Overall and progression-free survival of stage 4 cutaneous squamous cell carcinoma at a single large referral center
Authors: Gefei Alex Zhu, Anne Lynn Su Chang
Journal: Journal of the American Academy of Dermatology (2015)

See related works on pages 127 and 120 To the Editor: Cutaneous squamous cell carcinoma (SCC) is the second most common nonmelanoma skin cancer (NMSC) but accounts for the bulk of deaths from NMSCs due to its capacity to metastasize.1Weinstock M.A. Nonmelanoma skin cancer mortality in the United States, 1969 through 1988.Arch Dermatol. 1993; 129: 1286-1290Crossref PubMed Scopus (89) Google Scholar Although incidence is increasing in the United States, outcomes data are not reported in national cancer registries and disease mortality is not well-described in the literature.2Karia P.S. Han J. Schmults C.D. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012.J Am Acad Dermatol. 2013; 68: 957-966Abstract Full Text Full Text PDF PubMed Scopus (547) Google Scholar We report the overall survival (OS) and progression-free survival (PFS) in 36 patients with American Joint Committee on Cancer (AJCC) stage IV SCC in this retrospective cohort study at a large academic center. The Stanford Cancer Center Research Database was queried using the terms "metastatic," "cutaneous," "SCC," and "squamous cell carcinoma" for potential cases from 1997 to 2013 following institutional review board approval. Cases were included if there was documentation of a cutaneous primary site and biopsy-proven stage IV disease under the current AJCC TNM staging guidelines (7th ed, 2010).3AJCC Cancer Staging Handbook. 7th ed. American Joint Committee on Cancer, Chicago, IL2010Google Scholar ∗To qualify as Stage IV, there must be evidence of distant metastasis (M1) and/or involvement of at least 1 lymph node measuring at least 3 cm (N2 or N3) and/or direct tumor extension into the bony skeleton or perineural invasion of the skull base (T4).∗To qualify as Stage IV, there must be evidence of distant metastasis (M1) and/or involvement of at least 1 lymph node measuring at least 3 cm (N2 or N3) and/or direct tumor extension into the bony skeleton or perineural invasion of the skull base (T4). Clinical and demographic data were analyzed using STATA 12 (Statacorp LP). OS and PFS were estimated by Kaplan-Meier analysis with date of stage IV disease diagnosis as the start of follow-up. The endpoint for OS was the all-cause date of death ascertained through medical records or public records including the Social Security Death Index; the endpoint for PFS was the earliest date of disease progression, defined as development of new metastases, enlargement of existing tumors, recurrence, or all-cause death. Patients not meeting the endpoint before the data cutoff date of October 1, 2014, were right-censored. Thirty-six patients met inclusion criteria, of whom 31 were male and 33 were Caucasian. At the time of stage IV diagnosis, 14 had M1, 23 had N2/N3, and 5 had T4 disease. M1 disease developed in 10 patients during follow-up. The most common primary sites were head (n = 23), upper extremities (n = 4), and lower extremities, neck, and trunk (n = 1 for each). The most common metastatic sites were lymph nodes (n = 21), parotid gland (n = 12), and soft tissue (n = 5). Nine patients were immunosuppressed at the time of stage IV diagnosis. Following stage IV diagnosis, treatment types received were as follows: adjuvant radiation (n = 22), surgery (n = 19), chemotherapy (n = 18), and radiation (n = 17). The median (interquartile range) follow-up period was 1.87 (0.71-3.65) years, during which 26 patients died. The median OS was 2.19 (95% confidence interval [CI] 1.72-4.04; range 0.22-12.09) years and the median PFS was 0.67 (95% CI 0.54-1.03; range 0.06-12.09) years (Fig 1). The 5-year OS rate was 26% (95% CI 12%-43%). In Cox proportional hazard models, N2/N3 stage at diagnosis was significantly associated with worse OS (hazard ratio 2.81; 95% CI 1.17-6.77) and worse PFS (hazard ratio 2.31; 95% CI 1.04-5.16) compared with N0/N1 stage. Additionally, M1 stage at diagnosis or during follow-up was not associated with worse OS (hazard ratio 1.48; 95% CI 0.61-3.56) or worse PFS (hazard ratio 1.21; 95% CI 0.57-2.60) compared with M0 stage, likely due to an inadequate sample size. Neither immunosuppression nor AJCC T stage at diagnosis was associated with OS or PFS at P < .05 level. Treatment types (surgery, chemotherapy, radiation, adjuvant radiation) did not significantly alter OS or PFS. It is possible that current treatment modalities do not make a significant difference in OS or PFS or that the sample size was not large enough to detect such a difference. Our study provides a prognostic baseline for patients with AJCC stage IV SCC. The 5-year OS rate of 26% is comparable to the OS rate from an Australian study focused on M1 SCC, reported at 11%, ∗To qualify as Stage IV, there must be evidence of distant metastasis (M1) and/or involvement of at least 1 lymph node measuring at least 3 cm (N2 or N3) and/or direct tumor extension into the bony skeleton or perineural invasion of the skull base (T4). and is improved compared with data on N1-N3 SCC (80%).4Brunner M. Veness M.J. Ch'ng S. Elliott M. Clark J.R. Distant metastases from cutaneous squamous cell carcinoma–analysis of AJCC stage IV.Head Neck. 2013; 35: 72-75Crossref PubMed Scopus (49) Google Scholar Our findings await validation by larger multicenter studies of patients staged under the AJCC 7th edition guidelines.3AJCC Cancer Staging Handbook. 7th ed. American Joint Committee on Cancer, Chicago, IL2010Google Scholar