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1418
Outcomes of Patients with Local Recurrence of
Cutaneous Malignant Melanoma
A Population–Based Study
Gabriella Cohn-Cedermark, M.D.1
Eva Månsson-Brahme, M.D.1
Lars Erik Rutqvist, M.D., Ph.D.2
Olle Larsson, M.D., Ph.D.3
Toom Singnomklao, M.S.2
Ulrik Ringborg, M.D., Ph.D.1
BACKGROUND. The definition of local recurrence of cutaneous malignant melanoma varies. The outcomes of patients with a local recurrence reported in the
literature also vary, but the appearance of a local recurrence has generally been
1
Department of Oncology, Radiumhemmet,
Karolinska Hospital, Stockholm, Sweden.
2
The Oncologic Centre, Karolinska Hospital,
Stockholm, Sweden.
3
Department of Pathology, Karolinska Hospital,
Stockholm, Sweden.
Presented as an abstract at the 2nd International
Conference on the Adjuvant Therapy of Malignant Melanoma, London, United Kingdom,
March 14–15, 1997.
Supported by grants from the Cancer Society
in Stockholm.
The authors are deeply indebted to the members
of the Stockholm Melanoma Study Group for
supplying patient data and to Hemming Johansson for statistical analysis.
Address for reprints: Gabriella Cohn-Cedermark, M.D., Department of Oncology, Radiumhemmet, Karolinska Hospital, S-171 76
Stockholm, Sweden.
Received February 10, 1997; revision received
May 2, 1997; accepted May 27, 1997.
considered a negative prognostic sign. Few studies have been population-based
thus far.
METHODS. During the period 1976–1997, 3706 patients with cutaneous malignant
melanoma (including 575 patients with melanoma in situ) were registered in a
population-based regional cancer registry. Local recurrence was defined as a recurrence within the scar or transplant with no signs of regional or distant spread of
the disease. Prognostic factors were investigated using univariate and multivariate
analytic techniques. The prognostic importance of a local recurrence in terms of
survival was analyzed using the Cox proportional hazards regression model, with
local recurrence as a time-dependent covariate.
RESULTS. Local recurrence as a first event was rare (occurring in 48 of 3706 patients,
or 1.3%). Twenty-eight percent (11 of 39) of the patients with local recurrence of
invasive primary melanoma developed distant metastases and subsequently died.
Only ulceration had prognostic significance in univariate analysis. A Cox analysis,
with melanoma death as the endpoint and local recurrence as a time-dependent
covariate, demonstrated a relative risk of 1.3 associated with local recurrence;
however, this was not statistically significant (confidence interval, 0.7–2.3).
CONCLUSIONS. In this population-based study, local recurrence was a rare event.
The outcomes after diagnosis were relatively favorable. The results did not indicate
a major detrimental effect on survival from the local recurrence per se. Cancer
1997;80:1418–25. q 1997 American Cancer Society.
KEYWORDS: cutaneous malignant melanoma, local recurrence, prognosis, survival,
population-based.
L
ocal recurrence in patients with cutaneous malignant melanoma
is reported in the literature at an overall rate of 3%. This rate
appears to be lower for patients with thin melanomas (0 – 2%)1 and
higher for patients in whom the primary tumor thickness exceeds 2
mm.2 Randomized studies have shown that surgical margins can be
reduced for melanomas no thicker than 2.0 mm without any significant increase in local recurrences.3,4
The outcome of patients with local recurrence varies in the
literature. This may reflect the fact that local recurrence has not
been defined uniformly. Moreover, many reports are based on hospital data bases and few are population-based (Table 1).1,2,4 – 18 Prognostic factors in patients with cutaneous malignant melanoma have
q 1997 American Cancer Society
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Local Recurrence in Malignant Melanoma/Cohn-Cedermark et al.
