Pregnancy Worsens Melanoma Prognosis

By Brian D. Gastman, MD

Women who are diagnosed with cutaneous malignant melanoma while pregnant or within a year of giving birth have a significantly worse prognosis than their nonpregnant counterparts, according to the key findings of a retrospective study my coauthors and I published in the Journal of the American Academy of Dermatology.

After adjusting for age, tumor location and American Joint Committee on Cancer stage, we determined that women with pregnancy-associated malignant melanoma were five times more likely to die, nearly seven times more likely to experience metastasis and nine times more likely to have the cancer recur than were melanoma patients who were not pregnant.

To our knowledge, this is the first study to document reduced survival and poor prognosis in pregnancy-associated malignant melanoma patients, despite adjusting for patient age, tumor location and cancer stage. The magnitude of negative outcomes was a surprise to my colleagues and I. Our findings highlight the importance of melanoma screening and post-treatment surveillance in pregnant and recently pregnant women.

Documenting the pregnancy-melanoma association

The incidence of malignant melanoma in women has rapidly increased in recent decades. Our initial intent was to investigate the histopathology, staging, risk factors and outcomes of cutaneous melanoma in women younger than 50 years of age. Although pregnancy-associated melanoma is rare, the number of cases can be expected to grow, concomitant with the overall rise. Pregnancy’s impact on malignant melanoma patients’ prognosis has been unclear and subject to debate.

Cleveland Clinic’s early adoption of electronic medical records technology provided us the opportunity not only to review oncology and surgery notes, but to examine any type of medical history, including family practice and ob/gyn appointment records, dating back to 1998. As a result, we collected detailed diagnostic and outcomes data for 462 women younger than 50 years of age treated for biopsy-confirmed cutaneous malignant melanoma between 1998 and 2012.

Through this research, we confirmed an association between pregnancy and poor malignant melanoma outcomes. Forty-one women in our study cohort were diagnosed with melanoma while pregnant or within one year of giving birth. The mortality rate for pregnancy-associated malignant melanoma patients was 20 percent, compared with 10 percent for nonpregnant women (p = .06).

The incidence of metastasis was 25 percent among women with pregnancy-associated malignant melanoma compared with 12.7 percent for nonpregnant women (p = .03). Our research also found 12.5 percent of women diagnosed with melanoma during or after pregnancy experienced recurrence within the next 7.5 years, compared with 1.4 percent of their nonpregnant counterparts (p < .001).

Possible reasons for poor prognosis

Although our research did not investigate the pathophysiology of pregnancy-associated malignant melanoma, there are several possible explanations for the poorer outcomes this study revealed. Detection of malignant melanoma may be delayed in some patients due to the common belief that pigmented lesions typically darken during pregnancy and thus are not a cause for concern. A biologic aspect of pregnancy — elevated estrogen levels, heightened immunosuppression and/or enhanced lymphangiogenisis — may contribute to tumor aggressiveness or invasiveness. Further research is needed.

Previous studies examining melanoma prognosis and pregnancy have produced inconsistent results, possibly due to limitations in available patient data, methodological differences, and the exclusion of women diagnosed with melanoma during the postpartum period.

Spurring skin cancer awareness, prevention

Our hope is that this study creates greater awareness of melanoma’s risks, particularly during and soon after pregnancy, and that our findings will inform the assessment, treatment and counseling of these patients.

Women should be encouraged to talk with their physician if they are considering becoming pregnant and have obvious melanoma risk factors, such as excessive ultraviolet light exposure or a personal or family history of skin cancer. They should be counseled to perform a skin self-examination every month. Patients should be instructed to seek medical evaluation of any new or changing lesion noted during or soon after pregnancy.

As physicians, we should work to better educate the public about the dangers of excessive sun exposure. Frequent sunburns, especially during childhood, are associated with the development of melanomas on the trunk and legs. Ultimately, the best prevention originates with parents who are vigilant about their child’s exposure.

Finally, my coauthors and I hope our work leads to larger studies that will further explore the science underlying this link between pregnancy and melanoma prognosis, so that we can tailor therapies and prevention strategies.

Dr. Gastman is a staff member of Cleveland Clinic’s departments of Plastic Surgery and Immunology.