Mohs Surgery Improves Survival in Early-Stage Merkel Cell

SEATTLE ― The use of Mohs surgery may improve survival for patients with early-stage Merkel cell carcinoma (MCC), results from a large, retrospective study show.

As compared with conventional wide local excision, survival was significantly improved among patients treated with Mohs, and a subgroup analysis showed that the survival benefit remained for patients with risk factors.

“At 10 years, overall survival was about 21% higher for those treated with Moh’s surgery, vs those treated with conventional surgery,” said lead author Shayan Cheraghlou, MD, a dermatology resident at the New York University School of Medicine, New York. “On multivariable analysis, which controlled for tumor and patient factors, Mohs was associated with an over 40% reduction in the hazard for death.”

The findings were presented here at the American College of Mohs Surgery (ACMS) 2023 Annual Meeting.

MCC is a rare, aggressive, neuroendocrine cutaneous malignancy that carries a high mortality rate. The estimated 5-year survival for patients with localized disease is about 50%, Cheraghlou noted. “That extrapolates to about 55% for T1 tumors and down to about 30% for T4 tumors.”

Although it’s considered to be a rare cancer, the incidence of MCC has been rapidly rising, and in fact it doubled during the period from the 1990s to the 2010s.

Most commonly treated with wide local excision with or without adjuvant radiation therapy, Mohs as monotherapy may offer an alternative treatment option for patients with MCC. It is generally accepted that the optimal treatment for tumors without regional lymph node involvement is surgical, but the data regarding the optimal surgical approach are mixed. Current National Comprehensive Cancer Network (NCCN) guidelines state that either Mohs surgery or wide local excision can be used.

“However, these guidelines do not indicate a preference for one modality over the other,” said Cheraghlou, “and presents them as interchangeable treatment options.”

A growing body of literature supports Mohs surgery for many types of rare tumors, including MCC. For example, as previously reported by Medscape Medical News, one study found that Mohs surgery compared favorably with the standard treatment approach when it came to recurrence rates for patients with MCC. The 5-year disease-specific survival rate was 91.2% for patients with stage I disease and 68.6% for patients with stage IIa. These rates were comparable with rates for historical control patients who were treated with wide local excision, with or without radiation (81% to 87% for stage I disease, and 63% to 67% for stage II).

Study Details

In the current study, Cheraghlou and colleagues sought to evaluate the association of the type of surgical approach with patient survival after excision of early-stage MCC. They conducted a retrospective cohort study using the National Cancer Database to identify cases of MCC with T1/T2 tumors. A total of 2313 patients who were diagnosed from 2004–2018 with pathologically confirmed negative lymph node involvement and who were treated with Mohs surgery or wide lesion excision were included in the analysis.

“About 90% were T1 tumors, about 40% were located on the head and neck, and the vast majority — about 60% — were treated with wide local excision,” he explained. “Only about 5% received Mohs surgery for treatment of the primary tumor.”

But when the researchers assessed survival outcomes, they found that treatment with Mohs surgery was associated with significantly improved overall survival.

The unadjusted 3-, 5-, and 10-year survival rates for patients treated with Mohs was 87.4% (SE: 3.4%), 84.5% (SE: 3.9%), and 81.8% (SE: 4.6%), respectively, while for wide lesion excision, the rates were 86.1% (SE: 0.9%), 76.9% (SE: 1.2%), and 60.9% (SE: 2.0%), respectively,

For patients who underwent treatment with narrow margin excision, survival rates were similar as for those treated with wide lesion excision, with 3-, 5-, and 10-year survival rates of 84.8% (SE: 1.4%), 78.3% (SE: 1.7%), and 60.8% (SE: 3.6%), respectively.

On multivariable survival analysis, Mohs surgery was associated with significantly improved survival compared with wide lesion excision (hazard ratio [HR], 0.594; P = .038). This was also true after multivariable analysis for patients who had one or more NCCN risk factors, for whom improved survival was also seen with Mohs (HR, 0.530; P = .026).

The results did not differ after a sensitivity analysis that included T3 and T4 tumors.

Given that the use of Mohs was so infrequent in comparison with standard surgery, the researchers investigated the factors that were associated with the use of Mohs. High-volume MCC centers were significantly more likely to utilize Mohs than wide lesion excision (odds ratio, 1.993; P < .001), compared with other facilities.

“This study has important implications going forward,” Cheraghlou concluded. “We think it’s important how few patients were treated with Mohs for Merkel cell, and it was slightly more likely to happen in a high-volume center.”

The reasoning for that may be that high-volume centers are more likely to have a surgeon trained to perform Mohs surgery for MCC. “Or perhaps they are more attuned to the benefits of this procedure,” he said. “We can’t tell that from our data, but its notable that it’s such a small proportion of patients ― especially when we consider that it is associated with improved survival for the patients who receive it.”

He added that efforts to increase the utilization of Mohs may yield improved local control and overall survival for these patients. “And perhaps with more data, future versions of guidelines may indicate a preference for Mohs over conventional incisions.”

No Changes to Current Practice

Asked to comment on the study, Anthony J. Olszanski, RPh, MD, associate professor, Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, noted that while the results are intriguing, they must be interpreted with caution.

“This study was retrospective in nature, and unrecognized biases can influence results,” he said. “Additionally, given the relative rarity of Merkel cell carcinoma, the sample size is expectantly small.”

But importantly, Olszanski emphasized, Mohs surgery may more often have been recommended for patients with lesions that appear less aggressive. “[M]any patients undergoing wide lesion excision may have been referred by Mohs surgeons secondary to features or characteristics of lesions which were worrisome,” he explained. “The results of this study do not opine on why Mohs would impact overall survival over wide lesion excision, a point worthy of consideration. Presently, both modalities can be considered for patients with T1/T2 MCC. The results of this study should not change current practice and would lend themselves to a more robust study.”

No external funding of the study was reported. Cheraghlou has disclosed no relevant financial relationships. Olszanski has received financial support from Merck and BMS for participated on advisory boards.

American College of Mohs Surgery (ACMS) 2023 Annual Meeting: Presented May 5, 2023

Roxanne Nelson is a registered nurse and an award-winning medical writer who has written for many major news outlets and is a regular contributor to Medscape.

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