1419
TABLE 1
Data from the Literature on Local Recurrence as a First Event
Local recurrence/total
not investigated rate
Author, year
Bachaud et al.5 1992
Balch et al.6 1993
Baughan et al.7 1993
Cruse et al.8 1992
Eastwood et al.9 1984
Fusi et al.10 1993
Griffiths et al.2 1986
Heenan et al.11 1992
Karakousis et al.12 1996
Lukacs13 1993
Reintgen et al.15 1992
Roses et al.16 1983
Slingluff et al.17 1988
Urist et al.18 1985
Veronesi et al.4 1991
14/219
6%
6/486
1%
16/331
5%
24/382
6%
9/150
6%
42/1090
4%
48/638
8%
8/482
2%
28/737
4%
11/183
6%
360/4185
9%
7/672
1%
25/681
4%
95/3445
3%
4/612
1%
Follow-up
Definition of local
recurrence
Population–based
Mean, 6 yrs
Within 3 cm of scar
No
Median, 6 yrs
Within 2 cm of scar
No
Median, 5 yrs
within 5 cm of scar
No
Not indicated
Not indicated
No
Not indicated
In scar
No
Median, 7 yrs
‘‘At site of primary
tumor’’
In or at edge of scar and
IT
In or within 5 cm of scar
or graft and IT
Within 2 cm of scar
No
Median, 11 yrs
(range, 5–17 yrs)
Minimum 5 yrs
Median, 7.5 hrs
(range, 1 mo–10.5 yrs)
Minimum 5 yrs
No
Yes
No
In scar
No
Mean, 7 yrs
‘‘Local skin’’
No
Mean, 3.5 yrs
Within 5 cm of scar
No
Mean, 4 yrs
No
Median, 8 yrs
In scar and within 5 cm
of scar
Within 3 cm of scar
Mean, 7.5 yrs
Within 1 cm of scar
No
No
IT: in-transit metastasis.
been described by numerous authors. Thickness and
the presence of ulceration appear to be the most
dominant negative predictors.
The objective of this population-based study
was to describe the clinical consequences and prognostic impact of local recurrence from cutaneous
malignant melanoma as the first event in relation
to putative prognostic factors. Local recurrence was
defined as a recurrence strictly within the scar or
transplant.
MATERIAL AND METHODS
Patients
Since 1976 all new melanoma cases in the StockholmGotland region (population 1.7 million) have been registered prospectively in a regional cancer registry. This
registration comprises clinical and histopathologic parameters such as age at diagnosis, gender, site of the
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09-22-97 14:03:21
primary tumor, stage of disease, pigmentation, surgical treatment, histopathologic type, thickness according to Breslow, Clark’s level of invasion, regression, ulceration, and mitotic index. All histopathologic
slides routinely are reviewed by experienced pathologists. During 1976 – 1991, surgery of the primary lesion
was made with an at least 1 cm margin for cutaneous
melanoma ° 0.8 mm thick, unless the melanoma was
located in a technically difficult area. Most of the
thicker melanomas were surgically resected with a 2or 5-cm margin, often including split-thickness skin
grafting, due to an ongoing clinical trial. Elective
lymph node dissection was not performed routinely.
Physical examinations took place mainly in one institution (Radiumhemmet). The routine workup included history and physical examination, chest X-ray,
and liver function studies. Other diagnostic studies
were performed only as indicated based on clinical
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1420
CANCER October 15, 1997 / Volume 80 / Number 8
symptoms. The initial clinical staging procedure was
based on the original three-stage system. Stage I was
defined as primary tumor { satellites within 5 cm of
the primary tumor. Stage II encompassed regional
lymph node metastases and/or in-transit metastases,
(i.e., cutaneous or subcutaneous metastases 5 cm from
the primary tumor and in transit to the regional lymph
node basin). Stage III included disseminated disease
beyond the regional lymph node basin. During followup a local recurrence was defined as a recurrence in
the scar or transplant. In-transit recurrence comprised
a subcutaneous or cutaneous metastasis between the
scar and the regional lymph node station. Lymph
nodes were classified as regional according to the
American Joint Committee on Cancer staging of cancer. Locoregional recurrence and distant metastases
were diagnosed using cytology, histopathology, or unequivocal diagnostic radiologic imaging. Clinical follow-up examinations were scheduled every 3 months
during the first 5 years and once yearly thereafter up
to 10 years from the primary diagnosis. Since 1989
physical examinations were scheduled only for a total
of 5 years, except for patients with melanoma in situ
and for those with primary tumors with thickness °
0.8 mm, for whom clinical control for registration and
information only was performed once and twice, respectively. Once a recurrence was diagnosed, or if the
patient was primarily in Stage II or III the follow-up
schedule was intensified. Examining physicians report
to the registry at every single examination. Local recurrence, in-transit metastases, regional lymph node metastases, disseminated disease, and death are reported
to the registry and recorded prospectively.
