Dr. Ruiz Presents 10 Clinical Highlights in Cutaneous Oncology at Maui Derm

It was a big year in nonmelanoma skin cancer research, and Emily Ruiz, MD, said she could have spent more than an hour at Maui Derm 2025 speaking just about squamous cell carcinoma. Instead, she presented her top 10 clinical highlights from 2024.

10. Improved understanding of metastatic basal cell carcinoma (BCC)

Dr. Ruiz cited studies published in 2024 on patterns of metastasis¹ and risk factors, therapeutics, and outcomes.²

“There really is limited data, so it’s exciting to now have some newer data from the last year,” she said.

New research also was published on cemiplimab in metastatic BCC after hedgehog pathway inhibitors.³

“When you look at the injected response rate here—it’s just under 50%—you might think that’s really low, however, remember this is all second-line, and for a disease that’s really tough to get a response to, that’s actually not so bad. I think it will be really interesting to see how it responds in the first line.”

9. Neoadjuvant hedgehog pathway inhibitor (HHI) therapy for BCC

“Obviously, surgery is the mainstay for treating basal cell carcinomas, but what can we do to augment the treatment?” Dr. Ruiz said.

She cited a trial of vismodegib in neoadjuvant treatment of locally advanced basal cell carcinoma.⁴

“What they reported was that downstaging occurred in 80%, and if the patients took more than 4 months of hedgehog inhibitors, 87% downstaging,” she said.

Dr. Ruiz also addressed the possibility of immunotherapy in a neoadjuvant setting for BCC.

“We don’t really have data other than anecdotal reports,” she said, “but there’s no reason to think that it wouldn’t work. Some people are a little bit dissuaded due to the refractory second-line setting of only 31%, but … I think it might be higher when it’s first line.”

8. Predictors of poor outcomes of cutaneous sarcomas

Cutaneous sarcomas can be difficult to address, Dr. Ruiz said.

“Given the lack of data, it’s hard to know what to do with these patients,” she said. “You know, you have a transplant patient who now has a spindle cell tumor; maybe it’s a sarcoma. Is surgery enough? Do you need to do anything else? And, really, the literature is sparse and there are different opinions. If you go to the sarcoma group vs if you go to the dermatologist group … you’ll get totally different treatment approaches.”

Dr. Ruiz and her colleagues undertook a multicenter study, collecting data on almost 400 cutaneous sarcomas, from which 33 developed “major poor outcomes,” and they ran a multivariable analysis of the risk factors that were predictive of those poor outcomes.

The variables they identified were immune status, tumor diameter, lymphovascular invasion, and depth of invasion.

“Those are the factors that might trigger you to think, ‘OK, should I do something a little bit more for this patient?’” she said.

They also found that 39% of cases with poor outcomes also had a local recurrence of the tumor.

7. ctDNA for skin cancer monitoring

Circulating tumor DNA (ctDNA), which is tumor cell-derived DNA circulating in the blood or saliva, can be useful for monitoring minimal residual disease (MRD), response to systemic therapy, and surveillance, Dr. Ruiz said. The tests can be run either by comparing blood with libraries that are maintained for tumors or by using a biopsy to look  for a specific mutational profile of the tumor from the tissue in the blood.

“It’s really exciting in merkel cell carcinoma; it works really well,” she said, citing a study that showed high prognostic accuracy.⁵

Unfortunately, she said, it does not work as well for cutaneous squamous cell carcinoma (cSCC) because some active tumors have undetectable ctDNA.⁶

“If you have undetectable disease, it’s really meaningless because you don’t know if it’s undetectable because it never was or if it’s undetectable because there’s no disease,” she said.

6. Prognostic models improve CSCC stratification

“We’ve always had challenges with staging,” Dr. Ruiz said, explaining that both the American Joint Committee on Cancer (AJCC) 8th Edition and Brigham and Women’s Hospital (BWH) systems have limitations—primarily that tumors in a given stage have the same designated risk, and half the poor outcomes occur in low stages.

