In this podcast, Dr David Miller and Dr Vishal Patel discuss advances in the management of cutaneous squamous cell carcinoma (cSCC), exploring how neoadjuvant and adjuvant immunotherapy is transforming treatment paradigms and highlighting patient selection, toxicity management, and emerging strategies to improve patient care.
In this podcast, Dr David Miller, MD, PhD, FAAD and Dr Vishal Patel, MD discuss the evolving treatment landscape and immunotherapeutic strategies for cutaneous squamous cell carcinoma (cSCC) based on key data from pivotal studies that are reshaping standards of care, including:
Presenters:
David M. Miller, MD, PhD, FAAD
Director, Center for Merkel Cell Carcinoma
Co-Director, NMSC Multi-Disciplinary Clinic
Massachusetts General Cancer Center
Assistant Professor of Medicine and Dermatology
Harvard Medical School
Boston, Massachusetts
Vishal Anil Patel, MD
Director of Cutaneous Oncology, GW Cancer Center
Director of Dermatologic Surgery, GW Department of Dermatology
Associate Professor of Dermatology & of Medicine (Hematology/Oncology)
George Washington University School of Medicine & Health Sciences
Washington, DC
Link to full program:
https://bit.ly/3JbflO3
Dr. Miller: Hello, everyone. I am Dr. David Miller and I am joined today by my colleague and friend, Dr. Vishal Patel. Vishal, as always, it is great to be here with you.
Dr. Patel: Thanks, David. It is a pleasure to be here with you, especially good colleague, good friend, and expert in everything melanoma, non-melanoma skin cancer. Before we talk about what is new in cSCC, it is important to remember what has not changed, and cutaneous squamous cell carcinoma remains incredibly common, and the vast majority of cases that we see are cured with surgery alone, but there are a small subset that develop locally advanced or metastatic disease, and for those patients which account for the disproportionate share of mortality, it can be challenging, and that is what we are going to be talking about today.
What is exciting is how fast the field is evolving. For the first time, we now have immunotherapy approved in the adjuvant setting, cemiplimab for patients at high risk for recurrence after surgery and radiation, and that is really shifting how we think about treatment planning.
Dr. Miller: Exactly. It is truly a milestone moment for cSCC. We've moved from reactive care, treating recurrence once it happens, to proactive, preventive strategies designed to reduce recurrence and improve surgical outcomes, and throughout today's conversation, we are going to explore that full continuum, how neoadjuvant immunotherapy is helping downstage locally advanced tumors before surgery, how adjuvant PD-1 therapy is changing long-term outcomes for high-risk patients, what the data tell us about biomarkers, where they are useful, and where they fall short, and how we can use evidence-based management of immune-related adverse events to help keep patients safely on treatment.
Dr. Patel: Yes, it is really exciting, really interesting stuff. We'll also touch on some of the advanced treatment strategies for special populations, older adults, patients with limited life expectancies, patients with significant comorbidities. This is the majority of the types of patients that have cutaneous squamous cell carcinoma, the ones that have the advanced disease, and we need to think about balancing efficacy with tolerability.
Plus, we will look ahead to emerging approaches like intralesional immunotherapy for localized disease, a fascinating option, especially for me as a Mohs surgeon, thinking about how we can expand treatment for patients who cannot tolerate systemic therapy, but also not the ones that I want to cut on, not the ones that are good surgical candidates, really increasing our potential armamentarium of treatment options for these patients.
Dr. Miller: Vishal, that is a lot to cover, from prevention to personalization, but let us start by setting the stage with where we are today in cSCC management and why these new systemic options represent such a meaningful step forward.
So with that background, let us shift from prevention to what is happening before surgery, where immunotherapy is being used to make difficult operations less morbid and sometimes even unnecessary. The neoadjuvant setting has quickly become one of the most exciting frontiers in cSCC.
