Second primary melanomas in a cohort

of 977 melanoma patients within the

first 5 years of monitoring
Aimilios Lallas, MD, PhD, MSc,a Zoe Apalla, PhD,b Athanassios Kyrgidis, PhD,c
Chryssoula Papageorgiou, MD,a Ioannis Boukovinas, MD,d Mattheos Bobos, PhD,e
George Efthimiopoulos, MD,f Christina Nikolaidou, MD,g Andreas Moutsoudis, MD,a
Theodosia Gkentsidi, MD,a Konstantinos Lallas, MD,a Elizabeth Lazaridou, PhD,h Elena Sotiriou, PhD,a
Efstratios Vakirlis, PhD,a and Dimitrios Ioannides, PhDa
Thessaloniki, Greece

Background: In retrospective studies, a second primary melanoma (SPM) develops in 2%-20% of

melanoma patients. Scarce evidence exists on the usefulness of total-body photography (TBP) and digital
dermatoscopic documentation (DDD) for detecting SPMs.

Objective: The primary aim was to quantify the risk and investigate the time of occurrence of SPMs.
Secondary aims were to identify risk factors for SPM and to assess the usefulness of TBP and DDD for SPM
detection.

Methods: This prospective cohort included patients with recently diagnosed melanoma that underwent
sequential clinical and dermatoscopic examinations for up to 5 years. Life table analysis and Kaplan-Meier
survival analysis were performed. Multivariate Cox models were constructed to identify factors affecting the
outcome.

Results: An SPM developed in 46 of 977 (4.7%) patients. Life table analysis revealed a 5-year cumulative
risk of 8.0% for SPM. High nevus count, fair phototype, and occupational sun exposure were potent
predictors of SPM. Of all new melanomas, 17.3% were diagnosed by clinical and dermatoscopic
examination, 48.1% by TBP, and 34.6% by DDD.

Limitations: All patients followed the same protocol and diagnostic bias associated with sequential
dermatoscopic imaging.

Conclusion: In this cohort, melanoma patients were at 8% risk of an SPM developing within 5 years. TBP
and DDD significantly contributed to the early detection of SPM. ( J Am Acad Dermatol 2020;82:398-406.)

Key words: dermoscopy; digital dermoscopy; melanoma; nevus count; phototype; risk factors; second
primary melanoma; total-body photography.

stage.1,2 Subsequently, melanoma patients enter a

M elanoma management includes excision of

the primary tumor and additional proced-
ures that are determined according to the
follow-up period of clinical, imaging, and laboratory
examinations, depending on their stage. Protocols

From the First Department of Dermatology,a Department of
Clinical Pharmacology,c and Second Department of Dermato-
logy,h Aristotle University; State Clinic of Dermatology, Hospital
for Skin and Venereal Diseasesb; Oncology Unit, Bioclinic of
Thessalonikid; Microdiagnostics Pathology Laboratorye; Depart-
ment of Surgical Oncology, Theageneio Anticancer Hospitalf;
Department of Histopathology, Hippokration General Hospital,
Thessaloniki, Greece.g
Dr Lallas and Dr Apalla contributed equally to the preparation of
this manuscript.
Funding sources: None.
Conflicts of interest: None disclosed.
Accepted for publication August 28, 2019.
Reprints not available from the authors.
Correspondence to: Aimilios Lallas, MD, MSc, PhD, First
Department of Dermatology, Aristotle University, 124 Delfon
St, 54643, Thessaloniki, Greece. E-mail: emlallas@gmail.com.
Published online September 6, 2019.
0190-9622/$36.00
Ó 2019 by the American Academy of Dermatology, Inc.
https://doi.org/10.1016/j.jaad.2019.08.074

