Management of Melanoma During Pregnancy

Sancy A. Leachman, MD, PhD; Ryan Jackson, HBS; Mark J. Eliason, MD; April A. Larson, MD; Jean L. Bolognia, MD

Disclosures

Dermatology Nursing. 2007;19(2):145-152,161. 

In This Article

Management of Melanoma in Pregnancy

In general, the treatment of melanoma in pregnant women is similar to that in the general population, and the therapy is based upon stage. The primary differences in management arise because of the need to consider the well-being of the fetus. Especially in advanced melanoma, less-aggressive therapy may be preferable to avoid fetal side effects when more aggressive therapy offers little gain for the mother.

The approach to treatment for melanoma begins with the identification of a suspicious lesion. A change in the appearance or size of a melanocytic nevus during pregnancy should be regarded with at least the same suspicion as in nonpregnant patients. Biopsy of a suspicious lesion should not be deferred because of pregnancy. If a pathologic diagnosis of melanoma is made, the clinician should perform a complete history and a thorough examination to establish whether any other suspicious cutaneous lesions or lymphadenopathy exist. The clinician should also perform a complete excision with recommended margins (Veronesi et al., 1988). In the case of lower-risk lesions (nonulcerated, less than 1.0 mm in depth, Clark level I, I, or III), re-excision with close clinical followup to monitor for recurrence or new primary lesions is recommended. General anesthesia should be avoided if the mother is still in her first trimester of pregnancy (Kuczkowski, 2003).

If clinically palpable nodes are found, the etiology of the lymphadenopathy should first be determined. If the latter is due to metastatic melanoma, then a lymph node dissection should be considered. If the primary cutaneous melanoma has a Breslow's depth between 1 and 4 mm and there are no clinically palpable lymph nodes, a sentinel lymph node (SLN) biopsy should be considered. The SLN biopsy is a procedure based upon the premise that the lymph node that is the first to drain the area around a lesion is the one most likely to be primarily affected by lymphatic spread of the melanoma. The SLN biopsy has replaced the elective lymph node dissection (ELND) in melanoma staging because it has less associated operative and postoperative morbidity. The SLN biopsy permits early detection of lymph node metastases, allows a better estimate of prognosis for the patient, and prevents an ELND if the SLN is negative.

To perform a routine SLN biopsy, a surgeon injects a small amount of blue dye and technetium-99, a radioactive tracer, into the site of the primary lesion. After allowing the dye to drain through the lymphatics to the regional node basin, the physician uses a gamma probe to identify the location of the sentinel node and confirms the identity by the blue discoloration (Senagore, 2005). Once the lymph node has been identified the surgeon removes it and sends it for pathological evaluation.

Before performing a SLN biopsy in a pregnant patient, informed consent should be obtained and the risks, benefits, and limitations of the procedure should be discussed with the patient and the father. In particular, the couple should be aware that the procedure has not been proven to improve survival, and if further staging or treatment is not desired, it may represent an unnecessary risk. Although risk to the mother and fetus is relatively low, the SLN biopsy procedure does involve the potential for an allergic reaction to the dye, and fetal exposure to radiation from the tracer. Schwartz, Mozurkewich, and Johnson (2003) reported a 0.7% to 1.1% risk of anaphylaxis in response to the dye. To avoid the risk of anaphylaxis, it is possible to use the radioactive compound without the blue dye. The lymphatic mapping procedure is estimated to expose a fetus to < 5 mGy (<0.5 cGy) (Adelstein, 1999). (The Society of Nuclear Medicine recommends a pregnancy test for patients before they undergo any procedure that would expose a fetus to >50 mGy of radioactivity.) While the likelihood of radioactivity from the SLN biopsy procedure posing a threat to the fetus is small, Schwartz et al. (2003) notes that in the case of women who are in the later stages of pregnancy and have had an excision of their melanoma with clear histologic margins, it is reasonable to consider waiting to perform the SLN biopsy until after delivery, with close clinical followup in the interim. If this option is chosen, concern regarding altered lymphatic drainage may be reduced by doing a linear repair rather than a flap. Finally, some authors caution against the use of general anesthesia during the first trimester because of animal studies showing a potential for teratogenesis. In general, appropriate fetal monitoring during all trimesters should be performed whenever general anesthesia is employed (Kuczkowski, 2003). Overall, clear communication with the family about the purpose and risks of SLN biopsy is essential so that informed, joint decision-making can occur.