Dr. Patel: And not just cSCC, I mean, oncology as a whole, but cSCC is truly a great example of this innovative approach. And that story of that innovative approach really begins with early institutional experience at MD Anderson. A pilot study by Ferrarotto and colleagues where patients with resectable, but locally advanced cSCC received two doses of neoadjuvant cemiplimab before surgery.
And the results were remarkable. Fifty-five percent of those patients after two doses achieved a pathologic complete response. No tumor within the resected specimen. And another 20% had a major residual tumor regression, about less than 10% viable cells.
Now, that is a single-institution trial, but it essentially put neoadjuvant PD-1 therapy on the map for cSCC.
Dr. Miller: And those findings were later confirmed in the Phase III study by Gross, et al., published in the New England Journal of Medicine, where 50% of patients achieved a complete pathological response and another 13% had a major pathological response.
Dr. Patel: And we started also seeing confirmation across multiple other agents. The neo CE study looked at perioperative cemiplimab and reported pathologic responses in over half of patients, while Amatore, et al. at UPMC presented Phase II data with pembrolizumab at ASCO in 2024, showing a 57% pathologic complete response rate and an additional partial response, about 8% of patients.
Likewise, D.V. et al. in 2024 also demonstrated promising activity of atezolizumab, further reinforcing there appears to be a class effect. This neoadjuvant effect is not just PD-1. It can also work in PD-L1 blocking agents and across all the various agents.
Dr. Miller: And now we have combination data from the MATISSE trial, published in Nature Medicine, that randomized study compared nivolumab alone to nivolumab plus low-dose ipilimumab before surgery. Both arms performed impressively, 55% pathologic response with nivo alone and 80% with the combination. And about 20% of patients declined surgery altogether after achieving a complete clinical remission, and most remained disease-free beyond two years.
Dr. Patel: It is really extraordinary, Dr. Miller. I mean, these responses tend to occur very early, within 6-8 weeks. Toxicity has been acceptable, and we will dive into that a little bit more.
But the potential for functional preservation, it is really tremendous for a parotid or a scalp tumor where surgery would mean facial nerve sacrifice or a large free flap reconstruction or even in areas just that are complex in the corner of the eye involving the nose, where the lesions may be smaller, but equally as disfiguring. Neoadjuvant immunotherapy can convert an otherwise morbid and difficult operation into something much more manageable.
Dr. Miller: Exactly. And the consistency across the studies, whether cemiplimab, pembrolizumab, atezolizumab or nivo ± ipi is really striking, with pathological response rates hovering between 55-80% and durable disease control. And, you know, this is not just research anymore.
The latest NCCN guidelines formally acknowledges neoadjuvant PD-1 therapy as an option in select patients with borderline resectable, rapidly progressive, or very high-risk cSCC, especially when surgery alone would cause major functional or cosmetic loss. That endorsement really validates what we are seeing clinically.
Dr. Patel: And Dr. Miller, would you say that it has moved from investigational, more to the integrated or standard care practice that you are considering?
Dr. Miller: Absolutely. If I think about the most common reason I am not writing a prescription for anti-PD-1 therapy in our cSCC patients, it is in this preoperative setting.
Dr. Patel: Yes, I agree as well. It has moved from investigational to integrated, and I think of it as almost a pseudo first-line, or at least what we are reaching for and thinking about first. But we need to think about team-based planning when thinking about that approach, how to make that decision upfront, whether to start with systemic therapy instead of surgery, or when surgery is going to be incorporated, if at all.
It is a huge cultural shift. It is a huge shift in terms of how we think about this disease and its treatment.
Dr. Miller: And it is a logical transition to our next topic, how adjuvant postoperative PD-1 therapy is building on this same success to reduce recurrence risk after surgery.
So far, we have talked about the neoadjuvant setting, but let us shift gears to this adjuvant setting in space. Patients who've already undergone surgery, ± radiation, but remain at high risk for recurrence. This is where we have finally seen Phase III data that are reshaping this field.
