In the present study, the characteristics of EMPD patients in one single-institution were analyzed. As revealed in other Asian population-based studies7,12 the predominance of male gender in the distribution of EMPD patients was also noted in our cases. The most common affected site was penoscrotal region (40%), similar to the findings of other studies.13–15 The average size of lesion, the mean age of diagnosis, and rate of metastasis (12.72%) were also in compatible range with previous literature.4,5,7,12
The overall survival rates in our study were 80.00% (36-month follow up) and 65.45% (60-month follow up) (Table 2), which were compatible with those of previous male-predominant or Asian-predominant study.12,13 Previous studies had identified several potential risk factors of poor prognosis of EMPD, including the level of tumor invasion, lymph node metastases, elevated CEA, perianal lesion, old age, and male gender.5,12,13,16 In our study, based on the results of univariable Cox regression analysis (Table 3), regional or distant metastasis, age of 75 year-old or above, and deep dermal invasion were identified as significant harmful factors of the overall 5-year survival. Moreover, the Kaplan–Meier curves of overall survival revealed significantly poorer outcome in those with deep dermal invasion (p = 0.0007) (Fig. 3) and metastasis (p = 0.0040) (Fig. 4), showing similar outcomes with two population-based studies and previous reviews.6,12,17 The relationship between survival and microinvasive disease remains controversial, whereas deeply invasive EMPD was linked to poorer prognosis than the non-invasive counterpart.12,17 The association between prognosis and site of lesion had been reported, suggesting that anorectal EMPD has a statistically significantly decreased mean disease-specific survival compared with those without anorectal involvement.4 However, no significant difference in overall survival was observed between the different groups of lesion site in our study (Table 3).
The 5-year recurrence rate (15.69%) and the mean recurrence interval (15.5 months after diagnosed) in our study (Table 3) were similar to those of other EMPD studies that treated patients with wide local exicision.14,15,18 The recurrence-free survival rate was 70.59% at 36-month follow up and 60.78% at 60-month follow up (Table 5), consistent with those of other wide local excision studies.15,18 Based on the results of univariate Cox regression (Table 6), metastasis and dermal invasion were identified as potential risk factors of recurrence; the identical prognostic factors of overall survival had harmful effects on the recurrence, which coincided with that of a previous study,10 whereas another population-based study reported no relationship between dermal invasion and local recurrence.7 Previous literature observed a strong association between margin status and recurrence risk,15 whereas in our study (Table 6), no similar significant association was found. In the subgroup analysis of those with intraepithelial lesion, free-margin status revealed no improvement in recurrence-free survival compared with those without free excision margin (p = 0.3133), which was in conflict with previous literature.19 In our series, the Kaplan–Meier curves of recurrence-free survival revealed deep dermal invasion (Fig. 6) and distant metastasis (Fig. 7) as the factors with harmful effect on recurrence-free survival (p = 0.0032, 0.0014, respectively).
The rates of concurrent malignancy (38.18%), adnexal carcinoma (5.45%), and internal malignancy (32.73%) in our study were in compatible range with previous reviews.2,5,15,21 Several Asian population-based studies revealed a low concurrent internal malignancy rate in Asian EMPD patients,7,12,14 which is in contrast with the result of our study. The potential relationship between the anatomic site of EMPD lesion and internal malignancy was proposed in another study.20 We determined the perianal EMPD as a significant risk factor of gastrointestinal malignancy (odds ratio = 16.00, p = 0.0015), whereas no similar association was observed between the genital region EMPD and genitourinary malignancy (p = 0.3726) (Table 7).
Our study had several limitations. First, all the data were retrospectively extracted from the electronic patient record system, which may lead to potential bias in data extraction or misinterpretation. Inadequate description of pathology reports and outpatient department follow up may also lead to underestimation of the actual rate of dermis invasion and recurrence. In addition, given the long follow-up period of up to 5 years, phone interview was performed as an alternative way of evaluation, in which only limited information can be accessed. Finally, with the rarity of EMPD in Asian population, the present single-center study included 55 illegible patients. A multicenter, larger sample size study in Taiwanese population is still needed for further evaluation.
To the best of our knowledge, this research is the first study in the English language literature about the comprehensive survival analysis of EMPD in Taiwan population. Our report also identified similar disease characteristics and prognostic factors in Taiwan population, similar to other Asian population-based studies, and their differences.