Prognostic models can be a solution, Dr. Ruiz said, citing one model for metastatic risk⁷ as well as a new model called riSCC that is now available online. Dr. Ruiz and colleagues created riSCC by using more than 20,000 tumors from 12 centers in three countries. The model covers local recurrence, in transit metastasis, nodal metastasis, distant metastasis, and disease-specific death.

“We also compared our risk app to AJCC 8 and Brigham, and … the C-index, which is the measurement of performance, was much better for risk compared to AJCC and Brigham,” she said.

5. Immunotherapy for unresectable cSCC in renal transplant recipients

A study published in 2021 showed that acute rejection and graft loss was very high with immunotherapy in kidney transplant patients, although responses were good.⁸

However, Dr. Ruiz and colleagues published a study in 2024 on combining cemiplimab with mTOR inhibitors and pulse-dose prednisone for kidney transplant patients, and results were more positive.

“What was really remarkable was that we actually had zero graft losses, and we actually saw a 64% clinical benefit,” she said.

Another trial that is ongoing is promising, Dr. Ruiz said—ARTACUS is evaluating an intralesional RP1 injected into tumors, with a 25% response rate in SCC.⁹

“You might think (25%) is low, but again, these patients have very limited options,” Dr. Ruiz said.

4. Radiologic imaging for staging and surveillance in cSCC

Radiologic imaging should be considered for patients with cSCCs for both diagnosis and surveillance, Dr. Ruiz said.

“There are two roles of imaging at the diagnostic point,” she said. “The first is to evaluate the local extent of disease. … The second is to look at lymph node involvement.”

Dr. Ruiz said both CT scans (good for bone and soft tissue) and MRIs (good for perineural invasion) are strong options.

The 40-gene expression profile (40-GEP) test, meanwhile, can be used to enhance risk-aligned guidance for surveillance imaging in high-risk cSCC.¹⁰ However, the lack of radiologic surveillance guidelines from the National Comprehensive Cancer Network (NCCN) is a problem, Dr. Ruiz said.

3. Neoadjuvant immunotherapy for cSCC

Outcomes for advanced resectable cSCCs can be improved with neoadjuvants before surgery and adjuvants after surgery, Dr. Ruiz said.

Cemiplimab prior to surgery can produce “incredible responses,” she noted.¹¹

Does neoadjuvant immunotherapy impact long-term outcomes?

“The answer is yes and it is in our NCCN guidelines now and we can get it covered,” Dr. Ruiz said.

In terms of adjuvant therapy, new data on cemiplimab¹² is cause for optimism, she said.

“I didn’t think it could get better with neoadjuvant immunotherapy,” Dr. Ruiz said. “I thought it was really exciting and that that was going to be the best for squamous cell. But just this past week, we got a press release on adjuvant cemiplimab. … A 68% reduction in events in the cohort that got adjuvant immunotherapy after getting radiation, compared to patients who got placebo. Really exciting.”

2. Mohs surgery improves outcomes

Either Mohs or another form of complete peripheral margin assessment is recommended in the NCCN guidelines for very high-risk and high-risk SCCs.

“It’s really important to understand the differences between Mohs and wide local,” Dr. Ruiz said. “The way I like to describe it is: Mohs is like unwrapping a peanut butter cup and looking at that paper—you’re looking at the whole margin—whereas wide local you’re taking pieces of a bread loaf out and you’re looking at less than 2% of the margin.”

Two upcoming studies—one under review and one accepted for publication—comparing Mohs to wide local excisions looking for high-stage tumors showed that Mohs is cutting the risk of “basically all outcomes” in half, she added. Mohs is also preferred for basal cell skin cancer and larger/deeply invasive tumors, she said.

1. Multidisciplinary care saves lives

Dr. Ruiz concluded her presentation by citing a study on the impact of multidisciplinary cancer conferences on overall survival.¹³

“Multidisciplinary care does save lives,” she said. “[The study shows that] in other cancers, actually working as a team prolongs survival 19 months to 30 months.”

