The latest staging criteria for cutaneous squamous cell carcinoma (CSCC) from the American Joint Committee on Cancer (AJCC) improves the previous version in stratifying risk of disease-related outcomes, suggests a study published in December.
Using the AJCC Cancer Staging Manual, 8th edition (AJCC 8) tumor classification, which is specific to CSCCs of the head and neck, 17.8% of the cohort was classified in the high tumor categories (T3 and T4), and those accounted for 70.4% of poor outcomes in the overall cohort.
By comparison, using the 7th edition (AJCC 7), just 0.7% of tumors were T3 or T4, and they only accounted for 16.9% of poor outcomes, according to the results published in JAMA Dermatology.
That suggests the upper categories of AJCC 8 have a strong ability to stratify tumors with significant risk of disease-related poor outcomes, said study author Chrysalyne Schmults, M.D., drector of the Dermatologic Surgery Center at Brigham and Women's Hospital, Boston.
“The biggest improvement with AJCC 8 is that there's been a large expansion of cases that now qualify to be T3, and this has made it such that T3 and T4 now capture a lot more of the poor outcomes,” Dr. Schmults said in an interview with Dermatology Times.
T3 in particular is capturing most of the poor outcomes because T4 is still quite restrictive, according to Dr. Schmults, though between the two of them, they're capturing 71% of nodal metastases and 85% of deaths due to CSCC.
Using AJCC 7 criteria, the majority of poor outcomes occur in patients with tumors classified as T2, which is actually a large, heterogeneous group in terms of outcomes.
“There is a subset of people who are doing poorly (in T2 under AJCC 7), but they are mixed in with all these people who are doing well. It becomes impossible to pull them out of that larger group and decide, for example, who needs staging of their lymph nodes, who needs adjuvant treatment after surgery, or who would be good candidates for clinical trials,” Dr. Schmults said.
Most CSCCs have a favorable prognosis. Estimates previously published by Dr. Schmults and colleagues suggest a risk of 3.0% for local recurrence, 4.0% for nodal metastasis, and 1.5% for death.
Staging is pivotal to helping separate the rare, high-risk cases from the low-risk majority, according to Dr. Schmults.
The AJCC 7 criteria, introduced in 2010, represented an improvement over the previous edition, which had grouped all non-melanoma skin cancers together and used just a limited set of staging factors including tumor diameter and bone and intracranial invasion. AJCC 7 included, for the first time, risk factors including tumor thickness greater than 2 mm, perineural invasion, Clark level of IV or higher, and poorly differentiated histology.
However, studies began to show that AJCC 7 was not adequately stratifying disease-related outcomes.
In a retrospective cohort study published in JAMA Dermatology in 2013, Dr. Schmults and colleagues reviewed 256 primary high-risk CSCCs and found outcomes for AJCC tumor stages T2-T4 were “statistically indistinguishable” since less than 2% of the cohort qualified as stage T3 or T4; thus 83% of nodal metastases and 92% of deaths from CSCC occurred in cases classified as T2.
As part of that study, Dr. Schmults and colleagues proposed an alternative CSCC staging system to more precisely identify the small number of cases at high risk of metastasis and death. That system incorporates risk factors including poor differentiation, perineural invasion, tumor diameter ≥2 cm, and invasion beyond subcutaneous fat).
Using the alternative system, the tumors classified as T2b (2 to 3 of those risk factors present) or T3 (all 4 risk factors or bone invasion) comprised 19% of tumors and accounted for 72% of nodal metastases and 83% of deaths from CSCC, according to the published report.
In a subsequent study published in 2014 in the Journal of Clinical Oncology, Dr. Schmults and colleagues compared AJCC 7, the International Union Against Cancer (UICC) staging system, and a modified version of their own previously published alternative system in a larger cohort of patients (N = 1,818). Results suggested that the alternative system offered better prognostic discrimination versus AJCC 7 and UICC, leading the authors to call for further population-based validation.
Subsequently, Dr. Schmults and colleagues sought to validate the recently released the CSCC staging system released in AJCC 8, which is specific to CSCC tumors of the head and neck, since it was developed in conjunction with AJCC’s head and neck cancer committee.
“The head and neck surgical community, they grapple with the worst of these cases, and they really felt like, for their purposes, they needed something,” says Dr. Schmults, who also participated in development of the AJCC 8 staging system.
The new staging criteria, which were implemented in clinical practice starting in January 2017 and will be implemented by tumor registrars as of January 2018, includes changes based on findings related to independent prognostic factors in CSCC that have become available since AJCC 7, according to Dr. Schmults.
Notably, T2 is now restricted to tumors that are at least 2 cm, yet less than 4 cm in largest dimension with no risk factors, while the T3 definition was expanded to encompass tumors at least 4 cm in largest dimension or least one risk factor. Risk factors for T3 upstaging in AJCC 8 include deep invasion, perineural invasion, and minor bone invasion, while poorly differentiated histologic features was dropped as a risk factor for upstaging.
Although pleased with the improved performance of AJCC 8 in this most recent cohort study, Dr. Schmults noted that more changes will be needed. In particular, the cohort study of AJCC 8 demonstrated a considerable overlap between T2 and T3 categories in terms of 10-year cumulative incidence of local recurrence, nodal metastasis, and disease-specific death.
Together, T2 and T3 comprised about 23% of squamous cell cancers in this study. “If we suddenly started doing lymph node staging or offering treatment beyond surgery to 23% of squamous cell patients, we would be overtreating. We know that probably only around 5% to 10% of those people would ever really need or benefit from that,” she said.
Nevertheless, Dr. Schmults was hopeful that AJCC 8 will make an impact in the community and possibly allow for population-based registry tracking through the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute to validate and refine CSCC tumor classification.
“I hope that we can come to some kind of standardization across the country in reporting clinical tumor diameter and other prognostic factors on SCC pathology reports, so that whether SEER is able to do it or not, then at least, on institutional levels people would be able to use AJCC 8 staging and track SCC outcomes better,” she said.
Since the current staging systems applies to head and neck CSCCs, “I think it will be up to clinicians and researchers how to stage everybody else,” Dr. Schmults said. “I think a lot of people are going to end up using (AJCC 8 head and neck staging) for those non-head and neck CSCCs, rather than continuing to use AJCC 7, which had a lot of trouble.”
Dr. Schmults developed the Brigham and Women’s staging system for SCC and participated in the AJCC 8 cutaneous SCC task force.
Karia PS, Morgan FC, Califano JA, Schmults CD. “Comparison of Tumor Classifications for Cutaneous Squamous Cell Carcinoma of the Head and Neck in the 7th vs 8th Edition of the AJCC Cancer Staging Manual,” JAMA Dermatology. December 2017. DOI:10.1001/jamadermatol.2017.3960.
Karia PS, Han J, Schmults CD. “Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012,” Journal of the American Academy of Dermatology. DOI:10.1016/j.jaad.2012.11.037.
Jambusaria-Pahlajani A, Kanetsky PA, Karia PS, et al. “Evaluation of AJCC tumor staging for cutaneous squamous cell carcinoma and a proposed alternative tumor staging system,” JAMA Dermatology. 2013;149(4):402-410. doi:10.1001/jamadermatol.2013.2456.
Karia PS, Jambusaria-Pahlajani A, Harrington DP, et al. “Evaluation of American Joint Committee on Cancer, International Union Against Cancer, and Brigham and Women’s Hospital tumor staging for cutaneous squamous cell carcinoma,” Journal of Clinical Oncology. 2014. DOI:10.1200/JCO.2012.48.5326.