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.

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.

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.

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.

Radiation therapy for extramammary Paget's disease: treatment outcomes and prognostic factors.

BACKGROUND: Extramammary Paget's disease (EMPD) is a relatively rare malignancy, and there are few reports related to radiation therapy. In the present study, we investigated the outcome of radiation therapy for EMPD. PATIENTS AND METHODS: Forty-one patients with EMPD in the genitalia underwent radiation therapy with curative intent. Fifteen patients had regional lymph node metastases before radiation therapy, but none had distant metastasis. Total doses of 45-80.2 Gy (median, 60 Gy) were delivered to tumor sites in 23-43 fractions (median, 33 fractions). RESULTS: At a median follow-up period of 41 months, 16 patients had developed recurrences, including 5 with local progression within the radiation field and 12 with lymph node or/and distant metastases outside the radiation field. The local progression-free and disease-free rates were 88% and 55% at 3 years, and 82% and 46% at 5 years, respectively. Nine patients died at 6-73 months after irradiation; the causes of death were tumor progression in five patients, infectious pneumonia in two, renal failure in one and old age in one. The overall and cause-specific survival rates were 93% and 96% at 3 years, and 68% and 84% at 5 years, respectively. Tumor invasion into the dermis and regional lymph node metastasis were significant prognostic factors for both distant metastasis and survival. No therapy-related toxicities of grade ≥3 were observed. CONCLUSIONS: Radiation therapy is safe and effective for patients with EMPD. It appeared to contribute to prolonged survival owing to good tumor control, and to be a promising curative treatment option.

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.

Dermo Beta Brachytherapy with 188Re in extramammary Paget's disease.

AIM: Extramammary Paget's disease (EMPD) is a rare neoplastic pathology involving the vulva, scrotum, and perianal areas, and it is characterized by a slow and insidious course. EMPD may also be associated with internal malignancy, and its clinical presentation features long-standing pruritic lesions, eczema-like, refractory to any therapy. The pathogenesis is unclear, and univocal standardization of treatment is yet to be determined. As regard to the patients who suffer from it, women are more often affected than men. The therapeutic approach depends on the extent of involvement; wide surgical excision is the first choice among treatments, but other forms of therapy, alone or in combination, include imiquimod 5%, photodynamic therapy, Mohs surgery as well as external beam radiotherapy and Brachytherapy. In the present paper a new therapeutic alternative is proposed: Dermo-Beta-Brachytherapy (DBBT) with 188Re. METHODS: Five patients with EMPD, one secondary and four primary cases, have been treated by Brachytherapy with DBBT. This therapy has been successfully used for non-melanocytic skin tumors and basically consists in the topical application of a specially designed, tailor-made mould containing a radioactive beta-emitting isotope, rhenium-188. RESULTS: The patients healed completely, after one session in one case and after two sessions in four cases, with 34 months mean follow-up. CONCLUSION: Brachyterapy could represent a new alternative therapy, instead than invasive treatments as surgery and conventional radiotherapy, capable to treat EMPD independently of its extension, with aesthetic and functional satisfactory results.

Primary extramammary Paget's disease of the vulva: the clinicopathological features and treatment outcomes in a series of 43 patients.

OBJECTIVE: To characterize the clinicopathological features and evaluate the treatment outcomes for cases of primary extramammary Paget's disease of the vulva (EMPDV). METHODS: The medical records and pathology slides were reviewed and analyzed for 43 patients with primary EMPDV. RESULTS: The mean age of the patients was 68.6 years (range, 52-85). Intraepithelial EMPDV, invasive EMPDV and EMPDV with adnexal adenocarcinoma were observed in 33 (76.7%), 7 (16.3%) and 3 (7.0%) cases, respectively. Varied surgical procedures were initially performed in 35 (81.4%) cases. A positive incision margin was observed in 16 cases (47.0%). Definitive radiotherapy at a median dose of 60 Gy was performed in 8 (18.6%) patients. Six patients received postoperative radiotherapy due to a positive margin or lymph node metastasis after surgical excision. During a follow-up period of 6-169 months (median, 54), recurrence was observed in 12 (34.3%) patients. Nine (75.0%) patients underwent repeated surgery and 3 (25.0%) patients received radiotherapy. Long-term overall survival was observed in patients with intraepithelial EMPDV. The median overall survival was 124.5 months in intraepithelial cases, 70.8 months in invasive cases and 21.3 months in cases with adnexal adenocarcinoma (log rank, P=0.032). CONCLUSIONS: Intraepithelial EMPDV accounted for the majority of primary cases and had a better prognosis. Surgical excision was the standard curative treatment for EMPDV. Radiotherapy was an alternative choice for patients with medical contradiction or surgical difficulties. Postoperative radiotherapy could be considered in cases with positive surgical margin or lymph node metastasis. Recurrence was common and repeated excision was often necessary.

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.

[Radiotherapy and urogenital Paget disease]. / Le cas clinique du mois: Radiothérapie dans le cadre d'une maladie de Paget touchant la région génitale.

Urogenital Paget disease is usually treated by surgery. However, in case of recurrence or if multilating surgery is foreseen, radiotherapy seems to open a reasonable alternative. We report a successful treatment with radiotherapy in a patient with urogenital Paget's disease.

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.

Radiotherapy for extramammary Paget disease of the anogenital region.

Extramammary Paget disease is a rare condition that most commonly affects the anogenital region in the elderly. The treatment of choice has been surgical excision of the affected area with adequate depth and lateral margins, criteria that cannot always be fulfilled, especially when the vulva, anal canal, or penis are involved. More recently radiotherapy has been suggested as a suitable treatment when surgical excision or other modalities are not appropriate. We report a case of anogenital extramammary Paget disease and the clinical response to treatment with radiotherapy. The aim of this article is to review relevant aspects of radiotherapy as a first-choice curative treatment in specific situations of anogenital extramammary Paget disease in situ.

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.

Radiotherapy for perianal Paget's disease: a case report.

BACKGROUND: Perianal Paget's disease was first described in 1893. Since then, fewer than 300 cases have been reported in the literature. It might be associated with an underlying malignancy. Most of the patients are treated with surgical excision, which is often mutilating and of variable efficacy. In the present report, we describe the case of an 80-year-old woman with perianal Paget's disease. She was treated at our institution with radiotherapy with curative intent. The pertinent literature is reviewed, and the controversies in diagnosis and management are discussed. CONCLUSIONS: Our single-case experience supports the opinion that radiotherapy is a viable treatment option with curative potential for patients with perianal Paget's disease. For the treatment of in situ disease, hypofractionated regimens to a total dose of 40-44 Gy and orthovoltage X-ray beams are recommended.