Squamous Cell Carcinoma Treatment with Mohs

Divya Srivastava, MD, is an associate professor and the director of Mohs surgery and dermatologic oncology at UT Southwestern Medical Center in Dallas, TX, with a specialization in the treatment of skin cancer. Her expertise lies in Mohs micrographic surgery, and she is the director for the micrographic surgery and dermatologic oncology fellowship. She joined The Dermatologist to discuss her recent study, “Factors Predicting Outcomes of Patients With High-risk Squamous Cell Carcinoma Treated With Mohs Micrographic Surgery."

How should dermatologists go about determining if a patient with high-risk cutaneous squamous cell carcinomas (SCCs) should undergo Mohs micrographic surgery?
Most SCCs have an excellent prognosis, but there is a subset of more aggressive tumors that have higher metastatic rates of up to 20%. The death rate with these SCCs rivals melanoma and oropharyngeal carcinomas in the south and central United States. We are seeing a lot more aggressive SCCs, especially in patients who are immunosuppressed such as transplant recipients and patients with a history of lymphoma.

High-risk SCC has been somewhat of an ambiguous term because there has been a lack of registries and clinical trials. Prior to 2010, cutaneous SCC was lumped with all other nonmelanoma skin cancers. In the last decade, there has been more focused effort on trying to risk stratify these SCCs based on tumor features and patient features to help guide treatment and give patients the best cure.

Now, the goal of cure is going to be to prevent recurrence, metastasis, and death. Surgical removal has been shown to have the highest cure rate for SCC. The National Comprehensive Cancer Network guidelines recommend Mohs surgery, or surgery with 100% total peripheral and deep margin examination, as first-line for most high-risk SCCs.  Achieving a clear margin has been shown to provide the highest cure rate.

I will not proceed with Mohs surgery if I am concerned I cannot achieve a clear margin, eg, if the skin cancer is fixed to the bone or I am concerned about intracranial nerve involvement where patients have clinical perineural involvement that might extend intracranially, potentially even involving the skull base. 

Preoperatively, it is important to work with your entire multidisciplinary team including radiation oncology, head and neck oncology, and medical oncology. Preoperative staging with imaging and sentinel lymph node biopsy should be considered for patients with aggressive SCCs.

For most high-risk SCCs, Mohs surgery provides the best cure. Adjuvant radiation can be beneficial for patients with large caliber or extensive small nerve perineural invasion, or patients with positive margin after resection

Your January 2021¹ study noted that “in propensity score-matched case patients treated with adjuvant therapy and control patients treated with mohs alone, there was no significant difference in progression-free survival, but matching was imperfect.” What further research is needed on the effect of adjuvant treatment?
Is adjuvant radiation improving the cure rate?  Several groups are studying this question. Currently, there is uncertainty for clinicians for which patients will benefit from adjuvant radiation. Working closely with your radiation oncologist is important in these cases.

Our study only had 30 of 882 patients undergo Mohs with adjuvant radiation, which is such a small number to obtain meaningful results. Our study did not show a difference in outcome in patients who underwent surgery plus radiation vs surgery alone.  However, other studies, have shown that there is a significant difference in developing nodal metastases in patients with perineural invasion who did not undergo adjuvant radiation.² 

Moving forward, it's going to be essential to collaborate in multi-institutional studies and using organized registries to have larger patient numbers for more meaningful data. 

This study also states that “current SCC staging systems may be limited by inconsistent inclusion of poor differentiation.” How do you propose to counter this?
There are two main current SCC staging systems that most dermatologists and Mohs surgeons are using. One is the Brigham and Women's staging system which includes differentiation, and one is the AJCC 8th staging system, which does not include differentiation.

Now, the prior seventh edition AJCC staging system did include differentiation, but it was removed as it was felt that there is not consistent criteria for how pathologists were assigning levels of differentiation. One pathologist might call something moderately differentiated and a different pathologist might call it poorly differentiated. It is a little bit of a gray area. Also, often pathologists only get a small sample in a biopsy and they do not see the varied histologies within that sample. Working with dermatopathology could be helpful in further delineating specific criteria that would help accuracy of staging systems.

It is interesting that the AJCC stage T1 and T2 tumors that have poor outcomes are poorly differentiated tumors. The AJCC stage T3 tumors that have a good outcome are the ones that are well differentiated.

Our study also showed that the patients who had poorly differentiated tumors did do worse than the patients who had well-differentiated tumors. Differentiation likely plays a role, and we have to figure out exactly how to fit it into the staging system in a consistent and objective manner.

What could the findings of this study mean for other forms of skin cancer (basal cell, melanoma, or nonmelanoma)?
One aspect of our study is we wanted to show that mohs surgery alone gives the best cure rate for high-risk SCC. We already have data supporting that it gives us the best cure rate for basal cell carcinoma (BCC).  More data are emerging that will help risk stratify and create a useful staging system for BCCs.

There is also excellent data showing that early melanoma has at least an equivalent cure rate with Mohs vs wide local excision. There are also emerging data demonstrating that even deeper invasive melanomas respond very well to Mohs surgery. 

What tips or insights would you like to leave dermatologists regarding selecting MMS as a treatment for skin cancers?
The optimal technique to treat high risk squamous cell carcinoma is mohs surgery.  Mohs surgeons can provide an excellent cure for these patients because we are highly trained to do both the surgery and serve as the pathologist thereby accurately mapping out tumor extension and identifying small foci of perineural invasion and other high risk features.  Often these features are only seen during resection and can lead to upstaging the tumor which helps guide whether patients need additional management such as imaging, adjuvant radiation, or nodal surveillance.

It is important to have a multidisciplinary team for patients with high-risk skin cancers who might need adjuvant radiation, systemic chemotherapy, or immunotherapy after surgery.

References
1. Matsumoto A, Li JN, Matsumoto M, Pineider J, Nijhawan RI, Srivastava D. Factors predicting outcomes of patients with high-risk squamous cell carcinoma treated with Mohs micrographic surgery. J Am Acad Dermatol. Published online January 29, 2021. doi:10.1016/j.jaad.2021.01.063

2. Stevenson ML, Criscito MC, Wilken R, et al. Use of adjuvant radiotherapy in the treatment of high-risk cutaneous squamous cell carcinoma with perineural invasion. JAMA Dermatol. 2020;156(8):918-921. doi:10.1001/jamadermatol.2020.1984