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A pregnancy-associated melanoma (PAM) prognosis does not appear to be worse than melanoma in non-pregnant controls, researchers reported at EADV. Nonetheless, measures should be taken to protect the fetus in the treatment and imaging of PAM.
PARISâThe lack of any hard and fast guidelines for best clinical practices means that the management of moles and melanoma during pregnancy is a challenge, says Dr. Marie Aleth Richard reporting at the European Academy of Dermatology and Venereology (EADV) Congress last week in Parise.
Dr. Richard, of HÃ´pital de la Timone, Marseille, France, said that melanoma is a hormonally responsive tumor. Increased levels of hormones such as estrogen, progesterone and beta endorphin can increase melanocyte stimulation and cause an increase in pigmentation. Some melanomas have progesterone and estrogen receptors. As well as altered hormone levels, pregnancy also induces a state of immunosuppression, which decreases tumor surveillance and allows tumor progression.
Changes in lesions should not be attributed to pregnancy, she said, but any changing lesion should be immediately biopsied and excised.
CHANGES IN NEVI DURING PREGNANCY
Many clinicians believe that pregnancy comes with common changes in moles. While there are slight transient dermoscopic changes in nevi during pregnancy, normal nevi should only experience slight and non-significant clinical changes. Several studies have shown that changes in nevi size are only seen on the front of the body. “Pregnancy does not induce significant physiologic changes in nevi besides those on the breasts and abdomen, which grow with skin expansion,” Dr. Richard said. There is also no evidence to show that there is a darkening of nevi during pregnancy, another common misconception.
“Changes that occur in the nevi of pregnant patients should not be disregarded as a physiologic consequence of pregnancy. Any histopathological features consistent with melanoma should be viewed as melanoma,” she said.
The risks of biopsies and mole excisions under local anesthetic during pregnancy remain theoretical, Dr. Richard said. “The low doses of lidocaine and epinephrine that are used in dermatologic surgery are considered safe.” This means that biopsies and excisions, which should be obtained promptly from any suspicious or changing mole in pregnant women, can be performed safely during all stages of pregnancy.
MELANOMA IN PREGNANCY
Traditionally, clinicians have held the belief that women who are pregnant at the time of melanoma diagnosis have a poorer prognosis and a higher risk of progression than non-pregnant women. However, pregnancy-associated melanoma (PAM) prognosis does not appear to be worse than melanoma in non-pregnant controls. Nonetheless, measures should be taken to protect the fetus in the treatment and imaging of PAM.
“All surgical procedures can be done safely during pregnancy. Biopsy, excision and flap closure can all be done in the first trimester of pregnancy. Local anesthesia can be used in all these situations,” Dr. Richard said.
Sentinel lymph node (SLN) status is the most important prognostic factor in patients with greater than 1 mm melanoma, and SLN biopsy is generally considered safe in pregnant women. Patients should be made aware that SLN biopsy does not increase overall survival and that complications are more common in the second or third trimester.
When the risk of metastasis is low (e.g. at stages 1-2ab), there is no need for imaging. Imaging can be performed in later disease stages, and more extensively in stage three. Imaging modalities that use ionizing radiation and radionuclides should be limited in pregnant women.
“These treatments are associated with a risk of teratogenesis and miscarriage in the first trimester, as well as fetal injury and childhood cancer,” Dr. Richard said. Chest radiographs with appropriate shielding, ultrasonography and MRI are generally the techniques of choice in pregnant women, although CT scans without contrast and nuclear medicine studies can be performed if necessary. “Decisions about imaging should be made on a case-by-case basis, and the risk of lymph node involvement, for example, should be considered,” she said.
After a PAM, oral contraceptives and hormone replacement therapy do not seem to increase the risk for melanoma. There is no increased risk of melanoma after ovarian stimulation for in vitro fertilization, no effect of a subsequent pregnancy after a diagnosis of melanoma or PAM, and no need to defer pregnancies in women with localized or low-risk melanoma.
“Women with an increased risk of melanoma recurrence should be advised to wait for two to three years before becoming pregnant again,” she said. This is when recurrence is most common.
PD-1 and PD-L1 play a key role in maintaining fetal tolerance, and PD-1 and PD-L1 inhibitors for the treatment of melanoma may therefore affect pregnancy. In animal studies, anti-PD-1/PD-L1 significantly increased the risks of spontaneous abortions. “The use of an anti-PD-1/PD-L1 like pembrolizumab before a future pregnancy, such as an adjuvant setting in a young woman with a melanoma with high risk of recurrence, might also increase the risk of spontaneous abortion due to a decrease of the maternal immune tolerance to allo-antigens expressed by the fetus in future pregnancy,” she said.
In terms of best practice, Dr. Richard concludes that treatment of thin melanoma in stage one through three should be the same in pregnant and non-pregnant patients. In PAM with a low risk for nodal involvement, re-excision under local anesthesia is necessary, and it is reasonable to postpone the SLN biopsy until after delivery. In PAM with a high risk of recurrence or of nodal involvement, decisions for SLN biopsy or extensive imaging should be made on a case-by-case basis. Individual patient management should be based on the mother’s wishes, and she should receive enough information to make informed decisions about treatment, she said.
Richard, M-A. (2018). How to manage atypic naevi and stage I to III melanoma during pregnancy, The 27th European Academy of Dermatology and Venereology Congress, Paris, France, 15th September, 16:00 - 16:20