TUMOR THICKNESS AS A GUIDE TO SURGICAL

MANAGEMENT OF CLINICAL STAGE I

MELANOMA PATIENTS
CHARLES
M. BALCH,MD, TARIQ M. MURAD,MD, SENG-JAWSOONC,PHD,
ANNALEE INGALLS, RN, PETERC. RICHARDS,
MD,
A N D WILLIAMA. MADDOX,MD

An analysis of failure to control locally recurrent or metastatic melanoma was

used to substantiate the value of thickness as a guide to surgical management.
There were no local recurrences in patients with melanomas less than 0.76 mm
in thickness, regardless of the skin margins excised. The three year actuarial
incidence of subsequent regional metastases in patients initially treated by wide
local excision (WLE) of their melanoma was directly correlated with tumor
thickness (p = <0.001); it was 0% for lesions <0.76 mm, 25% for 0.76 to 1.50
mm lesions, 51% for 1.50 to 3.99 mm lesions and 62% for lesions >4.0 mm in
thickness. At five years, patients with melanomas of 1.50 to 3.99 mm thickness
who had WLE plus elective regional node dissection (RND) had a calculated
15% incidence of distant metastases and an actuarial survival rate of 83%, while
patients with melanomas of the same thickness who had WLE alone as their
initial surgical treatment had a 78% incidence of distant metastases and a 37%
survival rate (p = 0.001 and 0.01, respectively). In patients with melanomas
exceeding 4.0 mm in thickness, the potential benefits of RND were less apparent
because of a high risk (>70%) of distant metastases at the time of initial
diagnosis. Based upon this analysis, our initial surgical management of melano-
mas <0.76 is a WLE using a 2.0 cm margin of skin, while thicker lesions are
excised using a 3 to 5 cm skin margin. Elective RND is not indicated for lesion
C0.76 mm in thickness, but it is considered for 0.76 to 1.50 mm lesions in
selected patients and is employed for virtually all patients with lesions
exceeding 1.5 mm in thickness. The rationale of elective RND is improved
survival in patients with intermediate thickness lesions (0.76 to 3.99 mm) while
it is justifiable as a staging procedure for lesions exceeding 4.0 mm thickness.
Cancer 43:883-888, 1979.

V ERTICAL G R O W T H O F M E L A N O M A is
clearly an important determinant of
survival, especially in patients without detect-
able metastatic disease (clinical Stage I). The
histological level of melanoma penetration (as
staged by Clark), the measured thickness (as
advocated by Breslow) or a combination of the
two approaches have been utilized in several
retrospective studies to suggest a therapeutic
benefit of elective regional lymphadenectomy
in a subgroup of these patients, those with
lesions exceeding 1.5 mm in thickness or pen-
etrating to the reticular dermis (Level 111, IV
or V).3,6*799,10*11316
In a previous multifactorial
statistical analysis, we found that tumor thick-
ness had more predictive value as a prognostic
variable when compared to level of invasion.2
Within each of Clark’s Level 11. I11 and IV

Presented at the 31st Annual Meeting of The Society
of Surgical Oncology, San Diego, California, April 2-
6, 1978.
From the University of Alabama Medical Center De-
partments of Surgery, Pathology and Biostatistics and
the Comprehensive Cancer Center, University of Ala-
bama Medical Center, Birmingham, Alabama.
Supported by grants from the National Institutes of
Health (CA 13148, CA 19657). Dr. Balch is a recipient
of a Junior Faculty Fellowship from the American Cancer
Society.
0008-543X/79/0300/0883 $0.80 0 American Cancer Society
883
Address for reprints: Charles M. Balch, MD, Depart-
ment of Surgery, 750 Lyons-Harrison Research Bldg.,
University of Alabama Medical Center, Birmingham, AL
35294.
T h e authors thank Dr. John R. Durant, Director,
Comprehensive Cancer Center, UAB, for his support of
the Melanoma Registry and for reviewing the manu-
script, Mr. Wayne Satterwhite for assistance in the data,
Ms. Enying Hsu for assisting in the statistical analysis
and by Ms. Barbara Yarber, ART, for technical assistance.
Accepted for publication July 5, 1978.

