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2252
Follow-Up Recommendations for Patients with
American Joint Committee on Cancer Stages I–III
Malignant Melanoma
Wen-Jen Poo-Hwu, M.D., Ph.D.
Stephan Ariyan, M.D., M.B.A.
Lynne Lamb, R.N., M.S.N.
Rose Papac, M.D.
Daniel Zelterman, Ph.D.
Grace L. Hu, Ph.D.
Janis Brown, M.D.
David Fischer, M.D.
Jean Bolognia, M.D.
Antonio C. Buzaid, M.D.
Yale Melanoma Unit, Yale Comprehensive Cancer
Center, Yale University School of Medicine, New
Haven, Connecticut.
Supported by National Institutes of Health research
grant CA-16359 from the National Cancer Institute.
The authors are grateful to Ms. Diane Mozdziesz
for her special technical assistance in the preparation of this article.
Dr. Antonio C. Buzaid is currently at Hospital Sirio
Libanes, Sao Paulo, Brazil.
Dr. Grace L. Hu is currently at Novartis Pharmaceuticals Corporation, Summit, New Jersey.
Address for reprints: Dr. Wen-Jen Poo-Hwu, M.D.,
Ph.D., Section of Melanoma, Clinical Immunology
Service, Memorial Sloan-Kettering Cancer Center,
1275 York Avenue, New York, NY 10021.
Received March 30, 1999; accepted April 27,
1999.
© 1999 American Cancer Society
BACKGROUND. Guidelines for follow-up of melanoma patients are not established.
In 1987, a follow-up protocol was instituted at the Yale Melanoma Unit to improve
upon the detection of disease recurrence in patients with American Joint Committee on Cancer Stage I–III cutaneous melanoma. The follow-up protocol consists of
a patient education program and a surveillance schedule based on stage of disease.
METHODS. The authors retrospectively reviewed the records of 373 patients who
were seen and followed according to the surveillance protocol in the Yale Melanoma Unit between January 1988 and December 1994 to determine 1) the time
interval between the initial visit and recurrence; 2) the most common method of
detecting recurrences; 3) whether the surveillance schedule or the patient detects
more recurrences, i.e., asymptomatic recurrences versus symptomatic recurrences;
4) whether there is any survival difference between asymptomatic and symptomatic recurrences.
RESULTS. The 5-year overall survival rates for Stage I, II, and III patients were 95%,
72%, and 52%, respectively. Of the 78 recurrences, 44 (56%) were detected by
physician-directed surveillance examinations and 34 (44%) by patients. Most recurrences were found within the first (47%) or second (32%) year of follow-up. The
estimated 6-month hazard rates for death or recurrence were 0.0044, 0.0088, and
0.0278 for Stage I, II, and III patients, respectively. The group of asymptomatic
patients with recurrence had a survival advantage over the symptomatic recurrence group. In addition, patients with locoregional recurrence had better survival
than those with distant recurrence.
CONCLUSIONS. Although many recurrences arise rapidly and are recognized early
by patients, in this study more than half were found by surveillance examinations
before symptoms were manifest. Based on the hazard ratio for recurrences, the
authors recommend the following surveillance schedules in addition to the patient
education program for detection of recurrences: 1) Stage I, annually; 2) Stage II,
every 6 months for Years 1–2 and annually thereafter; 3) Stage III, every 3 months
for Year 1, every 4 months for Year 2, and every 6 months for Years 3–5; 4) at Year
6 and beyond, all patients should have surveillance annually, due to the risk of late
recurrence and/or metachronous multiple primaries. Cancer 1999;86:2252– 8.
© 1999 American Cancer Society.
KEYWORDS: medical oncology, cutaneous melanoma, recurrence detection, follow-up recommendation.
T
here will be 44,200 new cases of cutaneous melanoma diagnosed
in the United States in 1999, and over 80% of these cases will be
localized melanoma.1 The incidence of melanoma is increasing at an
annual rate of 6%. This rate of increase is faster than for any other
cancer in men and second to lung carcinoma in women.2 The death
rate from melanoma continues to rise '2% annually. The recurrence
Follow-Up of AJCC Stage I–III Melanoma/Poo-Hwu et al.
rates and survival statistics of patients with localized
melanoma vary with the stage of disease. For this
study, tumors were staged according to the 1983 staging system of the American Joint Committee on Cancer (AJCC)3 (the 1997 definitions of Stages II and III4
are somewhat different from 1983). According to that
staging system, Stage I tumors are defined as having a
tumor thickness # 1.5 mm (Stage IA, #0.75 mm, Stage
IB, 0.76 –1.50 mm). Stage II tumors have a thickness .
