Mohs Surgery Best for Early-Stage Merkel Cell Carcinoma?

Mohs micrographic surgery may offer a survival advantage over wide local excision for select patients with early-stage Merkel cell carcinoma (MCC), a retrospective cohort study suggested.

Over a mean follow-up of about 5 years, multivariable analysis found that Mohs surgery was associated with a 41% reduction in the risk for death compared with wide local excision for patients with localized MCC and pathologically confirmed node-negative disease (HR 0.59, 95% CI 0.36-0.97, P=0.04), John Carucci, MD, PhD, of New York University Grossman School of Medicine in New York City, and colleagues reported.

Their study in JAMA Dermatology relied on the National Cancer Database (NCDB), ultimately including more than 2,000 surgical cases of MCC across a 15-year period. In unadjusted analyses, landmark survival rates out to 10 years favored the small group of patients who received Mohs surgery rather than wide local excision:

• 3 years: 87.4% vs 86.1%, respectively
• 5 years: 84.5% vs 76.9%
• 10 years: 81.8% vs 60.9%

"This report provides preliminary data suggesting that treatment of localized, early-stage MCC with MMS [Mohs micrographic surgery] may result in the most optimal patient survival outcomes for this aggressive form of skin cancer," Carucci's team wrote.

MCC is one of the deadliest skin cancers, and it has a "propensity to rapidly metastasize to regional lymph nodes," the researchers noted. As a result, guidelines from the National Comprehensive Cancer Network (NCCN) recommend sentinel lymph node biopsy for all clinically node-negative patients who are fit for surgery.

But while surgery is considered the best definitive treatment for localized cases, controversy exists over the optimal approach due to a lack of evidence, according to the study authors, with current NCCN guidelines primarily recommending Mohs micrographic surgery, wide local excision, or "some other form of surgery with peripheral and deep en face margin assessment."

Prior registry studies had suggested no difference between Mohs and wide local excision, but the studies focused on clinically node-negative disease, and likely included patients with occult nodal involvement, the researchers noted.

The current data, they said, highlight the importance of confirming regional lymph node status given that anywhere from 25% to 40% of clinically node-negative cases actually have positive sentinel lymph nodes.

For their study, the researchers scraped the NCDB to find all surgical cases involving adults with T1/T2 MCC and pathologically confirmed node-negative disease from 2004 to 2018. Of the 2,313 total cases, most were treated with wide local excision (n=1,452), followed by narrow-margin excision (n=757) and Mohs micrographic surgery (n=104).

Multivariable analysis found that patients treated with narrow-margin excision had similar survival as those treated with wide local excision (HR 1.04, 95% CI 0.86-1.25), with survival rates at 3, 5, and 10 years of 84.8%, 78.3%, and 60.8%, respectively.

Patients were treated across 649 centers, with the 160 academic centers dealing with just over half of the cases. And while there were just 14 high-volume centers (2%), these facilities treated more than one-fifth of the MCC patients.

Overall, the patients had an average age of 71 years, 58% were men, and 94% were white. Nearly 60% of the tumors were located on the trunk or extremities and 82% were staged as pT1. Most patients (71%) had high-risk factors, though where its status was known, 77% of patients were free of lymphovascular invasion.

In patients with at least one high-risk factor per NCCN -- including larger primary tumors (>1 cm), primary tumors located on the head or neck, and lymphovascular invasion -- multivariable analysis also showed an association between Mohs surgery and better survival.

Mohs surgery was significantly more likely to be performed at high-volume centers (OR 1.99, 95% CI 1.63-2.44) but was less commonly used for T2 versus T1 MCCs (OR 0.67, 95% CI 0.53-0.85).

Radiation to the primary site was used in 45% of cases, and the researchers found that its use was less likely in older patients (OR 0.97 per year of age, 95% CI 0.96-0.98) and more likely in those with T2 tumors (OR 1.77, 95% CI 1.42-2.21) and tumors with lymphovascular invasion (OR 1.74, 95% CI 1.34-2.25). Academic and high-volume facilities were also less likely to use radiation.

The study could not assess whether adjuvant radiation provided a benefit for patients receiving Mohs micrographic surgery, but did control for its use.

"It may be hypothesized that the complete histopathologic clearance of the primary tumor that can be achieved with MMS may preclude the need for radiotherapy to the primary site as has been previously suggested," Carucci and team wrote. "However, this issue cannot be directly addressed with the data from the current study, and further investigation evaluating outcomes after MMS with and without radiotherapy is required to answer this question."

Limitations to the data included that locoregional recurrence and disease-specific survival could not be assessed, that immunosuppression status could not be controlled for, and the small size of the Mohs micrographic surgery group. Despite controlling for multiple factors (age, comorbidities, stage), the potential for selection bias exists as well.

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