Merkel cell carcinoma treatment with Mohs micrographic surgery versus wide local excision: A retrospective cohort survival analysis
Authors: Joshua D. Bloomstein, Daniel B. Eisen
Journal: Journal of the American Academy of Dermatology (2022)

Merkel cell carcinoma (MCC) is a rare, aggressive malignancy of the skin that most commonly presents on the face, extremities, or trunk. Historically, MCC surgical treatment has consisted of wide local excision (WLE). Mohs micrographic surgery (MMS) offers the dual benefits of tissue sparing and complete margin analysis. The low prevalence of MCC has led to a dearth of comparative analyses of surgical outcomes. One single-center study solely analyzed data on MMS.1Kline L. Coldiron B. Mohs micrographic surgery for the treatment of Merkel cell carcinoma.Dermatol Surg. 2016; 42: 945-951Crossref PubMed Scopus (36) Google Scholar Another study used a multicenter cohort, 1 compared MMS data with historical WLE controls, and 2 other studies examined the National Cancer Database.2Tarantola T.I. Vallow L.A. Halyard M.Y. et al.Prognostic factors in Merkel cell carcinoma: analysis of 240 cases.J Am Acad Dermatol. 2013; 68: 425-432Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar, 3Terushkin V. Brodland D.G. Sharon D.J. Zitelli J.A. Mohs surgery for early-stage Merkel cell carcinoma (MCC) achieves local control better than wide local excision ± radiation therapy with no increase in MCC-specific death.Int J Dermatol. 2021; 60: 1010-1012Crossref PubMed Scopus (4) Google Scholar, 4Su C. Bai H.X. Christensen S. Relative survival analysis in patients with stage I-II Merkel cell carcinoma treated with Mohs micrographic surgery or wide local excision.J Am Acad Dermatol. 2018; S0190-9622: 30816-30818Google Scholar, 5Singh B. Qureshi M.M. Truong M.T. Sahni D. Demographics and outcomes of stage I and II Merkel cell carcinoma treated with Mohs micrographic surgery compared with wide local excision in the National Cancer Database.J Am Acad Dermatol. 2018; 79: 126-134.e3Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar We retrospectively assessed the overall survival and progression-free survival in 57 patients with MCC who underwent MMS or WLE and received treatment at the University of California Davis Medical Center between 1994 and 2020. Eight additional patients diagnosed with MCC did not undergo surgical treatment and were excluded. Statistical analyses were performed using R version 4.1.1 and the packages "Survival," "Survminer," and "compareGroups." Cohort characteristics are listed in Table I. Overall survival based on complete follow-up period did not show the evidence of a significant difference between surgical modalities. Log-rank test P value was .67. The 3-year overall survival rates for MMS and WLE with 95% confidence intervals were 88.9% (70.6%-100%) and 88.1% (77.6%-100%), respectively. Progression-free survival, likewise, did not show evidence of a significant difference. The log-rank test P value was .22. The 3-year progression-free survival rates for MMS and WLE with 95% confidence intervals were 44.4% (22.4%-88.2%) and 71.6% (58.4%-87.7%), respectively. Figure 1 shows the Kaplan-Meier survival estimates of overall survival and progression-free survival, respectively.Table IPatient characteristics∗The staging is based on the American Joint Committee on Cancer Staging Manual, 8th edition. The Shapiro-Wilk test was used to assess for the normality of continuous variables. Student t test was used to compare continuous variables with normal distributions, and Mann-Whitney U test was used for nonnormal distributions. Tests of association with categorical variables were performed with χ2 or Fisher's exact tests for cell number of <5.CharacteristicAll patients (%)MMS (%)WLE (%)†One patient underwent WLE and parotidectomy.P valueAge at diagnosis, y‡Mean (standard deviation).71.5 (9.6)75.9 (10.3)70.4 (9.2).11Total12 (21.1)45 (78.9)Male39 (68.4)9 (75.0)30 (66.6).73Female18 (31.5)3 (25.0)15 (33.3)Stage I21 (36.8)6 (50.0)15 (33.3).06 IIA7 (12.2)1 (8.3)6 (13.3) IIB1 (1.7)0 (0)1 (2.2) IIIA12 (21)0 (0)12 (26.6) IIIB2 (3.5)1 (8.3)1 (2.2) Not reported14 (24.5)4 (33.3)10 (22.2)Preoperative size, cm§Median (first quartile to third quartile).1.5 (0.6-2.8)0.9 (0.7-1.1)1.5 (0.5-3.3).19Extent at diagnosis Local30 (52.6)6 (50)24 (53.3).41 Regional13 (22.8)1 (8.3)12 (26.6) Distant0 (0)0 (0)0 (0) Not reported14 (24.5)5 (41.6)9 (20)Tumor site Head31 (54.3)7 (58.3)24 (53.3) Lower extremity9 (15.7)2 (16.6)7 (15.5) Upper extremity9 (15.7)0 (0)9 (20) Neck4 (7)1 (8.3)3 (6.6) Anterior trunk1 (1.7)1 (8.3)0 (0) Posterior trunk2 (3.5)0 (0)2 (4.4) Not reported1 (1.7)1 (8.3)0 (0)RT36 (63.1)6 (50.0)30 (66.6).33No RT21 (36.8)6 (50.0)15 (33.3)Pharmacotherapy8 (14)0 (0)8 (17.7).18No pharmacotherapy49 (85.9)12 (100)37 (82.2)Immunosuppressive condition Yes6 (10.5)1 (8.3)5 (11.1)1 No45 (78.9)9 (75.0)36 (80.0) Not reported6 (10.5)2 (16.6)4 (8.8)Margin used, mm55-20Surgical stages‖Mean (range).1.4 (1-2)MMS, Mohs micrographic surgery; RT, radiation therapy; WLE, wide local excision.∗ The staging is based on the American Joint Committee on Cancer Staging Manual, 8th edition. The Shapiro-Wilk test was used to assess for the normality of continuous variables. Student t test was used to compare continuous variables with normal distributions, and Mann-Whitney U test was used for nonnormal distributions. Tests of association with categorical variables were performed with χ2 or Fisher's exact tests for cell number of <5.† One patient underwent WLE and parotidectomy.‡ Mean (standard deviation).§ Median (first quartile to third quartile).‖ Mean (range). Open table in a new tab MMS, Mohs micrographic surgery; RT, radiation therapy; WLE, wide local excision. Previous studies provide evidence of efficacy of MMS for MCC. A retrospective study of patients at a single institution calculated a local recurrence rate of 4.6% and metastasis rate of 13.6% at the 3.1-year follow-up.1Kline L. Coldiron B. Mohs micrographic surgery for the treatment of Merkel cell carcinoma.Dermatol Surg. 2016; 42: 945-951Crossref PubMed Scopus (36) Google Scholar However, we implemented a follow-up of 5.6 years, limiting the comparison of our results with the results of this study.1Kline L. Coldiron B. Mohs micrographic surgery for the treatment of Merkel cell carcinoma.Dermatol Surg. 2016; 42: 945-951Crossref PubMed Scopus (36) Google Scholar In a retrospective multicenter study, a subgroup analysis of patients with stage I and II (AJCC eighth edition) MCC reported a 3-year overall survival of 57.1% for patients treated with MMS (n = 8) and 79.2% for those treated with WLE (n = 45), with no statistically significant difference.2Tarantola T.I. Vallow L.A. Halyard M.Y. et al.Prognostic factors in Merkel cell carcinoma: analysis of 240 cases.J Am Acad Dermatol. 2013; 68: 425-432Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar Another study reported 5-year survival for stage I and IIA MCC treated with MMS alone was similar to historical controls treated with WLE with or without radiation therapy.3Terushkin V. Brodland D.G. Sharon D.J. Zitelli J.A. Mohs surgery for early-stage Merkel cell carcinoma (MCC) achieves local control better than wide local excision ± radiation therapy with no increase in MCC-specific death.Int J Dermatol. 2021; 60: 1010-1012Crossref PubMed Scopus (4) Google Scholar A retrospective study of the National Cancer Database found that the 3-year survival was not significantly different between patients with stage I and II MCC treated with MMS or WLE from 2004 to 2014.4Su C. Bai H.X. Christensen S. Relative survival analysis in patients with stage I-II Merkel cell carcinoma treated with Mohs micrographic surgery or wide local excision.J Am Acad Dermatol. 2018; S0190-9622: 30816-30818Google Scholar Although the sample size was large, charts were not individually reviewed. A previous analysis of National Cancer Database 1998-2011 stage I and II MCC, likewise, found no significant difference in the 3-year survival.5Singh B. Qureshi M.M. Truong M.T. Sahni D. Demographics and outcomes of stage I and II Merkel cell carcinoma treated with Mohs micrographic surgery compared with wide local excision in the National Cancer Database.J Am Acad Dermatol. 2018; 79: 126-134.e3Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Our results do not show evidence of significant difference in the overall or progression-free survival between MMS and WLE for MCC. To our knowledge, this is the largest study, and the first with survival analysis, based at a single center to date. The limitations include a relatively small sample size and retrospective design. Additional studies are warranted to further compare MCC surgical interventions. None disclosed.