Survival and Treatment Patterns in Vulvar Paget’s Disease: Evidence From SEER

Abstract

Introduction

Vulvar Paget’s disease (VPD) is a rare condition, and a comprehensive analysis of its clinical and pathological characteristics, treatment approaches, and prognosis has not yet been conducted.

Methods

We conducted a retrospective population-based cohort study using publicly available, de-identified data from the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed with VPD between 2004 and 2021were included. Kaplan-Meier and Cox models assessed impacts on overall and cancer-specific survival. Propensity score matching (PSM) balanced surgical and non-surgical groups.

Results

1,778 patients with VPD were included. Most patients were women aged ≥50 years (96.5%) and of White race (81.7%). The labium majus was the most commonly specified tumor site (203/1,778, 11.4%), although most cases were recorded as vulva, NOS. A total of 1,374 patients underwent surgical treatment. After PSM, surgery remained associated with improved survival. A generally similar trend was observed across subgroups, although not all subgroup comparisons reached statistical significance.

Conclusion

Based on the SEER database, this study found that surgery was beneficial for improving the prognosis of VPD patients, especially for those who were elderly.

Keywords

vulvar Paget’s disease SEER database prognosis surgery

Introduction

Extramammary Paget’s disease (EMPD) is a rare type of malignant skin tumor that predominantly occurs in areas rich in apocrine glands, particularly the genital and perianal skin.¹ As the most common type of EMPD, vulvar Paget’s disease (VPD) only accounts for approximately 1-2% of all malignant tumors in the vulvar region.² VPD is most commonly found in postmenopausal white women.² It is an intraepithelial disease characterized by vulvar scaly plaques with pruritus or burning as a common but nonspecific feature.^1,3 Therefore, at the initial clinical visit, VPD is often not recognized and is misdiagnosed as eczema or a fungal infection.⁴ Early skin biopsy is of significant importance for diagnosis. The presence of typical Paget cells in the epidermis, which are large atypical cells with abundant, clear cytoplasm that is sometimes eosinophilic, serves as the basis for diagnosing VPD.^4,5 However, the diagnosis of VPD remains difficult due to its latent and indolent course and the nonspecific symptoms and clinical manifestations.

Currently, surgery remains a major treatment approach for VPD, particularly when invasive disease is suspected or confirmed.^6-8 However, there is still controversy over whether to perform extensive resection. Some studies indicate that positive surgical margins are associated with an increased risk of recurrence in patients, but there are also studies reporting no correlation between positive surgical margins and overall patient survival rates.^9-11 Due to tissue and function damage caused by surgery, there is an increasing focus on alternative treatment methods for VPD. Common alternatives include topical medications, such as imiquimod (self-applied cream), radiation therapy, chemotherapy, photodynamic therapy (a form of phototherapy using photosensitizing compounds that selectively become toxic to targeted cancer cells and other diseased cells when exposed to light), laser therapy or a combination of these methods.^9,12,13 Among these alternatives, topical imiquimod has shown encouraging results in selected patients, although the effectiveness of non-surgical treatments overall still requires further validation.¹⁴ In addition, the high recurrence rate of VPD is also a therapeutic challenge that needs to be addressed currently.

In order to understand the course of this rare disease and optimize current treatment plans, this study conducts a comprehensive analysis of the clinical and pathological characteristics, treatment patterns, and prognostic features of VPD.

Method

Study Design and Ethics

This was a retrospective population-based cohort study based on publicly available, de-identified data from the Surveillance, Epidemiology, and End Results (SEER) database. This study was reported in accordance with the STROBE guideline.^15,16 Eligible patients were selectively identified from the SEER database according to predefined inclusion and exclusion criteria. All patient details were de-identified, and no identifiable private information was available to the investigators. Therefore, Institutional Review Board/Ethics Committee approval and informed consent were not required.

