DOI: 10.1111/jdv.

13722 JEADV

ORIGINAL ARTICLE

Pregnancy and melanoma: a European-wide survey to

assess current management and a critical literature
overview
S. Ribero,1,2,*, C. Longo,3, E. Dika,4 C. Fortes,5 S. Pasquali,6 E. Nagore,7 D. Glass,1 C. Robert,8
A.M. Eggermont,8 A. Testori,9 P. Quaglino,2 P. Nathan,10 G. Argenziano,11 S. Puig,12 V. Bataille,13
Members of the Melanoma Group of the EORTC
1
Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK
2
Department of Medical Sciences, University of Turin, Turin, Italy
3
Dermatology and Skin Cancer Unit, Arcispedale Santa Maria Nuova IRCCS, Reggio Emilia, Italy
4
Dermatology Department, University of Bologna, Bologna, Italy
5
Clinical Epidemiology Unit, IDI-IRCSS-FLMM Rome, Rome, Italy
6
Surgical Oncology, Veneto Institute of Oncology IRCCS, Padova, Italy
7
Department of Dermatology, Instituto Valenciano de Oncolog
a, Valencia, Spain
8

rologie, Institut Gustave Roussy, Villejuif, France
Institut de Cance
9
European Institute of Oncology, Milan, Italy
10
Mount Vernon Cancer Center, Northwood, UK
11
Dermatology Department, Federico II University of Naples, Naples, Italy
12
Melanoma Unit, Dermatology Department Hospital Clinic and University of Barcelona, CIBER de Enfermedades Raras, Barcelona,
Spain
13
Dermatology Department, West Herts NHS Trust, Herts, UK
*Correspondence: S. Ribero. E-mail: simone.ribero@unito.it

Abstract
Background Management of melanoma during pregnancy can be extremely challenging. The reported incidence of
melanoma in pregnancy ranges from 2.8 to 5.0 per 100 000 pregnancies. There are no guidelines for the management of
melanoma during pregnancy.
Methods The survey was designed to investigate the opinions of melanoma physicians on decision making in relation
to pregnancy and melanoma. A clinical scenario-based survey on management of pregnancy in melanoma was dis-
tributed all over Europe via the membership of the EORTC and other European melanoma societies.
Results A total of 290 questionnaires were returned with a larger participation from southern Europe. A large hetero-
geneity was found for the answers given in the different clinical scenarios with 50% of the answers showing discordance,
especially regarding sentinel lymph node biopsy during pregnancy. Discordant answers were also found for the coun-
selling of women about a potential delay in getting pregnant after a high-risk melanoma (35% for a 2 year wait minimum
vs. 57% no waiting needed), while for thin melanomas, as expected, there was more concordance with 70% of the
physicians recommending no delay. Fifteen per cent of physicians recommended an abortion in stage II melanoma dur-
ing the third month of pregnancy. Twenty per cent of the responders advised against hormonal replacement therapy in
melanoma patients.
Conclusions The management of melanoma during pregnancy varies widely in Europe. At present, there is a lack of
consensus in Europe, which may lead to very important decisions in women with melanoma, and guidelines are needed.
Received: 16 October 2015; Accepted: 18 January 2016

Conicts of interest
None declared.

Funding sources
None declared.

Both authors contributed equally.

JEADV 2017, 31, 6569 2016 European Academy of Dermatology and Venereology
66 Ribero et al.

