Research

JAMA Dermatology | Original Investigation

Comparison of Survival After Mohs Micrographic Surgery

vs Wide Margin Excision for Early-Stage Invasive Melanoma
Shayan Cheraghlou, BA; Sean R. Christensen, MD, PhD; George O. Agogo, PhD; Michael Girardi, MD

Editorial page 1229

IMPORTANCE Melanoma is among the most common malignant neoplasms in the United
States, with 91 270 cases estimated to be diagnosed in 2018. Since 2012, Mohs micrographic
surgery (MMS) has gained popularity in the treatment of melanoma in situ. Although current
guidelines for invasive melanoma without nodal metastases recommend surgery with wide
margin excision (WME), use of MMS for this disease has increased as well, particularly in early
stages. How the survival outcomes after each procedure compare with one another for
early-stage invasive melanoma is unknown to date.

OBJECTIVE To evaluate overall survival of patients with stage I melanoma defined by the
American Joint Committee on Cancer Cancer Staging Manual, 8th edition (AJCC-8) after MMS
vs traditional WME.

DESIGN, SETTING, AND ANALYSIS This retrospective cohort study includes all patients with
AJCC-8 stage I melanoma who underwent MMS or WME in the National Cancer Database
with a diagnosis from January 1, 2004, through December 31, 2014. The National Cancer
Database includes all reportable cases from Commission on Cancer–accredited facilities and
represents approximately 50% of all newly diagnosed melanoma cases in the United States.
Data were analyzed from November 13, 2018, through June 9, 2019.

EXPOSURES MMS vs WME.

MAIN OUTCOMES AND MEASURES Overall survival evaluated using multivariable Cox
proportional hazards regression analysis.

RESULTS A total of 70 319 eligible patients (52.3% male and 47.7% female; median [SD] age,
57.0 [16.2] years) were identified, including 67 085 treated with WME and 3234 treated with
MMS. Multivariable Cox proportional hazards regression survival analysis controlling for
clinical and tumor factors revealed that treatment with MMS was associated with a modest
improvement in overall survival relative to WME (hazard ratio [HR], 0.86; 95% CI, 0.76-0.97).
Propensity score–matched analysis of cohorts of patients treated with MMS vs WME also
found modestly improved survival for those treated with MMS (HR, 0.82; 95% CI,
0.68-0.98). Academic facilities were more likely to use MMS than nonacademic facilities
(odds ratio, 2.03; 95% CI, 1.88-2.18).

CONCLUSIONS AND RELEVANCE These findings suggest that Mohs surgery may provide an
alternative approach to traditional WME for appropriately selected cases of AJCC-8 stage I
melanoma without compromising patient survival.

Author Affiliations: Department of

Dermatology, Yale School of
Medicine, New Haven, Connecticut
(Cheraghlou, Christensen, Girardi);
Department of Internal Medicine,
Yale School of Medicine, New Haven,
Connecticut (Agogo).
Corresponding Author: Michael
Girardi, MD, Department of
Dermatology, Yale School of
Medicine, 333 Cedar St, PO Box
JAMA Dermatol. 2019;155(11):1252-1259. doi:10.1001/jamadermatol.2019.2890 208059, New Haven, CT 06520
Published online September 25, 2019. (michael.girardi@yale.edu).

