence, and 44 died during the study period. Twenty-nine patients presented with regional lymph node disease, which was independently associated with diminished survival (hazard ratio [HR], 4.08; 95% confidence interval [CI], 1.55–10.75; P = .005). Lymphadenectomy was independently associated with prolonged disease-free survival (median, 28.5 vs. 11.8 months; HR, .46; 95% CI, .22–.94; P = .034) but not overall survival (P = .25). Margin-negative excision of the primary tumor (60 of 73) was not significantly associated with either prolonged disease-free survival (median, 16 vs. 14 months) or overall survival (median, 54 vs. 34 months). Forty-eight patients received radiotherapy: 36 to the primary site and 31 to the regional lymph nodes. Radiotherapy to both sites was associated with a longer median time to first recurrence (primary site, 24.2 vs. 11.8 months; regional lymph nodes, 46.2 vs. 11.3 months) and survival (primary site, 53.9 vs. 45.7 months; regional lymph nodes, 103.1 vs. 34.2 months). Administration of any radiotherapy was significantly associated with a prolonged time to first recurrence (HR, .39; 95% CI, .20–.75; P = .004) and survival (HR, .39; 95% CI, .18–.82; P = .013) on the Cox regression multivariate analyses.

Conclusions

Adjuvant radiotherapy to the primary site after surgical excision is recommended in early-stage disease. Involved regional lymph nodes should be treated with radiotherapy with or without lymphadenectomy.

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REFERENCES

  1. Medina-Franco H, Marshall MU, Fiveash J, et al. Multimodality treatment of Merkel cell carcinoma: case series and literature review of 1024 cases. Ann Surg Oncol 2000; 8:204–8

    Article  Google Scholar 

  2. Poulson M. Merkel-cell carcinoma of the skin. Lancet Oncol 2004; 5:593–9

    Article  Google Scholar 

  3. Goessling W, McKee PH, Mayer RJ. Merkel cell carcinoma. J Clin Oncol 2002; 20:588–98

    Article  PubMed  Google Scholar 

  4. Tang C, Toker C. Trabecular carcinoma of the skin: an ultrastructural study. Cancer 1978; 42:2311–21

    Article  PubMed  CAS  Google Scholar 

  5. Boyle F, Pendlebury S, Bell D. Further insights into the natural history and management of primary cutaneous neuroendocrine (Merkel cell) carcinoma. Int J Radiat Oncol Biol Phys 1995;31:315–23

    Article  PubMed  CAS  Google Scholar 

  6. Toker C. Trabecular carcinoma of the skin. Arch Dermatol 1972; 105:107–10

    Article  PubMed  CAS  Google Scholar 

  7. Meeuwissen JA, Bourne RG, Kearsley JH. The importance of postoperative radiation therapy in the treatment of Merkel cell carcinoma. Int J Radiat Oncol Biol Phys 1995; 31:325–31

    Article  PubMed  CAS  Google Scholar 

  8. Kokoska ER, Kokoska MS, Brian IC, et al. Early aggressive treatment for Merkel cell carcinoma improves outcome. Am J Surg 1997; 174:688–93

    Article  PubMed  CAS  Google Scholar 

  9. Shaw JHF, Rumball E. Merkel cell tumour: clinical behaviour and treatment. Br J Surg 1991; 78:138–42

    Article  PubMed  CAS  Google Scholar 

  10. Meland NB, Jackson IT. Merkel cell tumour: diagnosis, prognosis, and management. Plast Reconstr Surg 1986; 77:632–8

    Article  PubMed  CAS  Google Scholar 

  11. Miller RW, Rabkin CS. Merkel cell carcinoma and melanoma: aetiological similarities and differences. Cancer Epidemiol Biomarkers Prev 1999; 8:153–8

    PubMed  CAS  Google Scholar 

  12. Yiengpruksawan A, Coit DG, Howard TT, et al. Merkel cell carcinoma. Prognosis and management. Arch Surg 1991; 126:1514–9

    PubMed  CAS  Google Scholar 

  13. Allen PJ, Bowne WB, Jacques DP, et al. Merkel cell carcinoma: prognosis and treatment of patients from a single institution. J Clin Oncol 2005; 23:2300–9