1.50 mm (Stage IIA, 1.51– 4.00 mm, Stage IIB, .4.0
mm). Stage III tumors have spread to regional lymph
nodes and/or in-transit metastases. Approximately
10 –30% of patients with AJCC Stage I and II disease
and over 60% of patients with Stage III disease eventually develop metastatic disease after initial surgery.5
Up to 10% of melanoma patients will develop a second
primary melanoma.6
At present, there is no general agreement on the
proper frequency of clinical examinations, on the
kind of diagnostic procedures, or on the follow-up
duration for patients with AJCC Stage I–III melanoma after surgical resection. Model schedules for
follow-up intervals for patients with Stage I melanoma were developed by Romero et al.7 based on a
survey of eight expert physicians. Several groups
suggested a follow-up schedule for patients with
Stage I melanoma after analyzing the risk and pattern of recurrence.8,9 Reintgen et al.,10 by evaluating
metastatic patterns, suggested frequent follow-up
during the first 3 years after surgical excision. Other
groups have reported both data and recommendations regarding the utility of follow-up tests for various stages of melanoma.11,12 Of particular note is a
study that was performed with intermediate and
high risk melanoma patients who were enrolled in
an adjuvant trial and were followed with frequent
blood analyses and chest X-rays.11 The majority of
recurrences were discovered by review of systems
and/or physical examination, despite the frequent
use of other follow-up tests. The data suggest that
diagnostic tests have limited value in the follow-up
of patients with resected intermediate and high risk
melanoma (Stage II and III melanoma).
Guidelines regarding the follow-up of patients
with AJCC Stage I–III cutaneous melanoma are needed
because of the high frequency of disease recurrence
and second primary melanomas. Follow-up visits after
potentially curative surgery for melanoma serve a
number of functions, including ensuring rehabilitation, evaluation of treatment, detection of new primary lesions, and early detection of recurrences that
may be amenable to treatment, including new investigational therapies.
2253
TABLE 1
Protocol Follow-Up Schedule for Patients with Stage I–III Melanoma
Month
Stage I
Stage II
Stage III
3
4
6
8
9
12
15
16
18
20
21
24
27
28
30
32
33
36
42
48
54
60
Annually thereafter
—
—
X
—
—
X
—
—
X
—
—
X
—
—
X
—
—
X
—
X
—
X
X
—
X
—
X
—
X
—
X
—
X
—
X
—
X
—
X
—
X
X
X
X
X
X
X
—
X
—
X
X
X
—
X
—
X
X
X
—
X
—
X
X
X
X
X
X
X
MATERIALS AND METHODS
Follow-Up Protocol
At the Yale Melanoma Unit, patients with resected
AJCC Stage I–III cutaneous melanoma are followed by
a multidisciplinary team of dermatologists, medical
oncologists, and plastic surgeons. In September 1987,
a uniform follow-up protocol was adopted that combined frequent, comprehensive examinations with extensive patient education. The patient education was
provided by the physicians and by clinical nurse specialists with direct discussion of clinical characteristics
of melanoma, in-transit metastases, and lymph node
drainage. During the first and/or second clinic visit, all
patients received instructions in performing self-examination of the skin and a list of signs and symptoms
of recurrence (i.e., pain, progressive fatigue, weight
loss, nausea and emesis, headache, shortness of
breath) that should alert them to contact their physicians. Pamphlets and videotape were used to educate
patients and family members for photoprotection and
melanoma prevention.
Patients who were clinically free of disease after
surgery were followed regularly according to the follow-up protocol shown in Table 1. Follow-up visits
were scheduled based on the stage of disease according to the 1983 AJCC four-stage system.3 At each visit,
a history, physical examination, complete blood
count, and liver function tests (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic
2254
CANCER December 1, 1999 / Volume 86 / Number 11
transaminase, alkaline phosphatase, and lactate dehydrogenase [LDH]) were performed. Chest X-rays were
obtained annually for all Stage I and II patients and
every 6 months for Stage III patients during the first 5
years of follow-up. All patients with Stage III disease
had a baseline computed tomography (CT) scan for
complete staging examination. Follow-up CT scans
were obtained in 6 –12 months only if there were abnormal findings initially that were not clearly indicative of metastatic disease. Patients who developed
multiple primary melanomas were continued on the
follow-up schedule according to the highest stage of
the invasive melanoma.