During 1976–1991, 3706 consecutive patients with
primary cutaneous malignant melanoma (575 with melanoma in situ) were registered in this population-based
regional cancer registry. The median follow-up time
from primary diagnosis was 8 years (range, 3–18 years).
Follow-up information was obtained through the clinical
records and the regional cancer registry. All patients also
were checked against official death registries. Among the
patients with a local recurrence, only 1 patient was lost
to follow-up 2 years after recurrence. Complete clinical
data were obtained for all the remaining patients. For
the purpose of this study the clinical records also were
reviewed with regard to the following parameters, which
are not routinely registered: extra visit, person who detected the recurrence, treatments after recurrence, and
the chronologic pattern of all metastases (the registry
routinely comprises only the first event of each type of
locoregional recurrence and the two first sites of distant
metastases).
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Statistics
Differences in proportions were analyzed with the chisquare homogeneity test. For comparisons of median
values the median test was used.19 The survival distributions were estimated using the actuarial method.
Death due to melanoma was the event of interest in
calculating the melanoma specific survival (MS). The
event of interest in calculating the disease free survival
(DFS) for the patients with a local recurrence as a first
event was the subsequent event, which was defined
as any recurrence or melanoma death. Deaths due to
unrelated causes were treated as censored observations in both calculations. The prognostic value (relative to melanoma death) of putative prognostic factors
was analyzed using the Cox proportional hazards regression model.20 Differences with a P value õ 0.05
(two-sided) were considered to be statistically significant. The prognostic importance of local recurrence in
terms of MS was analyzed using the Cox proportional
hazards regression model with local recurrence as a
time-dependent covariate. The model also included
the most well documented risk factors in cutaneous
malignant melanoma such as age, gender, tumor
thickness, and ulceration.
RESULTS
Patients
At a median follow-up of 8 years, a total of 48 patients
(9 with melanoma in situ) with local recurrence as a
first event were identified among the 3706 patients
(575 with melanoma in situ). The crude incidence of
local recurrence was thus 1.3%.
Median time to local recurrence was 15 months
(range, 1 – 166 months). The characteristics of the entire melanoma population and those with local metastases as the first recurrence are presented in Table 2.
There were significant differences in terms of age, tumor thickness, primary tumor site, histogenetic type,
Clark’s level, presence of ulceration, and mitotic index.
The median tumor thickness was 2.5 mm in the local
recurrence group versus 1.0 mm within the source
population. The mean resection margins of the primary tumors were 26 mm for the patients with a local
recurrence (27 of 48) as well as for those without a
local recurrence (3237 of 3658). The median margin
was 25 mm (range, 2 – 50 mm) for the the patients with
a local recurrence and 20 mm (range, 1 – 100 mm) for
those without a local recurrence as the first event. Patients with local recurrences were older and more
commonly displayed a head and neck location, primary nodular or lentiginous malignant melanoma,
Clark’s Level IV, and ulcerated primary tumors. Seven
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Local Recurrence in Malignant Melanoma/Cohn-Cedermark et al.
TABLE 2
Comparison of Clinical and Histopathologic Parameters in all
Patients and in Patients with Local Recurrence as the First Event
Parameter
All patients
n Å 3706 (%)
Patients with local
recurrence, n Å 48 (%)
Age at diagnosis (yrs)
Median
Range
57
13–96
66 years
14–89 years
Tumor thickness (mm)
Median
Range
1.0
0.1–50
2.5 mm
0.3–15.0 mm
Gender
Male
Female
1738 (47)
1968 (53)
20 (42)
28 (58)
Site
Trunk
Lower extremity
Upper extremity
Head and neck
1630 (44)
990 (27)
523 (14)
563 (15)
8 (17)
13 (27)
5 (10)
22 (46)
Stage
Stage I
Stage II
Stage III
3630 (98)
63 (1.7)
13 (0.4)
48 (100)
0
0
Histogenetic type
SSM
NM
LMM
ALM
MIS
Unable to classify
2247 (61)
432 (12)
98 (3)
73 (2)
575 (16)
281 (8)
19 (40)
8 (17)
5 (10)
2 (4)
9 (19)
5 (10)
Clark level
Level I
Level II
Level III
Level IV
Level V
Unable to classify
575 (16)
1278 (34)
1054 (28)
597 (16)
122 (3)
80 (2)
9 (19)
5 (10)
11 (23)
13 (27)
9 (19)
1 (2)
Ulceration
Present
Absent
Unknown
659 (18)
2081 (56)
966 (26)
18 (38)
30 (62)
0
Regression
Present
Absent
Unknown
462 (12)
3093 (84)
151 (4)
5 (10)
43 (90)
0
Mitosis
õ6 per 10 HPF
¢6 per 10 HPF
Unknown
1058 (29)
161 (4)
2487 (67)
34 (71)
14 (29)
0
P valuea
P õ 0.01
P õ 0.001
1421
of the nine melanoma in situ tumors with a local recurrence were located in the head and neck region.