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 Survival After Mohs Micrographic Surgery vs Wide Margin Excision for Early-Stage Invasive Melanoma
M
elanoma is among the most common malignant neo-
plasms in the United States, with 91 270 cases esti-
mated to be diagnosed in 2018.1 For cases of invasive
melanoma without nodal or extralymphatic metastasis, current
national guidelines recommend treatment with wide margin ex-
cision (WME) and consideration of sentinel lymph node biopsy,
depending on patient preference and comorbidities.2 Although
not currently espoused by guidelines for this indication, use of
Mohs micrographic surgery (MMS) has increased as an alterna-
tive to WME.3 Some controversy remains as to the potential ef-
fects of the 2 surgical techniques on patient survival, with pro-
ponents of MMS pointing to its complete margin evaluation and
critics of MMS concerned about residual disease in tumors with-
out contiguous growth patterns.4,5
Most of the work studying the efficacy of MMS for the
treatment of melanoma has focused on its use for melanoma in
situ, particularly the lentigo maligna subtype that, owing to
subclinical tumor extensions, frequently recurs after traditional
excision.6,7 For these tumors, treatment with traditional MMS
or staged surgical excisions with permanent sections has dem-
onstrated local control rates higher than those obtained with
WME.8-10 Based on the evidence available at the time, the Ameri-
can Academy of Dermatology/American College of Mohs Surgery/
American Society for Dermatologic Surgery Association/American
Society for Mohs Surgery Ad Hoc Task Force on Appropriate Use
Criteria for Mohs surgery11 concluded that MMS was appropri-
ate for all melanoma in situ lesions, with the exception of lesions
on the trunk or extremities, which were classified as uncertain
by the task force. The guidelines do not offer specific recommen-
dations on the use of MMS for invasive melanoma, however, and
this is an area of active investigation. Retrospective studies from
individual institutions of early-stage melanoma treated with MMS
have shown rates of recurrence and survival similar to those of
melanoma treated with WME.12-14 National registry studies of in-
vasive melanoma have also not shown any significant difference
in survival between MMS and WME, but these studies have not
focused on stage I invasive melanoma.15,16
We sought herein to investigate the association of the type
of surgical excision—WME or MMS—with overall survival for cases
of American Joint Committee on Cancer Cancer Staging Manual,
8th edition (AJCC-8) stage I invasive melanoma. We limited our
analysis to stage I tumors because we hypothesized that these
patients are least likely to have undetected disseminated disease
at presentation and therefore most likely to benefit from primary
tumor excision with the complete microscopic margin control
provided by MMS. We had a secondary aim of investigating the
factors that influence the type of surgical excision (MMS vs WME)
performed for individual cases. To accomplish this, we studied
a national cohort of 70 319 patients from the Commission on Can-
cer’s National Cancer Database (NCDB), with diagnosis from Janu-
ary 1, 2004, through December 31, 2014.
Methods
Data Source