Dr. Patel: Yes, the landmark study we are talking about here is the C-POST Phase III trial that tested adjuvant cemiplimab compared to placebo after surgery and radiation for high-risk cSCC. Now, this was a very long trial, almost a decade-long trial to answer this question, and it was very well thought out. That high-risk portion deserves a little bit of clarification because high-risk can mean a lot of different things. But high-risk in this scenario is really the worst of the worst locally advanced tumors.
High-risk, defined as tumors that had extracapsular extension of nodal metastases, or when there was nodal metastases, there were multiple, three or more, or tumors that had in-transit disease, which we know gives us concern of more diffuse potential spread, as well as deep primaries, primaries going all the way down to the bone or involving perineural invasion of large named nerves, clinically significant nerves, nerves where you can see radiographic invasion of the tumor.
And the results in those patients were practice-changing, I would say, Dr. Miller.
Dr. Miller: Right. C-POST enrolled 415 patients and showed a 68% reduction in the risk of recurrence or death with cemiplimab compared to placebo alone. Hazard ratio 0.32. That is about as good as I have seen in the adjuvants across diseases. Now, median follow-up was around 2 years, and a 24-month disease-free survival was 87% with cemiplimab versus 64% with placebo. Now, that is an enormous difference for a disease where recurrence after surgery and radiation used to mean very limited options.
Dr. Patel: Dr. Miller, you said this is as good as it gets. Maybe you can give a little color to our audience here and how they should think about that number, that hazard ratio of 0.32. Can you put that into context with the melanoma and the landscape of adjuvant therapy that has been approved for over a decade now?
Dr. Miller: Yes, that is right. When you think about skin cancer and you think about the diseases where we are using postoperative systemic therapy, most of them are postoperative immunotherapy, melanoma is that disease. Now, we do have some data in Merkel cell carcinoma in the postoperative setting, but nothing approved.
So, melanoma is where we are using single-agent anti-PD-1, combination BRAF-MEK inhibition, and the studies that validated those use in melanoma were impressive. Hazard ratios that range between 0.4, 0.5, 0.6. So, significant advantages for patients. But hazard ratio of 0.32 really is a tremendous risk reduction.
Dr. Patel: And not only a tremendous risk reduction, but impressive that the benefit was consistent across subgroups of the patients enrolled in the trial, both nodal disease patients, non-nodal patients, those risk factors that we discussed, either the primary tumor or patients that had nodal disease, or whether the tumors were PD-L1-positive, PD-L1-negative, the toxicities were manageable, no new signals. Grade 3 or higher immune-related events was about 24% of patients' treatment, and the treatment discontinuation, in about 10%, so consistent with kind of what we think about from an immunotherapy class standpoint as well as toxicity profile. And importantly, as I said, no new safety signals. It really reinforces the idea, the feasibility of using adjuvant PD-1 blockade.
Dr. Miller: And these data led to the FDA approval of cemiplimab as the first and only immunotherapy indicated for adjuvant treatment of high-risk cSCC following surgery and radiation. It is the first definitive advance we have seen in this disease setting.
Dr. Patel: What makes this especially interesting, the adjuvant landscape so interesting right now? That not all the data was uniformly positive. In fact, we had two trials running at the same time.
The other trial, a large Phase III trial, was KEYNOTE-630. This tested pembrolizumab compared to placebo after radiation and surgery in high-risk cSCC, and it was stopped early for futility. And at interim analysis, there was no improvement in recurrence-free or overall survival.
So now, we have two Phase III trials of adjuvant PD-1 therapy in cSCC, in the high-risk cSCC after surgery and radiation. C-POST with cemiplimab, KEYNOTE-630 with pembrolizumab, but with seemingly different outcomes. One positive, one negative.
How do you make sense of this, Dr. Miller?
Dr. Miller: Well, it is really interesting. I think this is where things do indeed get a bit nuanced. In our perspective on the science editorial that we recently published in the Journal of Cutaneous Oncology, we emphasize that these are not necessarily contradictory results, just different in meaningful ways.