884 CANCER
March 1979
groups, there were gradations of thickness
with statistically different survival rates. In
contrast, melanoma thickness was an inde-
pendent variable influencing five-year sur-
vival, even after twelve other prognostic factors
(such as sex, location, surgicql treatment and
growth pattern) had been accounted for.2
In this retrospective analysis, we examined
our surgical results in clinical Stage I patients
who were subgrouped according to their mel-
anorna thickness, since this parameter was
such a dovinant prognostic ‘@actor in our
series. We focused initially upon our surgical
failures to control diseases in order to examine
the relationship between tumor thickness and
1) the incidence of local recurrence in patients
with different margins of skin excision; and 2)
the incidence of regional and distant me-
tastases in patients treated initially by local ex-
cision with or without elective regional lymph-
adenectomy. We then examined the effect of
tumor thickness and elective lymphadenec-
tomy on long-term survival. While recogniz-
ing that there are some limitations of a retro-
spective analysis, the data strongly corrobo-
rate previous recommendations that tumor
thickness is a useful guide for selecting alter-
native surgical procedures in the management
of clinical Stage I cutaneous melanoma.
A N D METHODS
PATIENTS
Patient Population
The University of Alabama Melanoma Reg-
istry is comprised of over 384 melanoma pa-
tients with clinical and pathological data re-
corded in a computerized format. The records
of 287 clinical Stage I cutaqeous melanoma
patients were analyzed. This group constitutes
virtually all patients treated surgically by us
(WAM and CMB) from 1960 through July
1977. The original biopsy slides and/or paraf-
fin blocks of the primary cutaneous melanoma
were available from 173 patients. Twelve pa-
tients were excluded from this analysis be-
cause they had shave biopsies extending to the
deep margin, thus precluding an accurate
determination of thickness. Five patients were
excluded because their biopsy was misinter-
preted as benign and were untreated until
they were referred with locally recurrent and/
or metastatic disease. The remaining 156 mel-
anomas were all re-examined by one pa-
thologist (TMM) who did not have knowledge
of the clinical course in any of these patients.
Since our analysis was based primarily on re-
10970142, 1979, 3, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/1097-0142(197903)43:3<883::AID-CNCR2820430316>3.0.CO;2-V by Readcube (Labtiva Inc.), Wiley Online Library on [24/08/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
V O l . 43
examination of representative sections
through the lesion rather than the entire mel-
anoma, it is possible that thicker areas may
have existed in unsampled portions of the
specimen. A description of the pathological
staging methods used in this study has been
published.2 The thickness groups used in this
analysis were the same as that originally de-
scribed by Breslow3 except our data showed
more significant survival differences using 4
mm rather than 3 mm as an upper limit.2
Follow-up data were obtained from patient
records and by telephone interviews with the
patients, their families or their primary
physicians.
Surgical Treatment
Our standard surgical treatment is a wide
local excision (WLE) of the melanoma (or the
biopsy site) with a 3 to 5 cm circumferential
margin of skin, except where interdicted by
anatomical barriers, such as on the face. The
heep margin included the underlying fascia
aqd the defect was covered with a split-
thickness skin graft. In this analysis, w e used
the dimensions of skin margin described by
the surgeon in the operative note. In some
instances the skin margins were less in patients
whose melanomas were excised prior to
referral to this institution.
In half of the clinical Stage I patients, a
standard cervical, axillary or inguinal regional
node dissection (RND) was performed. Iliac
and hypogastric lymph nodes were not re-
moved. T h e indication for elective lymphade-
nectomy varied during the years reflecting a
changing consensus of national opinion
regarding its efficacy. A lymphadenectomy
was more often performed if the melanoma
was adjacent to the draining nodal basin and
could be removed en bloc with an incontinuity
dissection. It was performed less often if the
melanoma was located on the distal portion of
an extremity. When two or more nodal basins
were at risk, such as with midline melanomas,
elective lymphadenectomies were generally
not performed. Histopathological staging
(Clark’s and Breslow’s microstaging) did not
influence this decision until recent years, ex-
cept in a few instances (less than 10 patients)
where an elective lymphadenectomy was not
performed if the melanoma was confined to
the upper papillary dermis, and described as
“superficial” melanomas as defined by Allen
and Spitz.l Since 1976, we have performed
 10970142, 1979, 3, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/1097-0142(197903)43:3<883::AID-CNCR2820430316>3.0.CO;2-V by Readcube (Labtiva Inc.), Wiley Online Library on [24/08/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
No. 3 MELANOMA
THICKNESS TREATMENT
A N D SURGICAL * Balch et al. 885

