Recurrence rates following wide local excision (WLE) for extramammary Paget disease (EMPD) are high at 37.0% [1]. Margin control surgery for treating EMPD, including Mohs micrographic surgery (MMS) or complete circumferential peripheral and deep margin assessment, achieves a lower rate of recurrence at 18.7% [1, 2]. However, MMS and circumferential peripheral and deep margin assessment involve specialized, labor-intensive techniques requiring a lot of tissue sections for EMPD, so these may not always be feasible treatment options [2, 3]. Preoperative mapping biopsy (PMB) may be a useful alternative to margin control surgeries [1]. However, reports on PMB have been scarce.

In this study, we aimed to evaluate the effectiveness of PMB in patients with EMPD through a systematic review of previously published literature and retrospective analysis of our data. We compared the recurrence rate after WLE with or without PMB by combining our data with individual patient data found in the systematic review (methods detailed in online suppl. material 1; for all online suppl. material, see https://doi.org/10.1159/000539356). Cox’s proportional hazard models were used to assess the 5-year recurrence rates. All statistical analyses were performed using R software (version 4.0.2). This study was approved by the Institutional Review Board.

Fifty articles were screened, of which six met the inclusion criteria (Fig. 1) [3‒8]. Five studies involved cases of PMB followed by WLE, and the study by Niikura et al. involved cases of PMB followed by vulvectomy. Most studies had a low risk of bias, while a few studies had a moderate risk of bias (online suppl. Fig. 1). A retrospective review of the SNUH dermatosurgery clinic database revealed 20 patients with EMPD who underwent WLE (online suppl. Fig. 2) with or without PMB conducted by dermatosurgeons between January 2016 and May 2022 (J.-H.M., S.J.J.).

Fig. 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram on search strategy.

Fig. 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram on search strategy.

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A total of 146 EMPD cases from our database and literature search were included in the final analysis (Table 1): 109 patients underwent PMB before WLE and 37 patients underwent WLE without PMB. Recurrence was observed in 7 and 14 patients from each group, respectively. The recurrence rates at 2, 5, and 7 years were 4.0% (95% CI: 0.1–7.8%), 11.7% (95% CI: 2.1–20.4%), and 11.7% (95% CI: 2.1–20.4%) in the PMB group and 20.6% (95% CI: 5.7–33.1%), 45.5% (95% CI: 22.3–61.8%), and 50.9% (95% CI: 26.0–67.4%) in the WLE group. PMB was associated with a significantly reduced recurrence rate (HR 0.23; 95% CI: 0.09–0.59, p value = 0.002) (Fig. 2). There was no statistically significant difference among the various distances of PMB from clinical tumor margins at 1, 2, and >3 cm (online suppl. Fig. 3).

Table 1.

Clinical characteristics, recurrence rates, and follow-up duration of EMPD cases treated with and without PMB

StudyStudy designTotal number of EMPD cases treated surgically, method of surgical excisionEMPD treated with PMBEMPD treated without PMB
distance of PMB from clinical margins, cmnumber of casesmean agemales (n, %)number of recurrences (n, %)mean follow-up (range), monthsWLE margin, cmnumber of casesmean agemales (n, %)number of recurrences (n, %)mean follow-up (range), months
Niikura et al. [8] (2006) Retrospective 21, vulvectomy 1–2 14 70.4 0, 0 0, 0 49.2 (10–116) NS 70.1 0, 0 1, 14.3 68.7 (6–199) 
Jung et al. [4] (2013) Retrospective 19, WLE 12 67.3 12, 100 0, 0 14.4 (1–25) 69.3 7, 100 4, 57.1 36.3 (6–61) 
Kato et al. [5] (2013) Retrospective 17, WLE 1, 2, and 3 17 71.9 16, 94.1 1, 5.9 35.7 (10–75) N/A None N/A N/A N/A N/A 
Nagai et al. [7] (2016) Case series 6, WLE NS 74.6 3, 60 2, 40 41.0 (5.8–112) NS 78 1, 100 0, 0 50.2 (50.2) 
Park et al. [3] (2017) Retrospective 44, WLE 26 69.0 NS 3, 11.5 49* 2–3 18 66.4 NS 9, 50 57.5* 
Murata et al. [6] (2017) Prospective 19, WLE 1 and 3 19 70 12, 63.2 0, 0 17.2 (11–29) N/A None N/A N/A N/A N/A 
Our data Retrospective 20, WLE 16 66.7 12, 75 1, 6.2 17.1 (3–53)  67 4, 100 0, 0 23.2 (5–59) 
Total — 146, WLE and vulvectomy 1–3 109 69.5 55, 50.5 7, 6.4 32.5  37 68.0 12, 32.4 14, 37.8 51.7 
StudyStudy designTotal number of EMPD cases treated surgically, method of surgical excisionEMPD treated with PMBEMPD treated without PMB
distance of PMB from clinical margins, cmnumber of casesmean agemales (n, %)number of recurrences (n, %)mean follow-up (range), monthsWLE margin, cmnumber of casesmean agemales (n, %)number of recurrences (n, %)mean follow-up (range), months
Niikura et al. [8] (2006) Retrospective 21, vulvectomy 1–2 14 70.4 0, 0 0, 0 49.2 (10–116) NS 70.1 0, 0 1, 14.3 68.7 (6–199) 
Jung et al. [4] (2013) Retrospective 19, WLE 12 67.3 12, 100 0, 0 14.4 (1–25) 69.3 7, 100 4, 57.1 36.3 (6–61) 
Kato et al. [5] (2013) Retrospective 17, WLE 1, 2, and 3 17 71.9 16, 94.1 1, 5.9 35.7 (10–75) N/A None N/A N/A N/A N/A 
Nagai et al. [7] (2016) Case series 6, WLE NS 74.6 3, 60 2, 40 41.0 (5.8–112) NS 78 1, 100 0, 0 50.2 (50.2) 
Park et al. [3] (2017) Retrospective 44, WLE 26 69.0 NS 3, 11.5 49* 2–3 18 66.4 NS 9, 50 57.5* 
Murata et al. [6] (2017) Prospective 19, WLE 1 and 3 19 70 12, 63.2 0, 0 17.2 (11–29) N/A None N/A N/A N/A N/A 
Our data Retrospective 20, WLE 16 66.7 12, 75 1, 6.2 17.1 (3–53)  67 4, 100 0, 0 23.2 (5–59) 
Total — 146, WLE and vulvectomy 1–3 109 69.5 55, 50.5 7, 6.4 32.5  37 68.0 12, 32.4 14, 37.8 51.7 

