Omid Hamid, MD, and Morgana Freeman, MD, discuss primary treatment options for locally advanced or metastatic CSCC and when it’s appropriate to elect for surgery.

Transcript

Omid Hamid, MD: NCCN [National Comprehensive Cancer Network] guidelines recommend a full skin examination at the time of consultation with a Mohs micrographic surgeon or a surgical oncologist for resection. Depending on invasiveness, growth, and neurotropism, further imaging studies may be indicated. Upon examination, if nodal involvement is found, that’s an indication for a biopsy to evaluate nodal involvement, making this a metastatic cutaneous squamous cell carcinoma [CSCC]. Then, there is extensive disease evaluation.

Locally advanced versus a borderline resectable has to do a lot with the invasiveness—whether it’s adherent to any other area, or whether it’s recurred in an area that’s been previously treated, and then has come back and cannot be treated with surgery or radiation. There’s an evaluation of the local nodal basin. Sometimes what is resectable becomes unresectable given the location that it’s at and the deformity that it can create. So that may be an indication for where you may not go toward a surgical resection or irradiation.

Up until recently, we’ve had few options for locally advanced and metastatic cutaneous squamous cell carcinoma of the skin. The majority of experience of therapeutic options comes from head and neck squamous cell carcinoma, as these 2 tumors have similarities. Therefore, the chemotherapies that we’ve utilized for these tumors—including 5-FU [fluorouracil] and cisplatin-based regimens—have come from our experience and our successes with head and neck squamous cell carcinoma.

Again, the mutational load and the mutations that these tumors sometimes have are the same. Therefore, we have used targeted agents like cetuximab, the EGFR targeted agents, for these tumors. Unfortunately, the responses we see have not been equivalent. For cutaneous squamous cell carcinoma, targeted agents and chemotherapy have been fraught with toxicity, low response rates, and unfortunately, a very short duration of response.

At this time, we’re fortunate to have discovered immunotherapies for patients with locally advanced and metastatic cutaneous squamous cell carcinoma, which have changed the paradigm of how we treat these patients.

Morgana Freeman, MD: When thinking about what type of surgery should be presented to a patient, oftentimes that is left to the decision of the dermatologist. In some cases, if it’s a shallow lesion or a T1 lesion, for example, then simple excision should suffice. However, if there’s concern for a more deeply invasive lesion, and stages of surgery have to be done to obtain a final pathologic diagnosis, then Mohs surgery is more appropriate. In cases where there appears to be deeper structure involvement or possibly even the requirement for head and neck dissection, then we involve the services of an ENT [ears, nose, and throat surgeon] or plastic surgeon.

Omid Hamid, MD: The ability of determining whether an excisional surgery versus Mohs micrographic surgery is required for a patient with cutaneous squamous cell carcinoma of the skin is a multidisciplinary approach. For example, a very invasive lesion, or one in a very difficult area to do with Mohs, would be one where a surgical excision or a plastic surgeon may be indicated. Most lesions can be taken care of by Mohs. What we benefit from there is the ability to evaluate for skip lesions, and the ability to evaluate for negative margins during the procedure, with some information showing that we may have a lower risk of recurrence for patients who have Mohs micrographic surgery.

For my patients with cutaneous squamous cell carcinoma, we oftentimes involve a multidisciplinary team of a pathologist, a surgical oncologist, and a Mohs surgeon to evaluate the appropriateness of therapy. In some areas where there may be deformity, the radiation oncologist will be utilized to allow us to evaluate whether local irradiation can give us the desired outcome.

Morgana Freeman, MD: When detected dearly, CSCC is highly curable. In about 95% of cases, simple excision alone should suffice. There’s a fairly low risk right now with distant and local metastases in CSCC unless some of the important risk factors that I mentioned are present. We tend to not think of it as aggressive as we might with melanoma, which has a very high metastatic risk even with thin tumors. With CSCC, that isn’t quite the case, however that risk does still exist. Depending upon the comorbid risk factors, as well as the characteristics of the primary tumor, we might alter our surveillance plans to monitor that patient for any signs of relapse.

When thinking about whether a patient is an adequate surgical candidate, there are a number of factors to consider. It’s not only about the location of the primary tumor and what structures might be involved—primarily on the head and neck so there may be some disfigurement potentially or if there’s involvement of the orbit or the bone that may render them surgically inoperable. That’s why a multimodality team is really necessary in terms of those types of cases. This is also a disease that occurs in the elderly population, and for a majority of trials that have been done in CSCC, we understand the median age is about 70 years. By that point, many patients may have comorbid medical conditions such as diabetes, heart disease, or uncontrolled hypertension, and that may complicate a patient’s potential surgical plan.

Finally, the third factor to take into consideration when determining appropriateness for surgery is what is that patient’s relapse risk. We know that there’s a velocity to this disease, and patients will oftentimes have more than 1 tumor over time. If they’ve relapsed within a short period from their last surgery, then we may think that surgery is not the appropriate route to take and may want to elect either systemic therapy, radiation, or some combination thereof.

We’re very lucky in that we work within a multidisciplinary team at our institution. I serve as the medical oncologist who has expertise in this disease area, but I also work with a radiation oncologist, a dermatologist, a Mohs surgeon, a plastic surgeon, and a head and neck surgeon. Oftentimes, the first person who that patient might see is on the surgical side. If it appears that it’s a very complicated case or maybe something not easily solved by surgery, or if that patient needs some adjuvant treatment thereafter, it’s appropriate for all of us to discuss what might be the best route to take for that patient during the course of their disease.

On the medical oncology side, in particular, if that patient may be at risk later for metastatic relapse in the case, let’s say, of someone who’s immunocompromised or has a history of transplant, then I can make recommendations to them for whole body surveillance to look for distant metastases that may show up later on. It is absolutely critical to involve a multidisciplinary team, not only so that the best treatment plan can be formulated but also so that the patient can be educated in all of the options that might be available to them.