398
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VOLUME 82, NUMBER 2

for monitoring melanoma patients vary among was waived because the study did not affect the
different centers.3-6 routine diagnosis or therapeutic treatment of patients
The benefit of clinical periodic controls in mela- and was based on secondary analysis of suitably
noma patients is dual: they provide the earliest anonymized data sets.
possible detection of locoregional recurrence and Patients with a recently diagnosed primary cuta-
the earliest possible diagnosis of a second primary neous melanoma of any stage were enrolled after
melanoma (SPM), which develops in a proportion of having completed the treatment and staging proced-
patients.7 In the literature, ure. At baseline, several fac-
SPMs develop in 2%-20% of tors associated with the index
melanoma patients.8-16 CAPSULE SUMMARY melanoma and patient’s char-
Total-body photography acteristics were assessed and
(TBP) and sequential digital d
The risk of second primary melanoma recorded. These factors
dermatoscopic documenta- has only been assessed in retrospective included sex, age, reaction
tion (DDD) are indicated for studies. Our time-to-event analysis to sun exposure according
patients at high risk of devel- revealed a 5-year cumulative risk of 8.0% to the Fitzpatrick phototype
oping melanoma.17-26 Both for second primary melanoma. classification (I-V), familial
techniques improve the diag- Individuals with a high nevus count, fair melanoma history, skin color
nostic performance of clini- phototype, and history of occupational (fair, medium, or dark), eye
cians for melanoma exposure are at higher risk. Most color (blue; gray, green, or
diagnosis in terms of sensi- melanomas were diagnosed by total- hazel; or brown), hair color at
tivity and specificity.20 The body photography or by sequential young age (blond or red,
number needed to excise dermatoscopic imaging. The number brown or red-brown, or
(NNE), which reflects the needed to excise was 1:1.3. black or dark brown), pres-
ratio of malignant-to-benign d
Patients with a history of melanoma are ence of [50 freckles, history
excised lesions, significantly at high risk of developing a second of occupational sun expo-
improves when sequential primary melanoma and should be closely sure, total absolute nevus
imaging is used.17,18,22,24 It monitored with the use of total-body count (continuous variable),
has also been demonstrated photography and digital dermatoscopic assessed by TBP and DDD,
that most melanomas diag- imaging. location, Breslow thickness
nosed by TBP and DDD are and stage of index mela-
either in situ or early inva- noma, (using the 7th edition
sive.25,26 Although the pre- of the American Joint
cise indications for TBP and DDD are not based on Committee on Cancer staging system for patients
robust evidence, both methods are considered very enrolled until December 31, 2017 and the 8th edition
useful for the surveillance of at least 2 groups of for those enrolled after January 1, 2018), and use of
individuals: patients with melanoma history, which systemic agents for metastatic melanoma. After the
carry the highest risk for a new melanoma, and baseline visit, patients were scheduled for follow-up
individuals with multiple atypical nevi.27 according to the standard protocol of our institution.
The primary aim of the present study was to The time interval between follow-up visits was
investigate the prospective risk of SPM in a cohort of 4 months, except for patients with history of mela-
melanoma patients. Secondary aims were to inves- noma in situ, who were visited every 6 months. TBP
tigate risk factors for SPM and to assess the usefulness and DDD were repeated at all follow-up visits and
of TBP and DDD in SPM detection. were performed with the use of a commercially
available digital device that includes a standardized
MATERIALS AND METHODS protocol for capturing clinical images. All the images
This was a prospective observational study of a (clinical and dermatoscopic) were captured and
cohort of patients with melanoma history followed evaluated by clinicians specialized in skin cancer
up with TBP and DDD. The study was conducted in a diagnosis and management. All pigmented lesions
tertiary hospital that is a referral center for melanoma [2 mm in diameter were dermatoscopically docu-
patients in Northern Greece. Enrollment started on mented, with the exception of those that could be
January 1, 2013, and follow-up of patients was safely diagnosed as seborrheic keratosis, solar
ongoing as of the publication of this report. The lentigo, or dermatofibroma. The dermatoscopic
current analysis was conducted on September 2018 evaluation was based on the standardized
and included all patients enrolled during the study melanoma-specific structures plus recently described
period up to then. The ethics committee approval dermatoscopic predictors of melanoma in situ.28,29
