Urethral Involvement Key in Vulvar Melanoma Recurrence

Pam Harrison

October 25, 2019

Urethral involvement has been singled out for the first time as a key factor in the risk for recurrence in women with vulvar malignant melanoma, an observational study indicates.

That and tumor depth are the key features that predict time to death, according to the largest study of its kind with the longest follow-up of women with this rare but lethal malignancy.

"First of all, vulvar melanoma is an insidious disease, and in our study, urethral recurrence was significantly associated with time to death, so this was one of the very important take-home points from our findings," Mitul B. Modi, MD, resident physician, Penn Medicine, University of Pennsylvania Health System, Philadelphia, told Medscape Medical News.

The other key take-home point was that it often presents with clinical multifocality, meaning that when the vulva is examined, the patient often has multiple pigmented lesions, he added.

"These women need aggressive, long-term follow-up," Modi cautioned, "as the high local recurrence rate of vulvar malignant melanoma is associated with a high mortality rate," he added.

Vulvar melanoma accounts for 8% of all vulvar malignancies.

The study was presented at the American Society of Dermatopathology (ASDP) 56th Annual Meeting in San Diego, California.

Penn Medicine

The study involved 37 patients with vulvar malignant melanoma who presented to Penn Medicine between 1970 and 2000. The average age at presentation was 60.4 years, though it ranged from 23 to 83 years. The mean follow-up was 53 months.

In reviewing the tumor characteristics on pathology, Modi and colleagues found that clinical multifocality was present in 35% of the group; approximately one quarter of them had urethral involvement.

Histologically, amelanotic foci were present in approximately half of the tumors as well.

On univariable survival analysis, urethral involvement, age at diagnosis, tumor thickness, and Clark's level IV and V were all predictive of 5-year survival rates. Clark's level is a staging system; used in conjunction with Breslow's depth, it describes the level of anatomic invasion of the melanoma in the skin.

For example, at 5 years, 58% of women who had no urethral involvement on presentation were still alive.

This compared to only 15% of women who presented with urethral involvement (P = .036), Modi noted.

Similarly, 60% of women who were aged 23 to 64 years on presentation were still alive at 5 years, compared to only 25% of those 65 years of age or older.

The median time to death was 25 months in patients with urethral involvement, Modi also noted.

However, this greatly depended on the depth of the tumor on presentation. All of the women (100%) whose tumors measured 0 mm in thickness — in other words, melanoma in situ ― were still alive at 5 years, compared to only half (48%) of those whose tumors measured less than 1 mm in size and 25% of those whose tumors were greater than 1 mm on presentation (P = .003). Modi noted that almost 63% of tumors in their own series were greater than 1 mm.

The median time to death by Clark's level IV/V was 30 months.

Again, however, for patients with Clark's level II and III tumors, 55% were still alive at 5 years, compared to only 20% of those with Clark's level IV and V (P = .041). Some 43% of tumors in their own series presented as Clark's level IV and V.

The late stage at which patients present and high recurrence rates contribute to poor overall survival rates, which range from a low of 10% to approximately 60% at 5 years, as determined from a review of the literature.

Modi reported that in their own group of 37 patients, 40% developed local recurrence. On the basis of literature reports, local control is notoriously poor in vulvar melanoma, with recurrence rates of 30% to 50%, compared to only 3% in cutaneous melanomas.

Another 35% of the group developed regional lymph node recurrences, and almost one third of patients developed distant metastasis during follow-up as well.

In a review of seven studies that evaluated lymph node involvement as a predictor of survival in patients with the same malignancy, survival rates for those with lymph node involvement were only about 11% at 10 years, compared to almost 44% for patients with no lymph node involvement, Modi also noted.

At present, there are no uniform guidelines governing how frequently women with vulvar malignant melanoma should be followed up.

However, he believes that "follow-up for these patients should be more aggressive than it is for other cancers."

In general, women are followed every 6 to 8 weeks after surgical resection of the tumor, after which they are followed every 4 months for the first 2 years.

Follow-up may be reduced to twice a year in subsequent years.

Modi also suggested that punch biopsies be considered during follow-up visits because of the high risk for local persistence and recurrence.

Pathology excision specimens should be carefully reviewed, with particular attention to urethral involvement.

Difficult to Diagnose

Session chair Michi Shinohara, MD, associate professor of dermatology and dermatopathology, University of Washington Medical Center–Roosevelt, in Seattle, said that this study confirms that vulvar melanoma can be difficult to diagnose and manage and that it has the potential for poor outcomes for patients.

"Clinicians need to follow atypical lesions in the vulva carefully and be aware that sometimes melanoma in the vulva can lack pigment," Shinohara told Medscape Medical News in an email.

"If a vulvar melanoma is diagnosed, patients should have evaluation of their urethra with a gynecologist or urologist, as Dr Modi's study showed that urethral involvement was particularly linked to worse outcomes," she reaffirmed.

Neither Modi nor Shinohara have disclosed any relevant financial relationships.

American Society of Dermopathology: Abstract 1048-000156, presented October 17, 2019.

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