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Consider radiologic imaging for high-risk cutaneous SCC, expert advises


AT ASDS 2022

As best practices for screening and surveillance of high-risk cutaneous squamous cell carcinoma (CSCC) continue to evolve, mounting evidence supports the use of radiologic imaging.

In a study published in 2020, Emily Ruiz, MD, MPH, and colleagues identified 87 CSCC tumors in 83 patients who underwent baseline or surveillance imaging primary at the Brigham and Women’s Hospital Mohs Surgery Clinic and the Dana-Farber Cancer Institute High-Risk Skin Cancer Clinic, both in Boston, from Jan. 1, 2017, to June 1, 2019. Of the 87 primary CSCCs, 48 (58%) underwent surveillance imaging. The researchers found that imaging detected additional disease in 26 patients, or 30% of cases, “whether that be nodal metastasis, local invasion beyond what was clinically accepted, or in-transit disease,” Dr. Ruiz, academic director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s, said during the annual meeting of the American Society for Dermatologic Surgery. “But if you look at the 16 nodal metastases in this cohort, all were picked up on imaging and not on clinical exam.”

Dr. Emily Ruiz assistant professor of dermatology at Harvard Medical School

Dr. Emily Ruiz

Since publication of these results, Dr. Ruiz routinely considers baseline radiologic imaging in T2b and T3 tumors; borderline T2a tumors (which she said they are now calling “T2a high,” for those who have one risk factor plus another intermediate risk factor),” and T2a tumors in patients who are profoundly immunosuppressed.

“My preference is to always do [the imaging] before treatment unless I’m up-staging them during surgery,” said Dr. Ruiz, who also directs the High-Risk Skin Cancer Clinic at Dana Farber. “We have picked up nodal metastases before surgery, which enables us to create a good therapeutic plan for our patients before we start operating. Then we image them every 6 months or so for about 2 years. Sometimes we will extend that out to 3 years.”

Some clinicians use sentinel lymph node biopsy (SLNB) as a diagnostic test, but there are mixed results about its prognostic significance. A retrospective observational study of 720 patients with CSCC found that SLNB provided no benefit regarding further metastasis or tumor-specific survival, compared with those who received routine observation and follow-up, “but head and neck surgeons in the U.S. are putting together some prospective data from multiple centers,” Dr. Ruiz said. “I think in the coming years, you will have more multicenter data to inform us as to whether to do SLNB or not.”

Surgery may be the mainstay of treatment for resectable SCC, but the emerging role of neoadjuvant therapeutics is changing the way oncologists treat these tumors. For example, in a phase 2 trial recently published in the New England Journal of Medicine, 79 patients with stage II-IV CSCC received up to four doses of immunotherapy with the programmed death receptor–1 (PD-1) blocker cemiplimab administered every 3 weeks. The primary endpoint was a pathologic complete response, defined as the absence of viable tumor cells in the surgical specimen at a central laboratory. The researchers observed that 68% of patients had an objective response.

“These were patients with localized tumors that were either very aggressive or had nodal metastases,” said Dr, Ruiz, who was the site primary investigator at Dana Farber and a coauthor of the NEJM study. “This has altered the way we approach treating our larger tumors that could be resectable but have a lot of disease either locally or in the nodal basin. We think that we can shrink down the tumor and make it easier to resect, but also there is the possibility or improving outcomes.”

At Brigham and Women’s and the Dana Farber, she and her colleagues consider immunotherapy for multiple recurrent tumors that have been previously irradiated; cases of large tumor burden locally or in the nodal basin; tumors that have a complex surgical plan; cases where there is a low likelihood of achieving clear surgical margins; and cases of in-transit disease.

“We use two to four doses of immunotherapy prior to surgery and assess the tumor response after two doses both clinically and radiologically,” she said. “If the tumor continues to grow, we would do surgery sooner.”

The side-effect profile of immunotherapy is another consideration. “Some patients are not appropriate for a neoadjuvant immunotherapy approach, such as transplant patients,” she said.

According to the latest National Comprehensive Cancer Network guidelines, surgery with or without adjuvant radiation is the current standard of care for treating CSCC. These guidelines were developed without much data to support the use of radiation, but a 20-year retrospective cohort study at Brigham and Women’s Hospital and the Cleveland Clinic Foundation found that adjuvant radiation following margin resection in high T-stage CSCC cut the risk of local and locoregional recurrence in half.

“This is something that radiation oncologists have told us for years, but there was no data to support it, so it was nice to see that borne out in clinical data,” said Dr. Ruiz, the study’s lead author. The 10% risk of local recurrence observed in the study “may not be high enough for some of our older patients, so we wanted to see if we could identify a group of high tumors that had higher risk of local recurrence,” she said. They found that patients who had a greater than 20% risk of poor outcome were those with recurrent tumors, those with tumors 6 cm or greater in size, and those with all four BWH risk factors (tumor diameter ≥ 2 cm, poorly differentiated histology, perineural invasion ≥ 0.1 mm, or tumor invasion beyond fat excluding bone invasion).

“Those risks were also cut in half if you added radiation,” she said. “So, the way I now approach counseling patients is, I try to estimate their baseline risk as best I can based on the tumor itself. I tell them that if they want to do adjuvant radiation it would cut the risk in half. Some patients are too frail and want to pass on it, while others are very interested.”

Of patients who did not receive radiation but had a disease recurrence, just under half of tumors were salvageable, about 25% died of their disease, and 23% had persistent disease. “I think this does support using radiation earlier on for the appropriate patient,” Dr. Ruiz said. “I consider the baseline risks [and] balance that with the patient’s comorbidities.”

Limited data exists on adjuvant immunotherapy for CSCC, but two ongoing randomized prospective clinical trials underway are studying the PD-1 inhibitors cemiplimab and pembrolizumab versus placebo. “We don’t have data yet, but prior to randomization, patients undergo surgery with macroscopic gross resection of all disease,” Dr. Ruiz said. “All tumors receive ART [adjuvant radiation therapy] prior to randomization”

Dr. Ruiz disclosed that she is a consultant for Sanofi, Regeneron, Genentech, and Jaunce Therapeutics. She is also a member of the advisory board for Checkpoint Therapeutics and is an investigator for Merck, Sanofi, and Regeneron.

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