AAD 2025 Recap: Advanced Skin Cancer

Vishal Anil Patel, MD, serves as director of cutaneous oncology at the GW Cancer Center and director of dermatologic surgery in the GW Department of Dermatology, and is an associate professor of dermatology and of medicine/oncology at the George Washington University School of Medicine & Health Sciences in Washington, DC.

In this feature video Dr Patel discusses how immunotherapies and targeted agents are reshaping the treatment landscape for advanced skin cancer. He highlights the role of multidisciplinary care, patient-centered decision-making, and the expanding utility of injectable and neoadjuvant therapies. Dr Patel also offers practical insights into toxicity management and the evolving role of dermatologists in guiding complex care.

For patients with advanced skin cancer who experience disease progression despite treatment, what emerging therapeutic strategies or clinical trial options are most promising?

Dr Patel: There are a number of changes in the way we think about skin cancer, and specifically advanced skin cancer. Patients who progress after traditional treatment methods—such as surgery or adjuvant radiation therapy—now have a host of treatment options in both melanoma and non-melanoma skin cancer. 

We've seen the advent of immunotherapy, and that immunotherapy is being pushed further and further forward in the treatment journey. It's now being utilized in a neoadjuvant fashion—administered before a larger surgery—in hopes of achieving a more durable response and potentially avoiding longer, more toxic adjuvant therapies. We've seen some game-changing data in both melanoma and squamous cell carcinoma in the last year or two, and that has certainly changed how we think about these advanced patients. 

There are many treatments coming on the horizon—some of particular importance to dermatologists because they come in the form of injectable therapies, including injectable oncolytic viruses that are now seeing approval in refractory melanoma to be combined with systemic immunotherapy. These may be therapies dermatologists are already comfortable using, like existing targeted therapies, which are also being evaluated alongside new and interesting agents. 

There are numerous clinical trial options for patients who have progressed, but also for those with earlier-stage disease. Options include injectable PD-1 therapies for tumors that are non-surgical for a variety of reasons or in patients seeking non-surgical alternatives. We’re seeing a major paradigm shift because of immunotherapies, and as a result, we’re rethinking how to best utilize the options already available.

Multidisciplinary collaboration is increasingly important in complex skin cancer management. How do you recommend dermatologists integrate medical oncology, surgical oncology, and radiation oncology into their treatment planning? 
Dr Patel: Because we’re seeing such a transformation in the therapies available—and the incorporation of more systemic and advanced therapies—it’s more critical than ever for dermatologists to be part of a multidisciplinary collaborative team. 

The traditional linear model—where patients were managed by a dermatologist, then referred to a Mohs or head and neck surgeon, and then handed off to a medical or radiation oncologist depending on whether surgery or systemic therapy was needed—has fundamentally changed. 

Patients are now being evaluated for systemic therapy before surgery. As mentioned earlier, this includes neoadjuvant approaches in both melanoma and non-melanoma skin cancer. Radiation is being considered alongside targeted therapies, such as hedgehog inhibitors in basal cell carcinoma, with new evidence showing improved outcomes. 

So, when dealing with complex or advanced disease—and I like to distinguish these from large tumors versus smaller, harder-to-treat tumors that dermatologists may see more often—these patients increasingly require input from multiple specialists to achieve the best outcomes. 

Dermatologists should begin to either formally or informally build networks of collaborators—people you can reach out to or co-manage patients with. Strengthen those ties, whether through formal tumor boards or informal channels like text threads, email chains, or listservs—resources that can help you stay up to date and tailor care across the diverse spectrum of skin cancer presentations.

What factors should dermatologists consider when determining whether a patient may benefit from systemic therapies or advanced surgical interventions? 
Dr Patel: First and foremost, shared decision-making with the patient is critical. Understanding the patient’s values, needs, and unique medical or social situation is essential to determining the right course of action. 

An elderly patient, for example, might not be a good candidate for systemic immunotherapy because of the potential side effects they may not tolerate well. On the other hand, they might also be poor candidates for surgery. Having these discussions with patients and their families is essential. 

There are other factors, too, such as how important it is to the patient to avoid downtime, or concerns about surgical cure rates or cosmetic outcomes. Dermatologists—who often know the patient best—play a key role in understanding these values and guiding discussions. They may not make the final treatment decision, but they are instrumental in educating patients on potential options, including newer therapies with less data, nonsurgical treatments, and systemic approaches that can often be confusing. 

It’s important to consider the whole patient and understand not only what the therapy offers, but when and how it fits into their treatment journey—before, during, or after surgery.

Many advanced skin cancer treatments, including immunotherapies and targeted therapies, come with significant adverse effects. What are the most critical toxicities dermatologists should be aware of, and how can they best mitigate them? 
Dr Patel: In the current era of immunotherapy, particularly for skin cancer, we are using systemic checkpoint inhibitors like pembrolizumab, nivolumab, and ipilimumab for melanoma, and cemiplimab for squamous and basal cell carcinoma. 

Dermatologists should be aware that these therapies can cause side effects in virtually any organ system. They stimulate the immune system and can lead to inflammatory responses—from hepatitis to pneumonitis to nephritis. But more commonly, we see cutaneous adverse events such as dermatitis, blistering disorders, and other inflammatory skin conditions. These are likely the most common side effects dermatologists will encounter. 

Importantly, these reactions can occur not only during therapy but also after it has been completed. 

Other therapies, like targeted treatments—hedgehog inhibitors for basal cell carcinoma or BRAF/MEK inhibitors—also have side effect profiles dermatologists should be aware of. For instance, hedgehog inhibitors like sonidegib and vismodegib, while sharing a mechanism of action, have pharmacokinetic differences that allow for dose modifications to mitigate side effects. 

Sonidegib, for example, allows for longer drug holidays while maintaining efficacy, helping patients tolerate therapy longer and possibly delaying or avoiding immunotherapy altogether. Understanding these nuances is increasingly important as we integrate these therapies earlier in the disease course.

Is there anything else you’d like to share with your colleagues regarding advanced skin cancer? 
Dr Patel: As the gatekeepers of the skin, dermatologists are the first point of contact for most patients with skin cancer. We’re experts in diagnosis, management, and referrals. 

It’s important to stay informed about advanced presentations and the evolving landscape of treatment. The future holds exciting changes—such as anti–PD-1 therapies shifting from infusion to subcutaneous delivery, which could make them more accessible to both patients and providers comfortable administering them. 

Additionally, intralesional therapies are being explored for earlier tumors—well within the scope of dermatologists. Even if you’re not using these therapies yet, understanding the full spectrum of disease, from melanoma to non-melanoma and rarer tumors, is vital. This knowledge will be increasingly important in the future of skin cancer care.