Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study.

BACKGROUND: Cutaneous squamous-cell carcinomas (SCC) are among the most common cancers capable of metastasis. Current Tumour Node Metastasis (TNM) staging includes horizontal tumour size, involvement of extradermal structures, and degree of differentiation. The aim of this study was to prospectively analyse the key factors predicting metastasis and local recurrence in cutaneous SCC.
METHODS: We assessed prospectively investigated potential risk factors for metastasis or local recurrence of SCC, previously suggested by retrospective studies and small case series, in 615 white patients. Between Jan 1, 1990, and Dec 31, 2001, all patients underwent surgery for cutaneous SCC with complete histological examination of the three-dimensional excision margins (3D-histology) in one centre. Univariate and multivariate analysis included tumour thickness, horizontal size, body site, histological differentiation, desmoplastic growth, history of multiple SCC, and immunosuppression. Primary endpoints were time to metastasis and time to local recurrence, defined as the time from date of diagnosis of the primary tumour to the date of diagnosis of metastasis or local recurrence, respectively.
FINDINGS: 653 patients were enrolled in the study. 38 patients were lost to follow-up leaving 615 assessable patients (median age 73 years [range 27-98]). During a median follow-up period of 43 months (range 1-165), 26 (4%) of 615 patients developed metastases and 20 patients developed local recurrence (3%). Tumours 2.0 mm or less in thickness did not metastasise. Metastases occurred in 12 (4%) of 318 tumours between 2.1 mm and 6.0 mm in thickness, and in 14 (16%) of 90 tumours with a thickness greater than 6.0 mm. On multivariate analysis, key prognostic factors for metastasis were increased tumour thickness (hazard ratio 4.79 [95% CI 2.22-10.36]; p<0.0001), immunosuppression (4.32 [1.62-11.52]; p=0.0035), localisation at the ear (3.61 [1.51-8.67]; p=0.0040), and increased horizontal size (2.22 [1.18-4.15]; p=0.0128). The risk of local recurrence depended on increased tumour thickness (6.03 [2.71-13.43]; p<0.0001) and desmoplasia (16.11 [6.57-39.49]; p<0.0001).
INTERPRETATION: Only SCC greater than 2.0 mm in thickness are associated with a significant risk of metastasis. Tumours greater than 6.0 mm are associated with a high risk of metastasis and local recurrence. Desmoplastic growth is an independent risk factor for local recurrence. Studies should assess the role of follow-up visits and sentinel-lymph-node biopsy in high-risk patients.