Data originated primarily from the NCDB, with diagnosis from
January 1, 2004, through December 31, 2014.17 This study was
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Original Investigation Research
Key Points
Question How does the survival of patients undergoing excision
of stage I melanoma (defined by the American Joint Committee on
Cancer Cancer Staging Manual, 8th edition) with Mohs
micrographic surgery compare with that of patients receiving
traditional wide margin excision?
Findings In this cohort analysis of the National Cancer Database,
treatment of early-stage invasive melanoma with Mohs
micrographic surgery was associated with moderately improved
overall survival compared with traditional wide margin excision.
Meaning These findings suggest that Mohs micrographic surgery
may provide an alternative to wide margin excision for
appropriately selected cases of early-stage invasive melanoma
without compromising patient survival.
determined to be exempt from institutional review by the Yale
Human Investigation Committee, which waived the need for
informed consent for the use of publicly available data. This
study followed the Strengthening the Reporting of Observa-
tional Studies in Epidemiology (STROBE) reporting guideline.
Study Population
We identified adults with melanoma (n = 525 271) with a pri-
mary site in the skin using the International Classification of
Diseases for Oncology, 3rd Edition, histology codes 8720 to
8780 and primary site codes C44.0 to C44.9. We excluded
patients if they had previous or other cancer diagnoses
(n = 147 024); did not have their primary tumor excised
(n = 19 714); received excisions other than WME or MMS
(n = 130 966); had tumors defined as in situ (n = 44 643);
had nodal (n = 6204) or extralymphatic (n = 1286) distant
metastases at the time of presentation; had AJCC-8 patho-
logic stage II or greater disease (n = 40 742); received any
adjuvant therapy, including chemotherapy (n = 672), immu-
notherapy (n = 2096), or radiotherapy (n = 497); had miss-
ing or incomplete follow-up information (n = 10 716); or
were missing data on surgical excision (n = 50), adjuvant
therapies (n = 3985), clinical N (n = 38 103) or M (n = 1641)
staging, Breslow thickness (n = 3511), or tumor ulceration
status (n = 3102). All inclusion and exclusion criteria were
determined a priori.
Patients were defined as having received WME if they re-
ceived a primary excision or reexcision after diagnostic bi-
opsy with margins greater than 1 cm. Patients were included
in the MMS group if they received MMS as the primary treat-
ment or as definitive surgery after diagnostic biopsy, regard-
less of the size of margins.
Statistical Analysis
Data were analyzed from November 13, 2018, through June
9, 2019. We performed Kaplan-Meier analysis stratified by
type of excision. Our primary outcome was overall survival.
Sensitivity analysis was also performed for cases excluded
owing to missing data. We also conducted multivariable sur-
vival analyses using Cox proportional hazards regression
models. Hazard ratios (HRs) calculated from these models
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 Research Original Investigation Survival After Mohs Micrographic Surgery vs Wide Margin Excision for Early-Stage Invasive Melanoma