Patient Selection

Patients with a pathological diagnosis of VPD in the SEER database between 2004 and 2021 were retrospectively identified. Cases were screened using ICD-O-3 morphology codes 8542/2 and 8542/3, corresponding to preinvasive/in situ and invasive Paget’s disease, respectively, together with vulvar primary site codes C51.0, C51.1, C51.2, C51.8, and C51.9. To minimize the inclusion of secondary Paget’s disease and preferentially identify primary VPD, only patients with sequence number indicating one primary tumor were retained. Patients were excluded if they lacked pathological confirmation, had incomplete surgical information, or had unclear or missing clinicopathological characteristics or follow-up data. A total of 1,778 potentially eligible cases were initially identified. The patient selection flowchart is shown in Figure 1.

Figure 1.

Flowchart of inclusion and exclusion of patients in this study

Statistical Analysis

Categorical variables were expressed as numbers (percentages). The Kaplan-Meier method and Cox proportional hazards model were used to evaluate the effects of clinicopathological characteristics and treatment patterns on overall survival (OS). OS was defined as the time from diagnosis to death from any cause. Propensity score matching (PSM) was performed to reduce baseline confounding between the surgical and non-surgical groups. A 1:3 nearest-neighbor matching strategy was applied using a caliper width of 0.2 without replacement. The propensity score model included the following baseline covariates: age, race, marital status, year of diagnosis, primary tumor site, tumor size, the International Federation of Gynecology and Obstetrics (FIGO) stage (2018) and time from diagnosis to treatment. Standardized mean differences (SMDs) were used to assess covariate balance before and after matching, and Love plots were generated to visualize the balance of covariates after matching. Statistical significance was defined as a two-tailed p-value <0.05. All statistical analyses were conducted using R (version 4.3.2).

In accordance with the journal’s guidelines, we will provide our data for independent analysis by a selected team by the Editorial Team for the purposes of additional data analysis or for the reproducibility of this study in other centers if such is requested.

Results

Patient Demographics and Clinicopathological Characteristics

A total of 1,778 patients with VPD were included in this study. The patient selection process is shown in Figure 1. The baseline demographic and clinicopathological characteristics are summarized in Table 1. Most patients were aged >50 years (1,715/1,778, 96.5%), and the majority were White (1,453/1,778, 81.7%). Patients diagnosed between 2015 and 2021 accounted for 48.1% of the cohort (856/1,778), and the annual number of recorded cases showed an overall increasing trend over time (Figure 2).

Table 1.

Patient Demographics and Baseline Characteristics

Characteristic	N = 1778
Year of diagnosis
2004-2008	339 (19.1%)
2009-2014	583 (32.8%)
2015-2021	856 (48.1%)
Race
White	1,453 (81.7%)
Black	19 (1.1%)
Others	306 (17.2%)
Age
<50	63 (3.5%)
50-65	454 (25.5%)
>65	1,261 (70.9%)
Marital status at diagnosis
Single (never married)	156 (8.8%)
Married or domestic partner	842 (47.4%)
Divorced, separated, or widowed	533 (30.0%)
Unknown	247 (13.9%)
Rural-Urban Continuum Code
Counties in metropolitan areas	1,560 (87.7%)
Nonmetropolitan counties	214 (12.0%)
Unknown	4 (0.2%)
Median household income inflation
<$59,999	221 (12.4%)
$60,000 - $99,999	1,167 (65.6%)
> $100,000	390 (21.9%)
Time from diagnosis to treatment in days recode
≤30	527 (29.6%)
>30	961 (54.0%)
Unknown	290 (16.3%)
Primary Site
Labium majus	203 (11.4%)
Labium minus	34 (1.9%)
Clitoris	6 (0.3%)
Overlapping lesion of vulva	101 (5.7%)
Vulva, Nos	1,434 (80.7%)
Grade
Well differentiated	26 (1.5%)
Moderately differentiated	33 (1.9%)
Poorly differentiated	35 (2.0%)
Undifferentiated	3 (0.2%)
Unknown	1,681 (94.5%)
Tumor Size
<20mm	222 (12.5%)
20-40mm	269 (15.1%)
>40mm	263 (14.8%)
Unknown	1,024 (57.6%)
Combined Stage
Tis	557 (31.3%)
Localized	910 (51.2%)
Regional	122 (6.9%)
Distant	21 (1.2%)
Unknown	168 (9.4%)
T
Tis	390 (21.9%)
1	720 (40.5%)
2	123 (6.9%)
3	25 (1.4%)
Unknown	520 (29.2%)
N
0	1,416 (79.6%)
1	20 (1.1%)
2	15 (0.8%)
3	4 (0.2%)
Unknown	323 (18.2%)
FIGO stage
Tis	390 (21.9%)
I	675 (38.0%)
II	110 (6.2%)
III	27 (1.5%)
IV	41 (2.3%)
Unknown	535 (30.1%)
Surgery
No	432 (22.7%)
Yes	1,374 (77.3%)
Radiation
No/ Unknown	1,736 (97.7%)
Yes	42 (2.3%)
Chemotherapy
No/ Unknown	1,735 (97.6%)
Yes	43 (2.4%)