Background Table 1 Absolute and relative frequencies of the results of the

The effects of pregnancy and hormones on melanoma prognosis questionnaire according to ve different scenarios
are still a matter of debate.1 The reason why melanoma may be Answer A Answer B Answer C Missing
relevant in pregnant women is because it is the most common Scenario 1 102 (35%) 20 (7%) 168 (59%) 0
malignancy encountered during pregnancy, accounting for 31% Scenario 2 67 (23%) 14 (5%) 204 (72%) 5
of all primary malignancies in pregnant women.24 The reported Scenario 3 222 (78%) 64 (22%) NA 4
incidence of melanoma in pregnancy ranges from 2.8 to 5.0 per Scenario 4 114 (40%) 107 (38%) 62 (22%) 7
100 000 pregnancies.5 Despite this figure, there is no consensus Scenario 5 39 (13%) 250 (87%) NA 1
regarding treatment of melanoma during pregnancy.6,7 Scenario 1
It has been hypothesized that hormones and growth factors A 37-year-old lady with a melanoma of 3.5 mm in thickness is seen for fol
during pregnancy might influence melanoma development or low-up 6 months after her diagnosis. She is asking you whether it is safe
for her to get pregnant within the next 2 years. She is worried as she is
recurrence and thus possibly worsening its prognosis.8 Recently, afraid that if she delays her pregnancy plans it may affect her fertility as
two large epidemiological cohort studies have been published: she is nearing 40. What do you advise her?
one study from the UK reported a significantly increased risk of A: You advise her to wait 2 years as the risk of recurrence is highest in the
melanoma after childbirth, while another study from Sweden rst 2 years.
did not support these findings.9,10 In the review of Lens et al.,11 B: You advise her to wait 5 years.
it is showed that hormones do not contribute to an increased C: You tell her that she can get pregnant but that this may cause some dif
risk of melanoma and that melanoma prognosis does not appear culties if there is a relapse during the pregnancy in terms of treatment and
to be affected by pregnancy. minimal risk for the fetus.
Herein, we aim to report on the advice given to pregnant Scenario 2
patients with melanoma based on a clinical-based survey among A 30-year-old lady wishes to get pregnant 3 months after the diagnosis of
melanoma clinicians in Europe. a 1 mm melanoma. She is asking your advice. What do you tell her?
A: You tell her to wait 2 years.
Materials and methods B: You tell her to wait 5 years.
A survey was sent between January 2015 and July 2015 by e-mail C: You tell her that she can get pregnant whenever as the risk of relapse is
to melanoma physicians via the European Organization of very small.
Research and Treatment of Cancer (EORTC) membership and Scenario 3
A 55-year-old lady who has had a melanoma of 1.5 mm excised 1 year
other European societies.
ago has had hot ushes and suffers from osteoporosis and has been
advised to go on HRT. What do you tell her?
Questionnaire A: You tell her that HRT has not been shown to be associated with an
The questionnaire was designed to cover common scenarios increased risk of relapse and she is free to try it if she wishes.
relating to pregnancy and melanoma. Basic information was col- B: You advise her to avoid HRT.
lected on the responders regarding the country of practice, sex, Scenario 4
seniority (academic/consultant/senior trainee), specialty, type of A 35-year-old lady is diagnosed with a melanoma of 2.5 mm during her
practice (teaching hospital, district general hospital or private) sixth month of pregnancy. What do you tell her?

and numbers of melanomas seen per month. The survey was first
piloted in 20 senior melanoma specialists from dermatology,
surgery and oncology departments. The aim of this pilot was to
make sure the scenarios were applicable for most melanoma
clinics. The identity of the responders remained anonymous to
authors throughout the study. The questionnaires were sent back
by e-mail and returned back to the principal investigator (VB)
who separated the questionnaire from the e-mail as soon as it
was received, so no link could be made between the question-
naire and the individual responder. The different scenarios are
listed in Table 1.
Statistical analyses
Pearsons chi-squared test and Students t test were performed
to compare categorical and continuous variables respectively.
KruskalWallis tests were used to analyse the differences between
medians in non-parametric analyses. All statistical tests were two
A: You tell her that wide excision and sentinel node biopsy should be
immediately performed.
B: You tell her that wide excision should be immediately performed and
sentinel node biopsy postponed after delivery.
C: You tell her that wide excision should be immediately performed and
sentinel node biopsy avoided and too late to be performed after delivery.
Scenario 5
A 32-year-old lady is diagnosed with a melanoma of 4 mm during her third
month of pregnancy. What do you tell her?
A: You tell her that therapeutic abortion should be performed because of
the risk of motherfetal transmission of the disease.
B: You tell her that the risk of motherfetal transmission of the disease is
such a rare event that the pregnancy can continue.
sided and p 0.05 were considered significant. The analyses
were performed in STATA 12 (StataCorp LP, College Station,
TX, USA).

