High-dose-rate brachytherapy in scrotal extramammary Paget's disease: A case report.

PURPOSE: Extramammary Paget's disease (EMPD) is a rare but lethal intraepithelial malignancy without standardized guidelines concerning diagnostic or therapeutic approaches. We report a case of EMPD of the scrotum treated with excellent results using high-dose brachytherapy. METHODS AND MATERIALS: A 76-year-old male originally presented in 2015 with pruritus and erythema of the right scrotum, biopsy proved to represent extramammary Paget's disease. He was treated for a year with topical creams without sustained relief. In July 2016 he underwent a right hemiscrotectomy which revealed stage 1 EMPD of the right scrotum and the medial thigh with positive margins but no deep invasion. Brachytherapy was selected as the most appropriate treatment option and carried out in December 2016 using HDR with a H.A.M. applicator and CT treatment planning. RESULTS: On December 2021, at 5 years of clinical and pathological follow up, the patient remains NED with minimal skin toxicity. CONCLUSIONS: High-Dose-Rate Brachytherapy appears to be a feasible treatment alternative as adjuvant therapy in patients with EMPD with incomplete resection.

Postoperative radiation therapy improves prognoses in extramammary Paget's disease presenting with multiple lymph node metastases.

Invasive extramammary Paget's disease may cause lymph node and distant metastases. Complete lymph node dissection is generally performed for extramammary Paget's disease presenting with lymph node metastases. Patients with extramammary Paget's disease and multiple lymph node metastases typically have poor prognoses, and there is no effective postoperative treatment to prevent recurrence or further metastases in such patients to date. This study aimed to evaluate the efficacy of postoperative radiotherapy in patients with extramammary Paget's disease and multiple lymph node metastases. We enrolled 26 patients with extramammary Paget's disease with ≥3 lymph node metastases who were treated at the National Cancer Center Hospital in Japan between January 2000 and June 2021. The patients were divided into those who underwent complete lymph node dissection only or with postoperative radiotherapy. We evaluated recurrence-free survival, distant metastasis-free survival, and overall survival outcomes with Kaplan-Meier curves. Among the 26 enrolled patients, 16 underwent complete lymph node dissection only and 10 underwent complete lymph node dissection with postoperative radiotherapy. The median follow-up period was 16 months. The 5-year recurrence-free, distant metastasis-free, and overall survival values were 47.3%, 63.0%, and 90% in those with complete lymph node dissection and postoperative radiotherapy, while these outcomes were all 0% (p = 0.001, 0.004, and 0.009, respectively) in those with only complete lymph node dissection. Thus, survival was significantly prolonged with postoperative radiotherapy. Additional postoperative radiotherapy may substantially improve the prognoses of patients with extramammary Paget's disease and ≥3 lymph node metastases, and undergoing curative surgery.

Paget's disease of scrotum and penis case report of a re-irradiation and review of the literature.

Extramammary Paget's disease (EMPD) is a rare cutaneous adenocarcinoma generally arising in the anogenital region. Surgery is still considered the treatment of choice for patients with EMPD, while Radiotherapy is a common alternative for inoperable cases and it's necessary in case of lack of surgical radicality. In this article, we described our experience and a review of the literature, with a particular focus on radiation-induced toxicity and on the feasibility of re-irradiation. A 70-year-old patient with EPMD underwent adjuvant radiotherapy in 2015. After 28 months for recurrence another radiant treatment was performed. No G3 (CTCAE v4) toxicity were recorded. In the last follow-up visit at 18 months, no signs of relapse were reported. A search strategy of the bibliographic database PubMed was performed. The inclusion criteria for the articles were case report, clinical prospective, or retrospective studies with histological confirmation of EMPD of scrotum and penis; studies with patients undergoing RT; studies in the past 30 years. In most of the 14 reported studies, RT was overall well tolerated. The major observed toxicity was G3 skin toxicity in one study. To our knowledge, there are no other cases of EPMD re-irradiation in literature. Our patient showed an excellent response and tolerated very well the high doses of both the radiation treatments. This suggests that the tolerance of skin to re-irradiation following a long period between the two treatments may be comparable to the normal constraints.

Vulvo-Perineal and Perianal Paget Disease. Radical Excision and Reconstruction with Singapore Flap.

Extramammary Paget disease (EMPD) is an uncommon intraepithelial malignancy, affecting the vulvo-perineal and perianal region, occurring in 6.5% of all Paget diseases. Usually, an underlying invasive adenocarcinoma denotes a more aggressive behaviour of the disease. We present the multidisciplinary approach in a 75-year old patient with this rare disease. The patient underwent a radical surgical excision and, subsequently, a Singapore flap was used for primary closure. The final histology confirmed the presence of a non-invasive Paget tumor, but a focus of high-grade invasive adenocarcinoma was noted in a perineal nodule. The histological margins were free of tumor. The patient did not undergo any adjuvant treatment because of severe chronic medical problems, although, eighteen months after treatment, she remains well, with no signs of recurrence. In conclusion, radical surgical excision, often necessitating reconstruction techniques, remains the gold standard of care and further adjuvant treatment should be individualised.