Patient Selection
We retrospectively evaluated the records of 419 patients with Stage I–III melanoma who were seen and
followed in the Yale Melanoma Unit from January
1988 to December 1994. To be eligible for the study,
patients were required to have pathologically confirmed cutaneous melanoma and no clinical evidence
of disease after surgery. Patients who presented with
AJCC Stage IV disease (tumor metastatic to lymph
nodes beyond the regional lymph nodes or to distant
sites) or noncutaneous melanoma were excluded. Patients who had inadequate medical records or inadequate follow-up at the Yale Melanoma Unit also were
excluded from analysis. Forty-six patients were excluded from this study: 4 patients had noncutaneous
melanoma (mucosal melanoma), 39 patients had inadequate follow-up at Yale (#2 visits), 2 patients had
nonresectable Stage III disease, and 1 patient had 2 in
situ lesions only. In all, 373 patients were surveyed.
The following issues were evaluated by a review of
the records for all patients with recurrent melanomas:
1) What was the time interval between the initial visit
and diagnosis of recurrence? 2) Was the recurrence
detected during a scheduled visit by a physician, or
was recurrence recognized by the patient between
scheduled visits by self examination or symptoms? 3)
Which procedure(s) identified recurrence(s) in the
asymptomatic patient (i.e., review of systems and
physical examination, complete blood count, liver
function tests, chest X-ray, or others)? 4) Where was
(were) the site(s) of disease recurrence, locoregional
metastases, and/or systemic metastases? 5) What was
the survival after recurrence? 6) Did the patient develop another primary melanoma during the follow-up period?
Statistical Analysis
For each patient who experienced disease recurrence,
a data abstract sheet summarized the demographic
information, the date recurrence was diagnosed, and
symptoms or procedures that led to the diagnosis of
recurrence. It also recorded the various treatments the
patient received for recurrent disease, such as surgery,
neoadjuvant or adjuvant therapy, and the treatment
outcome. All analyses were descriptive, intended to
extract as much information as possible from existing
data, to help formulate better strategies for monitoring patients with early stage melanoma. The results
from procedures (review of systems, physical examination, complete blood count, liver function tests, and
chest X-ray) that were abnormal at the time of disease
recurrence were tabulated. The risk of recurrence for
every 6-month period after surgery and initial visit was
estimated by the hazard function. For every 6-month
period after the remission of disease, the hazard function is the ratio of the number of patients who experience disease recurrence during the period divided by
the number of disease free patients at the start of that
period. The cumulative disease free survival curves
were calculated according to the Kaplan–Meier product-limit method. The population was evaluated and
stratified by stage of disease. Disease free interval and
survival curves were constructed separately for the
group of patients with recurrences and for subsets of
patients defined by the methods of detection (symptomatic vs. asymptomatic) and by the site of recurrence (locoregional vs. distant).
RESULTS
Patient Population
The analysis in the current study was based on 373
patients who were followed according to the protocol
schedule. Of these patients, 193 patients (52%) had
AJCC Stage I disease (Stage IA, n 5 84 patients; Stage
IB, n 5 109 patients), 117 patients (31%) had Stage II
disease (Stage IIA, n 5 85 patients; Stage IIB, n 5 32
patients), and 63 patients (17%) had Stage III disease.
All patients had more than 2 routine clinic visits. The
clinical characteristics of these patients are shown in
Table 2. The cumulative disease free survival was analyzed for each disease stage, as shown in Figure 1.
The minimum follow-up for all patients is 2 years. The
5-year overall survival rates for patients with Stage I, II,
and III disease were 95%, 72%, and 52%, respectively.
Of the 78 patients who experienced disease recurrence, 34 patients (44%) developed symptoms that
indicated recurrence, and the other 44 patients (56%)
were diagnosed by procedure(s) performed during a
scheduled visit.
The detection of recurrences by patients or at
scheduled follow-up visits are compared in Table 3.
