Staging Accuracy for Squamous Cell Carcinoma

At the American College of Mohs Surgery 54th Annual Meeting in Philadelphia, Pennsylvania, held May 12 to 15, Chrysalyne D. Schmults, MD, MScE, vice chair of surgical oncology in department of dermatology and program director of micrographic surgery and dermatologic oncology fellowship program at Brigham and Women’s Hospital as well as an associate professor at Harvard Medical School, both in Boston, Massachusetts, discussed molecular diagnostics for squamous cell carcinoma (SCC).¹

She noted that the American Joint Committee on Cancer (AJCC) staging guidance, for determining the risk of tumors, does not work as well for SCC as it does for melanoma, where it is higher predictive. The AJCC puts about a quarter of all SCCs into a late-stage group.² Schmults explained that clinicians do not want to be doing radiologic surveillance and adjuvant therapy on 25% of all patients who have this disease.

Brigham staging offers better guidance, according to Schmults, with about half as many tumors being inappropriately upstaged.² However, a reviewing multiple studies on the topic will find numbers for risk of local recurrence, double metastasis, and death. In data from the Brigham cohort, a 6% risk, rather than a 20% risk, of local recurrence, nodal metastasis, and death were found about T2B cases, Schmults explained.

About 40% of the patients in the Brigham cohort were treated with Mohs surgery, the rest got wide local excision. Mohs was found to perform better in the cohort of T2B and T3 cases. She emphasized that for the SCCs staged at T2B and T3 with the Brigham staging, it failed to predict 30% of metastases of tumors as well as missing 8% of deaths. With the application of a C statistic, which is interpreted as the probability that a randomly selected subject who experienced the outcome will have a higher predicted probability of having the outcome occur than a randomly selected subject who did not experience the outcome³, this outcome may be improved.

When using a C statistic of .81, Brigham staging performs about as well as AJCC for lung and breast cancer. “So that begs the question, are we really going to be able to do much better than Brigham staging when we are just basing the stage on clinical and histologic risk factors?” Schmults said.

With molecular prognostics, this may improve, Schmults said. If a physician knows that the risk of a group of patient risk of their SCC being a T2B is 6%, but there may be a possibility that people in that group have a higher risk, Schmutls asked the question, can molecular prognostics help identify it?

In the data for Castle Biosciences, patients that have a Brigham T2B staging and a Castle stage of 2B have a 50% risk of metastasis, which is significantly higher than the 6% risk noted with Brigham staging.⁴ She also noted that this is awaiting validation and a large prospective validation study is currently underway.

More research is also being done to cut the risk of recurrence and metastasis in SCC. A recent study found that the risk of local recurrence and nodal metastasis is cut in half when adjuvant radiation is used for high SCC.⁵ For recurrent tumors, tumors over 6 centimeters, or T3 cases, it can reduce the 30% risk of recurrence to 15%.⁵ However, with patients who are thought to have a risk of 6%, many may wonder if it’s worth the 3% risk reduction.

Disclosure

Schmults disclosed that she is a member of the steering committee for Castle Biosciences.

References

1. Schumlts, C. Cutaneous Oncology Essentials. Presented at: 2022 American College of Mohs Surgery Annual Meeting; May 12-15, 2022; Philadelphia, Pennsylvania.
2. Ruiz ES, Karia PS, Besaw R, Schmults CD. Performance of the american joint committee on cancer staging manual, 8th edition vs the brigham and women’s hospital tumor classification system for cutaneous squamous cell carcinoma. JAMA Dermatol. 2019;155(7):819. doi:10.1001/jamadermatol.2019.0032
3. Logan, PhD B. ROC Curves and the C statistic. Published online December 2013. Accessed May 16, 2022. https://www.mcw.edu/-/media/MCW/Departments/Biostatistics/vo19no4.pdf
4. Wysong A, Newman JG, Covington KR, et al. Validation of a 40-gene expression profile test to predict metastatic risk in localized high-risk cutaneous squamous cell carcinoma. Journal of the American Academy of Dermatology. 2021;84(2):361-369. doi:10.1016/j.jaad.2020.04.088
5. Adjuvant radiation following clear margin resection of high T-stage cutaneous squamous cell carcinoma halves the risk of local and locoregional recurrence: A dual-center retrospective study. Journal of the American Academy of Dermatology. Published online March 29, 2022. doi:10.1016/j.jaad.2022.03.044