The trials varied slightly in eligibility and timing, factors that can shape outcomes. And it is worth remembering that KEYNOTE-630 has only been presented in abstract form so far. So, not yet peer-reviewed. Therefore, many of the finer details are still emerging.
Dr. Patel: And that brings up some of those other key points, that these trials were not truly opposite. They are not opposite results necessarily. Even in the KEYNOTE-630 trial, the hazard ratio still favored pembrolizumab, around 0.76. It just did not reach statistical significance. And when you look at the tolerability data, both studies trend in the same direction. PD-1 blockade reduces the risk of recurrence. The difference is not about one drug working and another not.
It is more about nuances in trial design, eligibility, and the baseline risk.
Dr. Miller: Exactly. And we actually did a Bayesian synthesis of the two trials, using C-POST as the prior, KEYNOTE-630 as the likelihood, to see what happens when you combine the evidence, rather than treating it as a binary. And the results showed a broadly consistent protective effect for PD-1 therapy across both data sets.
And I think that is really the broader message: not to think of these as contradictory studies, but as complementary pieces of evidence pointing toward a benefit that is strongest in the highest-risk, fully resected patients.
Dr. Patel: That is a great way to put it, David. I think that is really important for our listeners to key on and understand. It certainly is the way that I understand the two trials, that the quote-unquote negative trial is actually a conformational study from the standing of C-POST.
The evidence supports adjuvant immunotherapy as a new standard. And the key is for select high-risk patients. It reminds us that not all patients will equally benefit. And by understanding the difference between the two trials, we can tease out how the timing, the specific risk factors and the risk profile, as well as how a clinician and a multidisciplinary team can synthesize that data and make a decision is key to getting it right and utilizing that information.
Dr. Miller: Such an important point. The bigger takeaway is that we finally have one positive, fully powered Phase III trial with a survival signal. And the NCCN guidelines now reflect that. They designate adjuvant cemiplimab as a Category 1 preferred option for patients with high-risk disease after surgery and radiation.
Dr. Patel: And we can say now with confidence that adjuvant cemiplimab is the new standard of care for the right patient. And that is the key. Those with deep invasive primaries, those that go and invade the bone, those with perineural spread, not just any perineural, but clinical or radiographic nerves, the very large caliber, the nerves that when you resect a tumor, you can actually see the nerve. Or patients with nodal involvement, and not just one node, but multiple nodes, or nodes that are more extensively involved, such that the tumor is spreading outside the capsule. And in those patients, and what is key is that some of those risk factors, you do not realize until after you have done surgery.
And so after resection, when these patients are quote-unquote upstage, or the surgeon and the team realize this is a much higher risk than they initially anticipated, the patients are going to be recommended for radiation. And now we can consider adjuvant cemiplimab therapy.
It is what is exciting in how this is all coming together. We discussed earlier how we had really exciting evidence about the use of immunotherapy before surgery. Now we have confirmatory evidence that has an FDA approval for after surgery. Neoadjuvant can shrink tumors, adjuvant can prevent recurrences. It really is quite remarkable. It is a remarkable shift in how we think about and how we manage this disease.
Dr. Miller: It absolutely is. It is important data to have. You know what? It is still, to me, like there's still some unanswered questions. We know in melanoma, for example, we are thinking we have data from S1801 and NADINA, that show that preoperative immunotherapy is superior to postoperative immunotherapy. And squamous cell carcinoma, we do not have that data.
We do not know. So now we have data that shows, again, we talked about the clinical benefit of preoperative therapy, we talked about the benefit of postoperative immunotherapy. And I think you really highlight and underscore, it is a potential standard for the right patient. But we still need to figure out who that right patient is and how to employ preoperative and postoperative options.
Dr. Patel: And, David, we are also early in this period, right? And so things are evolving.