JEADV 2017, 31, 6569 2016 European Academy of Dermatology and Venereology
Survey on the management of pregnancy in melanoma patients
Results
A total of 290 melanoma physicians (89% response rate) from
18 different European countries completed the survey. We split
Europe in southern countries (Spain, Italy, Serbia, Turkey,
Greece, Portugal and France) and northern countries (UK, Ger-
many, Ukraine, Poland, Denmark, Belgium, Finland, Checz
Republic, Switzerland, Netherlands and Austria). A total of 239
questionnaires came from southern Europe and 51 from the
northern countries. The survey report is listed in Table 1. Forty-
eight per cent of the responders were women. The majority of
responders worked in teaching hospital (44%), 38% in private
practice and the remaining in district general hospitals. The
mean number of melanoma patients seen per month was
15  30. The majority of the responders were dermatologists
(80%), followed by surgeons (12%) and oncologists (8%).
Forty-two per cent of physicians reported seeing melanoma
patients in stages III and IV, while 68% only saw melanoma
patients in stage I or II.
The first scenario covered recommendation regarding waiting
time for a future pregnancy following a diagnosis of melanoma
of 3.5 mm in thickness. Sixty per cent of the responders do not
recommend any specific waiting time, 35% of the physicians
suggested waiting for 2 years for a further pregnancy and 7% a
wait of 5 years. No differences in the answers were found
according to different specialties.
Another similar scenario described a young woman with a
1-mm thick melanoma and 70% of the responders recom-
mended no waiting for a further pregnancy, while 5% still rec-
ommended to wait for 5 years. There were no differences seen
for the answers given according to age, sex and specialty among
responders.
The third scenario covered possible use of hormone replace-
ment therapy (HRT) in a 55-year-old patient with a melanoma of
1.5 mm in thickness removed 1 year previously and who suffered
from menopausal symptoms. Twenty-two per cent were against
the use of HRT and 94% of them came from southern Europe.
There were no differences according to sex, age, number of cases
seen each month and specialty regarding the advice given, while
38% of those opposed to HRT worked in private practice.
The fourth scenario covered the issue of sentinel lymph node
biopsy (SLNB) after a recent melanoma diagnosis of 2.5 mm in
thickness during pregnancy. Eighty per cent of the physicians
recommended a SLN biopsy. However, almost half of those
(37%) would perform it after the delivery but would, in that
case, perform the wide local excision immediately. Sixty-two per
cent of the surgeons surveyed recommended the SLN biopsy
immediately against 40% in the dermatology group (P = 0.016).
No differences were found according to hospitals, sex or age. No
differences were found in the number of melanoma cases treated
according to the answers provided.
The fifth scenario assessed the issue of a potential abortion for
a pregnant woman recently diagnosed with a thick melanoma
JEADV 2017, 31, 6569
67
(4 mm). Eighty-six per cent of the responders did not recom-
mend abortion, while the remaining 14% supported it. Almost
10% of the responders (9.6% in support and 11.1% opposed,
P = ns) stated that their advice was influenced by personal views
on abortion. The seniority seemed to influence the advice given
as 67% of trainees (only senior trainee dermatologists looking
after melanoma patients were included) did not recommend an
abortion against 88% at consultant level and 91% for academic
consultant (P = 0.02). The majority of those supporting an
abortion were females (18% females vs. 9% males). Age, spe-
cialty and type of hospital were not associated with the answer
