Risk factors and Prognosis of SCC

The Lancet Oncology Early Online Publication, 9 July 2008

Lancet Oncology DOI:10.1016/S1470-2045(08)70178-5

Articles


Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study
Kay D Brantsch MD a, Christoph Meisner PhD b, Birgitt Schönfisch PhD b, Birgit Trilling Dipl Inform Med c, Jörg Wehner-Caroli MD a, Prof Martin Röcken MD a and Prof Helmut Breuninger MD a

Summary
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.

Also, This Summary of the article came from Journal Watch

Which Squamous Cell Carcinomas Are the Bad Actors?
Tumor thickness, immunosuppression, location on the ear, and horizontal size were associated with increased risk for metastasis in cutaneous SCC.


Squamous cell carcinoma (SCC) is seen daily in most dermatologists’ offices. Most are taken care of, never to be heard from again, but, occasionally, an SCC will recur or metastasize. In this prospective, longitudinal study from Germany, 615 white patients with primary SCC referred to a university dermatology department for definitive treatment were followed for at least 4 years. The tumors were resected using "3D-histology," which consists of en face examination of the peripheral and deep margins and vertical sections from the center of the specimen with examination of permanent sections. The data were subject to rigorous multivariate analysis.

Metastases developed in 4% of patients. The first metastatic focus was always in the regional draining lymph nodes. The risk for metastasis increased with tumor thickness, location on the ear, horizontal tumor size, and immunosuppression. No metastasis occurred in tumors that were 2.0 mm or thinner; 4% of tumors 2.1 mm to 6.0 mm thick metastasized, as did 16% of tumors thicker than 6.0 mm. Lip lesions and poorly differentiated lesions were not associated with increased risk for metastasis. Local recurrences developed in 3% of patients, all within 6 years. Recurrence developed in 12% of tumors thicker than 6 mm and 24% of tumors with a desmoplastic histologic pattern.

Comment: This study confirms what we see in practice: SCCs that are thick, large, desmoplastic, poorly differentiated, or present in immunosuppressed patients behave more aggressively. To the ear, I would add lip, temple, and genitals as locations of more-aggressive SCC lesions. The number of patients in the study may have been too small to detect differences for other anatomic sites.
— George J. Hruza, MD