And I like to think that this gives us options for our patients, patients who did not have an option for neoadjuvant and recognize they are very-high risk, well, now we can give adjuvant. That does not necessarily mean that that is the approach I am taking when a patient walks in the door, if we have that locally advanced tumor. But I think that understanding it as things evolve, as it has with melanoma, we have moved earlier, we are moving to smaller doses. It is about optimizing patient selection and managing toxicities. Would you not say?
Dr. Miller: Yes, I totally agree. And I think, again, just to go back to this idea of a standard of care, like it is a standard. It is a standard option. But I think it is also reasonable to have a detailed conversation, nuanced conversation with the patient that, yes, at this moment, we have a disease-free survival advantage. We do not have an overall survival advantage that is definitively established with using postoperative treatment. And we do not know, are we able to rescue or salvage patients that recur after surgery in radiation with a neoadjuvant approach?
There is still a lot that we have to learn in this field and learn from our patients. But it is an important option, certainly, to have.
Dr. Patel: And with this disease, it is important, whether you are 60 or 80, and I think that is what you are getting at as well, is that because of that continuum of presentation, standard can mean a different thing for a different patient.
Dr. Miller: Absolutely. It is about optimizing patient selection and managing toxicity.
So it is going to bring us to our next section, biomarkers and risk stratification, the next piece of the puzzle. So listeners might be wondering, should I be ordering tests like PD-L1 or other biomarkers before starting these therapies?
Dr. Patel: Yes, it is a logical question. In a lot of other oncological solid tumors, that certainly is considered or, you know, looking at targeted mutations and profiles. In short, the answer is no.
For cutaneous squamous cell carcinoma as a whole, we do not utilize biomarkers in C-POST and other data sets. The PD-L1 expression has not been predictive. That does not mean that there is a correlation, but it has not necessarily been predictive.
There are tumors that are high or low levels that both have responded. Right now, we are really relying more on the clinical risk factors, the clinical presentation, the tumor size, the nodal involvement, the perinodal invasion. Again, pulling from the clinical trial inclusion criteria, as being which are the patients that were enrolled and had a benefit, those are the ones that are driving decisions today.
Dr. Miller: Exactly, and while tumor mutational burden and novel biomarkers are exciting areas of research, they are not ready yet for routine practice in cSCC. I think the take-home should be: do not wait on a biomarker result if the patient is clearly high-risk.
Dr. Patel: Yes, and as we celebrate the impact of immunotherapy in cSCC, we need to acknowledge its complexity. These are not benign treatments. Even when toxicity is not life-threatening, it can be profoundly life-altering.
Patient selection, multidisciplinary care are absolutely critical when initiating these therapies.
Dr. Miller: Right. Most papers headline the rates of grade 3 or higher immune-related adverse events, usually somewhere between 10-25% across the neoadjuvant and adjuvant trials, but that does not capture the full story. What we see in practice is that a much larger group of patients experience moderate grade 2 toxicities, rashes, fatigue, diarrhea, thyroiditis that may not make the manuscript table upfront, but still causes a major burden.
Dr. Patel: Absolutely. Those moderate events are often the ones that disrupt daily life. They can lead to steroid courses, treatment holds, repeat labs, specialist visits. They may not require hospitalization, but they absolutely can impact the quality of life. That is what I think is underappreciated, the time toxicity of these drugs, the clinic visits, the scans, the lab drugs, the coordination that it takes to keep patients on track.
Dr. Miller: Completely agree. It is not just time toxicity. There is financial toxicity and emotional fatigue too. Managing chronic low-grade rash or diarrhea for months on end can wear patients down. That is why these therapies should not be given lightly. They need to be administered by clinicians and teams who are experienced in recognizing subtle early signs and know when to intervene.
Dr. Patel: It is where the multidisciplinary piece becomes essential. Also, I will say for clinicians who may be thinking, "I am not going to utilize this," or "this is not really within my wheelhouse," early identification is key. Being aware of patients on it and keeping your antennas up to be able to get them to the multidisciplinary team is key as well.