Figure 2.

Distribution of the number of cases of vulvar Paget’s disease from 2004 to 2021

Regarding tumor location, 203 (11.4%) cases involved the labium majus, 34 (1.9%) the labium minus, 6 (0.3%) the clitoris, and 101 (5.7%) overlapping vulvar lesions, whereas 1,434 (80.7%) were recorded as vulva, NOS. Tumor size was <20 mm in 222 (12.5%) patients, 20–40 mm in 269 (15.1%), and >40 mm in 263 (14.8%), while 1,024 (57.6%) had unknown tumor size. In the combined stage variable, 557 (31.3%) patients were classified as Tis, 910 (51.2%) as localized, 122 (6.9%) as regional, and 21 (1.2%) as distant disease. According to the FIGO stage (2018) variable, 390 (21.9%) patients were classified as Tis, 675 (38.0%) as stage I, 110 (6.2%) as stage II, 27 (1.5%) as stage III, and 41 (2.3%) as stage IV, while 535 (30.1%) had unknown stage.

In terms of treatment, 1,374 (77.3%) patients underwent surgery and 404 (22.7%) did not. Only 42 (2.3%) patients received radiotherapy and 43 (2.4%) received chemotherapy.

Survival Analysis Before PSM

Before PSM, the 1-, 3-, and 5-year OS rates for the entire cohort were 96.5% (95% CI: 95.7%–97.4%), 88.3% (95% CI: 86.8%–90.0%), and 81.1% (95% CI: 79.1%–83.2%), respectively (Table 2). Stratified by surgical status, the corresponding 1-, 3-, and 5-year OS rates were 90.7%, 75.4%, and 62.8% in the non-surgical group, compared with 98.2%, 91.9%, and 85.8% in the surgical group (log-rank p<0.001).

Table 2.

Kaplan-Meier Estimates of 1.3.5-Year Survival (95% Confidence Intervals) Before PSM

Characteristic	N	Event N	1 year	3 years	5 years	p-value¹
Overall	1,778	502	96.5% (95.7%, 97.4%)	88.3% (86.8%, 90.0%)	81.1% (79.1%, 83.2%)
Surgery	1,778	502				<0.001
No			90.7% (87.8%, 93.7%)	75.4% (70.9%, 80.2%)	62.8% (57.3%, 68.8%)
Yes			98.2% (97.5%, 98.9%)	91.9% (90.3%, 93.4%)	85.8% (83.8%, 87.9%)

¹Log-rank test.

Kaplan–Meier analyses before matching showed significant differences in OS according to age (p<0.0001), FIGO/stage-related categories (p<0.0001), and surgical status (p<0.0001), whereas the difference according to primary site did not reach statistical significance (p=0.056). The corresponding Kaplan–Meier curves are shown in Figure 3.

Figure 3.

Kaplan-Meier curves for OS before PSM stratified by age (A), SEER-recorded FIGO/stage-related categories (B), primary tumor site (C), and surgical status (D)

Baseline Covariates of the Surgical and Non-surgical Groups Before and After PSM

Before matching, substantial imbalance was observed between the surgical and non-surgical groups for several baseline covariates, particularly time from diagnosis to treatment, tumor size, and selected stage-related variables (Table 3). For example, before PSM, the SMDs for the categories of time from diagnosis to treatment ranged from -1.303 to 1.333, and those for tumor size ranged from -0.704 to 0.927.

Table 3.