elective lymphadenectomy for all patients 1. Skin Margins Excised for Melanomas less
TABLE
whose melanomas had a thickness exceeding than 0.76 mm Thickness
1.5 mm and where the regional draining nodal Margin (cm) No. patients
basin could be reasonably predicted.
0.0-0.9 3
Statistics 1.0- 1.9 5
2.0-2.9 3
The UAB Melanoma Registry is an ongoing 3.0-3.9 9
4.0-4.9 7
retrospective/prospective analysis of all pa- 5.0 9
tients with malignant melanoma treated at the TOTAL 36
University of Alabama Medical Center. De-
tailed clinical and pathological information N o patient in this group had a local recurrence.
was computerized to facilitate data manage-
ment and statistical analysis. Actuarial rates of Melanoma Thickness and Distant Metastases
recurrences or survival were calculated based
upon the method of Kaplan and Meier.'* Chi- In this analysis, the effect of the initial sur-
square tests were also employed in statistical gical procedure (WLE with or without RND)
assessments where appropriate. and melanoma thickness was compared with
the incidence of subsequent distant metasta-
REsu LTS ses. An actuarial five year incidence rate was
used because most patients developed distant
Melanoma ThicknessAnd Local Recurrences metastases within this time period (Fig. 2).
None of 36 patients,with melanomas less Regardless of the surgical treatment em-
than 0.76 mm thickness had a local recurrenc ployed, patients with lesions less than 0.76 mm
'i
within or immediately around the surgica in thickness did not develop distant metasta-
scar. The skin margins varied from 0.5 t6 ses. For lesions of 0.76 to 1.49 mm thickness,
5.0 cm, with 30% less than a 3.0 cm r a d h s the difference between the two procedures
(Table 1). Eight patients (3%)developed local was 17% (25% vs 8%, p = NS). In patients
recurrences from the entire group of 287 with melanomas of 1.50 to 3.99 mm thickness,
Stage I cutaneous melanoma patients. The the calculated risk for distant metastases at 5
melanomas ranged from 1.2 to 9.0 mm in years for the WLE groub was 78% compared
thickness (median 4.0 mm) and extended into to 15% for those who had WLE + RND
the reticular dermis or beyond (Level IV or (p = 0.001). i t is notable that patients in this
V) in the seven patients, with histopathological thickness group who had WLE alone con-
staging (Table 2). While local recurrences tinued to develop distant metastases after five
were confined to patients with thicker melano- years. Thus, the actuarial rate for distant me-
mas and tended to occur in patients with nar- tastases at 8 years was 86% for the WLE
rower skin margins, the incidence was too low group compared to 16% in the WLE + RND
for meaningful comparisons. group (data not shown). The benefit of elective
RND was not apparent in patients with mela-
Melanoma Thickness and Regional
Metastases
2. Local Recurrences from this Entire Group of
TABLE
The clinical course of all 78 clinical Stage I 282 Stage I Melanoma Patients
patients whose initial surgical treatment was a
Margin of
wide local excision (WLE) of their melanoma ID Loca- excised Thickness Level of
was examined for their incidence of sub- no. tion skin* (mm) invasion
sequknt regional node metastases. An actuarial
incidence rate was calculated for a three year 1. 430 Chest 2.5 1.2 IV
follo&-up period because the majority of fail- 2. 220 Back t 2.6 IV
3. 234 Face $5 3.9 IV
ures dkcurred within this time. There was a 4. 217 Arm 2.0 4.0 IV
highly significant correlation between mela- 5. 410 Scalp 1.o 5.3 V
noma thickness and the incidence of nodal 6. 254 Chest 4.0 7.0 IV
metastasgs (p = 0.001). The three year actu- 7. 304 Face 1 .o 9.0 V
arial incidence ranged from 0% for lesions
8. 298 Leg 4.0 t t
<0.76 mm thickness to 62% for lesions 24.0 * Skin margins as reported in the operative note.
mm (Fig. 1). t Original report or biopsy not obtainable.
 10970142, 1979, 3, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/1097-0142(197903)43:3<883::AID-CNCR2820430316>3.0.CO;2-V by Readcube (Labtiva Inc.), Wiley Online Library on [24/08/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
886 CANCER
March 1979 VOl. 43