There were 9 recurrences in patients with Stage I disease (5%), with a median time interval between initial
visit and diagnosis of recurrence of 22.0 months
(range, 2.0 – 60.5 months); 35 recurrences in patients
with Stage II disease (30%), with a median time inter-
Follow-Up of AJCC Stage I–III Melanoma/Poo-Hwu et al.
TABLE 2
Clinical Characteristics of 373 Patients with American Joint
Committee on Cancer Stage I–III Cutaneous Melanoma
Characteristic
Ages (yrs)
Mean
Range
Stage
I
II
III
Site of primary tumor
Head/neck
Trunk
Upper limb
Lower limb
Unknown
2255
TABLE 3
Distribution of 78 Recurrences in Patients with Stage I–III Cutaneous
Melanoma
Males
(n 5 210)
Females
(n 5 163)
Total
(n 5 373)
52.3
16–81
47.2
12–81
49.8
12–81
91
74
45
102
43
18
193
117
63
47
106
26
27
4
8
50
31
73
1
55
156
57
100
5
Characteristic
Gender
Male
Female
Total (%)
Stage
I
II
III
Location of recurrences
Distant metastases (%)
Locoregional (%)
Local relapses
Regional lymph nodes
Patient
detected
Physician
detected
Two-sided exact
P valuea
24
10
34 (44)
28
16
44 (56)
—
—
0.63
2
16
16
7
19
18
—
0.47
—
14 of 34 (41)
20 of 34 (59)
12
8
25 of 44 (57)
19 of 44 (43)
7
12
—
—
0.25
a
P values were determined by using the Fisher exact two-sided test of equality of symptomatic and
asymptomatic rates.
TABLE 4
Distribution of Physician-Detected Recurrences by Detection
Methods
FIGURE 1. Graph showing overall survival for 373 patients with American
Joint Committee on Cancer (AJCC) Stage I–III cutaneous melanoma: 193
patients with Stage I disease, 117 patients with Stage II disease, and 63
patients with Stage III disease.
val between initial visit and diagnosis of recurrence of
13.2 months (range, 2.4 –71.0 months); and 34 recurrences in patients with Stage III disease (54%), with a
median time interval between initial visit and diagnosis of recurrence of 10.6 months (range, 2.3–53.8
months). Half of the locoregional recurrences (20 of 39
recurrences) were detected by patients, whereas more
than half of the distant metastases were detected by
physicians (25 of 39 recurrences). It is illustrated in
Table 4 that 25 of the 44 physician-detected recurrences (57%) were identified by either history or physical examination. There were 8 recurrences identified
by abnormal chest X-ray and 10 by other imaging
examinations (CT scan or magnetic resonance imaging [MRI]). CT scans and MRIs were obtained either
because there were abnormal findings on the baseline
scan that were not clearly indicative of metastatic
Method
No. of
recurrences
Physician-detected
recurrences (%)
All recurrences
(%)
H&P
CBC/LFTs
Chest X-ray
Othersa
25
1
8
10
57
2
18
23
32
1
10
13
H&P: history and physical examination; CBC: complete blood cell count; LFTs: liver function tests
(serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, and lactate dehydrogenase).
a
Computed tomography or magnetic resonance imaging scans.
disease or there were suspicious findings on physical
examination. Although the results of laboratory studies were abnormal at the time of detection of recurrence in 38% of patients, there was only 1 patient in
whom an abnormal laboratory test result (elevated
LDH) was the sole indicator of recurrent disease.
Most patients developed recurrences within either
the first year (47%) or the second year (32%) of followup, and these were divided equally between locoregional sites and distant sites. Five patients (6%) developed recurrences after 5 years of follow-up; 1 patient
developed symptoms, 2 were detected by physical examination, and 2 were detected by annual chest X-ray.
The group with locoregional recurrences, as expected,
had a better survival rate compared with the patients
with distant recurrences. The median survivals were
34 months and 13 months for locoregional and distant
recurrences, respectively (log-rank test; P 5 0.03) (Fig.
3). Patients with regional lymph node metastases were
2256
CANCER December 1, 1999 / Volume 86 / Number 11
FIGURE 2. Graph showing the survival of patients after disease recurrence
comparing locoregional recurrences with distant recurrences. The median
survivals were 34 months (39 patients) and 13 months (39 patients) for
locoregional recurrences and distant recurrences, respectively (log-rank test;
P 5 0.03).
enrolled in adjuvant immunotherapy protocols after
resection. Patients with unresectable locoregional recurrences were treated on neoadjuvant chemotherapy
protocols followed by resection of residual disease.