400 Lallas et al
Abbreviations used:
CI: confidence interval
DDD: digital dermatoscopic documentation
NNE: number needed to excise
SPM: second primary melanoma
TBP: total-body photography
The primary endpoint of the current analysis was
to calculate the annual and cumulative risk of SPM
within 5 years from the diagnosis of the index
melanoma. Secondary endpoints were to identify
predictors of SPM associated with either the patient’s
phenotype or characteristics of the index melanoma
and to assess the usefulness of TBP and DDD for SPM
detection.
Statistical analysis
Pearson x2 test was used for different exposure
group comparisons. Life table analysis and Kaplan-
Meier survival analysis were performed. The log rank
test was used for survival time comparisons.
Multivariate Cox proportional hazards regression
model was used to assess the effects of covariates
on the length of the interval. Multivariate Cox models
were constructed to determine which factors inde-
pendently affect the outcome. Various models were
compared by the likelihood ratio test. Alpha level
was set at 0.05, while an alpha level of 0.10 was used
as the cutoff for variable removal in the automated
model selection for multivariate regression.
Statistical analyses were performed using the IBM
SPSS 23.0 package (Armonk, NY).
RESULTS
Epidemiologic data and characteristics of
index melanomas
The cohort consisted of 977 melanoma patients
who visited our department during this study, from
the first follow-up visit of the study to the time of this
analysis. Patients’ data and the characteristics of their
index melanoma are shown in Table I. The mean
age 6 standard deviation (SD) at baseline was
54.69 6 15.05 years (range 15-89 years), and the
male-to-female ratio was 1.1:1. At the baseline visit,
the mean time from index melanoma diagnosis was
1.6 months, ranging 1-4 months. The index mela-
noma was invasive in 756 patients (77.4%) and in situ
in 220 (22.6%). The mean Breslow thickness 6 SD of
invasive melanomas was 1.92 6 1.55 mm (range 0.2-
9.0 mm). The stage of the index melanoma at
baseline was 0 in 220 patients (22.6%), IA in 143
patients (14.6%), IB in 182 patients (18.6%), IIA in 79
patients (8.1%), IIB in 76 patients (7.8%), IIC in 45
J AM ACAD DERMATOL
FEBRUARY 2020
patients (4.6%), III in 113 patients (11.6%), and IV in
119 patients (12.2%). The mean nevus count 6 SD
was 32.6 6 9.5 (range 1-149). Concerning screening
before the diagnosis of the index melanoma, 13.4%
of patients reported sequential visits yearly or every
2 years, and 29.9% reported occasional visits.
Patients’ enrollment by year, total follow-up
period, and survival
The study participants’ flow is shown in Table II.
Within the last year (2018), 143 patients had been
enrolled up to the moment that the current analysis
was conducted. At the time of the analysis, 807 of 977
patients (82.6%) had completed 1 year of follow-up
(those enrolled during 2013-2016 and part of those
enrolled in 2017), 560 (57.3%) had completed 2 years
(those enrolled during 2013-2015 and part of those
enrolled in 2016), 349 (35.7%) had completed 3 years
(those enrolled in 2013 and 2014 and part of those
enrolled in 2015), 172 (17.6%) had completed 4 years
(those enrolled in 2013 and part of those enrolled in
2014), and 114 (11.7%) had completed 5 years of
follow-up (part of those enrolled in 2013). Finally,
131 (13.4%) study participants were within their first
year of follow-up. Of the remaining patients, 185
(18.9%) had died, and 51 (5.2%) were lost during
follow-up. Of the 185 deaths, 145 were associated
with melanoma and 40 with other comorbidities. The
median overall survival of patients in our cohort at
the time of the current analysis was 51 (95% confi-
dence interval [CI] 47.7-54.2) months. During the
study period, 102 patients received systemic treat-
ment for advanced disease. Of these, 29 (28.4%)
received targeted therapy, 14 (13.7%) targeted ther-
apy and subsequent immunotherapy, 51 (50.0%)
immunotherapy, and 8 (7.8%) other treatments.
Occurrence and characteristics of new
primary melanomas
Overall, SPM developed in 46 of 977 patients
(4.7%). Of these 46, a third primary melanoma
developed in 4 patients and a fourth in 2 patients
within the study period, resulting in a total of 52 new
primary melanomas in the cohort. Analytic data
concerning the time of appearance of SPMs are
shown in Table III. The annual risk for an SPM was
2.46% within the first year, 1.61% within the second
year, 1.43% within the third year, 1.43% within the
fourth year, and 1.17% within the fifth year of follow-
up. Life table analysis showed that the cumulative
proportion of patients who did not developed an
SPM in the 60-month period was 92.0%. Thus, the
risk of developing an SPM within the first 5 years was
8.0% (Fig 1).
J AM ACAD DERMATOL Lallas et al 401
VOLUME 82, NUMBER 2