Boron neutron capture therapy for vulvar melanoma and genital extramammary Paget's disease with curative responses.

BACKGROUND: Although the most commonly recommended treatment for melanoma and extramammary Paget's disease (EMPD) of the genital region is wide surgical excision of the lesion, the procedure is highly invasive and can lead to functional and sexual problems. Alternative treatments have been used for local control when wide local excision was not feasible. Here, we describe four patients with genital malignancies who were treated with boron neutron capture therapy (BNCT). METHODS: The four patients included one patient with vulvar melanoma (VM) and three with genital EMPD. They underwent BNCT at the Kyoto University Research Reactor between 2005 and 2014 using para-boronophenylalanine as the boron delivery agent. They were irradiated with an epithermal neutron beam between the curative tumor dose and the tolerable skin/mucosal doses. RESULTS: All patients showed similar tumor and normal tissue responses following BNCT and achieved complete responses within 6 months. The most severe normal tissue response was moderate skin erosion during the first 2 months, which diminished gradually thereafter. Dysuria or contact pain persisted for 2 months and resolved completely by 4 months. CONCLUSIONS: Treating VM and EMPD with BNCT resulted in complete local tumor control. Based on our clinical experience, we conclude that BNCT is a promising treatment for primary VM and EMPD of the genital region. Trial registration numbers UMIN000005124.

The Role of Radiotherapy in Extramammary Paget Disease: A Systematic Review.

OBJECTIVE/PURPOSE: Extramammary Paget disease (EMPD) is a rare neoplasm of the skin generally affecting the anogenital area. Because of the low-frequency of the disease, no specific guidelines about the treatment strategy are available. Surgery is the recommended therapy for resectable and localized disease, but several other local treatments have been reported such as radiotherapy (RT). Most articles report small retrospective studies, referring to patients treated decades ago with large heterogeneity in terms of RT dose and technique. The aim of this study was to systematically review the main experiences in RT for the treatment of EMPD in the past 30 years. MATERIALS AND METHODS: A systematic search of the bibliographic databases PubMed and Scopus from January 1986 to January 2017 was performed including studies published in English, Italian, Spanish, French, and German language. RESULTS: According to the search strategy, 19 full-text articles, published from 1991 to 2015, fulfilled inclusion criteria and were included in the final review. All articles were retrospective analyses with no randomized controlled trials. These studies evaluated 195 EMPD patients treated with RT, delivered in several settings. A large variability in terms of RT doses, fractionation, clinical setting, and techniques was found.Radiotherapy was administered as definitive treatment for primary or recurrent disease after surgery in 18 studies with doses ranging from 30 to 80.2 Gy delivered in 3 to 43 fractions. Radiotherapy was administered as postoperative adjuvant treatment in 9 articles with doses ranging between 32 and 64.8 Gy in 20 to 30 fractions. Two studies reported the RT use in preoperative neoadjuvant setting with doses ranging between 40 and 43.30 Gy, and 2 experiences reported the RT treatment for in situ EMPD, using 39.6 to 40 Gy. Adverse events were reported in almost all but 2 articles and were grade 2 or lower.The 18 studies evaluating RT as definitive treatment for primary or recurrent disease after surgery reported a complete response rate ranging from 50% to 100%, with a variable rate of local relapse or persistent disease ranging from 0% to 80% of cases. The 9 studies evaluating RT as postoperative adjuvant treatment reported a local relapse or persistent disease rate of 0% to 62.5%. A dose-response relationship was reported suggesting doses greater than or equal to 60 Gy for gross tumor volume treatment. Local control, disease-free survival, and overall survival at 12, 20, and 60 months have been retrieved for available data, respectively.In patients with EMPD and concurrent underlying internal malignancy, the prognosis was often worsened by the latter. In this setting, literature analysis showed a potential RT palliative role for symptoms control or local control maintenance.Derma tumor invasion greater than 1 mm and lymph node metastases were reported to be important prognostic factors for distant metastases or death. CONCLUSIONS: To date, literature highlights the role of RT in the management of EMPD, but with low level of evidences.

Paget's Disease of the Vulva: A Review of 20 Years' Experience.