Baseline Covariates of the Surgical and Non-surgical Groups Before and After Matching

Variables	Level	Before matching			After matching
Variables	Level	Surgical group (n=1374)	Non-surgical group (n=404)	SMD¹	Surgical group (n=380)	Non-surgical group (n=148)	SMD¹
Year of diagnosis (%)	2004-2008	294 (21.4)	45 (11.1)	-0.326	35 (9.2)	22 (14.9)	0.032
	2009-2014	461 (33.6)	122 (30.2)	-0.073	85 (22.4)	31 (20.9)	-0.044
	2015-2021	619 (45.1)	237 (58.7)	0.276	260 (68.4)	95 (64.2)	0.021
Age (%)	<50	55 (4.0)	8 (2.0)	-0.145	12 (3.2)	4 (2.7)	-0.040
	50-65	386 (28.1)	68 (16.8)	-0.301	91 (23.9)	34 (23.0)	-0.045
	>65	933 (67.9)	328 (81.2)	0.340	277 (72.9)	110 (74.3)	0.058
Race (%)	White	1121 (81.6)	332 (82.2)	0.015	334 (87.9)	130 (87.8)	-0.015
	Black	16 (1.2)	3 (0.7)	-0.049	6 (1.6)	2 (1.4)	0.000
	Others	237 (17.2)	69 (17.1)	-0.005	40 (10.5)	16 (10.8)	0.015
Marital status at diagnosis (%)	Single (never married)	140 (10.2)	16 (4.0)	-0.319	26 (6.8)	10 (6.8)	-0.012
	Married or domestic partner	706 (51.4)	136 (33.7)	-0.375	195 (51.3)	70 (47.3)	-0.055
	Divorced, separated, or widowed	418 (30.4)	115 (28.5)	-0.043	111 (29.2)	46 (31.1)	0.037
	Unknown	110 (8.0)	137 (33.9)	0.547	48 (12.6)	22 (14.9)	0.024
Rural-Urban Continuum Code (%)	Counties in metropolitan areas	1193 (86.8)	367 (90.8)	0.139	350 (92.1)	132 (89.2)	-0.066
	Nonmetropolitan counties	177 (12.9)	37 (9.2)	-0.129	30 (7.9)	16 (10.8)	0.066
	Unknown	4 (0.3)	0 (0.0)	-0.061	0 (0.0)	0 (0.0)	0.000
Median household income inflation (%)	<$59,999	176 (12.8)	45 (11.1)	-0.053	35 (9.2)	15 (10.1)	0.014
	$60,000 - $99,999	914 (66.5)	253 (62.6)	-0.081	236 (62.1)	94 (63.5)	0.014
	> $100,000	284 (20.7)	106 (26.2)	0.127	109 (28.7)	39 (26.4)	-0.026
Time from diagnosis to treatment in days recode	≤30	454 (33.0)	73 (18.1)	-0.389	164 (43.2)	63 (42.6)	0.047
	>30	894 (65.1)	67 (16.6)	-1.303	191 (50.3)	62 (41.9)	-0.103
	Unknown	26 (1.9)	264 (65.3)	1.333	25 (6.6)	23 (15.5)	0.043
Primary Site (%)	Labium majus	158 (11.5)	45 (11.1)	-0.011	39 (10.3)	19 (12.8)	0.086
	Labium minus	23 (1.7)	11 (2.7)	0.064	9 (2.4)	5 (3.4)	0.048
	Clitoris	6 (0.4)	0 (0.0)	-0.075	0 (0.0)	0 (0.0)	0.000
	Overlapping lesion of vulva	88 (6.4)	13 (3.2)	-0.181	24 (6.3)	8 (5.4)	-0.057