Table 1. Characteristics of the Analytic Sample

Treatment Groupa
Before Propensity Score After Propensity Score
Matching Matching
All WME MMS WME MMS
Variable (N = 70 319) (n = 67 085) (n = 3234) (n = 2589) (n = 2589)
Age, median (SD) 57.0 (16.2) 57.0 (16.2) 61.0 (16.3) 60.0 (15.8) 60.0 (15.8)
Sex
Male 36 810 (52.3) 35 036 (52.2) 1774 (54.9) 1431 (55.3) 1431 (55.3)
Female 33 509 (47.7) 32 049 (47.8) 1460 (45.1) 1158 (44.7) 1158 (44.7)
Race/ethnicity
White 68 104 (96.9) 64 983 (96.9) 3121 (96.5) 2493 (96.3) 2504 (96.7)
Black 211 (0.3) 197 (0.3) 14 (0.4) 7 (0.3) 8 (0.3)
Hispanic 662 (0.9) 639 (1.0) 23 (0.7) 25 (1.0) 16 (0.6)
Asian or Pacific Islander 133 (0.2) 129 (0.2) 4 (0.1) 4 (0.2) 4 (0.2)
Other or unknown 1209 (1.7) 1137 (1.7) 72 (2.2) 60 (2.3) 57 (2.2)
Charlson-Deyo comorbidity scoreb
0 62 861 (89.4) 59 891 (89.3) 2970 (91.8) 2477 (95.7) 2480 (95.8)
1 6370 (9.1) 6147 (9.2) 223 (6.9) 110 (4.2) 108 (4.2)
2 832 (1.2) 803 (1.2) 29 (0.9) 2 (0.1) 1 (0.03)
≥3 256 (0.4) 244 (0.4) 12 (0.4) 0 0
Insurance
Private 44 900 (63.9) 43 044 (64.2) 1856 (57.4) 1613 (62.3) 1612 (62.3)
Government 22 721 (32.3) 21 470 (32.0) 1251 (38.7) 942 (36.4) 943 (36.4)
None 1545 (2.2) 1472 (2.2) 73 (2.3) 23 (0.9) 22 (0.8)
Unknown 1153 (1.6) 1099 (1.6) 54 (1.7) 11 (0.4) 12 (0.5)
Facility type
Nonacademic 43 343 (61.6) 41 951 (62.5) 1392 (43.0) 1158 (44.7) 1157 (44.7)
Academic 26 976 (38.4) 25 134 (37.5) 1842 (57.0) 1431 (55.3) 1432 (55.3)
Anatomical site
Trunk 23 770 (33.8) 22 991 (34.3) 779 (24.1) 703 (27.2) 702 (27.1)
Upper limb or shoulder 18 387 (26.1) 17 711 (26.4) 676 (20.9) 572 (22.1) 575 (22.2)
Lower limb or hip 14 426 (20.5) 13 962 (20.8) 464 (14.3) 378 (14.6) 377 (14.6)
Face 8460 (12.0) 7443 (11.1) 1017 (31.4) 757 (29.2) 757 (29.2)
Scalp or neck 4917 (7.0) 4640 (6.9) 277 (8.6) 174 (6.7) 174 (6.7)
Overlapping or NOS 359 (0.5) 338 (0.5) 21 (0.6) 5 (0.2) 4 (0.2)
Histologic subtype
Superficial spreading 28 590 (40.7) 27 502 (41.0) 1088 (33.6) 928 (35.8) 926 (35.8)
Lentigo maligna 3774 (5.4) 4252 (6.3) 552 (17.1) 350 (13.5) 351 (13.6)
Nodular 2720 (3.9) 2658 (4.0) 62 (1.9) 15 (0.6) 17 (0.7)
Malignant acral lentiginous 610 (0.9) 589 (0.9) 21 (0.6) 3 (0.1) 4 (0.2)
Malignant desmoplastic 450 (0.6) 431 (0.6) 19 (0.6) 3 (0.1) 3 (0.1)
Spindle cell 430 (0.6) 414 (0.6) 16 (0.5) 2 (0.1) 2 (0.1)
Other or NOS 33 745 (48.0) 32 239 (48.1) 1506 (46.6) 1288 (49.7) 1288 (49.8)
Ulceration
Not present 67 291 (95.7) 64 159 (95.6) 3132 (96.8) 2563 (99.0) 2559 (98.8) Abbreviations: MMS, Mohs
micrographic surgery;
Present 3028 (4.3) 2926 (4.4) 102 (3.2) 126 (4.9) 30 (1.2)
NA, not applicable; NOS, not
Breslow thickness, mm otherwise specified; WME, wide
<0.80 45 167 (64.2) 42 569 (63.5) 2598 (80.3) 2154 (83.2) 2156 (83.3) margin excision.
a
0.80-1.00 8916 (12.7) 8633 (12.9) 283 (8.8) 178 (6.9) 176 (6.8) Unless otherwise indicated, data are
expressed as number (percentage)
1.01-2.00 16 236 (23.1) 15 883 (23.7) 353 (10.9) 257 (9.9) 257 (9.9) of patients. Percentages have been
Type of excision rounded and may not total 100.
b
WME 67 085 (95.4) 67 085 (100.0) NA 2589 (100.0) NA Lower score indicates a lower
comorbidity burden; higher score,
MMS 3234 (4.6) NA 3234 (100.0) NA 2589 (100.0)
a higher comorbidity burden.