BACKGROUND: Extramammary Paget's disease is a rare condition, and the vulva is a common site for it to occur. Despite this, there is a paucity of literature on Paget's disease of the vulva (VPD). A Cochrane meta-analysis could not draw any conclusions on interventions in VPD. Our aim was to review our practice and improve further management of VPD in our center. METHODS: We reviewed all the cases presented to Leeds Gynaecological Oncology Centre between 1988 and 2016. All cases identified in this interval were followed up until April 2016. All case notes and electronic patient data were retrieved to collate the data. RESULTS: We identified 18 cases of VPD. The median age at presentation was 76.9 years. Primary surgery was used in 18 cases. Eight patients had wide local excision with graft reconstruction. Ten women had wide local excision with primary reconstruction. Margins were negative in 27% of the excisions. Sixty percent of patients with clear surgical margins had a recurrence, and 69% of patients with positive margins had a recurrence; there was no statistical difference between the 2 groups for recurrence (P > 0.05). Fifty-eight percent of patients who had recurrence had coexisting malignancy. Logistic regression showed no correlation of recurrence rates due to either age, margin status, or coexisting malignancies. CONCLUSIONS: Paget's disease of the vulva is a rare condition. Our experience indicates that most cases may be amenable to surgical treatment at first presentation. Negative margin status does not reduce the chance of recurrence, and hence patients should be under follow-up for life. The benefit of radical surgery in the absence of reduced recurrences, based on margin status, is questionable. Radiotherapy and imiquimod are options for extensive lesions or recurrent settings. Coexisting malignancies are associated with VPD.

Primary extramammary invasive Paget's vulvar disease: what is the standard, what are the challenges and what is the future for radiotherapy?

BACKGROUND: Primary invasive Extramammary Paget's vulvar disease is a rare tumor that is challenging to control. Wide surgical excision represents the standard treatment approach for Primary invasive Extramammary Paget's vulvar disease. The goal of the current study was to analyze the appropriate indications of radiotherapy in Primary invasive Extramammary Paget's vulvar disease because they are still controversial. DISCUSSION: We searched the Cochrane Gynecological Cancer Group Trials Register, Cochrane Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE database up to September 2015. Radiotherapy was delivered as a treatment in various settings: i) Radical in 28 cases (range: 60-63 Gy), ii) Adjuvant in 25 cases (range: 39-60 Gy), iii) Salvage in recurrence of 3 patients (63 Gy) and iv) Neoadjuvant in one patient (43.3 Gy). A radiotherapy field that covered the gross tumor site with a 2-5 cm margin for the microscopic disease has been used. Radiotherapy of the inguinal, pelvic or para-aortic lymph node should be considered only for the cases with lymph node metastases within these areas. Radiotherapy alone is an alternative therapeutic approach for patients with extensive inoperable disease or medical contraindications. Definitive radiotherapy can be used in elderly patients and/or with medical contraindications. Adjuvant radiotherapy may be considered in presence of risk factors associated with local recurrence as dermal invasion, lymph node metastasis, close or positive surgical margins, perineal, large tumor diameter, multifocal lesions, extensive disease, coexisting histology of adenocarcinoma or vulvar carcinoma, high Ki-67 expression, adnexal involvement and probably in overexpression of HER-2/neu. Salvage radiotherapy can be given in inoperable loco-regional recurrence and to those who refused additional surgery.

Extramammary Paget disease of the vulva: minimal excision with adjuvant radiation treatment for optimal aesthetic results.

AIMS AND BACKGROUND: Extramammary Paget disease (EMPD) is an uncommon malignant neoplasm that occurs in areas containing apocrine glands, and the vulva is the most commonly involved site. Wide surgical excision with subsequent defect reconstruction is widely accepted as the first-line treatment for EMPD. More recently, radiation treatment has been considered an appropriate primary or adjuvant treatment. In an effort to replace wide excision and avoid unfavorable aesthetic results and sexual dysfunction, we decided to excise the tumor minimally and to add adjuvant radiation treatment. METHODS: A 71-year-old woman had EMPD at the right labium majus. The patient was treated by minimal excision with a 1-cm safety margin and by adjuvant radiation treatment weekly from 1 month to 3 months after surgery to a total dose of 70.2 Gy. Four months after completing the radiation treatment, a 10-point surgical biopsy around the site of previous resection was performed. Radiation treatment caused hypertrophy of the left labium minus, which was treated by additional labiaplasty (labium minus reduction) to obtain optimal aesthetic results. RESULTS: Surgical biopsy revealed no definite evidence of recurrence. Currently, the patient had no EMPD symptoms, is satisfied with a symmetrical vagina, and experiences no discomfort during ordinary activities or intercourse. CONCLUSIONS: Minimal tumor excision (with a 1-cm safety margin), adjuvant radiotherapy, and additional labiaplasty were performed to treat EMPD. Complete tumor removal without recurrence, an aesthetically satisfactory result, and normal sexual function were achieved in this patient.

External beam radiotherapy of extramammary Paget disease.