    Article  PubMed  Google Scholar 

  14. Eng TY, Naguib M, Fuller CD, et al. Treatment of recurrent Merkel cell carcinoma: an analysis of 46 cases. Am J Clin Oncol 2004; 27:576–83

    Article  PubMed  Google Scholar 

  15. Hitchcock CL, Bland KI, Laney RG, et al. Neuroendocrine (Merkel cell) carcinoma of the skin: its natural history, diagnosis, and treatment. Ann Surg 1988; 207:201–7

    Article  PubMed  CAS  Google Scholar 

  16. Meyer-Pannwitt U, Kummerfeldt K, Boubaris P, et al. Merkel cell tumour or neuroendocrine skin carcinoma. Langenbecks Arch Chir 1997; 382:349–358

    Google Scholar 

  17. Eng TY, Boersma MGK, Fuller CD, et al. Treatment of Merkel cell carcinoma. Am J Clin Oncol 2004; 27:510–5

    Article  PubMed  Google Scholar 

  18. Allen PJ, Zhang ZF, Coit DG. Surgical management of Merkel cell carcinoma: prognosis and management. Ann Surg 1999; 229:97–105

    Article  PubMed  CAS  Google Scholar 

  19. McAfee WJ, Morris CG, Mendenhall CM, et al. Merkel cell carcinoma: treatment and outcomes. Cancer 2005; 15:1761–4

    Article  Google Scholar 

  20. Muller A, Keus R, Neumann N, Lammering G, et al. Management of Merkel cell carcinoma: case series of 36 patients. Oncol Rep 2003; 10:577–85

    PubMed  Google Scholar 

  21. Connelly TJ, Cribier B, Brown TJ, et al. Complete spontaneous regression of the Merkel cell carcinoma: a review of the ten reported cases. Dermatol Surg 2000; 26:853–6

    Article  PubMed  CAS  Google Scholar 

  22. Goepfert H, Remmler D, Silva E, et al. Merkel cell carcinoma (endocrine carcinoma of the skin) of the head and neck. Arch Otolaryngol 1984; 110:707–12

    PubMed  CAS  Google Scholar 

  23. O’Connor WJ, Roenigk RK, Brodland DG. Merkel cell carcinoma: comparison of Mohs micrographic surgery and wide excision in eighty-six patients. Dermatol Surg 1997; 23:929–33

    Article  PubMed  CAS  Google Scholar 

  24. Poulsen M, Harvey J. Is there a diminishing role for surgery for Merkel cell carcinoma of the skin? A review of current management. Aust N Z J Surg 2002; 72:142–6

    Article  CAS  Google Scholar 

  25. Fenig E, Brenner B, Katz A, et al. The role of radiation therapy and chemotherapy in the treatment of Merkel cell carcinoma. Cancer 1997;80:881–5

    Article  PubMed  CAS  Google Scholar 

  26. Allen PJ, Zhang ZF, Coit DG. The surgical management of Merkel cell carcinoma. Ann Surg 1999; 229:97–105

    Article  PubMed  CAS  Google Scholar 

  27. Charlson ME, Sax FL, MacKenzie CR, et al. Assessing illness severity: does clinical judgment work? J Chronic Dis 1986; 39:439–52

    Article  PubMed  CAS  Google Scholar 

  28. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40:373–83

    Article  PubMed  CAS  Google Scholar 

  29. Charlson M, Szatrowski TP, Peterson J, et al. Validation of a combined comorbidity index. J Clin Epidemiol 1994; 47:1245–51

    Article  PubMed  CAS  Google Scholar 

  30. Uren RF, Howman-Giles R, Thompson JF, et al. Patterns of lymphatic drainage from the skin in patients with melanoma. J Nucl Med 2003; 44:570–82

    PubMed  Google Scholar 

  31. De Wilt JH, Thompson JF, Uren RF, et al. Correlation between preoperative lymphoscintigraphy and metastatic nodal disease sites in 362 patients with cutaneous melanomas of the head and neck. Ann Surg 2004; 239:544–52