1. Groover M, et al. Patterns of metastasis from a multicenter cohort of metastatic basal cell carcinoma. J Am Acad Dermatol. 2024;90(6):1252-1254. doi: 10.1016/j.jaad.2024.01.069. Epub 2024 Feb 7.
2. Groover M, et al. A multicenter real-world analysis of risk factors, therapeutics, and outcomes of patients with metastatic basal cell carcinoma. J Am Acad Dermatol. 2024;90(3):545-551. doi: 10.1016/j.jaad.2023.10.060. Epub 2023 Nov 8.
3. Lewis KD, et al. Final analysis of phase II results with cemiplimab in metastatic basal cell carcinoma after hedgehog pathway inhibitors. Ann Oncol. 2024;35(2):221-228. doi: 10.1016/j.annonc.2023.10.123. Epub 2023 Dec 9.
4. Bertrand N, et al. Vismodegib in neoadjuvant treatment of locally advanced basal cell carcinoma: First results of a multicenter, open-label, phase 2 trial (VISMONEO study): Neoadjuvant Vismodegib in Locally Advanced Basal Cell Carcinoma. EClinicalMedicine. 2021;35:100844. doi: 10.1016/j.eclinm.2021.100844.
5. Akaike T, et al. Circulating Tumor DNA Assay Detects Merkel Cell Carcinoma Recurrence, Disease Progression, and Minimal Residual Disease: Surveillance and Prognostic Implications. J Clin Oncol. 2024;42(26):3151-3161. doi: 10.1200/JCO.23.02054. Epub 2024 Jul 25.
6. Kim EY, Ruiz ES, Hanna GJ, Thakuria M, Silk AW. Sensitivity of personalized circulating tumor DNA assay in advanced cutaneous squamous cell carcinoma. J Am Acad Dermatol. 2024;90(2):427-429. doi: 10.1016/j.jaad.2023.10.011. Epub 2023 Oct 14.
7. Rentroia-Pacheco B, et al. Personalised decision making to predict absolute metastatic risk in cutaneous squamous cell carcinoma: development and validation of a clinico-pathological model. EClinicalMedicine. 2023;63:102150. doi: 10.1016/j.eclinm.2023.102150.
8. Murakami N, et al. Immune Checkpoint Inhibitors in Solid Organ Transplant Consortium. A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant. Kidney Int. 2021;100(1):196-205. doi: 10.1016/j.kint.2020.12.015. Epub 2020 Dec 24.
9. Migden MR, et al. Abstract CT003: Initial results from an open-label phase 1b/2 study of RP1 oncolytic immunotherapy in solid organ transplant recipients with advanced cutaneous malignancies (ARTACUS). Cancer Res. 2024;84(7_Supplement):CT003. Doi: 10.1158/1538-7445.AM2024-CT003.
10. Ruiz, et al. The 40-gene expression profile (40-GEP) test enhances risk-aligned guidance for surveillance imaging in high-risk cutaneous squamous cell carcinoma (cSCC). Presented at the 2024 American Society for Dermatologic Surgery (ASDS) Annual Meeting. October 2024.
11. Gross ND, et al. Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma. N Engl J Med. 2022;387(17):1557-1568. doi: 10.1056/NEJMoa2209813. Epub 2022 Sep 12.
12. Adjuvant Libtayo® (cemiplimab) Significantly Improves Disease-Free Survival (DFS) After Surgery in High-Risk Cutaneous Squamous Cell Carcinoma (CSCC) in Phase 3 Trial. Regeneron website. Published January 13, 2025. Accessed January 31, 2025. https://investor.regeneron.com/news-releases/news-release-details/adjuvant-libtayor-cemiplimab-significantly-improves-disease-free.
13. Huang RS, Mihalache A, Nafees A, Hasan A, Ye XY, Liu Z, Leighl NB, Raman S. The impact of multidisciplinary cancer conferences on overall survival: a meta-analysis. J Natl Cancer Inst. 2024 Mar 7;116(3):356-369. doi: 10.1093/jnci/djad268.