	Vulva, Nos	1099 (80.0)	335 (82.9)	0.078	308 (81.1)	116 (78.4)	-0.066
Grade (%)	Well differentiated	26 (1.9)	0 (0.0)	-0.158	0 (0.0)	0 (0.0)	0.000
	Moderately differentiated	31 (2.3)	2 (0.5)	-0.251	0 (0.0)	1 (0.7)	0.096
	Poorly differentiated	30 (2.2)	5 (1.2)	-0.086	8 (2.1)	4 (2.7)	-0.010
	Undifferentiated	3 (0.2)	0 (0.0)	-0.053	0 (0.0)	0 (0.0)	0.000
	Unknown	1284 (93.4)	397 (98.3)	0.369	372 (97.9)	143 (96.6)	-0.043
Tumor Size (%)	<20mm	197 (14.3)	25 (6.2)	-0.338	31 (8.2)	12 (8.1)	-0.023
	20-40mm	252 (18.3)	17 (4.2)	-0.704	18 (4.7)	11 (7.4)	0.129
	>40mm	240 (17.5)	23 (5.7)	-0.508	30 (7.9)	14 (9.5)	0.058
	Unknown	685 (49.9)	339 (83.9)	0.927	301 (79.2)	111 (75.0)	-0.092
Combined Stage (%)	Tis	456 (33.2)	101 (25.0)	-0.189	134 (35.3)	45 (30.4)	-0.060
	Localized	747 (54.4)	163 (40.3)	-0.286	189 (49.7)	75 (50.7)	0.002
	Regional	103 (7.5)	19 (4.7)	-0.132	20 (5.3)	9 (6.1)	0.005
	Distant	8 (0.6)	13 (3.2)	0.149	5 (1.3)	5 (3.4)	0.070
	Unknown	60 (4.4)	108 (26.7)	0.505	32 (8.4)	14 (9.5)	0.025
T (%)	Tis	330 (24.0)	60 (14.9)	-0.258	63 (16.6)	19 (12.8)	-0.082
	1	589 (42.9)	131 (32.4)	-0.223	172 (45.3)	62 (41.9)	-0.031
	2	108 (7.9)	15 (3.7)	-0.219	14 (3.7)	7 (4.7)	0.012
	3	22 (1.6)	3 (0.7)	-0.100	1 (0.3)	2 (1.4)	0.131
	Unknown	325 (23.7)	195 (48.3)	0.493	130 (34.2)	58 (39.2)	0.061
N (%)	Tis	1165 (84.8)	251 (62.1)	-0.467	272 (71.6)	103 (69.6)	-0.037
	1	17 (1.2)	3 (0.7)	-0.058	2 (0.5)	3 (2.0)	0.184
	2	9 (0.7)	6 (1.5)	0.069	4 (1.1)	3 (2.0)	0.047
	3	1 (0.1)	3 (0.7)	0.078	1 (0.3)	1 (0.7)	0.000
	Unknown	182 (13.2)	141 (34.9)	0.454	101 (26.6)	38 (25.7)	-0.007
FIGO stage (%)	Tis	330 (24.0)	60 (14.9)	-0.258	63 (16.6)	19 (12.8)	-0.082
	I	556 (40.5)	119 (29.5)	-0.242	165 (43.4)	60 (40.5)	-0.025
	II	101 (7.4)	9 (2.2)	-0.347	10 (2.6)	4 (2.7)	0.000
	III	23 (1.7)	4 (1.0)	-0.069	5 (1.3)	2 (1.4)	0.011
	IV	27 (2.0)	14 (3.5)	0.082	5 (1.3)	6 (4.1)	0.086
	Unknown	337 (24.5)	198 (49.0)	0.490	132 (34.7)	57 (38.5)	0.047
Radiation (%)	No	1350 (98.3)	386 (95.5)	-0.131	366 (96.3)	139 (93.9)	-0.016
Radiation (%)	Yes	24 (1.7)	18 (4.5)	0.131	14 (3.7)	9 (6.1)	0.016
Chemotherapy (%)	No	1354 (98.5)	381 (94.3)	-0.183	369 (97.1)	140 (94.6)	-0.015
Chemotherapy (%)	Yes	20 (1.5)	23 (5.7)	0.183	11 (2.9)	8 (5.4)	0.015