    Article  PubMed  Google Scholar 

  32. Poulsen M, Rischin D, Walpole E, et al. Analysis of toxicity of Merkel cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group Study. Int J Radiat Oncol Biol Phys 2001; 51:153–63

    Article  Google Scholar 

  33. Poulsen M, Rischin D, Walpole E, et al. High-risk Merkel cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group Study—TROG 96:07. J Clin Oncol 2003; 21:4371–6

    Article  PubMed  CAS  Google Scholar 

  34. Venness MJ, Perera L, McCourt J, et al. Merkel cell carcinoma: improved outcome with adjuvant radiotherapy. Aust N Z J Surg 2005; 75:275–81

    Article  Google Scholar 

  35. Ott MJ, Tanabe KK, Gadd MA, et al. Multimodality management of Merkel cell carcinoma. Arch Surg 1999; 134:388–93

    Article  PubMed  CAS  Google Scholar 

  36. Wilder RB, Harari PM, Graham AR, et al. Improved locoregional control with postoperative radiation therapy. Cancer 1991; 68:1004–8

    Article  PubMed  CAS  Google Scholar 

  37. Marks ME, Kim RY, Salter MM. Radiotherapy as an adjunct in the management of Merkel cell carcinoma. Cancer 1990; 5:60–4

    Article  Google Scholar 

  38. Tennvall J, Biorklund A, Johansson L, et al. Merkel cell carcinoma: management of primary, recurrent and metastatic disease. A clinicopathologic study of 17 patients. Eur J Surg Oncol 1989; 15:1–9

    PubMed  CAS  Google Scholar 

  39. Gillenwater AM, Hessel AC, Morrison WH, et al. Merkel cell carcinoma of the head and neck: effect of surgical excision and radiation on recurrence and survival. Arch Otolaryngol Head Neck Surg 2001; 127:149–54

    PubMed  CAS  Google Scholar 

  40. Morrison WH, Peters LJ, Silva EG, et al. The essential role of radiation therapy in securing locoregional control of Merkel cell carcinoma. Int J Radiat Oncol Biol Phys 1990; 19:583–91

    PubMed  CAS  Google Scholar 

  41. Bielamowicz S, Smith D, Abemayor E. Merkel cell carcinoma: an aggressive skin neoplasm. Laryngoscope 1990; 104:528–32

    Article  Google Scholar 

  42. Wong KC, Zuletta F, Clarke J, et al. Clinical management and treatment outcomes of Merkel cell carcinoma. Aust N Z J Surg 1998; 68:354–8

    PubMed  CAS  Google Scholar 

  43. O’Connor WJ, Brodland DG: Merkel cell carcinoma. Dermatol Surg 1996; 22:262–7

    Article  PubMed  CAS  Google Scholar 

  44. Perez JA, Poblete MT, Castillo P, et al. Merkel cell carcinoma. Report of 4 cases (in Spanish). Rev Med Chil 1998;126:553–8

    PubMed  CAS  Google Scholar 

  45. Pergolizzi J, Pelczar M, Conaway GL. Merkel cell carcinoma: an aggressive malignancy. Am Surg 1997; 63:450–4

    PubMed  Google Scholar 

  46. Boyer JD, Zitelli JA, Brodland DG, et al. Local control of primary Merkel cell carcinoma: review of 45 cases treated with Mohs micrographic surgery with and without adjuvant radiation. Dermatol Surg 2002; 47:885–92

    Google Scholar 

  47. Veness MJ. Merkel cell carcinoma: improved outcome with the addition of adjuvant therapy. J Clin Oncol 2005; 23:7235–6

    Article  PubMed  Google Scholar 

  48. Bourne RG, O’Rourke MG. Management of Merkel cell tumour. Aust N Z J Surg 1988; 58:971–4

    PubMed  CAS  Google Scholar 

  49. Smith DE, Bielamowicz S, Kagan AR, et al. Cutaneous neuroendocrine (Merkel cell) carcinoma. Am J Clin Oncol 1995; 18:199–204