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 Survival After Mohs Micrographic Surgery vs Wide Margin Excision for Early-Stage Invasive Melanoma Original Investigation Research

refer to the relative risk of death. All patient, tumor, and

Table 2. Multivariable Analysis of Factors Associated
treatment variables outlined in Table 1 were tested for With Overall Survivala
appropriateness for inclusion as covariates in these models
Variable HR (95% CI) P Value
using Akaike information criterion minimization.18 Akaike
Age 1.08 (1.07-1.08) <.001
information criterion minimization ensures parsimony of
Sex
the multivariable model. We additionally performed a pro-
Male 1.40 (1.33-1.48) <.001
pensity score–matched analysis of patients who received
Female 1 [Reference] NA
WME and MMS. This method controls for differences in out-
Charlson-Deyo comorbidity scoreb
comes due to systemic differences between treatment
0 1 [Reference] NA
groups.19-26 Scores were calculated using a logistic regres-
1 1.49 (1.40-1.59) <.001
sion with the factors outlined in Table 1 except for excision
2 2.48 (2.18-2.82) <.001
type, with groups generated using a 1-to-1 nearest-neighbor
match without replacement. We also performed a multivari- ≥3 3.55 (2.88-4.37) <.001

able logistic analysis of factors associated with the type of Insurance

excision received. This model was also optimized using Private 1 [Reference] NA

Akaike information criterion minimization. Although cases Government 1.28 (1.19-1.37) <.001
treated with narrow margin excision (NME) were excluded None 2.02 (1.66-2.46) <.001
from the primary analysis owing to WME being the standard Unknown 1.15 (0.95-1.39) .15
of care for comparison with MMS, a sensitivity analysis was Facility type
performed including cases treated with NME. Statistical sig- Nonacademic 1 [Reference] NA
nificance was determined at 2-tailed P < .05. Data analysis Academic 0.93 (0.88-0.97) .003
was performed using Stata, version 13 (StataCorp LP). Anatomical site
Trunk 1 [Reference] NA
Upper limb or shoulder 0.87 (0.81-0.93) <.001
Lower limb or hip 0.79 (0.72-0.86) <.001
Results
Face 1.20 (1.12-1.29) <.001
The demographic and clinical characteristics of the study Scalp or neck 1.31 (1.20-1.42) <.001
sample are presented in Table 1 (52.3% male and 47.7% Overlapping or NOS 1.69 (1.31-2.19) <.001
female; median [SD] age, 57.0 [16.2] years). Most of the Histologic subtype
patients were white (96.9%) with a Charlson-Deyo comor- Superficial spreading 1 [Reference] NA
bidity score of 0 (89.4%). Most patients were treated at non- Lentigo maligna 1.00 (0.91-1.10) >.99
academic centers (61.6%) and held private insurance Nodular 1.63 (1.47-1.81) <.001
(63.9%). The most common anatomical subsite was the Malignant acral lentiginous 1.54 (1.24-1.92) <.001
trunk (33.8%), followed by the upper limb or shoulder Malignant desmoplastic 1.01 (0.80-1.27) .95
(26.1%), the lower limb or hip (20.5%), and the face (12.0%). Spindle cell 1.13 (0.90-1.42) .30
Among the most common histologic tumor subtypes were Other or NOS 1.07 (1.01-1.13) .02
superficial spreading melanoma (40.7%), lentigo maligna Ulceration
melanoma (5.4%), and nodular melanoma (3.9%), although
Not present 1 [Reference] NA
the most common subtype was other or not otherwise
Present 2.24 (2.06-2.43) <.001
specified (48.0%). Most tumors were smaller than 0.8 mm,
Breslow thickness, mm
with a median (SD) Breslow thickness of 0.58 (0.48) mm.
<0.80 1 [Reference] NA
Wide margin excision was used in a much larger proportion
0.80-1.00 1.09 (1.01-1.17) .04
of cases (95.4%) than MMS (4.6%). Mean (SD) follow-up was
1.01-2.00 1.46 (1.38-1.55) <.001
4.81 (2.86) years, with a maximum follow-up of 13.09 years.
Type of excision
Sensitivity analysis of patients with known survival data
WME 1 [Reference] NA
who were excluded owing to missing data revealed that
MMS 0.86 (0.76-0.97) .02
cases without missing data demonstrated slightly improved
survival. Overall survival at 3 years was 95.2% (SE, 0.1%); at Abbreviations: HR, hazard ratio; MMS, Mohs micrographic surgery; NA, not
applicable; NOS, not otherwise specified; WME, wide margin excision.
5 years, 90.9% (SE, 0.1%); and at 10 years, 80.0% (SE, 0.3%)
a
Patient race/ethnicity was excluded from the multivariable model after Akaike
for the analytic cohort. Among cases excluded owing to
information criterion minimization.
missing data, 3-year overall survival was 93.8% (SE, 0.1%); b
Lower score indicates a lower comorbidity burden; higher score, a higher
5-year overall survival, 89.4% (SE, 0.2%); and 10-year sur- comorbidity burden.
vival, 79.2% (SE, 0.2%).
On Kaplan-Meier univariable analysis, patients treated with
MMS demonstrated similar overall survival relative to those overall survival, 80.0% (SE, 0.3%). Among patients treated with
treated with WME (HR, 1.01; 95% CI, 0.90-1.14). Among pa- MMS, 3-year overall survival was 95.4% (SE, 0.4%); 5-year over-
tients treated with WME, 3-year overall survival was 95.2% (SE, all survival, 90.5% (SE, 0.7%); and 10-year overall survival,
0.1%); 5-year overall survival, 90.9% (SE, 0.1%); and 10-year 79.2% (SE, 1.6%).