Twelve patients with locoregional recurrences (30%)
remained disease free after 5 years.
Of the 39 patients with systemic metastases, all
were enrolled in the ongoing clinical trials of systemic
therapy. As a group, these patients had a shorter survival compared with the patients who had locoregional recurrences (Fig. 2). However, 4 patients (10%)
responded to systemic therapy, underwent resection
of residual visceral disease, and remained disease free
at 5 years. Comparison of survival after disease recurrence detected either at routine examination (asymptomatic) or by the patients (symptomatic) is shown in
Figure 3. The median survival of asymptomatic and
symptomatic recurrences were 27 months and 14.5
months, respectively. This was statistically significant
(P 5 0.02) in a multivariate analysis (Cox regression)
controlling for stage, symptomatic versus asymptomatic, and local versus distant recurrences. The estimated 6-month hazard rates for death or recurrence
after the date of the first Yale Melanoma Unit visit
were 0.0044, 0.0088, and 0.0278, respectively, for patients with Stage I, II, and III disease or roughly a ratio
of 1:2:6.3 (Fig. 4).
All 19 patients with multiple primary melanomas
were identified by physician-performed physical examination. Three patients had synchronous lesions at
the initial diagnosis. Seventeen patients had 2 primary
melanomas, 1 patient had 3 primary melanomas, and
1 patient had 12 primary melanomas. Seven of the
patients with metachronous melanomas were diag-
FIGURE 3. Graph showing the survival of patients after recurrence comparing asymptomatic recurrences with symptomatic recurrences. The median
survivals of asymptomatic patients (n 5 44 patients) and symptomatic patients
(34 5 patients) patients were 27 months and 14.5 months, respectively (Cox
regression analysis; P 5 0.02).
FIGURE 4. Smoothed hazard function by stage of disease.
nosed in the first year of follow-up, 4 patients were
diagnosed in the second year, and 5 patients were
diagnosed thereafter (range, 32–125 months). The
thickness of the initial melanoma ranged from 0.3 mm
to 6.0 mm, and the subsequent melanoma ranged in
thickness from melanoma in situ to 3.0 mm. In general, the subsequent melanomas were thinner than
the first primary lesions, as reported previously by our
group.6
DISCUSSION
There are no established surveillance programs for patients with localized melanoma. Because of the substantial risk for recurrent disease and the tendency for late
recurrence,13,14 extended postoperative follow-up visits
at frequent intervals have become a common strategy
for all melanoma centers. Although several centers have
examined the outcome of surveillance programs, there is
Follow-Up of AJCC Stage I–III Melanoma/Poo-Hwu et al.
no published evidence documenting a beneficial effect
of these procedures.9,15–17 Nevertheless, such programs
are useful in identifying new primary lesions, in providing patient reassurance, and in sometimes detecting a
cohort of patients with resectable lesions with a potential
for long term disease control. Locoregional recurrence
possibly is curable in some instances, and even solitary
visceral sites, when they are resectable, are known to be
associated with an improved prognosis.9,18 In 1987, we
developed a patient education program and a follow-up
schedule to provide a framework for early detection of
recurrence by both patients and physicians. This protocol assumed that early recurrences may be more amenable to treatment. Although current chemotherapeutic
regimens have had only marginal success in treating
metastatic melanoma, numerous clinical trials are investigating new strategies and drugs for this disease. At
centers where such trials are offered, early detection of
recurrence offers potential value in the development of
effective therapy.
In 1994, our preliminary evaluation concluded
that '90% of the recurrences were detected by patients.19 In 1997, 10 years after the commencement of
these educational and surveillance programs, we reviewed the outcome of an expanded series with additional follow-up, which led to a more accurate construction of guidelines for the follow-up of patients
with Stage I–III malignant melanoma. The modified
conclusion was reported briefly in a letter to the editor
of The Journal of the American Medical Association.20
The outcome as a result of educating patients
during repetitive clinic visits to carry out self-examination and to recognize the signs and symptoms of
recurrent melanoma revealed that 44% of recurrences
were detected by the patients (Table 3). Although recurrence may develop rapidly and may be recognizable by patients between scheduled visits, 56% of the
recurrences were detected only by thorough examination by physicians, and the majority were found as a
result of history and physical examination. In one type
of recurrence, namely, recurrence at a locoregional
site, detection by patients was more frequent than
detection by physicians (59% by patients). This emphasizes the equal importance of patient education
and surveillance examination.