given. However, there was a significant north/south gradient: the
majority of physicians supporting an abortion (92%) came from
southern Europe (P = 0.07).
Discussion
This European-wide survey investigated melanoma management
in pregnancy. In all, 290 physicians took part in the survey and
most of them were dermatologists from 18 European countries.
A possible limitation of the study is the higher prevalence of der-
matologists and the over-representation of southern European
countries. However, in most European countries, melanoma is
managed by dermatologists in stages III so this may explain the
low number of oncologists and surgeons in this survey.
The two major issues regarding melanoma in pregnant
patients are related to the management of the disease during
pregnancy and the counselling of woman with a melanoma diag-
nosis who would like to get pregnant. Hormones during preg-
nancy are able to affect melanocytes and pigmentation as many
women do report a change in the pigmentation and size of their
naevi.1214 The criteria for removing a suspicious naevus in preg-
nant patients should be the same as for non-pregnant patients
and the pregnancy should not delay the removal of suspicious
melanocytic lesions.
In fact, there is no evidence that pregnancy per se affects mela-
noma risk or that being pregnant affects the risk of melanoma
recurrence.11 Similarly, there is no evidence that HRT does affect
melanoma risk or its prognosis.15
Up to 15% of patients with localized melanoma (stages III)
may experience recurrence16 and approximately 50% of these
recurrences occur within 3 years.17,18 If recurrences appear dur-
ing pregnancy, this will generate significant medical and emo-
tional issues, potentially altering imaging and treatment.19
Delay of further pregnancy after a melanoma diagnosis varies
from case to case depending on melanoma stage, the wish of the
mother, the age of the mother and as to whether they already
have a family. Time delay for further pregnancies after a
melanoma diagnosis ranged between 0 and 5 years in published
studies.18 For example, a 40-year-old woman with a melanoma
of 0.3-mm thickness would not be advised to wait if she wanted
to become pregnant considering a risk of 1% to 3% of 5-year
recurrence. In contrast, a 21-year-old woman with a 4.0-mm
2016 European Academy of Dermatology and Venereology
68
melanoma would be advised to wait for 35 years (period
with the greatest risk of recurrence). This survey shows that
there was quite a lot of discordance in the two scenarios covering
the issue of future pregnancy both in thin and thick melanoma
scenario.
SLNB
SLNB is a staging procedure able to stratify patients in different
prognostic categories.20,21
As SLNB is a staging procedure, the debate as to whether
performing this procedure during pregnancy is still open.17,18,22
The issue that produced the largest heterogeneity was concern-
ing advice. Seventy-eight per cent of the responders were for
the procedure, while 22% were against. Almost half of the
physicians in favour of SLN recommended performing it after
the pregnancy, while the other half during the pregnancy.
Moreover, the type of hospital where the responder worked
(private/district hospital/university hospital) did not influence
the answer, suggesting that even in tertiary centres, where SLNB
is routinely performed, physicians are not really sure of the
advice to be given for SLNB during pregnancy. However, sur-
geons were more likely to recommend SNB during pregnancy.
SLNB after a long delay in months when the wide local exci-
sion has already been performed could affect the lymphatic drai-
nage on the primary site and increase the potential false negative
results. However, despite theoretically limitations, it has been