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 Research Original Investigation
Figure. Overall Survival for Propensity Score–Matched Cohorts of Patients Treated
Using Mohs Micrographic Surgery vs Wide Margin Excision
100
80
60
Survival, %
40
20
0
0 1 2 3
No. at risk
Wide margin excision 2589 2428 2137 1747
Mohs micrographic surgery 2589 2440 2109 1690
After controlling for covariates via multivariable and propen-
sity score–matched analyses, patients treated with MMS were
found to have improved overall survival compared with those
treated with WME. Multivariable Cox proportional hazards re-
gression modeling (Table 2) demonstrated improved overall sur-
vival for those treated with MMS as opposed to WME (HR, 0.86;
95% CI, 0.76-0.97). Subgroup analyses of patients with stages IA
(HR, 0.88; 95% CI, 0.77-1.01) and IB (HR, 0.78; 95% CI, 0.56-1.07)
disease revealed nonsignificant improved overall survival for pa-
tients receiving MMS. Analysis including only patients with pri-
mary lesions located on the head and neck similarly demon-
strated improved overall survival for patients treated with MMS
as opposed to WME (HR, 0.81; 95% CI, 0.69-0.96). Treatment
with MMS was associated with similar overall survival to treat-
ment with WME (HR, 0.92; 95% CI, 0.77-1.11) for patients with
primary lesions outside the head and neck.
The demographic and clinical characteristics of propen-
sity score–matched cohorts of patients treated with WME and
MMS are presented in Table 1. Analysis of these cohorts also
revealed improved overall survival for patients treated with
MMS compared with those treated with WME (HR, 0.82; 95%
CI, 0.68-0.98). Survival curves of these matched cohorts are
presented in the Figure. Within these cohorts, 3-year overall
survival was 95.0% (SE, 0.5%), 5-year overall survival was
90.0% (SE, 0.7%), and 10-year overall survival was 76.7% (SE,
1.7%) among patients treated with WME. Among those treated
with MMS, 3-year overall survival was 96.3% (SE, 0.4%), 5-year
overall survival was 91.8% (SE, 0.7%), and 10-year overall sur-
vival was 80.4% (SE, 1.8%). Sensitivity analysis using a mul-
tivariable Cox proportional hazards regression model that in-
cluded cases treated with NME revealed no survival difference
between MMS and NME. Exclusion of cases found to have posi-
tive pathologic lymph nodes after presentation did not change
the results.
We additionally performed a subgroup analysis of low-
risk patients. Multivariable survival analysis of cases with a
Breslow thickness of less than 0.80 mm with or without
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Survival After Mohs Micrographic Surgery vs Wide Margin Excision for Early-Stage Invasive Melanoma
Mohs micrographic surgery
Wide margin excision
Log rank test: P = .03
4 5 6 7 8 9 10 11 12
Duration of Survival, y
1415 1096 813 575 385 265 166 73 18
1312 962 674 446 278 182 112 51 14
tumor ulceration using a Cox proportional hazards regres-
sion model demonstrated nonsignificant improved overall
survival with MMS as opposed to WME (HR, 0.87; 95% CI.
0.75-1.00). Multivariable survival analysis of cases without
tumor ulceration revealed improved overall survival for
patients receiving MMS compared with those who received
WME (HR, 0.85; 95% CI, 0.75-0.97).
Several factors were found to be associated with the type
of excision used (Table 3). Mohs micrographic surgery was more
likely to be used for the eldest group of patients (≥75 years) com-
pared with the youngest (<55 years) (odds ratio [OR], 1.16; 95%
CI, 1.04-1.30). Male patients were less likely to receive MMS
than female patients (OR, 0.91; 95% CI, 0.85-0.99). Patient in-
surance status was not found to be associated with likelihood
of MMS treatment and was excluded from the model after
Akaike information criterion minimization, whereas black
patients were found to be more likely to receive MMS than
white patients (OR, 1.87; 95% CI, 1.07-3.28). Significant differ-
ences in treatment practices based on the treatment facility
were noted, with academic facilities more than twice as likely
as nonacademic facilities to use MMS (OR, 2.03; 95% CI, 1.88-
2.18). Results also indicate that MMS is less commonly used
for more aggressive subtypes of melanoma, with lower rates
of use for nodular melanoma compared with superficial spread-
ing melanoma (OR, 0.75; 95% CI, 0.57-0.97), as well as for tu-
mors with Breslow thickness of 0.80 to 1.00 mm (OR, 0.58;
95% CI, 0.51-0.66) or 1.01 to 2.00 mm (OR, 0.37; 95% CI, 0.33-
0.42) compared with tumors with Breslow thickness of less
than 0.80 mm. Conversely, lentigo maligna melanomas were
nearly twice as likely to be excised by MMS than superficial
spreading melanomas (OR, 1.95; 95% CI, 1.73-2.21). Variation
was noted in the use of MMS by the anatomical subsite of dis-
ease. Facial tumors were the most likely to be excised with
MMS, more than 3 times as likely as truncal tumors (OR, 3.17;
95% CI, 2.86-3.52). Scalp and neck tumors were also more likely
to be removed by MMS than truncal tumors (OR, 1.60; 95% CI,
1.38-1.85).
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 Survival After Mohs Micrographic Surgery vs Wide Margin Excision for Early-Stage Invasive Melanoma Original Investigation Research