In our study, the 5-year overall survival rates for
patients with Stage I and II disease were 95% and 72%,
respectively. These figures are very close to the rates
reported by Balch et al.5 The 5-year survival rate for
patients with Stage III disease was 55%, which is
higher than the reported rate of 40%.5 Because of the
relatively small number of patients in our study (63
patients vs. 520 patients), this difference is not statistically significant. In our study, the survival advantage
was seen in the asymptomatic recurrence over the
2257
symptomatic recurrence. The same advantage also
was seen in patients with locoregional recurrence over
distant recurrence. This may be accounted for in part
by aggressive combined surgery and neoadjuvant and
adjuvant therapy, as reported previously by us.21
The majority of melanoma recurrences in our
study occurred by the end of the third year of follow-up. Ideally, follow-up visits would be frequent
in the first 3 years to facilitate early detection of
recurrence. However, because the numbers of patients who require follow-up are increasing, it is
important to find a compromise between the need
for early detection of recurrences and the resources
available to detect them. Accordingly, follow-up
based on the risk of recurrence for individual patients, as estimated by their stage specific hazard
functions, is discernible. We estimate that these are
roughly at a ratio of 1:2:6 for patients with Stage I, II,
and III disease, respectively. Over the course of this
series, the hazard rate for Stage I patients did not
change substantially; therefore, we recommend only
annual follow-up for such patients. Stage II patients
have twice the risk of recurrence for the first 2 years;
therefore, twice yearly follow-up visits for the first 2
years and annual follow-up after that is recommended. Stage III patients have an initial hazard
rate 4 – 6 times greater than that of Stage I patients,
and we recommend examination of these patients at
3-month intervals for the first year. The estimated
hazard rate for Stage III patients then decreases
quickly, and our recommendation for their subsequent follow-up is every 4 months for the second
year and every 6 months thereafter up to 5 years.
Each scheduled visit should include a complete review of systems, physical examination, complete
blood count, and liver function tests. Chest X-rays
should be performed annually. These guidelines for
testing are relatively simple and inexpensive. Chest
X-rays will detect the commonest site of visceral
disease, and the LDH level is often a sensitive
marker for tumor burden. Abnormalities in the complete blood count and liver function tests indicate a
need for more sophisticated testing. A similar strategy was recommended independently in a recent
review.22 Patients with second primary melanomas
should be continued on the surveillance schedule in
accordance with their highest stage of invasive melanoma.
Because of the extremely high risk of recurrence,
all patients with Stage III disease should be encouraged to participate in adjuvant therapy trials. All adjuvant trials have a requirement of baseline body CT
scans for complete staging examination. Follow-up CT
scans often are performed in 3– 6 months if there are
abnormal findings.
2258
CANCER December 1, 1999 / Volume 86 / Number 11
TABLE 5
Recommended Follow-Up Schedule for Patients with Stage I–III
Melanoma
6.
7.
Month
Stage I
Stage II
Stage III
3
6
9
12
16
18
20
24
30
36
42
48
54
60
Annually thereafter
—
—
—
X
—
—
—
X
—
X
—
X
—
X
X
—
X
—
X
—
X
—
X
—
X
—
X
—
X
X
X
X
X
X
X
—
X
X
X
X
X
X
X
X
X
8.
9.
10.
11.
12.
The importance of life-time follow-up for patients
with melanoma is a recognized practice in many melanoma centers.9,22,23 All patients should continue to
be examined by a physician annually, either a primary
care physician or a dermatologist, after the fifth year.
Our recommended surveillance schedule is
shown in Table 5. Based on the estimated hazard
rates, less frequent surveillance visits are needed. The
results of the current study strongly suggest that these
surveillance schedules and patient education programs complement each other; both have a place in
the early detection of disease recurrence in patients
with malignant melanoma. The effectiveness and benefit of these surveillance guidelines in the reduction of
overall disease-related mortality can be evaluated only
in large, prospective, randomized studies.
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