Although regular examinations every 3 months
were performed, as many as 21 of 48 patients applied
for an extra visit due to the local recurrence. In 19
cases it was first noted by the physician. The recurrence was surgically removed in 47 patients. One patient received radiation therapy alone. After radical
surgery for the first local recurrence, complementary
treatment comprised of regional hyperthermic cytostatic perfusion therapy given to one patient and radiation therapy to another.
NS
P õ 0.001
NS
P õ 0.01
P õ 0.001
P õ 0.05
NS
P õ 0.001
SSM: superficial spreading melanoma; NM: nodular melanoma; LMM: lentigo maligna melanoma;
ALM: acral lentiginous melanoma; MIS: melanoma in situ; HPF: high-power field.
a
For grouped data: chi-square homogeneity test. For medians: the median test. NS: not significant (P
ú 0.05).
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Distribution of Recurrences, Follow-Up, and Survival
Twenty-three of the 39 patients with invasive melanoma (59%) had 1 local recurrence exclusively. The
remaining 16 patients initially had a local recurrence
that later was followed by other recurrences (in 5 patients only as regional metastases). Eleven patients
(28%) developed distant metastases and subsequently
died of melanoma. The median follow-up time after
local recurrence was 7.5 years (range, 6 months – 17
years). In the patients who died, the median time after
the first local recurrence to melanoma death was 3
years (range, 8 months – 6 years). One patient died with
regional disease but of another obvious cause 27
months after local recurrence. At last follow-up, 26
patients were alive and 10 died of other causes but
were free of disease. Only one patient with melanoma
in situ experienced a second event. DFS and MS after
the first local recurrence for all 48 patients with local
recurrence are shown in Figure 1. The 5-year MS rate
was 83% and the 5-year DFS rate was 69%. When considering only the 39 patients with primary invasive
melanoma, the 5-year MS rate was 69% and the 5-year
DFS rate was 61%.
Prognostic Analyses
When the clinical features and histopathologic parameters of the primary tumor shown in Table 2
were tested individually in a univariate analyses,
only ulceration yielded significant prognostic information after local recurrence with regard to melanoma survival (Table 3). Nevertheless there was a
tendency toward an increased relative risk in relation to melanoma death in patients age ¢ 65 years,
disease free interval õ 1 year, primary nodular melanoma, primary trunk melanoma, primary tumor
thickness ¢ 2 mm, and mitosis ¢ 6 per 10 highpowered fields. The prognostic impact of a local
recurrence as a first event in relation to melanoma
death was assessed in a regression model (Table 4)
with local recurrence as a time-dependent covari-
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CANCER October 15, 1997 / Volume 80 / Number 8
FIGURE 1. Disease free survival (DFS) and melanoma specific survival
(MS) in 48 patients with local recurrence as the first event, calculated
from date of first local recurrence.
ate; consideration of well documented risk factors
such as age, gender, primary tumor thickness, and
ulceration (information on all risk factors was available for 2525 patients within the source population)
demonstrated a relative risk of 1.3 associated with
local recurrence (95% confidence interval [CI] 0.7 –
2.3).
DISCUSSION
When discussing the significance and clinical consequences of local recurrence in patients with cutaneous
malignant melanoma it is important to define this entity unequivocally. Because there is a lack of uniformity in the literature it also is difficult to draw conclusions regarding its significance in patients with cutaneous malignant melanoma (Table 1).2,4 – 18 In many
reports a local recurrence is defined as a recurrence
within 2 – 5 cm of the scar; in other reports, local disease includes regional metastases as well.1,5 – 7,12,16,17,21
A local recurrence using the authors’ definition was
easy to distinguish from in-transit metastases; only
patients who developed only local recurrence as the
first negative event were included in the study so as
not to mistakenly characterize a local recurrence developing concurrently with in-transit metastases as a
local recurrence. This more likely represents a more
widespread disease in the lymphatic region. The incidence of local recurrence in this study was 1.3%, which
is understandably on the low side of the reported overall mean incidence of 3% (range, 0 – 6%),1 although the
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authors’ definition is more strict than in most other
comparable studies.