Table I. Epidemiologic characteristics of enrolled Table I. Cont’d

patients (N = 977) and characteristics of the index Characteristic Value
primary melanomas
Screening visits before first melanoma
Characteristic Value diagnosis
Age, y, mean 6 SD 54.69 6 15.05 Information missing 311 (31.8)
Sex, n Annual or every 2 years 131 (13.4)
Male 520 Occasional 292 (29.9)
Female 457 Never 243 (24.9)
Previous melanoma type
In situ 220 (22.6) Values are n (%) unless indicated otherwise.
SD, Standard deviation; SLNB, sentinel lymph node biopsy.
Invasive 756 (77.4)
Previous melanoma stage
0 220 (22.6) The majority of new primary melanomas (35/52,
IA 143 (14.6) 67.3%) were in situ, and 17 (32.7%) were invasive.
IB 182 (18.6)
The mean Breslow thickness of invasive SPMs was
IIA 79 (8.1)
0.49 mm, ranging 0.2-0.9 mm. Of the 52 melanomas,
IIB 76 (7.8)
IIC 45 (4.6) 6 (11.5%) were nevus associated, and 46 (88.5%)
III 113 (11.6) developed de novo.
IV 119 (12.2)
SLNB status of previous melanoma Predictors of SPM
Not performed or unknown 407 (41.7) Our multivariate analysis revealed 3 potent pre-
Positive 120 (12.3) dictors of SPM: nevus count, phototype, and occu-
Negative 450 (46.0) pational sun exposure (Table IV). In detail, the
BRAF status of previous melanoma
hazard for developing an SPM was increased by 6%
Unknown 737 (75.4)
for each nevus added (hazard ratio 1.061, 95% CI
Mutated 101 (10.3)
Wild type 139 (14.3) 1.039-1.084; P \ .001). The hazard risk for an SPM
Family history or known predisposing was reduced by 50% per each phototype level, from I
mutations to IV. Finally, the history of occupational sun
Yes 85 (8.7) exposure posed a 35-fold increased risk for SPM.
No 892 (91.3) All hazards were adjusted for the effect of patients’
Fitzpatrick phototype sex and age, location and Breslow thickness of the
I 52 (5.3) index melanoma, skin color, eye color, hair color,
II 231 (23.7) and the presence of freckles. No other variable had a
III 412 (42.2) significant effect on the probability of SPM develop-
IV 225 (23.0)
ment in the multivariate analysis. Family history was
V 57 (5.8)
associated with a marginally nonsignificant higher
Skin color
Fair 184 (18.8) probability of SPM. Stage IV index melanomas and
Medium 575 (58.9) intake of systemic drugs were associated with a
Dark 218 (22.3) lower probability of an SPM in the univariate
Eye color analysis, but the effect was lost in the multivariate
Blue 181 (18.5) model. Annual screening visits before the diagnosis
Gray, green, or hazel 145 (14.8) of the first melanoma was associated with a lower
Brown 651 (66.7) Breslow thickness of the index melanoma but not the
Hair color SPM.
Blond-red 139 (14.2)
Brown-red or brown 342 (35.0)
Dark brown or black 496 (50.8)
Impact of TBP and DDD
Presence of [50 freckles Overall, 121 lesions were excised during the study
Yes 193 (19.7) period. Of these, 52 were histopathologically diag-
No 784 (80.3) nosed as melanoma, 67 as nevus, and 2 as seborrheic
History of occupational exposure keratosis, resulting in an NNE of 1:1.3. Of 52
Yes 258 (26.4) melanomas, 10 (19.2%) were diagnosed by clinical
No 719 (73.6) and dermatoscopic examination at baseline, and 25
Continued (48.1%) were new lesions, meaning that they were
402 Lallas et al J AM ACAD DERMATOL
FEBRUARY 2020

Table II. Enrollment and outflow of patients during study years

Enrollment year Follow-up period Enrolled Lost Died Active Second primary melanomas
2018 \12 months 143 4 8 131 4
2017 12-23 183 12 20 151 7
2016 24-35 174 8 30 136 9
2015 36-47 170 6 36 128 10
2014 48-59 145 11 43 91 10
2013 $60 162 10 48 114 12
Total 977 51 185 751 52

