Supplementary Material for: A territory wide follow-up of primary and secondary extramammary Paget disease of two decades – effects of local disease on survival

Introduction
Extramammary Paget disease (EMPD) is an uncommon malignant cutaneous neoplasm that are divided into primary and secondary forms. In this multicenter study, histologically proven cases of primary and secondary EMPD were reviewed for clinical outcomes with subgroup analysis for secondary EMPD.

Methodology
Cases of EMPD were identified from pathology report of the involved institutions over a period of over two decades. Cases of secondary EMPD were identified review of case notes, radiology, and pathology reports. Clinicopathological and outcome data were retrieved for statistical analysis.

Results
A total of 109 cases were retrieved, including 19 cases of secondary EMPD, most commonly associated with colorectal (n=6), anal (n=5) and prostatic carcinomas (n=3). A difference was observed between older age and secondary (versus primary) EMPD (p=0.016), but no differences were seen in other clinico-demographical parameters. Male sex (p=0.018), age over 60 years old (p=0.004) and involvement of margins (resectable) (p=0.018) were associated with shorter OS. For DSS, involvement of margins (p=0.009) was an adverse predictor. Secondary EMPD had a shorter DSS than primary EMPD (p=0.005). Multivariable analysis confirmed all above associations (p<0.05). In subgroup analysis for secondary EMPD, margin involvement remained associated with shorter OS (p = 0.007) and DSS (p = 0.003).

Conclusions
Secondary EMPD is associated with poorer outcomes. Margin involvement is strong and independent indicator of shorter OS and DSS, including secondary EMPD. Resectability is a strong predictor of favorable outcome and excision with clear margins should be attempted when surgically feasible.

## 引言
乳房外佩吉特病（Extramammary Paget disease, EMPD）是一种少见的皮肤恶性肿瘤，可分为原发性与继发性两种类型。本多中心研究对经组织学证实的原发性及继发性乳房外佩吉特病病例进行回顾分析，以明确其临床结局，并针对继发性乳房外佩吉特病开展亚组分析。

## 研究方法
本研究在二十余年的时间跨度内，从参与研究机构的病理报告中筛选乳房外佩吉特病病例。继发性乳房外佩吉特病病例通过回顾病例笔记、影像学资料及病理报告进行筛选。研究人员检索了所有病例的临床病理及预后数据，用于统计学分析。

## 研究结果
本研究共纳入109例病例，其中19例为继发性乳房外佩吉特病，最常见的关联原发恶性肿瘤为结直肠癌（n=6）、肛管癌（n=5）及前列腺癌（n=3）。年龄较高与继发性（相较于原发性）乳房外佩吉特病存在显著相关性（p=0.016），其余临床人口统计学参数则无显著差异。男性性别（p=0.018）、年龄≥60岁（p=0.004）及切缘受累（可切除亚组，p=0.018）与更短的总生存期（Overall Survival, OS）相关。针对疾病特异性生存期（Disease-Specific Survival, DSS），切缘受累（p=0.009）为不良预后预测因素。继发性乳房外佩吉特病的疾病特异性生存期短于原发性病例（p=0.005）。多变量分析证实了上述所有相关性（p<0.05）。在继发性乳房外佩吉特病的亚组分析中，切缘受累仍与更短的总生存期（p=0.007）及疾病特异性生存期（p=0.003）相关。

## 结论
继发性乳房外佩吉特病预后较差。切缘受累是总生存期与疾病特异性生存期缩短的强独立预测因素，这一结论同样适用于继发性乳房外佩吉特病病例。可切除性是良好预后的强预测因素，若手术可行，应尝试实施切缘阴性的切除手术。