¹Standardized Mean Difference.

After 1:1 nearest-neighbor PSM, 380 surgical patients and 148 non-surgical patients were retained. Overall covariate balance improved after matching, although residual imbalance remained in some variables, particularly those with a high proportion of unknown values. Detailed pre- and post-match covariate distributions and SMDs are presented in Table 3, and the post-match balance is further illustrated in Supplementary Figure 1.

Survival Analysis After PSM

After PSM, the median OS in the matched cohort was 154.0 months (95% CI: 138.0–NA) (Table 4). The corresponding 1-, 3-, and 5-year OS rates were 96.6% (95% CI: 95.0%–98.2%), 87.4% (95% CI: 84.3%–90.6%), and 79.8% (95% CI: 75.6%–84.2%), respectively (Table 5).

Table 4.

Median Survival Time of Surgical and Non-surgical Groups After PSM

Characteristic	Median Survival (Months)
Overall	154.0 (138.0, NA)
Surgery
No	90.0 (72.0, NA)
Yes	179.0 (146.0, NA)

Kaplan-Meier estimates

Table 5.

Kaplan-Meier Estimates of 1.3.5-Year Survival (95% Confidence Intervals) After PSM

Characteristic	N	Event N	1-years	3-years	5-years	p-value¹
Overall	528	109	96.6% (95.0%, 98.2%)	87.4% (84.3%, 90.6%)	79.8% (75.6%, 84.2%)
Surgery	528	109				<0.001
No			93.4% (89.4%, 97.7%)	78.9% (71.8%, 86.8%)	64.5% (55.4%, 75.2%)
Yes			97.8% (96.3%, 99.3%)	90.6% (87.4%, 94.0%)	85.8% (81.5%, 90.3%)

¹Log-rank test.

In the matched non-surgical group, the median OS was 90.0 months (95% CI: 72.0–NA), whereas in the matched surgical group, the median OS was 179.0 months (95% CI: 146.0–NA). The corresponding 1-, 3-, and 5-year OS rates were 93.4%, 78.9%, and 64.5% in the non-surgical group, compared with 97.8%, 90.6%, and 85.8% in the surgical group. The difference in OS between the matched surgical and non-surgical groups remained statistically significant (log-rank p<0.001). The Kaplan–Meier curves after matching are shown in Figure 4.

Figure 4.

Kaplan-Meier curves for OS after PSM stratified by age (A), SEER-recorded FIGO/stage-related categories (B), primary tumor site (C), and surgical status (D)

Stratified Survival Analysis According to Invasion Status

Because the cohort included both preinvasive/in situ and invasive VPD, additional Kaplan-Meier analyses stratified by invasion status were performed. As shown in Supplementary Figure 2, surgery was associated with better OS in both the in situ and invasive subsets before and after PSM. In patients with in situ disease, the difference between the surgical and non-surgical groups was significant both before PSM (p<0.0001) and after PSM (p=0.024). In patients with invasive disease, the difference was also significant both before PSM (p<0.0001) and after PSM (p=0.00019). These analyses were performed to distinguish the survival patterns of biologically distinct disease subsets and to avoid interpreting tumors in situ together with invasive stage I–IV disease.

Discussion

VPD is a rare and slowly developing vulvar epithelial neoplastic lesion, and there is no clear diagnosis and treatment guideline at present. Difficulty in diagnosis, high recurrence rate, and tissue defects and functional damage caused by surgery are the main problems encountered.^1,17 We utilized the SEER database to gain further insights into VPD with the aim of refining current treatment plans and enhancing patient outcomes.

Consistent with previous studies, we found that VPD occurred more frequently in elderly white women. Labium majus was the most common site of involvement.^17,18 In our study, we found that elderly and advanced stages VPD patients tended to have poorer OS. This may be related to the generally poorer physical condition of elderly patients. Patients at late stages may have lymph node or distant metastases, and the tumor may often penetrate the basement membrane to infiltrate into the dermis and subcutaneous fat layers, leading to rapid progression of the disease through lymphatic or blood pathways. Previous studies also concluded that the depth of invasion and lymph node metastasis were significant factors contributing to a poorer prognosis.^6,19 Van der Linden et al also showed that VPD had a lower survival rate after infiltration occurs.⁴ This further illustrated the importance of specifying the depth of VPD infiltration. Because preinvasive and invasive vulvar Paget’s disease differ in biological behavior and prognosis, distinguishing these two entities is clinically important when interpreting treatment patterns and survival outcomes.