reported that its accuracy may not be damaged by WLE.22
These issues should be discussed openly with women being
offered SLNB during or after the pregnancy. Physicians should
also discuss risks and benefits of a positive result, as the morbid-
ity of lymphadenectomy shortly after delivering a baby needs to
be addressed.23
It is well known that the risk of radiation exposure to the
fetus associated with the SLNB is minimal,24,25 and staging
with magnetic resonance imaging (MRI)26 or ultrasound can
be used during pregnancy in advanced melanoma.27 Further-
more, local anaesthesia is preferred over general anaesthesia if
possible.28
Melanoma prognosis during pregnancy
When matched for tumour thickness and stage, multiple studies
have shown no differences in overall melanoma survival in preg-
nant women compared to non-pregnant women.29,30
Despite this evidence, we found that 13% of physicians still
advised that the risk of maternalfetal transmission was signifi-
cant and suggested an abortion in stage II melanoma.
Guidelines on this specific clinical presentation are therefore
needed as in many cases abortion may be avoided. A wide
heterogeneity in counselling is seen regarding melanoma and
further pregnancies or abortion reflecting a clear lack of consen-
sus. Studies may be needed to look at the risk of recurrence in
women having a baby within 5 years of diagnosis.
JEADV 2017, 31, 6569
Ribero et al.
Conclusions
This survey showed a disparity in the management of melanoma
during or after pregnancy. The biggest discordance was for the
use of SLNB.
A consensus document is needed in order to assist clinicians
in making decisions about treating women of child-bearing age.
Acknowledgements
The authors are thankful to all clinicians who took part in this
survey.
Author contributions
Dr(s) had full access to all of the data in the study and take
responsibility for the integrity of the data and the accuracy of
the data analysis. Ribero, Bataille, Puig, Robert, Eggermont and
Testori contributed to the study concept and design. Ribero,
Bataille, Longo, Fortes, Dika, Pasquali, Nagore, Glass, Quaglino,
Nathan and de Schaetzen contributed to the acquisition, analysis
and interpretation of the data. Ribero, Longo and Bataille
drafted the manuscript. Critical revision of the manuscript for
important intellectual content was carried out by Argenziano,
Bataille, Eggermont, Robert and Testori. Ribero did the statisti-
cal analysis. Study supervision was performed by Bataille,
Robert, Eggermont, Testori and Nathan.
References
1 Tsao H, Atkins MB, Sober AJ. Management of cutaneous melanoma.
N Engl J Med 2004; 351: 9981012.
2 Lens M, Rosdahl I, Newton-Bishop J. Cutaneous melanoma during preg-
nancy: is the controversy over? J Clin Oncol 2009; 27: e11e12; authors
reply e134.
3 Bannister-Tyrrell M, Roberts CL, Hasovits C et al. Incidence and out-
comes of pregnancy-associated melanoma in New South Wales 1994-
2008. Aust N Z J Obstet Gynaecol, 2015; 55: 116122.
4 Lee Y, Roberts C, Dobbins T et al. Incidence and outcomes of preg-
nancy-associated cancer in Australia, 19942008: a population-based
linkage study. BJOG 2012; 119: 15721582.
5 Dillman RO, Vandermolen LA, Barth NM et al. Malignant melanoma
and pregnancy ten questions. West J Med 1996; 164: 156161.
6 Byrom L, Olsen CM, Knight L et al. Increased mortality for pregnancy-
associated melanoma: systematic review and meta-analysis. J Eur Acad
Dermatol Venereol 2015; 29: 14571466.
7 Kyrgidis A, Argenziano G, Moscarella E et al. Increased mortality for
pregnancy-associated melanoma: different outcomes pooled together,
selection and publication biases. J Eur Acad Dermatol Venereol 2015.
DOI: 10.1111/jdv.13202.
8 Johnston SR, Broadley K, Henson G, Fisher C, Henk M, Gore ME. Man-
agement of metastatic melanoma during pregnancy. BMJ 1998; 316: 848
