Available Staging Systems for Cutaneous Squamous Cell Carcinoma

EP: 1.Cutaneous Squamous Cell Carcinoma: Incidence and Risk Factors

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EP: 2.Available Staging Systems for Cutaneous Squamous Cell Carcinoma

EP: 3.Optimal Risk Stratification in Patients With Cutaneous Squamous Cell Carcinoma

EP: 4.Defining Resectability in CSCC

EP: 5.Staging and Risk Stratification’s Impact on Treatment Approach in CSCC

EP: 6.Real World Experience With Resectable Cutaneous Squamous Cell Carcinoma

EP: 7.Evolving Treatment Paradigm of Resectable CSCC

EP: 8.Clinical Experience With Neoadjuvant IO Therapy in Melanoma

EP: 9.Lessons Learned in Other Cancers and Suggested Endpoints in Future Trials

EP: 10.Neoadjuvant IO Therapy Trials in Resectable CSCC and Cemiplimab Data Updates

EP: 11.CSCC: Translating Cemiplimab Data Into Practice

EP: 12.Other Emerging Treatment Modalities in Cutaneous Squamous Cell Carcinoma

EP: 13.Best Practices in Multidisciplinary Care for CSCC

EP: 14.CSCC: Escalating Therapy for High-risk Patients

EP: 15.Practical Advice on the Evolving Management of CSCC

Transcript:

Jason J. Luke, MD: Thinking about staging. Staging is a complicated topic, and I’m quite happy that Dr Patel gets to talk after me, because I can pass it to him. But what I’ll say is that we have a couple of different systems to think about, and they fall along the lines of your classic anatomic TNM [classification for malignant tumors] staging for AJCC [American Joint Committee on Cancer], which is better understood in the context of melanoma, I would say. And then we have this risk-based staging. And we’ll talk about risk stratification even a bit after that. But even the staging system is infused by these risk characteristics, and I have to say, frankly, I dabble a bit from both. I don’t directly use one or the other, but rather use it as an amalgamation of risk prediction. Dr Patel, I’m sure, could give a more nuanced breakdown of the staging, but it’s important to understand it’s probably a bit of both of these.

Vishal A. Patel, MD, FAAD, FACMS: Yes. You’ve hit the nail on the head. And from a historical standpoint, especially for our medical-oncologist colleagues who are joining us. In the world of oncology, we’re so used to staging for all types of tumors, but historically speaking, cutaneous squamous cell did not have a dedicated staging system until the seventh edition of the AJCC. And at that time, it was a subpar system as it relates to outcomes, which is what we want staging systems to help us with. Know what the outcome of certain stage patients is, and then we can determine the appropriate treatment or aggressiveness of that therapy. A lot of work that was done by colleagues at the Brigham and Women’s Hospital to identify the shortcomings of the seventh edition, and then propose the alternative statement, what’s now known as the BWH Staging System, as Dr Luke said, uses 4 risk factors and breaks down the staging into essentially 3 stage components: T1, 2, and 3, with stage II being an A and B risk stratification division. The risk factors that it utilizes are: the size of the tumor being greater than 2 cm; perineural invasion, specifically of greater than 0.1 mm diameter—that’s key because historically we have clumped together all types of perineural invasion, but there has been some seminal work to show that the size of the diameter of the nerve matters—invasion beyond the subcutaneous fat …; and core differentiation. The work that was done for this and the staging system has been quite useful, and I agree with Dr Luke that I use both of them. It helped improve and inform the eighth edition. And when the AJCC met, they incorporated much of that work that went into that alternative system.

And now we have the eighth edition, which utilizes also risk factors to essentially stage into the traditional 1 through 4 kind of staging system we think of with AJCC, and the risk factors there overlapped with Brigham and Women’s tumor size. There’s stratification of 2 [cm] and 4 cm [that] divides T2 and T3 tumors, and then also includes deep invasions defined similarly beyond the subcutaneous fat, as well as numerically 6 mm greater of depth, similar to what we think about with Breslow’s depth thickness. And then perineural invasion, the same, greater than 0.1 mm or more. The important distinction here is poor differentiation, that histological differentiation, which we know is a risk factor, was not included in the AJCC. And because there has not been standardization of how we define poor differentiation, our pathologist colleagues sometimes have different views as to what that definition is. But also, these tumors are large, and we may biopsy one area that’s moderately differentiated, but in fact the tumor is poorly differentiated. There is agreement that this is a risk factor, but we need to still define how we’re going to include that in the staging system. As a whole, in summary, I agree, as Dr Luke said, we’re using both of them. AJCC is so critical to talk to all of our colleagues across specialties. BWH started dermatology, but some of the work to show the discrimination of the 2 systems kind of favors BWH, but the reality is, in our practical sense of the types of patients we’re thinking about who are high risk, these are probably ones that by both systems are going to be staged as T3 in either one, and we’re thinking about what we’re going to be discussing today, things beyond surgery that we would do to help improve the outcomes of these patients.

Nikhil I. Khushalani, MD: Both of you make excellent points. BWH, or Brigham and Women’s Hospital Staging System, being a risk-based staging system, I’ve always tended to recall or remember that as a 3D’s, plus perineural invasion. So D, standing for diameter, D standing for different degree of differentiation, and D standing for depth. That’s what I often will tell our trainees. Now, again, as medical oncologists, and Dr [Martin F.] Dietrich, Dr Luke would certainly attest to this, we rarely see patients in medical oncology at that earlier stage of tumor, where we have to assign risk for recurrence. That being said, in the context of today’s program, we’re now looking at patients or seeing patients earlier in the course of their disease. For example, resectable stage II disease. It is important that staging come to the forefront, particularly as we design newer clinical trials for these patients, so that we have our standard, or our staging systems standardized across these trials. Or it would be a heterogeneous group of patients if a different study or different trials utilize alternate staging mechanisms for their patients, and therefore it would be difficult to make cross-trial comparisons in those situations. So a good understanding of the staging system certainly becomes important. Do you see a particular drawback right now to the AJCC, Dr Patel?

Vishal A. Patel, MD, FAAD, FACMS: The biggest drawback that we have is probably in those borderline cases—earlier cases. For example, there’s not as much discrimination between T2 and T3 outcomes, depending on which patients you look at. Many of the T2 patients can’t perform like T3, when we look at the Kaplan-Meier survivor curves that have been published by different institutions, as they look back on their cases and their case histories, and their registries. And that likely is, as I earlier mentioned, due to the poor differentiation or other types of risk factors not included in the staging system, either host risk factors, like we talked about, immunosuppression, or other more rare risk factors, lymphovascular invasion, desmoplastic differentiation, these types of things. And so that is one of the drawbacks for those earlier stage tumors, T2 tumors for AJCC. They may, in fact, be much higher risk that we need to take more seriously and think about adjuvant radiation or, in the context of clinical trials, maybe eligible or the right patients we want to enroll in adjuvant or neoadjuvant types of studies. But as a whole, when we look at the T3 and above tumors and certainly the T4 tumors, we know those are going to do poorly. And so, we’re usually getting it right at that point. It’s in those early ones in predicting where we want to have some better differentiation.

Nikhil I. Khushalani, MD: Yes. You also raised a good point about the importance of the pathologist in this multidisciplinary group. These are individuals who are seeing these slides, trying to gauge some of the important information that we as clinicians eventually utilize. Their role in helping us manage this disease certainly cannot be [understated].

Transcript edited for clarity.