Brantsch Kay D, Meisner Christoph, Schönfisch Birgitt, Trilling Birgit, Wehner-Caroli Jörg, Röcken Martin, Breuninger Helmut
Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
Lancet Oncol. 2008 Aug;9(8):713-20. doi: 10.1016/S1470-2045(08)70178-5. Epub 2008 Jul 9.
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.
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.
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).
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.
皮肤鳞状细胞癌（SCC）是最常见的可发生转移的癌症之一。当前的肿瘤淋巴结转移（TNM）分期包括肿瘤的水平大小、皮外结构受累情况以及分化程度。本研究的目的是前瞻性分析预测皮肤SCC转移和局部复发的关键因素。
我们前瞻性评估了615例白人患者中SCC转移或局部复发的潜在危险因素，这些因素先前由回顾性研究和小病例系列提出。在1990年1月1日至2001年12月31日期间，所有患者均在一个中心接受了皮肤SCC手术，并对三维切除边缘进行了完整的组织学检查（三维组织学）。单因素和多因素分析包括肿瘤厚度、水平大小、身体部位、组织学分化、促结缔组织增生性生长、多发性SCC病史和免疫抑制。主要终点是转移时间和局部复发时间，分别定义为从原发性肿瘤诊断日期到转移或局部复发诊断日期的时间。
653例患者纳入研究。38例患者失访，剩余615例可评估患者（中位年龄73岁[范围27 - 98岁]）。在中位随访期43个月（范围1 - 165个月）内，615例患者中有26例（4%）发生转移，20例患者发生局部复发（3%）。厚度为2.0 mm或更小的肿瘤未发生转移。厚度在2.1 mm至6.0 mm之间的318例肿瘤中有12例（4%）发生转移，厚度大于6.0 mm的90例肿瘤中有14例（16%）发生转移。多因素分析显示，转移的关键预后因素包括肿瘤厚度增加（风险比4.79 [95%置信区间为2.22 - 10.36]；p < 0.0001）、免疫抑制（4.32 [1.62 - 11.52]；p = 0.0035）、耳部定位（3.61 [1.51 - 8.67]；p = 0.0040）以及水平大小增加（2.22 [1.18 - 4.15]；p = 0.0128）。局部复发风险取决于肿瘤厚度增加（6.03 [2.71 - 13.43]；p < 0.0001）和促结缔组织增生（16.11 [6.57 - 39.49]；p < 0.0001）。
仅厚度大于2.0 mm的皮肤SCC具有显著的转移风险。厚度大于6.0 mm的肿瘤具有高转移风险和局部复发风险。促结缔组织增生性生长是局部复发的独立危险因素。研究应评估随访和前哨淋巴结活检在高危患者中的作用。
