Paul Nghiem, MD, PhD, is professor and founding chair of the Department of Dermatology at the University of Washington, Seattle. He is also a member of the Immunotherapy Integrated Research Center at Fred Hutch Cancer Center, Seattle.

Nghiem is considered one of the world’s top experts on Merkel cell carcinoma (MCC), a rare and aggressive form of skin cancer that most often occurs in people aged 50 years or older with histories of long-term sun exposure or a weakened immune system. In addition to caring for patients with MCC, Nghiem is actively involved in trials focused on the biology, treatment, and prevention of skin cancers.

Nghiem, who delivered a plenary lecture on MCC at the American Academy of Dermatology (AAD) 2026 Annual Meeting in March, spoke with Medscape Dermatology about the current state of MCC research and care, as well as outstanding challenges and future investigative directions.

There have been recent advances in treatments of MCC, including approved immunotherapy agents — retifanlimab (Zynyz), avelumab (Bavencio), and pembrolizumab (Keytruda) — which marked a shift from chemotherapy toward immunotherapy. What has the impact been so far on outcomes and survival?

The impact has been breathtaking in terms of outcomes and survival. Importantly, this is apparent not only in clinical trials and patients treated at academic centers but also in national statistics. In a 2025 study led by Kelly Paulson using Surveillance, Epidemiology, and End Results data, 2-year relative survival for patients with metastatic MCC increased from 23% to 54% between 2010-2012 and 2019-2021, corresponding with the introduction of immune checkpoint inhibitors. Thus, at a population level, survival for advanced MCC has more than doubled in the immunotherapy era.

In a previous lecture, you mentioned a new paper you co-authored in the Journal of the American Academy of Dermatology that addresses postoperative radiation in this population. What were the key findings of that research?

This study, led by Emily Huynh, BS, a researcher in the Department of Dermatology at the University of Washington, Seattle, reported that using far less postoperative radiation [after excision of MCC excised with narrow margins in patients with stage I to II MCC], with substantially less treatment burden and toxicity, still achieved superb local control. Importantly, local control was clearly better than when postoperative radiation was omitted.

This suggests that, for appropriately selected patients, we may be able to substantially de-escalate radiation without sacrificing its benefit.

What should dermatologists know about checking for and identifying MCC? Why is a multidisciplinary approach particularly useful for MCC?

Unfortunately, identifying MCC clinically is nearly impossible because there are really no specific features. However, a lesion that is new, asymptomatic, and rapidly growing on sun-exposed skin — particularly in an older or immunosuppressed person — deserves consideration for biopsy. It may or may not be MCC, but it could well be some form of skin cancer.

A multidisciplinary approach is particularly important because there are many trade-offs between treatment benefit and toxicity, and most patients will need more than one treatment modality. Surgery and radiation are commonly used early in management, with immunotherapy increasingly important in appropriate settings. Having input from multiple disciplines at the outset is therefore extremely helpful.

You have previously observed that, in the US, about 80% of MCC cases are related to the Merkel cell polyoma virus and 20% to sunlight — but this is flipped in Australia. What is the most likely explanation for this stark difference?

We believe the major explanation is ultraviolet (UV) exposure. Australia has a large population of fair-skinned people with very extensive lifetime sun exposure, and many develop MCC through UV-induced mutations without the Merkel cell polyomavirus being involved.

The converse is also informative. In Japan and Korea, where there is greater natural protection from UV through skin pigmentation as well as greater sun avoidance for cultural reasons, roughly 90% of MCCs are virus-associated. Thus, the geographic variation appears largely to reflect how much opportunity there is for UV radiation to provide an alternative pathway to developing MCC.

For those who may not be aware, what is the Merkel Cell Recurrence Risk Calculator and how does it work?

The Merkel Cell Recurrence Risk Calculator provides an individualized estimate of a patient’s risk of MCC recurrence. In addition to cancer stage, it incorporates simple but important variables that staging systems do not capture, including age, sex, immune suppression, primary tumor site and whether there was a known primary tumor. These factors can produce substantial differences in recurrence risk among patients with the same stage.

An especially important feature is that the calculator incorporates time since diagnosis. MCC recurrence risk falls rapidly over time, with the great majority of recurrences occurring during the first 3 years. Thus, the calculator can eventually tell a patient who has remained disease-free that very little recurrence risk remains and that active surveillance can be substantially reduced, typically by 4 or 5 years after diagnosis.

What are the biggest remaining challenges when it comes to treating MCC?

The biggest remaining challenge is what to do for patients whose cancers no longer respond to immunotherapy. Unfortunately, this ultimately applies to more than half of the patients who require systemic therapy: They either do not respond initially or later develop resistance.

There are many exciting trials addressing this problem, and it is where much of our effort is now focused. Because resistance to immune checkpoint therapy is a major problem across oncology, insights gained in MCC could also be relevant to more common cancers.

What are some of the trials currently underway that you find most intriguing from an MCC perspective?

We are particularly excited about two planned multicenter trials. Both are being developed as large trials, and we hope they will begin within approximately the next year.

The TOMMORRoW trial— Treatment On Merkel Molecular Recurrence with Retifanlimab Without Clinical Evidence of Disease — takes advantage of highly sensitive blood-based testing to identify molecular recurrence before disease becomes detectable by examination or imaging. Patients who become molecularly positive despite having no clinically evident disease have approximately an 80% chance of developing a clinically evident recurrence within a year. We plan to randomize these patients between the current standard (close observation) and early immunotherapy with retifanlimab. If successful, this strategy could allow us to substantially de-escalate therapy for the majority of patients who have no molecular evidence of disease, while identifying and treating the relatively small subset at very high risk.

We are also very excited about the MATRiX-2 trial, which is being developed for patients with MCC who are refractory to immunotherapy. This trial will evaluate a combination of low-dose radiation, immunotherapy and an ATR inhibitor, with the goal of restoring an effective immune response against the tumor.

There are also trials that target the DLL3 protein as well as plans for vaccine-based trials in MCC that could be very interesting.

Is there anything else you would like our clinician audience to be aware of regarding current knowledge of MCC and its related therapies?

The management of MCC is changing extremely rapidly. One particularly important advance is the development of two highly accurate blood-based biomarkers that can detect recurrences early and, for many patients, reduce reliance on routine surveillance imaging.

I would also emphasize the importance of obtaining multidisciplinary input early after diagnosis. Because MCC is uncommon and management involves important trade-offs among surgery, radiation, systemic therapy and surveillance, an initial consultation with a team experienced in MCC can meaningfully inform the treatment plan.

Nghiem reported his institution has received research funding from Incyte Corporation for biomarker studies in MCC.

Scott Harris has covered dermatology for more than a decade. He lives near Washington, DC.