I00 than 4. mm in thickness) (Fig. 3). In contrast,

010
-i
Re ionol 50
80
70

60 -
-
57%
patients who underwent WLE of an inter-
mediate thickness of melanoma (0.77-3.99
mm) plus elective RND had a greater 5 and 8
year survivals (86% and 82%, respectively)
than those who had melanomas of the same
thickness excised without elective RND (58%
and 25%, respectively) (p = 0.002). These
Me?osla5cr
40 - figures indicate that patients in the WLE group
were continuing to die with metastatic mel-
30 - 25% anoma after 5 years of follow-up, while only
- one patient died with metastatic melanoma
20
- +
who was alive 5 years after WLE RND.
I0 Melanomas of intermediate thickness were
0% further subdivided into two thickness groups
MELANOMA
THICKNESS 50.76 077-1.49 1.50-199 Z4.0
and the comparisons of surgical treatments
(mm) analyzed at 5 years (Fig. 3). An apparent bene-
fit of WLE plus elective RND was observed
FIG. 1. Actuarial three year incidence of regional node
metastases in patients whose initial surgical treatment is for melanomas measuring 0.76 to 1.49 mm
wide local excision alone. compared to those with WLE alone by 5 year
actuarial survival rates (p = 0.04). T h e great-
nomas 24.0 mm in thickness, where the in- est benefit was observed in patients with mel-
cidence of distant metastases was 70% com- anomas measuring 1.50 to 3.99 mm in thick-
pared to 80% for those undergoing WLE ness, where 83% in the WLE + RND group
alone (Fig. 2). were alive at 5 years, compared to only 37%
in the WLE alone group (p = 0.01).
Effect of Melanoma Thickness and DISCUSSION
Surgical Treatment on Survival
An analysis of failure to control locally re-
T o ascertain whether these differences in current or metastatic melanoma was used to
the incidence of distant metastases affected substantiate the value of tumor thickness as a
survival rate, we compared the two types of guide to surgical management.
+
initial surgical treatment (WLE RND) with Local recurrences in our series were asso-
the calculated acturial survival at 5 years post- ciated with intermediate and thick melano-
operatively. Two subgroups of patients did mas but not with any lesions less than 0.76
not benefit from elective lymphadenectomy: mm, despite variations in the excised skin
those with thin lesions (less than 0.76 mm in margins around the tumor. Breslow reported
thickness) and those with thick lesions (greater no local recurrences in a series of 62 patients
with melanomas less than 0.76 mm, followed
00-
more than five years.4 The width of the re-
90-
section margin described in the pathology re-
port ranged from 0.10 to 5.50 cm with 32%

i
80- suprr
omrnrm
being 1.O cm or less. Das Gupta found that 8 of
70-
rnWLE+RND 10 local recurrences were associated with
60 - Level IV or V melanomas while none oc-
n
DbIoN 50 - curred in 33 patients with Level I1 melano-
MsbrlocU
40 - m a ~ Hanson
.~ showed no difference in sur-
30
- 25% vival in patients with melanomas less than 1.5
XI- mm who had simple excision compared to
lo- those who had a wide excision.1° While a three
ox,on L4.0 dimensional resection of the primary mela-
noma biopsy site is important in all cases to re-
ma No
RTlEMTs n II I* eo I0 m IS s
move any residual melanoma cells, the above
P VUIK w P.O.23 P*O.Oo( NS data indicate that reduced margins for excising
FIG. 2. Actuarial five gear incidence of distant metasta- thin melanomas can be safely employed. A
ses comparing two surgical treatments as initial manage- generally prudent approach is to excise thin
ment of cutaneous melanoma. melanomas using a 2 cm margin and employ