Table III. Time of occurrence of SPMs in cohort of
977 melanoma patients
Follow-up No. patients who Annual risk
period entered that year No. of SPMs of SPM, %
1st year 977 24 2.46
2nd year 807 13 1.61
3rd year 560 8 1.43
4th year 349 5 1.43
5th year 172 2 1.17
SPM, Second primary melanoma.
not present at baseline and appeared in the period
between the 2 sequential visits, as revealed by
sequential TBP (Figs 2 and 3). The mean time to
diagnosis for the 25 new lesions was 27 (95% CI
22.3-30.7) months. Finally, 17 (32.7%) melanomas
were present but not recognized at baseline and
were detected because of morphologic changes on
DDD. The melanomas of this group were monitored
for a mean 6 SD period of 6.81 6 3.98 months,
ranging 3-16 months. No melanoma required a
dermatoscopic follow-up longer than 16 months to
be detected. Of the 17 melanomas present but not
recognized at baseline, 4 were histopathologically
nevus associated, and we cannot conclude if the
lesion documented at baseline was only the
pre-existing nevus or if the melanoma had already
developed. Melanomas diagnosed by TBP or DDD
were more frequently in situ (73.8%) than those
diagnosed at baseline (73.8% vs 40%, P = .011). The
mean age of patients with melanomas diagnosed by
TBP (51.5 years) or DDD (49.8 years) was higher
than the age of those with melanoma diagnosed at
baseline (41.5 years, P = .134).
Dermatoscopic characteristics of new primary
melanomas
Dermatoscopically, 34 of 52 (65.4%) new mela-
nomas displayed a reticular global pattern, 10 a
globular pattern, and 4 a pseudonetwork, and 4
were structureless. Melanoma-specific criteria were
detected in 21 of 52 (40.4%) melanomas at the time of
excision. The remaining 31 melanomas did not
develop melanoma-specific criteria and were de-
tected either because they were new lesions or
because of changes on DDD.
DISCUSSION
The main finding of the present cohort study was
that 4.7% of melanoma patients had an SPM within a
period of 5 years, and the 5-year cumulative risk was
8.0%. This finding justifies the necessity of close
clinical and dermatoscopic monitoring of melanoma
patients at least for the first 5 years after diagnosis.
Our results also suggest a higher annual risk during
the first year (2.46%), which becomes lower in the
second (1.61%) and slightly and steadily decreases
the following 4 years down to 1.17% during the 5th
year of monitoring (Table III). However, the risk in
the first year might be falsely increased by SPMs
diagnosed at the first follow-up visit because we
cannot exclude that some of these melanomas might
have developed earlier. If the SPM diagnosed at the
first visit are not included, then the risk of the first
year becomes comparable to the annual risk seen in
subsequent years.
The reported percentage of melanoma patients
with SPMs in the literature varies significantly, and a
comparison of the different studies is limited by the
diversity of design and measures.8-16 The highest
incidence of SPM was reported by Siskin
and colleagues in Australia.8 In that study, the
investigators recontacted 1083 melanoma patients
and reported that in 20% of them an additional
primary melanoma developed. In studies conducted
in the United States, the reported percentage of
melanoma patients who have an SPM develop
ranges 7%-12%.9-14 Studies in European populations
show lower rates of SPM.15,16 Schuurman and
colleagues analyzed the Dutch cancer registry and
reported a 5-year cumulative risk of 3.7% and a
conditional cumulative risk for the years 5-10 of 4.6%
for SPM.14 The variable rates of SPM in the literature
J AM ACAD DERMATOL Lallas et al 403
VOLUME 82, NUMBER 2

Fig 1. Kaplan-Meier survival analysis. Months to development of second primary melanoma in

the cohort of 977 melanoma patients and number of individuals at risk at each study year. Cum,
Cumulative; NPM, new primary melanoma.

