Squamous cell cancer: Management from in situ to metastasis

Dr. Schmults: “Dermatologists need to know the subset that is at risk of metastasis.”

Chrysalyne D. Schmults, MD, MSCE, loves a challenge. After graduating from Yale College and Yale School of Medicine and completing her residency at NYU, Dr. Schmults went on to become director of the Brigham and Women’s Hospital (BWH) Mohs and Dermatologic Surgery Center in 2007. One year later, she founded the BWH High-Risk Skin Cancer Clinic, where she made it her mission to care for patients who have multiple skin cancers, severe sun damage, or tumors at high risk for recurrence. In the last 10 years, the clinic has become a referral center for patients who have locally advanced and metastatic basal and squamous cell carcinoma (BCC and SCC respectively), and are in need of advanced multidisciplinary care and clinical trials.

Now, Dr. Schmults is associate professor of dermatology at Harvard Medical School. At Friday’s Plenary session, she discussed high-risk SCC, prognostic stratification, field cancerization, and emerging therapies. It is an exciting and rewarding time to be in the field, she said, but even more than that, it is about saving lives.

“I’ve been working on cutaneous squamous cell carcinoma (cSCC) for 15 years now,” said Dr. Schmults. “It doesn’t seem like that long, especially in comparison to melanoma, where my colleagues have worked on it for 40-plus years. If you look at the knowledge that we’ve accumulated for cSCC versus melanoma, it’s unfortunately been like night and day.”

Only recently has medical claims data emerged that revealed the incidence of cSCC to be equal with BCC, making them the leading forms of cancer in the United States. And while cSCC has a high rate of recovery, there is a subset of patients who have suppressed immune systems or multiple tumors that put them at an increased risk of metastasis and death. According to Dr. Schmults, people who have had 10 or more squamous cell tumors that are dermally invasive (not in situ) have a 35% chance of metastasis.

One of the biggest challenges dermatologists have is knowing how to identify those high-risk patients while they still have time to be treated effectively. There are four features to look for during staging:

  1. A tumor diameter of 2 centimeters or more.
  2. A depth of invasion past subcutaneous fat.
  3. Poor differentiation (cells are highly abnormal under the microscope).
  4. Lab caliber nerve invasion (0.1 millimeters or more in diameter).

These recently established high-risk factors are considered to be more valid than previous staging research, and all of them except differentiation (because of its grading system, which is difficult to uniformly apply) have been incorporated into the AJCC 8th Edition. Dr. Schmults stressed the importance of tumor staging.

“Even though most patients do well and are easily cured, because cSCC is so common, the number of deaths comes close to the number of deaths from melanoma. Dermatologists need to know the subset that is at risk of metastasis,” she said.

Dr. Schmults went on to examine some of the emerging therapies used to manage cSCC. One type of new treatment that has just finished trials and is in the final steps of FDA approval is cemiplimab. This is meant for patients whose tumors metastasize, especially with large or multiple lymph nodes, or become locally advanced, meaning they are not amenable to surgery or radiation.

“This anti-PD-1 immunotherapy drug given via intravenous infusion has a 50% response rate, which is more than double what we’ve seen with prior therapies,” said Dr. Schmults.

For people who have multiple cSCCs, dermatologists should consider Soriatane® (acitretin) as prophylaxis. Side effects are possible, but are less common with low doses, and it helps prevent further occurrences more than 60% of the time. Other topical treatments, such as 5-fluorouracil (a cream that patients apply two times a day for four weeks), can also help reduce the risk of having further cSCCs develop.

“Treating field cancerization is important in that we know that treating field disease does decrease cSCC,” Dr. Schmults said. “If you can use these [treatments] to decrease background skin damage, it will decrease the number of cSCCs people get.”

Another option for prophylaxis for patients with multiple cSCCs is 500 milligrams of over-the-counter nicotinamide, a vitamin B2 derivative, taken twice a day. According to a randomized, placebo-based Australian study, this can decrease the risk of new cSCCs by about 30%. Daily use of high-SPF sunscreen is a universal go-to method to prevent and reduce skin damage and cSCC.

It is critical that dermatologists hear and understand the message that patients who were once, essentially, left to die, now have options and opportunities. And although metastatic and unresectable cSCC is just “getting on the map,” Dr. Schmults is happy to be a part of it forging ahead.

“For so many years when patients would have tumors that we worried about, we didn’t know what to do for them,” she said. “Now, I feel like after working in this field, I still don’t have clear answers, but I have better knowledge to manage these patients. I have a better sense of who needs close watch or further treatment after surgery. Now, I’m doing some good for an underserved population of patients who used to have so few options.”


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