EMPD, extramammary Paget disease; WLE; wide local excision; NS, not specified; N/A, not applicable; PMB, preoperative mapping biopsy.

*This study did not report the range of follow-up periods, only the mean and standard deviation (±23.75 in EMPD treated with PMB cohort; ±26.20 in EMPD treated without PMB cohort).

Fig. 2.

Kaplan-Meier plot for the recurrence rate of EMPD treated with or without PMB followed by WLE. PMB was associated with a significantly reduced recurrence rate (HR 0.23; 95% CI: 0.09–0.59, p value = 0.002).

Fig. 2.

Kaplan-Meier plot for the recurrence rate of EMPD treated with or without PMB followed by WLE. PMB was associated with a significantly reduced recurrence rate (HR 0.23; 95% CI: 0.09–0.59, p value = 0.002).

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Ensuring complete clearance to prevent local recurrence is critical for EMPD treatment. Guidelines state that 4 cm margins for penoscrotal and vulvar areas and 3.5 cm margins for perianal and axillary sites should achieve 95% tumor clearance [1]. Taking such large margins may not always be anatomically feasible and are technically challenging; thus, margin control excision methods, such as MMS, are recommended.

PMB may be a useful alternative to margin control surgery. Compared to margin control surgery, taking several 3–4 mm-sized punch biopsies 0.5–2 cm away from the clinical margin of EMPD is less labor-intensive and can conserve more tissue than WLE alone. In this study, we found that PMB reduces the recurrence rate of EMPD. PMB with subsequent WLE resulted in a 5-year recurrence rate of 11.7%, whereas WLE without PMB yielded a recurrence rate of 45.5%. Although the initial starting margins were not fully established, the data revealed no statistical differences between the different distances of PMB from the clinical tumor margin. This suggests that obtaining multiple biopsies at 1 cm from the clinical tumor margins is a practical approach.

Limitations of our study include the small sample size and the retrospective nature of our data. Moreover, there was considerable heterogeneity and nonspecified data in the studies. Lastly, we could not directly compare the therapeutic efficacy of PMB with that of margin control surgery such as MMS. A previous meta-analysis of individual patient data showed that the recurrence rate at 5 years after MMS was estimated to be 16.4% (95% CI: 74.0–94.5%) [9], which is similar to our data.

In summary, this study found that PMB before WLE reduced the risk of recurrence when treating EMPD. Further prospective studies are necessary to compare the recurrence rates of PMB, MMS, and WLE for EMPD management.

This study protocol was reviewed and approved by the Institutional Review Board of Seoul National University Hospital (approval number: 2212-0371382). PROSPERO registration for systematic review component: CRD42022315937. The patients in this manuscript have given written informed consent to publication of their case details.

The authors have no conflict of interest to declare.

This article has no funding source.

Sophie Soyeon Lim: analysis and interpretation of data, drafting and reviewing the work, formal analysis, investigation, data curation, writing – original draft, and visualization. Ji Su Lee, Hyun Jeong Ju: formal analysis, investigation, data curation, writing – original draft, and visualization. Jung Min Bae: validation, resources, writing – review and editing, and project administration. Seong Jin Jo: investigation and writing – review and editing. Je-Ho Mun: conceptualization, methodology, investigation, validation, resources, writing – review and editing, supervision, and project administration.

Additional Information

Sophie Soyeon Lim, Ji Su Lee, and Hyun Jeong Ju contributed equally to this work.

The data underlying this article are available in the article and in its online supplementary material. Further inquiries can be directed to the corresponding author.

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