No. 3 THICKNESS
MELANOMA TREATMENT
A N D SURGICAL Balch et al.
a primary skin closure if possible. For thicker
lesions, we are continuing to use a 3 to 4 cm
skin margins circumferentially and employ
split-thickness skin grafts.
A primary objective of this analysis was to
examine whether removal of clinically normal
regional lymph nodes would decrease the in-
cidence of distant metastases, presumably by
excising nodal micrometastases before they
spread to distant sites. Elective lymphade-
nectomy for Stage I melanoma patients is one
of the most controversial aspects of surgical
management. Many surgeons have previously
suggested that elective node dissections had
little therapeutic benefit, but in almost all of
these clinical series the histopathological stag-
ing was not considered. More recent retro-
spective analyses have suggested therapeutic
benefit of elective node dissection for patients
with melanomas exceeding 1.5 mm in thick-
~ ~ s s . ~ * ~The
O Jyield
' J ~ of occult nodal metasta-
ses in the surgical specimen after lymphade-
nectomy in these series was about 20%. These
figures may underestimate the actual inci-
dence of nodal metastases, however, because
micrometastases may have been present in un-
sampled areas of the specimen. An analysis
of failures in patients treated initially by wide
excision alone probably reflects the incidence
of lymph node metastases more accurately.
Our analysis of regional failures in patients
whose melanomas were widely excised as the
initial form of treatment clearly demonstrates
that melanoma thickness correlates with risk
of regional metastases. Since thin lesions were
associated with virtually no risk of regional
or distant metastases, there is no indication
for elective lymphadenectomy in this select
patient group. Beyond 0.76 mm in thickness,
there is a gradually increasing risk of micro-
scopic or occult metastases in regional nodes
or at distant sites at the time of initial diagnosis
in Stage I patients. The risk for regional nodal
metastases was 57% or greater for melano-
mas exceeding 1.5 mm in thickness. Further-
more, patients had an increased incidence of
distant metastases as a group, despite a thera-
peutic lymphadenectorny in those that sub-
sequently develop nodal metastases. This ob-
servation indicates that nodal metastases are
more curable in a subclinical stage and that a
delay of two or more years waiting for micro-
scopic nodal metastases to enlarge to a clinically
detectable size is a critical interval during which
regional metastases may disseminate to distant
sites. Further evidence for this is the observa-
tion that patients with clinically occult nodal
10970142, 1979, 3, Downloaded from https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/1097-0142(197903)43:3<883::AID-CNCR2820430316>3.0.CO;2-V by Readcube (Labtiva Inc.), Wiley Online Library on [24/08/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
887
00%IOOY.
THlCNYfSS 576 077-149 150-3- t4OO
lnrl
Y PATIENTS 30 40 56 22
? VALUE us 0 04 0 01 US
FIG. 3. Actuarial five year survival rate after different
surgical treatment.
metastases (clinical Stage I, pathological Stage
11) have a better prognosis than those with
clinically apparent nodal metastases (clinical
Stage 11, pathological Stage II).6,7*'3
Immediate regional lymphadenectomy is
justified for lesions of 1.50 to 3.99 mm thick-
ness, despite its attendant morbidity, because
of the significant differences in five year sur-
vival rates (83% vs. 37%) comparing the two
types of initial surgical options. The potential
benefit is less in patients with melanomas of
0.76 to 1.49 mrn thickness, and the decision
regarding lymphadenectorny would have to
be individualized according to its actual thick-
ness as well as other factors such as patient
age, anatomical location of the melanoma and
the associated morbidity of lymphadenectorny
at different sites. For melanomas exceeding
4.0 mm in thickness, the potential benefits of
immediate lymphadenectorny are much less
because the incidence of simultaneous metas-
tases at distant sites appear to diminish the
beneficial effects of removing any regional
metastases. Nevertheless, elective lymphade-
nectomy seems justifiable to remove regional
metastases present in the majority of these
patients and for staging purposes to delineate
those patients with detectable nodal metasta-
ses for entry into clinical trials employing in-
tensive adjuvant systemic therapy.
The World Health Organization (WHO)
Melanoma Group recently reported their re-
sults of a randomized study to evaluate the
efficacy of elective RND for extremity mela-
n o m a ~ . They
'~ concluded that a delayed dis-
section of clinically enlarged lymph nodes
was as effective in the control of disease as
immediate dissection based upon a compari-
son of actuarial five year survival rates. While
their conclusions are diametric to those

888 CANCER
March 1979
reached from this study, several points should
be emphasized: 1) Their study was confined
to melanomas occurring on the distal two-
thirds of extremities, whereas our analysis in-
cluded cutaneous melanomas from all ana-
tomical sites, 2) although the WHO study was
prospective and randomized, patients were
not stratified according to histopathological
staging (either by thickness or level of in-
vasion); the two groups appeared comparable,
however, when the pathological specimens
were reviewed retrospectively, 3) in the WHO
series, there was some evidence of improved
+
survival for WLE RND patients with mel-
anoma thickness of 1.6 to 4.5 mm (78.5% vs.
69.7% for WLE patients), while there was no
apparent survival differences in patients with
melanomas <1.5 or >4.6 mm in thickness.
These trends correspond to those described
in our analysis, although the actual rates were
different.
Preliminary results of a similar prospective,
randomized study from the Mayo Clinic has
also indicated that elective lymphadenectomy
may not be effi~aci0us.l~ However, their
follow-up period is limited and two-thirds of
their patients had lesions less than 1.5 mm in
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Vol. 43
thickness. A subgroup of melanoma patients
with Level IV and V lesions and lesions ex-
ceeding 1.5 mm in thickness also showed no
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tomy. We also observed an apparent lack of
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analyzing our surgical treatment groups by
level of invasion (unpublished observations),
and have attributed this to the wide varia-
tions in thickness among Level IV and V
lesions.2 Finally, the survival differences be-
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continued to increase after the fifth postopera-
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significant with longer follow-up.
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clearly not indicated for all patients with
Stage I melanoma. However, our data, as well
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detectable regional metastases have substan-
tially improved survival rates when elective
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initial surgical management.
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