Our study suggested that surgery was associated with improved survival in this cohort; however, this finding should be interpreted in the context of the heterogeneous biological spectrum of VPD. According to the size and location of the lesion, the surgical procedures that can be chosen include radical vulvectomy, radical partial vulvectomy, and simple partial vulvectomy.²⁰ Due to the multi-focal nature and microscopic dissemination characteristics of VPD, the positive surgical margin rate is typically high.^17,21 Whether surgery should pursue negative margins is currently a matter of debate. Sopracordevole²² and Nasioudis¹⁷ et al believe that the surgical margin status of VPD is not correlated with disease recurrence and prognosis, while a recent retrospective study suggests that positive margins are associated with an increased risk of local recurrence and all-cause mortality.²¹ Therefore, the value of negative surgical margins in VPD still requires further research confirmation.

For patients with severe comorbidities or extensive metastases who cannot tolerate surgery or have recurrent disease after surgery, non-invasive treatment options such as imiquimod therapy, radiotherapy, carbon dioxide laser ablation, photodynamic therapy (PDT), and chemotherapy is available. However, our study indicated that chemotherapy and radiotherapy didn’t improve the prognosis. In addition to the reason that VPD is not sensitive to chemotherapy and radiotherapy, it may also be led to the number of patients included in our study who underwent chemotherapy and radiotherapy was relatively small.^23,24 Topical application of 5% imiquimod cream can avoid tissue damage caused by surgery and has been proven to be effective for both primary and recurrent disease.²⁵ However, the specific target population for its use still needs further research.

This study is the largest known real-world study of VPD to date. The SEER database widely represents the US population and has a high degree of integrity and accuracy in disease diagnosis and follow-up, making the trends observed in this study reliable. Nevertheless, our study had certain limitations. Firstly, retrospective studies have their inevitable inherent biases. Secondly, the SEER database lacks specific surgical procedures and other variables, which are also important for improving the prognosis of VPD patients. Thirdly, subgroup analyses were exploratory in nature, were not adjusted for multiple comparisons, and should be interpreted with caution, especially in small subgroups. Further prospective studies are highly necessary.

Conclusion

Based on the SEER database, this study conducted an in-depth investigation into the clinical pathological characteristics, treatment, and prognosis of VPD. The findings indicated that surgery was beneficial for improving the prognosis of VPD patients. Patients with VPD who underwent surgery had improved survival in this cohort; however, findings from subgroup analyses, especially those related to treatment timing, should be interpreted cautiously.

Supplemental Material

Supplemental Material - Survival and Treatment Patterns in Vulvar Paget’s Disease: Evidence From SEER

Supplemental Material for Survival and Treatment Patterns in Vulvar Paget’s Disease: Evidence From SEER by Lele Chang, Yaxin Kang, Jing Liu, Cuibo Lin and Qin Xu by Cancer Control.

Supplemental Material

Supplemental Material - Survival and Treatment Patterns in Vulvar Paget’s Disease: Evidence From SEER

Supplemental Material for Survival and Treatment Patterns in Vulvar Paget’s Disease: Evidence From SEER by Lele Chang, Yaxin Kang, Jing Liu, Cuibo Lin and Qin Xu by Cancer Control.

Footnotes

ORCID iD

Qin Xu

Ethical Considerations

This study was conducted using publicly available, de-identified data from the SEER database. Therefore, Institutional Review Board/Ethics Committee approval was not required for this study.

Consent to Participate

Informed consent was also not required because no identifiable private information was involved.

Consent for Publication

All the authors agreed to publish this work.

Author Contributions

LC and YK proposed the main idea and drafted the initial version of the manuscript. JL conducted the data analysis, while JL were responsible for data collection and validation. QX and CL provided guidance on the methodology and structure of the article. QX and JL contributed to funding acquisition. QX and LC had carefully polished and revised the overall article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Fujian Cancer Hospital High-Level Talent Training Program (2023YNG09), Joint Funds for the innovation of science and Technology, Fujian province (Grant number: 2023Y9449), Natural Science Foundation of Fujian Province (Grant number: 2024J011099 and 2023J011273).

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data Availability Statement

The datasets used and analysed during the current study available from the corresponding author on reasonable request.*

Supplemental Material

Supplemental material for this article is available online.

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Supplementary Material

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