That multidisciplinary team can include dermatologists, oncologists, pulmonologists, gastroenterologists, cardiologists, everyone working from the same playbook. Many centers now use a standardized toxicity protocol as well as patient education materials, some shared electronic alerts that can help ensure that issues are not missed between visits.
Dr. Miller, are you using any of those types of systems within your integrated center in Boston?
Dr. Miller: Absolutely. We have a pretty well-established network now of specialists that we refer to. We have a specialized, protocolized inpatient service or severe immunotherapy complication service that really focuses on helping patients get through the treatment journey as successfully as possible.
We also have to be honest about patient selection. Not every patient benefits equally. For some, the potential for immune-related toxicity outweighs the advantage.
I think the best outcomes come when we individualize therapy, as you mentioned before, factoring in comorbidities, patient support systems, and how much follow-up intensity a patient can realistically tolerate.
Dr. Patel: Yes. PD-1 therapy has transformed outcomes when we think about just the disease state and think about patients that did not have many options. It has been transformative, but it has also redefined what care means, what it means for them.
And that is why I think I go back to understanding how that conversation or that decision is so different from a 50- and 60-year-old to an 80- or 90-year-old. We are not just managing the disease and the drug. We are managing the whole ongoing immune process, and that can be different at different stages of life.
These treatments clearly save lives. If you have not had a chance to look at the images, they are remarkable, eye-opening resolutions of tumors. But they also require vigilance, experience, and respect of the human cost that comes with that success.
Dr. Miller: And as we have been saying, these advances are incredibly meaningful, but they also demand thoughtful integration into real-world practice. That includes understanding how immunotherapy fits alongside other modalities and how we tailor care for patients with comorbidities or advanced age.
Dr. Patel: Exactly. And I know I have been hammering the point around age, but it is also around different types of treatment. One area that is gaining momentum is radiation immunotherapy sequencing.
Radiation does not just control tumors. It can actually act as an immune primer. Moderate hypofractionated regimens, such as 8 gray or 3 fractions, appears to release a stronger immunogenic signal than conventional low-dose schedules by inducing a type 1 interferon signaling and antigen release.
Most of the data are from preclinical or translational, but the biological rationale is compelling. I can say from patients that we have treated in the metastatic setting, that required radiation for bone mets, for potential impending fractures just from a safety standpoint, we have sometimes seen some robust responses because what we believe is that up-regulation, the antigen release, and that up-regulation of type 1 interferon signaling. But ultimately, we need more prospective trials to explore this optimal sequencing with PD-1 therapy.
Dr. Miller: Totally agree. Also, we are seeing parallel innovation in intralesional immunotherapy, which you mentioned earlier. A Phase I trial of intralesional cemiplimab and recurrent resectable cSCC reported a pathological complete response rate of 76% across dose levels with no new safety signals. For frail or comorbid patients who cannot tolerate systemic therapy, targeted intralesional delivery could achieve meaningful local control while potentially minimizing systemic toxicity.
Dr. Patel: Exactly. And importantly, Phase III randomized trial of low-dose intralesional cemiplimab versus primary surgery, specifically Mohs surgery, in early-stage cSCC is now underway. We are very excited about this.
The study is called CLEAR CSCC. It is a trial in progress. No results yet. But this intralesional approach, while it may be investigational, it is a very promising option that I certainly am watching closely for, thinking about my patients that are frail or comorbid, or ones that just have had so many surgeries that now they have become fatigued or they have run out of areas that we can do surgery safely and easily, and ones that we are not able to necessarily give or have evidence to suggest utilizing systemic therapy in those earlier lower-risk tumors.
What that dovetails us into is also the geriatric population. This represents the majority of our cSCC patients. The good news is that the efficacy appears to be preserved even in patients over 80, but the tolerability profile is different.
Fatigue, thyroid dysfunction, dermatitis can have outsized effects and impacts on independence and quality of life. Tools like the G8 screening assessment or comprehensive geriatric evaluation can help us individualize treatment intensity.
