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Sunandana Chandra, MD, MS, discusses how resectability, anatomy, prior therapy, and patient fitness guide multidisciplinary treatment decisions in CSCC.
Treatment selection in cutaneous squamous cell carcinoma (CSCC) should be individualized based on resectability, anatomic constraints, prior therapy, and patient fitness, with multidisciplinary coordination increasingly essential as immunotherapy use expands across disease settings, according to Sunandana Chandra, MD, MS.
In an interview with OncLive®, Chandra described the factors that inform up-front decision-making for patients with CSCC. She also delved into key multidisciplinary approaches utilized for disease management and provided a perspective on the evolving role of immunotherapy agents across the disease continuum.
Chandra is an associate professor of medicine (hematology and oncology) at the Northwestern University Feinberg School of Medicine at Northwestern Medicine in Chicago, Illinois.
Chandra: A lot of things go into that decision-making. If a person is before us with perhaps a small cancer that’s easily excisable or resectable with surgery, and they have no evidence of unresectable disease or distant disease, full surgical resection to render them disease-free is always something that we are hoping to achieve.
However, there are certainly situations where either the person is not quite well enough for the type of surgery that needs to occur, or—very commonly—it’s on an anatomical part of the body where a full surgical resection to render them disease-free might be quite difficult. That could be on the face, the ear, the nose, or perhaps the distal parts of the extremities—areas where a full surgical resection may not always be possible.
If those factors exist, or if a person is coming to us with recurrent disease, previously radiated disease, or metastatic disease, then often we may talk with them about a nonsurgical approach.
Factors that may put a particular CSCC at higher risk include tumor size; histology, meaning whether it’s well differentiated, moderately differentiated, or poorly differentiated, with risk increasing as differentiation worsens; whether there is perineural invasion, vascular invasion, or lymphovascular invasion; and whether tumor depth is quite significant.
Certainly, if [the tumor] has been radiated in the past, or if there was a very quick recurrence after prior definitive therapy, all of those factors play a role in how high-risk we consider that lesion to be.
Patient-specific characteristics are also important, such as [ECOG] performance status, functional status, comorbidities, and whether the patient is immunocompromised from another illness or disease state. All of these are very important considerations.
CSCC is one of those cancers that benefits tremendously from a multidisciplinary approach. It’s very important that all key stakeholders are aligned around what may be best for the patient in front of us.
That often includes dermatology, medical oncology, surgical oncology—sometimes very specific surgeons such as ear, nose, and throat surgeons, Mohs dermatologists, radiation oncologists, and pathologists or dermatopathologists. If we have questions about perineural invasion, lymphovascular invasion, or tumor depth, we often engage pathology colleagues. If there are imaging questions, we involve radiology.
Together, this becomes a robust discussion aimed at achieving consensus on the best approach for that individual patient.
The agents we currently use in unresectable, advanced, or metastatic CSCC all target the PD-1 axis. Cosibelimab is the newest FDA-approved drug; it’s an anti–PD-L1 antibody, and it also has a dual mechanism involving antibody-dependent cellular cytotoxicity.
How much that second mechanism contributes to cancer cell killing remains unclear, but it differentiates it from agents like cemiplimab-rwlc [Libtayo] or pembrolizumab [Keytruda], which are anti–PD-1 antibodies. Broadly, all of these drugs target the PD-1 axis and allow us to harness the patient’s immune system to fight the cancer. Other options we may consider include cetuximab [Erbitux], chemotherapy, or radiation, depending on the clinical scenario.
The phase 3 C-POST trial [NCT03969004] data showed a statistically significant advantage to using cemiplimab in the adjuvant setting, often after radiation. The goal of adjuvant therapy is to proactively reduce the risk of recurrence or metastasis.
The data are intriguing, but not all studies in the adjuvant space have been statistically significant, so this is not a one-size-fits-all approach. It requires honest discussions with patients about the potential benefits and risks. For example, in very frail patients or those with serious autoimmune conditions, PD-1–targeted therapy in the adjuvant setting may not be appropriate.
That’s another great question, and unfortunately, we don’t yet have definitive answers. As data mature, we’ll better understand outcomes for patients who are rechallenged after recurrence. Based on experience in other cancers, rechallenge may be reasonable depending on timing. If a patient progresses while actively receiving an anti–PD-1 agent, continuing it makes little sense. However, if recurrence occurs many months or years [after completing treatment], rechallenging with a similar agent may be biologically reasonable.
Timing is likely critical, and we’ll learn more as postprogression data from adjuvant trials become available.
We’ll see more combination approaches, often with a PD-1–axis backbone plus another target. CSCC is a highly immunogenic cancer, so further immune-based strategies make sense. We also need to consider sequencing, because more is not always better. If a patient doesn’t respond to PD-1–targeted therapy, what should come next?
Finally, many patients are immunocompromised, which can affect both efficacy and safety. This is an area where we still need better options, especially since only approximately 50% of patients respond to current therapies.
