Merkel Cell Carcinoma Much More Likely to Recur vs Other Skin Cancers

Patients with Merkel cell carcinoma (MCC) face higher recurrence rates compared with other skin cancers, according to a prospective cohort study.

The 5-year recurrence rate for MCC was 40%, and the vast majority of these recurrences (95%) occurred within 3 years of initial treatment, reported Paul Nghiem, MD, PhD, of the University of Washington in Seattle, and colleagues in JAMA Dermatology.

“This tells us these patients need to be followed closely — but not forever,” Nghiem told MedPage Today. “With over 90% of recurrences happening within 3 years, you can really de-escalate surveillance intensity, follow-up intensity, and scan intensity over a few years.”

Nghiem and colleagues noted that the 40% recurrence rate was near the median reported in previous studies (27%-77%). MCC recurs at a much higher rate than melanoma (approximately 19%), as well as squamous cell carcinoma (approximately 5%-9%) and basal cell carcinoma (approximately 1%-2%).

“This cancer is much more significantly likely to recur than any of the more common ones, like melanoma,” Nghiem added. “So this does deserve attention in terms of that high risk of recurrence, and now that we have immune therapies that can really meaningfully help patients with advanced disease, it is important to identify recurrences early.”

The researchers pointed out that disease stage was a potent prognostic factor for risk of recurrence:

• 11% for pathologic stage I
• 33% for pathologic stage IIA/IIB
• 30% for pathologic stage IIIA
• 45% for pathologic stage IIIB
• 58% for pathologic stage IV

After adjusting for stage, the team also found that immunosuppression was strongly associated with an increased risk of recurrence (HR 2.4, 95% CI 1.7-3.3, P<0.001), as was older age (HR 1.1, 95% CI 1.0-1.3, P=0.06 for each 10-year increase), male sex (HR 1.9, 95% CI 1.4-2.5, P<0.001), and known primary lesion among patients with clinically detectable nodal disease (HR 2.3, 95% CI 1.4-4.0, P=0.001).

The study included 618 patients (median age 69, 37% women) with pathologically confirmed MCC who were prospectively enrolled in a repository maintained by the University of Washington from 2003 to 2019. Median follow-up was 4.3 years.

Among the patients who experienced a recurrence, 60% developed distant metastatic disease, with the proportion of patients increasing with higher disease stage at presentation: 5% for patients with pathologic stage I disease, 26% for pathologic stage IIIA, and 58% for pathologic stage IV.

Of the 187 deaths in the cohort, 65% were due to MCC.

The MCC-specific survival rate was also strongly stage dependent, at 95% at 5 years for patients with pathologic stage I disease versus 41% for pathologic stage IV disease, Nghiem and colleagues noted. They suggested that MCC-specific survival was a more accurate measure of disease risk than overall survival in an older population with comorbidities that put them at a higher risk of dying from causes other than their cancer.

“These patients should be managed in a multidisciplinary setting where people are really familiar with how to manage this tricky cancer,” Nghiem said. “These patients usually need more than just surgery. They may need radiation, they may need a sentinel lymph node biopsy, and they’ll probably need scans, so there is a lot of tricky management issues for this cancer in general, and then to realize that it will come back in almost half of patients no matter how optimally it is managed means the stakes are very high, at least for a few years.”