Table 3. Multivariable Analysis of Factors Associated

Discussion With Odds of Receiving MMSa

Variable OR (95% CI)b P Value

Although this study is the first, to our knowledge, to report im-
Age, y
proved survival for early-stage (AJCC-8 stage I) invasive mela-
≤54 1 [Reference] NA
noma treated with MMS rather than WME, our findings are
55-64 1.07 (0.97-1.17) .20
similar to those of several studies14-16 that have suggested that
65-74 1.08 (0.98-1.20) .13
MMS is noninferior to WME for localized invasive melanoma.
A recent study of all subtypes of melanoma (melanoma in situ, ≥75 1.16 (1.04-1.30) .006

localized invasive melanoma, invasive melanoma with Sex

regional spread, and invasive melanoma with distant Male 0.91 (0.86-0.99) .02
metastasis) 15 found that MMS was noninferior to WME Female 1 [Reference] NA
and NME. Race
Historically, one of the most significant barriers to the White 1 [Reference] NA
use of MMS for melanoma excision was the difficulty in Black 1.87 (1.07-3.28) .03
interpreting melanoma with frozen sections. However, the Hispanic 0.76 (0.50-1.17) .21
rise of immunostains, in particular melanoma antigen rec- Asian or Pacific Islander 0.76 (0.28-2.07) .59
ognized by T cells (MART-1), has made the histopathological Other or unknown 1.19 (0.93-1.53) .16
interpretation of melanoma more feasible.4,27-30 Recently, Charlson-Deyo comorbidity scorec
several single-institution studies12-14 have reported excel- 0 1 [Reference] NA
lent outcomes with invasive melanoma treated with MMS 1 0.72 (0.63-0.83) <.001
and MART-1 immunostaining, with local recurrence rates 2 0.67 (0.46-0.98) .04
ranging from 0 to 1.43%. ≥3 0.93 (0.51-1.69) .81
We identified several factors associated with the use of
Facility type
MMS for invasive melanoma as opposed to traditional exci-
Nonacademic 1 [Reference] NA
sion. Although previous reports studying the use of MMS in
Academic 2.03 (1.88-2.18) <.001
nonmelanoma skin cancer have suggested that patient insur-
Anatomical site
ance is associated with the rate of use of MMS, patient insur-
Trunk 1 [Reference] NA
ance was found not to be significantly associated with the use
Upper limb or shoulder 1.09 (0.98-1.21) .11
of MMS in our cohort of patients with AJCC-8 stage I invasive
Lower limb or hip 0.97 (0.86-1.09) .59
melanoma.31 In addition, although previous work32 has dem-
Face 3.17 (2.86-3.52) <.001
onstrated less use of MMS for nonmelanoma skin cancer in
black patients, such patients in our cohort were more likely to Scalp or neck 1.60 (1.38-1.85) <.001

receive MMS than white patients. These findings may be ow- Overlapping or NOS 1.62 (1.03-2.54) .04