    Article  PubMed  CAS  Google Scholar 

  50. Mehrany K, Otley CC, Weenig RH, et al. A meta-analysis of the prognostic significance of sentinel lymph node status in Merkel cell carcinoma. Dermatol Surg 2002; 28:113–7

    Article  PubMed  Google Scholar 

  51. Victor NS, Morton B, Smith JW. Merkel cell cancer: is prophylactic lymph node dissection indicated? Am Surg 1996; 62:879–82

    PubMed  CAS  Google Scholar 

  52. Gollard R, Weber R, Kosty MP, et al. Merkel cell carcinoma: review of 22 cases with surgical, pathologic, and therapeutic considerations. Cancer 2000; 88:1842–51

    Article  PubMed  CAS  Google Scholar 

  53. Eich HT, Eich D, Staar S, et al. Role of post-operative radiotherapy in the management of Merkel cell carcinoma. Am J Clin Oncol 2002; 25:50–6

    Article  PubMed  Google Scholar 

  54. Voog E, Biron P, Martin JP, et al. Chemotherapy for patients with locally advanced or metastatic Merkel cell carcinoma. Cancer 1999;15:2589–95

    Article  Google Scholar 

  55. Haag M, Glass LF, Fenske NA. Merkel cell carcinoma: diagnosis and treatment. Dermatol Surg 1995; 21:669–83

    Article  PubMed  CAS  Google Scholar 

  56. Suntharalingam M, Rudoltz M, Mendenhall W, et al. Radiotherapy for Merkel cell carcinoma of the skin of the head and neck. Head Neck 1995; 17:96–101

    Article  PubMed  CAS  Google Scholar 

  57. Raaf JH, Urmacher C, Knapper WK, et al. Trabecular (Merkel cell) carcinoma of the skin: treatment of primary, recurrent, and metastatic disease. Cancer 1986; 57:178–82

    Article  PubMed  CAS  Google Scholar 

  58. Pilotti S, Rilke F, Bartoli C, et al. Clinicopathologic correlations of cutaneous neuroendocrine Merkel cell carcinoma. J Clin Oncol 1988; 6:1863–73

    PubMed  CAS  Google Scholar 

  59. Silva EG, Mackay B, Goepfert H, et al. Endocrine carcinoma of the skin (Merkel cell carcinoma). Pathol Ann 1984; 19:1–30

    Google Scholar 

  60. Pitale M, Sessions RB, Husain S. An analysis of prognostic factors in cutaneous neuroendocrine carcinoma. Laryngoscope 1992; 102:244–9

    Article  PubMed  CAS  Google Scholar 

  61. Cotlar AM, Gates JO, Gibbs FA. Merkel cell carcinoma: combined surgery and radiation therapy. Am Surg 1986; 52:159–64

    PubMed  CAS  Google Scholar 

  62. Tsang G, O’Brien P, Robertson R, et al. All delays before radiotherapy risk progression of Merkel cell carcinoma. Australas Radiol 2004; 48:371–5

    Article  PubMed  CAS  Google Scholar 

  63. Bischof M, Van Kampen M, Huber P, et al. Merkel cell carcinoma: the role of radiation therapy in general management. Strahlenther Onkol 1999; 175:611–5

    Article  PubMed  CAS  Google Scholar 

  64. Gould EV, Moll R, Moll I, et al. Biology of disease: neuroendocrine (Merkel) cells of the skin—hyperplasias, dysplasias, and neoplasms. Lab Invest 1985; 52:334–53

    PubMed  CAS  Google Scholar 

  65. Ratner D, Nelson BR, Brown MD, et al. Merkel cell carcinoma. J Am Acad Dermatol 1999; 29:143–56

    Article  Google Scholar 

  66. Al-Ghazal SK, Arora DS, Simpson RH, et al. Merkel cell carcinoma of the skin. Br J Plast Surg 1996; 49:491–6

    Article  PubMed  CAS  Google Scholar 

  67. Buell JF, Trofe J, Hanaway MJ, et al. Immunosuppression and Merkel cell cancer. Transplant Proc 2002; 34:1780–1

    Article  PubMed  CAS  Google Scholar 

  68. Bordea C, Wonjnarowska F, Millard PR, et al. Skin cancers in renal-transplant recipients occur more commonly than previously recognized in a temperate climate. Transplantation 2004; 77:574–9