849.
9 Moller H, Purushotham A, Linklater KM et al. Recent childbirth is an
adverse prognostic factor in breast cancer and melanoma, but not in
Hodgkin lymphoma. Eur J Cancer 2013; 49: 36863693.
10 Johansson AL, Andersson TM, Plym A et al. Mortality in women with
pregnancy-associated malignant melanoma. J Am Acad Dermatol 2014;
71: 10931101.
11 Lens M, Bataille V. Melanoma in relation to reproductive and hormonal
factors in women: current review on controversial issues. Cancer Causes
Control 2008; 19: 437442.
2016 European Academy of Dermatology and Venereology
Survey on the management of pregnancy in melanoma patients
12 Lecavalier MA, From L, Gaid N. Absence of estrogen receptors in dysplas-
tic nevi and malignant melanoma. J Am Acad Dermatol, 1990; 23:
242246.
13 Akturk AS, Bilen N, Bayramg urler D et al. Dermoscopy is a suitable
method for the observation of the pregnancy-related changes in melano-
cytic nevi. J Eur Acad Dermatol Venereol 2007; 21: 10861090.
14 Foucar E, Bentley TJ, Laube DW et al. A histopathologic evaluation
of nevocellular nevi in pregnancy. Arch Dermatol, 1985; 121:
350354.
15 Durvasula R, Ahmed SM, Vashisht A et al. Hormone replacement therapy
and malignant melanoma: to prescribe or not to prescribe? Climacteric
2002; 5: 197200.
16 Soong SJ, Harrison RA, McCarthy WH et al. Factors affecting survival
following local, regional, or distant recurrence from localized melanoma.
J Surg Oncol 1998; 67: 228233.
17 Osella-Abate S, Ribero S, Sanlorenzo M et al. Risk factors related to late
metastases in 1372 melanoma patients disease free more than 10 years.
Int J Cancer 2015; 15: 136.
18 Schwartz JL, Mozurkewich EL, Jonhson TM. Current management of
patients with melanoma who are pregnant, want to get pregnant, or do
not want to get pregnant. Cancer 2003; 97: 21302133.
19 Altman JF, Lowe L, Redman B et al. Placental metastasis of maternal mel-
anoma. J Am Acad Dermatol 2003; 49: 11501154.
20 Morton DL, Thompson JF, Cochran AJ et al. ; MSLT Group. Sen-
tinel-node biopsy or nodal observation in melanoma. N Engl J Med
2006; 355: 13071317. Erratum in: N Engl J Med. 2006; 355(18):
1944.
JEADV 2017, 31, 6569
69
21 Ribero S, Osella-Abate S, Sanlorenzo M et al. Sentinel lymph node biopsy
in thick-melanoma patients (N = 350): What is its prognostic role? Ann
Surg Oncol 2015; 22: 19671973.
22 Gannon CJ, Rousseau DL Jr, Ross MI et al. Accuracy of lymphatic map-
ping and sentinel lymph node biopsy after previous wide local excision in
patients with primary melanoma. Cancer 2006; 107: 26472652.
23 McMasters KM, Reintgen DS, Ross MI et al. Sentinel lymph node biopsy
for melanoma: controversy despite widespread agreement. J Clin Oncol
2001; 19: 28512855.
24 Keleher A, Wendt R III, Delpassand E et al. The safety of lymphatic map-
ping in pregnant breast cancer patients using Tc-99 m sulfur colloid.
Breast J 2004; 10: 492495.
25 Mondi MM, Cuenca RE, Ollila DW et al. Sentinel lymph node biopsy
during pregnancy: initial clinical experience. Ann Surg Oncol 2007; 14:
218221.
26 Zwinkels H, Dorr J, Kloet F, et al. Pregnancy in women with gliomas: a
case-series and review of the literature. J Neurooncol. 2013; 115: 293301.
27 Nicklas AH, Baker ME. Imaging strategies in the pregnant cancer patient.
Semin Oncol 2000; 27: 623632.
28 Gerstenfeld TS, Chang DT, Pliego AR et al. Nonobstetrical abdominal
surgery during pregnancy in Womens Hospital. J Matern Fetal Med 2000;
9: 170172.
29 OMeara AT, Cress R, Xing G et al. Malignant melanoma in pregnancy.
A population-based evaluation. Cancer 2005; 103: 12171226.
30 Alexander A, Samlowski WE, Grossman D et al. Metastatic melanoma in
pregnancy: risk of transplacental metastases in the infant. J Clin Oncol
2003; 21: 21792186.
2016 European Academy of Dermatology and Venereology