Extramammary Paget disease (EMPD) is an insidious intraepithelial neoplasm that is difficult to control with surgery, as large resections typically are required. An effective alternative is external beam radiotherapy (EBRT), which typically results in rapid resolution of EMPD. In this study, we analyzed long-term outcomes in 7 patients who were treated with EBRT for EMPD.

Extensive invasive extramammary Paget disease evaluated by F-18 FDG PET/CT: a case report.

Extramammary Paget disease (EMPD) is a rare cutaneous, intraepithelial adenocarcinoma. Because of its rarity, little is known about the value of fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in evaluating this disease. Our case report aims to increase current knowledge of FDG PET/CT in EMPD as a noninvasive imaging tool for assessing the extension of the disease and detecting distant metastases.We reported a 64-year-old Chinese man who presented with a slowly progressive, ill-margined erythematous lesion with a crusted, eroded, and scaly surface involving multiple sites of penis, scrotum, left pelvic wall, hip, groin, and thigh for >4 years, which became extensive in the past 1 year. He was referred for an FDG PET/CT examination to further evaluate the lesions. A following skin biopsy was performed to obtain a definitive histological diagnosis.FDG PET/CT imaging revealed mild FDG uptake at the extensive cutaneous lesion with subcutaneous invasion, involvement of lymph nodes, and multiple intense FDG-avid of skeletal metastases. According to the appearance of FDG PET/CT, a provisional diagnosis of advanced cutaneous malignancy was made. Histopathology findings indicated characteristic of EMPD. The patient was treated with radiation therapy and died from complications 2 months after the last dose of radiotherapy.Our case highlighted that a whole-body FDG PET/CT should be incorporated into the diagnostic algorithm of EMPD to give a comprehensive assessment of this disease.

Postoperative radiation therapy for extramammary Paget's disease.

BACKGROUND: Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy that is usually treated with surgery. Patients with positive surgical margins require adjuvant therapy, but there have been few reports on the use of radiation therapy. OBJECTIVES: To investigate the effectiveness of postoperative radiation therapy in EMPD. MATERIALS AND METHODS: Twenty-one patients with EMPD involving the genitalia underwent radiation therapy as adjuvant therapy after surgery. Ten patients had inguinal lymph node involvement before radiation therapy, but none had distant metastases. A median total dose of 59·4 Gy (range, 45-64·8 Gy) was delivered to the tumour bed in 30 fractions (range, 23-36 fractions). RESULTS: At a median follow-up period of 38 months, all patients had local control. However, six patients had developed distant metastases 6-43 months after radiation therapy. The distant metastasis-free rates were 66% at 3 years and 55% at 5 years. Inguinal lymph node involvement was a significant risk factor for distant metastases. Four patients died 33-58 months after irradiation; the causes of death were tumour progression in three patients and infectious pneumonia in one. The overall and cause-specific survival rates were both 92% at 3 years, and 62% and 71% at 5 years, respectively. No therapy-related toxicities of grade ≥ 3 were observed. CONCLUSIONS: Postoperative radiation therapy is safe and effective in maintaining local control in patients with EMPD.

Clinical research of holmium laser therapy in extramammary Paget's disease.

This study aims to investigate the safety and efficiency of the holmium laser therapy in extramammary Paget's disease. The clinical data of 61 patients was collected since 2002 to 2012, confirmed as non-subcutaneous invasive extramammary Paget's disease by biopsy and underwent surgery. All patients were divided into two groups. Group A included 30 patients who underwent the holmium laser therapy. Group B included 31 patients who underwent the traditional surgical therapy. The clinical data of all patients included preoperative, intraoperative, and postoperative management and follow-up records. Compared with the traditional operation group, the holmium laser group had a shorter operation time and was easier to perform. There were no significant differences between the two groups in cases of intraoperative and postoperative complications, the recurrence-free survival, and the disease-specific survival. But the holmium laser group had a longer recovery time than the traditional operation group in large and deep nidus. Multiple-factor analysis of prognostic parameters of 61 patients confirmed that any of these two methods chosen was not a prognostic parameter for recurrence-free survival. The holmium laser therapy might prove to be a preferable alternative to the traditional operative therapy of extramammary Paget's disease. However, the holmium laser therapy did not demonstrate to have an obvious advantage over traditional operative therapy in the recurrence-free survival and the disease-specific survival.

Technical and clinical description of a case of extensive anogenital Paget's disease associated with anal cancer treated by tomotherapy.

In this paper we describe a case of extramammary Paget's disease associated with anal cancer, which was successfully treated by intensity-modulated radiotherapy using tomotherapy with a simultaneous integrated boost and daily image guidance. The main pitfall in this report is the relatively short follow-up (1 year), which means that the evaluated data is promising but not conclusive. Considering the rarity and wide extension of our patient's Paget's disease in the anogenital region, and the lack of literature reports about curative radiotherapy in this particular setting, this case report may be considered the first related to extensive extramammary Paget's disease treated by tomotherapy.