ing to the controversy surrounding the use of MMS for inva- Histologic subtype
sive melanoma and will need to be monitored should MMS gain Superficial spreading 1 [Reference] NA
more widespread acceptance as a potential treatment. Why aca- Lentigo maligna 1.95 (1.73-2.21) <.001
demic centers were found to be almost twice as likely to use Nodular 0.75 (0.57-0.97) .03
MMS than were nonacademic centers is not clear. Malignant acral lentiginous 0.99 (0.63-1.55) .96
Malignant desmoplastic 0.97 (0.61-1.56) .91
Limitations Spindle cell 0.93 (0.56-1.55) .78
There are several limitations to this study. First, we did not have Other or NOS 1.08 (1.00-1.17) .07
access to data on the type of stains that were used in margin Ulceration
evaluation for the WME or MMS cohorts. The frequency of im- Not present 1 [Reference] NA
munostain use with MMS is unknown in this cohort, but those Present 0.66 (0.54-0.81) <.001
cases that did not use immunostains likely would have biased Breslow thickness, mm
our results toward detecting no difference in survival or poorer <0.80 1 [Reference] NA
survival for cases treated with MMS. Further, although the NCDB
0.80-1.00 0.58 (0.51-0.66) <.001
captures approximately 70% of new cancer cases in the United
1.01-2.00 0.37 (0.33-0.42) <.001
States, recent work suggests that the coverage for incident mela-
noma is closer to 50%, likely owing to more outpatient treatment Abbreviations: MMS, Mohs micrographic surgery; NA, not applicable; NOS, not
otherwise specified; OR, odds ratio.
of melanoma compared with other malignant neoplasms.33 The a
Patient insurance status was excluded from the multivariable model after
NCDB is designed as a large convenience sample, capturing cases Akaike information criterion minimization.
only at Commission on Cancer–accredited facilities, rather than b
Indicates in reference to wide margin excision.
a population-based sample such as the Surveillance, Epidemi- c
Lower score indicates a lower comorbidity burden; higher score, a higher
ology, and End Results registry. Although this limitation is comorbidity burden.
less of a concern for analyses of treatment outcomes than inci-
dence studies, this distinction may make our results less appli-

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 Research Original Investigation Survival After Mohs Micrographic Surgery vs Wide Margin Excision for Early-Stage Invasive Melanoma

cable to melanoma treatment outside of Commission on Cancer–
accredited institutions. In addition, owing to the nature of the
NCDB, we did not have access to data on recurrence or reexci-
sion. Particularly because of the potential benefit of MMS to pro-
vide lower recurrence rates with less tissue removal, this aspect
of these 2 procedures should be assessed in future studies. Fur-
thermore, although we controlled for key tumor risk features such
as histologic subtype, ulceration, and Breslow thickness, patients
who received MMS may have had divergent rates of additional
high-risk features that were not captured in our analysis, such
as increased mitotic rate or absent tumor-infiltrating lympho-
cytes. Thus, controlling for these variables might reveal that MMS
is associated with better or worse survival than suggested by
our analysis.
In addition, although 1 cm is the recommended excision mar-
gin for stage IA melanoma, these patients were excluded from
our primary analysis owing to NCDB skin surgery coding that in-
cluded all patients with margins of 1 cm or less in the same group.
For stage IB disease, the recommended excision margin is 1 to 2
cm. This recommended excision margin is included in our analy-
sis of WME (>1 cm), but we were unable to determine the exact
margins used that were greater than 1 cm for these cases. Finally,
results generated from such retrospective registry studies are hy-
pothesis generating in nature and must be further studied via
clinical trials because of previous observational studies being in-
consistently reproduced with randomized clinical trials.34
Conclusions
In this analysis of a large sample of early-stage invasive mela-
nomas, we found that treatment with MMS was associated with
a modest survival advantage compared with treatment
with traditional WME. These data suggest that MMS is an ef-
fective approach compared with WME for AJCC-8 stage I
invasive melanoma.

ARTICLE INFORMATION
Accepted for Publication: July 30, 2019.
Published Online: September 25, 2019.
doi:10.1001/jamadermatol.2019.2890
Author Contributions: Mr Cheraghlou and Dr
Girardi had full access to all the data in the study
and take responsibility for the integrity of the data
and the accuracy of the data analysis.
Concept and design: Cheraghlou, Agogo, Girardi.
Acquisition, analysis, or interpretation of data: All
authors.
Drafting of the manuscript: Cheraghlou, Agogo.
Critical revision of the manuscript for important
intellectual content: Christensen, Agogo, Girardi.
Statistical analysis: Cheraghlou, Agogo, Girardi.
Administrative, technical, or material support:
Girardi.
Supervision: Christensen, Girardi.
Conflict of Interest Disclosures: None reported.
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