In the general population, a positive SLN biopsy may also be an indication for more complete imaging techniques, such as computerized tomography (CT) scans and positron emission tomography scans for staging (McMasters, 2003). However, an abdominal CT exposes the fetus to 30 mGy (3 cGy) of radiation, and depending on the gestational stage, doses above 50 mGy (5 cGy) may pose risk to the fetus. During the first and second trimesters, exposures of >100 mGy (10 cGy) are associated with decreased intelligence quotient, and an increased frequency of childhood cancer (Parry, Glaze, & Archer, 1999). In pregnant patients with stage III and or suspected stage IV melanoma, an ultrasound can be performed safely. A magnetic resonance image (MRI) is another imaging technique that can be used to stage a cancer, and does not use radiation, though there is a small theoretical risk of tissue heating caused by the radiofrequency pulses during the first trimester. The American College of Radiology approves of the use of MRI in all stages of pregnancy when other non-ionizing modalities are not sufficient, and the referring physician believes that the diagnostic benefit outweighs the risk (Kanal et al., 2002).

The data available on advanced melanoma (regional or distant metastatic spread) during pregnancy are limited to a few published case reports and case series (Alexander et al., 2003; Beyeler et al., 2005; Harkin, Drumm, O'Brien, & Daly, 1990). As noted in Table 1 , in the larger studies of pregnant patients with melanoma, only a small number had regional or distant disease. In a recent case series of three pregnant patients with stage III or IV melanoma and literature review by Beyeler et al. (2005), the authors proposed the following treatment algorithm. If a SLN biopsy confirms regional spread, imaging studies should be done and limited to modalities associated with the lowest exposure to ionizing radiation (ultrasonography and MRI) whenever possible (Beyeler et al., 2005). Following surgical resection of the primary lesion, Beyler et al. (2005) advise waiting until the mother is postpartum to initiate adjuvant (for example, interferon or vaccines) or other therapy (for example, dacarbazine, temozolamide, stereotactic radiosurgery, etc.). Current chemotherapeutic options do not offer sufficient benefit to the mother to justify the potential for fetal harm during gestation. If the physician and patient decide to treat with chemotherapy or irradiation, they should consider whether they can wait and induce delivery at 34 weeks, prior to beginning the therapy. This approach is acceptable if done in an institution with a neonatal care unit, as in this setting the perinatal mortality at 34 weeks approaches that of a term delivery.

In the case of nonresectable metastases, palliative surgical resection of large abdominal masses may be required to permit continuation of the pregnancy (Alexander, Harris, Grossman, Bruggers, & Leachman, 2004). Only a limited number of chemotherapeutic options exist and none have demonstrated a significant increase in survival (see Table 3 ). In general, pregnant patients treated with chemotherapy have survived for 3 to 8 months, results similar to those seen in nonpregnant patients with advanced disease who received such therapy. It is important to note that some authors have advised that termination of pregnancy may be useful in treating advanced disease as the effect of therapeutic agents upon the fetus would no longer be an issue (Driscoll, Jorgensen, & Kels, 1993). However, termination of pregnancies has not been associated with regression of melanoma or an improvement in maternal outcome (Driscoll et al., 1993). Again, before pursuing an aggressive treatment course, the rather dismal prognosis of stage IV disease should be made clear to the couple (Chang, Karnell, & Menck, 1998).

A team approach by a clinical staff that includes nurses and social workers is essential to provide the support and guidance needed by those in the unfortunate situation of pregnancy confounded by a diagnosis of advanced melanoma. The nursing staff plays an important role beyond caring for the physical needs of the patient; responsibilities also include serving as a liaison with the treating clinicians and answering the many questions the patient and her family will have. The team will need to help them become as informed as possible in preparation for making the difficult decisions regarding treatment and end-of-life issues (for example, hospice) as well as plan for continued caregiving for the baby in the event of the mother's passing. The team will also need to coordinate care with the obstetricians so that there is appropriate preparation for monitoring the fetus before, during, and after delivery for evidence of malignancy.

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