Due to the cancer care program in practice since
1976, the surgical procedure for the primary melanoma has been performed in a defined manner
throughout the region. There was no difference regarding mean resection margins for the melanoma
population and the patients with a local recurrence.
Unfortunately data regarding the surgical margins
were available only in 56% of the patients (27 of 48
patients) with a local recurrence as opposed to 88%
of the patients without a local recurrence (3237 of
3658). One reason for this difference in missing data
might be due to the higher proportion of head and
neck lesions in the local recurrence group. The imbalance in data regarding the resection margins does not
contradict the belief that the majority of the local recurrences might be caused by residual disease. However, conclusions regarding resection margins should
be based on prospective randomized trials, and over
the last 5 years several authors in large controlled studies have found local recurrence rates to be independent of the margin width. The current tendency worldwide is to practice a differentiated approach in relation
to the depth and location of the primary tumor.3,4,6,22 – 25
Balch et al.6 advocate 2-cm margins for intermediatethickness melanomas (1 – 4 mm) because the results
of a randomized trial showed no difference in respect
to local recurrence or survival for patients with trunk
or proximal extremity lesions. The long term results
of this prospective multiinstitutional randomized
study, as well the patients with distal extremity or head
and neck melanomas who all were treated with a 2cm margin, were reported by Karakousis et al.12 and
their conclusion regarding the surgical margins is in
accordance with their previous report. Ringborg et al.3
showed no difference in respect to local recurrence
rate or survival when comparing 2-cm versus 5-cm
margins for patients with melanomas with a tumor
thickness of ú 0.8 mm and ° 2.0 mm.
Local recurrence generally has been associated
with a grave prognosis. Dismal survival rates after local
recurrence with a mortality rate of 67% have been
reported by Griffiths et al.2 According to Urist et al.,18
50% of patients died within 3 years of the local recurrence and recently Karakousis et al.12 reported that
82% of patients with local recurrence died of disease
progression. Brown and Zitelli26 reported a high rate
of cure after local recurrence, defined as a recurrence
within the scar with an in situ component. Their material was comprised of as much as 52% melanoma in
situ tumors, mostly lentigo maligna tumors; 42 of 50
tumors (84%) were located in the head and neck re-
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1423
TABLE 3
Cox’s Univariate Analysis of Prognostic Factors for Mortality Due to Melanoma in 39 Patients with Invasive Cutaneous Malignant Melanoma and
Local Recurrence as the first Event
Parameter
No. of patients
with local
recurrence
No. of
melanoma
deaths
Crude
RR
95% CI
Test for
trenda
Gender
Male
Female
17
22
5
6
1.0
1.0
0.3–3.2
P Å 0.95
Age at diagnosis (yrs)
õ65
¢65
18
21
4
7
1.0
2.6
0.7–8.9
P Å 0.12
Disease free interval
õ1 year
¢1 year
16
23
7
4
1.0
0.3
0.1–1.1
P Å 0.06
Site
Trunk
Extremity
Head and neck
6
18
15
3
5
3
1.0
0.3
0.4
0.1–1.2
0.1–1.8
P Å 0.18
Histogenetic type
SSM
NM
LMM, ALM, Unable to classify
19
8
12
6
4
1
1.0
1.6
0.2
0.5–5.8
0.03–1.9
P Å 0.14
Clark’s level
II / III
III / IV
16
22
5
6
1.0
0.9
0.3–2.7
P Å 0.77
Ulceration
Present
Absent
18
21
8
3
1.0
0.2
0.1–0.9
P Å 0.03
Regression
Present
Absent
4
35
2
9
1.0
0.6
0.1–2.8
P Å 0.50
25
14
6
5
1.0
1.8
0.5–5.8
P Å 0.35
15
24
3
8
1.0
2.1
0.5–6.4
P Å 0.42
Mitotic index
õ6
¢6
b
Tumor thickness (mm)
õ2
¢2
RR: relative risk of death due to malignant melanoma; 95% CI: 95% confidence interval; SSM: superficial spreading melanoma; NM: nodular melanoma; LMM: lentigo maligna melanoma; ALM: acral lentiginous
melanoma.
a
The categories are coded 0 for the first category and 1 for the other.