Dr. Miller: True. And this is really about balance: Bring the benefits of immunotherapy to more patients while being honest about the trade-offs. Whether it is combining radiation, using intralesional approaches, or treating older adults, the key is precision. Matching the intervention to the patient's physiology, their goals, and their support system.
Dr. Patel: Well said. Progress for cSCC is not just about new drugs. It is about responsible implementation. And that extends also to our implementation of how we utilize surgery, especially with an aging population, a skin cancer epidemic, the cost of that to the healthcare system. We need to leverage science while respecting the lived realities of the patients that we are treating as well as the whole health ecosystem.
Dr. Miller: So today we have covered a lot. Neoadjuvant therapy, adjuvant cemiplimab, biomarkers, toxicity management, and emerging strategies like radiation immunotherapy, and intralesional approaches. Dr. Patel, this field is moving fast.
Dr. Patel: Yes, it is moving very fast. But the practical message is simple: Use what we have now for high-risk patients, stay proactive about toxicity, and be ready to integrate new strategies as data matures.
Dr. Miller: Well said, But before we sign off, let us look briefly at what is on the horizon. Where do you see the next breakthroughs coming from, Vishal?
Dr. Patel: Well, I think we are going to see big shifts, three big shifts, over the next few years. First, personalized immunotherapy. Moving away from a one-size-fits-all PD-1 blockade towards risk-adapted or biomarker-informed strategies. We are learning that spatial immune profiling, circulating tumor DNA (ctDNA) and early on-treatment response signatures may help refine who truly benefits from prolonged therapy.
Second, we are also likely to see next-generation immunomodulators entering into the picture. Things like bispecific checkpoint antibodies, STING agonist and oncolytic viral therapies that are designed specifically for skin cancers.
Early trials are already showing us intriguing signals, but I will also say third, and what I am really excited about, and I am going to push you to tell us a little bit about your research, Dr. Miller, is pushing the envelope a little bit forward in reducing dose, dose frequency, or even utilizing preventative approaches with immunotherapy that I think are really exciting, that I think our listeners would maybe like to get a brief glimpse of as well.
Dr. Miller: Yes, I think there are areas to innovate to continue to help patients. We have, all of us, a collection of patients that have what people refer to as actinic dysplasia syndrome or field cancerization, where they have developed scores of keratinocyte carcinomas over their lifetime, and they are really suffering from treatment fatigue, and also very high-risk for regional and distance spread.
At the moment, we just have kind of an inferior, suboptimal armamentarium for those patients. Can we use immunotherapy, some of these strategies that we have been talking about for the last half hour, to help those patients prevent future malignancies? The immunopreventive strategy front is one that I find interesting and one that I am really inspired to innovate on.
Then, how many doses of therapy do these patients truly need is a question that has not been answered as well. We look to the pharmacokinetics of some of these antibodies, some of the responses that you mentioned earlier about rapid responses. We need to better define how many doses of immunotherapy a patient actually needs in order to address some of those other toxicities that we talked about, the time toxicity, the financial toxicity.
I think we need to find the right amount of treatment. We do not want to undertreat people, but we do not want to overtreat them either. I think those are really important areas.
I will add another area that needs to be I am excited about, and that is real-world integration. That is another frontier: How we implement all of this safely outside tertiary centers, simplifying dosing schedules, building community-based toxicity monitoring, and creating pragmatic pathways for older patients or rural patients. It is going to be essential to expanding access.
Dr. Patel: Exactly. The science is moving quickly, but the real success will be measured by how broadly and equitably we deliver these advances. If we can make these therapies understood by all providers and patients, as well as accessible, affordable, and sustainable, then with this growing epidemic of skin cancer, we will truly change and make a dent and improve the outcomes of patients with cSCC.
Thank you, Drs. Miller and Patel for a great discussion and for sharing your expertise with us. And many thanks to you, our listeners, for joining us today. Be sure to check back for more episodes on important oncology topics!