    Article  PubMed  CAS  Google Scholar 

  69. Engels E, Frisch M, Goedart J, et al. Merkel cell carcinoma and HIV infection. Lancet 2002; 359:497–8

    Article  PubMed  Google Scholar 

  70. Scott MP, Helm KF. Cytokeratin 20: a marker for diagnosing Merkel cell carcinoma. Am J Dermatopathol 1999; 21:16–20

    Article  PubMed  CAS  Google Scholar 

  71. Hanly AJ, Elgart GW, Jorda M, et al. Analysis of thyroid transcription factor-1 and cytokeratin 20 separates Merkel cell carcinoma from small cell carcinoma of lung. J Cutan Pathol 2000; 27:118–20

    Article  PubMed  CAS  Google Scholar 

  72. Haneke E, Schulze HJ, Mahrle G, et al. Immunohistochemical and immunoelectron microscopic demonstration of chromogranin A in formalin-fixed tissue of Merkel cell carcinoma. J Am Acad Dermatol 1993; 28:222–6

    PubMed  CAS  Google Scholar 

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ACKNOWLEDGMENTS

The authors thank Dr. Fran Boyle (Clinical Oncology, Royal North Shore Hospital, Sydney), Christine Hill (Anatomical Pathology, Royal Prince Alfred Hospital, Sydney), Janice Falzon (Medical Records, Royal Prince Alfred Hospital, Sydney), and Vasuki Pious (Medical Records, Concord Repatriation General Hospital, Sydney) for their tireless assistance and support.

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Authors and Affiliations

  1. Sydney Cancer Centre, Sydney, Australia

    James Jabbour BSc(Med), MBBS, MPH & Richard A. Scolyer MD, FRCPA

  2. School of Public Health, University of Sydney, Sydney, Australia

    James Jabbour BSc(Med), MBBS, MPH & Robert Cumming MBBS, MPH, PhD

  3. St. Vincent’s Hospital, Sydney, Australia

    James Jabbour BSc(Med), MBBS, MPH

  4. Concord Repatriation General Hospital, Hospital Road, Concord, NSW, 2139, Australia

    James Jabbour BSc(Med), MBBS, MPH

  5. Centre for Research in Aging (CERA), Concord Repatriation General Hospital, Hospital Road, Concord, NSW, 2139, Australia

    Robert Cumming MBBS, MPH, PhD

  6. Department of Anatomical Pathology, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW, 2050, Australia

    Richard A. Scolyer MD, FRCPA

  7. Sydney Melanoma Unit, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW, 2050, Australia

    Richard A. Scolyer MD, FRCPA, George Hruby MBBS, FRANZCR & John F. Thompson MD, FRACS

  8. Melanoma and Skin Cancer Research Institute (MASCRI), Sydney, Australia

    Richard A. Scolyer MD, FRCPA & John F. Thompson MD, FRACS

  9. Department of Radiation Oncology, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW, 2050, Australia

    George Hruby MBBS, FRANZCR

  10. Department of Dermatology, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW, 2050, Australia

    Stephen Lee MBBS, FACD

  11. Department of Dermatology, Concord Repatriation General Hospital, Hospital Road, Concord, NSW, 2139, Australia

    Stephen Lee MBBS, FACD

  12. 16 Kingsland Rd., Strathfield, New South Wales, 2135, Australia

    James Jabbour BSc(Med), MBBS, MPH

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  1. James Jabbour BSc(Med), MBBS, MPH
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Correspondence to James Jabbour BSc(Med), MBBS, MPH.

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Jabbour, J., Cumming, R., Scolyer, R.A. et al. Merkel Cell Carcinoma: Assessing the Effect of Wide Local Excision, Lymph Node Dissection, and Radiotherapy on Recurrence and Survival in Early-Stage Disease—Results From a Review of 82 Consecutive Cases Diagnosed Between 1992 and 2004. Ann Surg Oncol 14, 1943–1952 (2007). https://doi.org/10.1245/s10434-006-9327-y

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