b
Number of mitoses per 10 high-powered fields.
gion. These patients were referred after treatment of
the primary tumor with excision, cryosurgery, or electrosurgery and the recurrence was treated with small
resection margins with a special technique.26 They
showed a 5-year DFS rate of 66%, and a 5-year survival
rate of 98%.26 However, because of the patient selection, this study is hardly representative of local recurrence in all melanomas. In the current study material,
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which was population-based with few possible referral
biases and comprised all cases of local recurrences
from patients with primary malignant melanomas diagnosed over a 15-year period, the 5-year DFS was
69%, and the MS was 83%. The corresponding figures,
when considering only the patients with primary invasive melanoma, was 61% and 69%, respectively. By 7
years no additional events were observed.
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CANCER October 15, 1997 / Volume 80 / Number 8
TABLE 4
Multivariate Cox Analysis of Prognostic Factors with Local
Recurrence as Time–Dependent Covariatea
Risk factor
Age (yrs)
õ65
¢65
Gender
Female
Male
Tumor thickness
(mm)
õ2
¢2
Ulceration
Absent
Present
Local recurrenceb
First event
No
Yes
Events/patients
RR (95% CI)
200/1645
159/880
1.0
1.2 (0.9–1.5)
134/1308
225/1217
1.0
1.7 (1.3–2.0)
127/1900
232/625
1.0
4.4 (3.4–5.6)
145/1877
214/648
1.0
2.5 (2.0–3.2)
348/2486
11/39
1.0
1.3 (0.7–2.3)
RR: relative risk of death due to malignant melanoma; 95% CI: 95% confidence interval.
a
The analysis was based on 2525 patients with cutaneous malignant melanoma. The endpoint was
melanoma death (n Å 359).
b
Treated as a time-dependent covariate with the value 0 until the occurence of a local failure and the
value 1 at the time of local failure.
In Sweden, there is a fairly rigourous followup program for patients with invasive malignant
melanoma with scheduled controls every 3 months
during the first 5 years after the primary treatment.
The majority of the patients in the current study
were examined by oncologists with special interest
in malignant melanoma and some patients were
examined by plastic surgeons. In spite of this 21 of
48 patients applied for an extra physical examination because they had noticed the local recurrence.
People in Sweden generally are well educated and
well informed, and patients also are instructed in
self-examination techniques. Furthermore, 92% of
the local recurrences were diagnosed within 5 years
of the primary treatment, while patients still were
undergoing follow-up examinations.
One question that remains to be answered is
what impact the various types of locoregional recurrences have on survival. The traditional definition is
that local recurrences are retained portions of the
primary tumor but also may be the first manifestation of disseminated disease.1 According to Cruse et
al., Balch et al., and Roses et al.,8,16,27 the appearance
of a local metastases after definitive excision is a
significant indicator of systemic disease. Other authors claim that local and lymph node metastases
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may represent a host control of the disease and do
not necessarily reflect occult systemic dissemination.10,15 Furthermore, there are no unequivocal
methods to predict which of these recurrences
within each group actually will be lethal. In fact,
some authors have shown that once there is a diagnosis of recurrent melanoma several known prognostic factors of the primary tumor bear no influence on the outcome.10,28 – 30 However, others have
found location, disease free interval, thickness, and
ulceration of the primary tumor to be of prognostic
value even after local recurrence.14 In the current
study only the presence of ulceration in the primary
tumor provided significant prognostic information
regarding risk of melanoma death. The other tested
known prognosticators regarding the primary tumor
only showed a trend toward importance after a local
recurrence. These results might have been caused
by the fairly small numbers of patients (Table 3).
When local recurrence was treated as a time-dependent covariate in a regression model, the associated
relative risk of melanoma death was 1.3 (95% CI, 0.7 –
2.3). Thus, no major detrimental impact on survival
could be demonstrated with this statistical technique. Even with the assumption that this trend was
true, the putative excess risk of having developed a
local recurrence (defined as a recurrence within the
scar or transplant) would be moderate.
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Ringborg U, Andersson R, Eldh J, Glaumann B, Hafstrom L,
Jacobsson S, et al. Resection margins of 2 versus 5 cm for
cutaneous malignant melanoma with a tumor thickness of
0.8 to 2.0 mm. Cancer 1996;77:1809–14.
Veronesi U, Cascinelli N. Narrow excision (1 cm margin):
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