Table IV. Potent predictors of second primary

previous studies is difficult. Our reported risk for
melanoma after multivariate analysis in cohort of
SPM is higher than previous studies in Europe and is
977 melanoma patients after the first 5 years of
rather comparable to risk rates reported in the United
follow-up
States. This discrepancy might be partially explained
95.0% CL for HR by the differences between a population-based
Variable P Cox HR Lower Upper study and an institutional cohort study. It might
Nevus count \.001 1.061 1.039 1.084 also be attributed to the fact that our data was derived
Occupational \.001 35.164 6.550 188.770 from a prospective close surveillance of melanoma
exposure patients, which increased the possibility of detection
Phototype .010 0.505 0.300 0.851 of SPM and minimized the number of patients lost
(ordinal) during follow-up. Despite the different reported
Variables entered in the model were sex, age, location, Breslow
rates, all studies agree on a significant risk of SPM
depth, stage, nevus count, family history, freckles [50, skin color, in patients with melanoma history.8-16
eye color, hair color, phototype, and occupational exposure. In several of the studies mentioned, risk factors of
CL, Confidence limit; HR, hazard ratio. SPM were investigated.8,11,12,14 Overall, most of the
known melanoma risk factors have been suggested
might reflect epidemiologic differences in melanoma also as predictors of SPM, with the high total nevus
incidence among populations or might be attri- count assessed as the strongest predictor.8,14 This is
butable to significantly different study designs and in absolute agreement with our findings that suggest
measures. For the same reasons, a direct comparison a 6.0% increase of the risk for SPM for every added
of the rate of SPM found in our and those found in nevus. Fair skin type, inability to tan, and a fair
404 Lallas et al
Fig 2. Melanoma. The baseline visit (A) and a visit at 6 months (B). The small pigmented lesion
seen (circle) was not present at baseline. C, Dermatoscopy reveals globules suggestive of a
melanocytic tumor. The lesion was excised and diagnosed as melanoma with a Breslow
thickness of 0.3 mm.
complex have also been proposed as risk factors for
SPM.8,11,12,14 In our cohort, each phototype level
(from I to V) added a 50.0% risk for SPM. Finally, we
found occupational sun exposure to be associated
with a significantly higher risk of SPM, which is
consistent to a previous study.14 Although stratifying
melanoma patients according to their risk of an SPM
remains of great research interest, we suggest that all
melanoma patients should be closely monitored,
considering they all carry a significant risk for SPM.
Our study also highlights the usefulness of TBP
and sequential DDD as integral parts of follow-up
visits of patients with melanoma history. Of all new
melanomas, 67.3% were in situ, and the remaining
32.7% were thinner than 1 mm, suggesting a high
efficacy of the applied monitoring protocol in early
SPM diagnosis. Furthermore, the NNE for melanoma
diagnosis was 1:1.3, suggesting a high positive pre-
dictive value of the used diagnostic techniques. Of 52
SPMs, 48.1% were detected by TBP, which highlights
the high value of clinical photography in detecting
new lesions. The mean age of patients with SPMs
diagnosed by TBP was higher than the age of those
diagnosed at baseline or by DDD. This finding
suggests that the interpretation of a newly appearing
lesion largely depends on patient age, since the
J AM ACAD DERMATOL
FEBRUARY 2020
probability that a new lesion is a melanoma increases
with age and the probability of it being a nevus
decreases accordingly. Another 34.6% of SPMs were
diagnosed by sequential DDD. The latter finding
highlights that some melanomas are diagnosed only
by dermatoscopic changes during follow-up,
without developing melanoma-specific dermato-
scopic criteria. This observation has been previously
described and is considered to be the justification for
photographic documentation of large proportions of
each patient’s moles, even those that do not display
dermatoscopic atypia.30 Although our data suggest a
high efficacy of TBP and DDD in detecting SPM in
patients with melanoma history, this conclusion
cannot be extrapolated to other categories of in-
dividuals, such as those with multiple nevi. The
sensitivity and specificity of TBP and DDD in other
groups needs to be assessed in appropriately de-
signed studies and adjusted to the time cost.
In our cohort, the longest period required to
dermatoscopically monitor a featureless melanoma
in order to recognize it was 16 months. This finding is
reasonable, since a melanoma is very unlikely to
remain dermatoscopically stable for a very long
period. Although we cannot exclude that in a larger
cohort this time could be prolonged, the data from
J AM ACAD DERMATOL
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Fig 3. Melanoma. Baseline visit (A) and a visit at 4 months (B). A and C, A clinically and
dermatoscopically occult melanoma hidden among numerous nevi. C and D, The sequential
digital dermatoscopy reveals a significant growth of the lesion, which is highly suspicious for
such a short interval between visits. The tumor was excised and histopathologically diagnosed
as melanoma in situ.
the current cohort suggest that a lesion that remains
stable at DDD for a long period (16 or 24 months)
does not require further dermatoscopic documenta-
tion. This could reduce the time required for the
sequential visits and improve the applicability of the
monitoring strategy.
The main strength of our study was the prospec-
tive cohort design that allowed a time-to-event
analysis. The main limitation was that all included
patients followed the same monitoring protocol,
which did not allow for an assessment of the optimal
intervals between sequential visits. Another limita-
tion is associated with the possible diagnostic bias
induced by the use of sequential dermatoscopic
images, which could have forced pathologists to
diagnose in situ lesions (that might have been
otherwise classified as atypical or dysplastic nevi)
as melanomas.
In conclusion, our study revealed an 8.0% 5-year
risk of SPM in a cohort of melanoma patients. It also
highlighted that TBP and sequential DDD signifi-
cantly contribute in the early detection of SPM. Our
findings justify the need for close clinical and
dermatoscopic monitoring of melanoma patients.
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