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Gynecologic Oncology Feb 2017Treatment of locally advanced vulva cancer (LAVC) remains challenging. Due to the lack of randomised trials many questions regarding the indications for different... (Review)
Review
Locally advanced vulva cancer: A single centre review of anovulvectomy and a systematic review of surgical, chemotherapy and radiotherapy alternatives. Is an international collaborative RCT destined for the "too difficult to do" box?
INTRODUCTION
Treatment of locally advanced vulva cancer (LAVC) remains challenging. Due to the lack of randomised trials many questions regarding the indications for different treatment options and their efficacy remain unanswered.
METHODS
In this retrospective study we provide the largest published series of LAVC patients treated with anovulvectomy, reporting oncological outcomes and morbidity. Additionally, a systematic literature review was performed for all treatment options 1946-2015.
RESULTS
In our case series, 57/70 (81%) patients were treated in the primary setting with anovulvectomy and 13 patients underwent anovulvectomy for recurrent disease. The median overall survival (OS) was 69months (1-336) with disease specific survival of 159months (1-336). Following anovulvectomy for primary disease, time to progression and OS were significantly higher in node negative disease (10 vs. 96months; 19 vs. 121months, p<0.0001). Post-surgical complications were observed in 36 (51.4%), the majority of which were Grade I/II infections. There was one peri-operative death. Review of the literature showed that chemotherapy, radiotherapy or combination treatments are alternatives to surgery. Evidence relating to all of these consisted mostly of small retrospective series, which varied considerably in terms of patient characteristics and treatment schedules. Significant patient and treatment heterogeneity prevented meta-analysis with significant biases in these studies. It was unclear if survival or morbidity was better in any one group with a lack of data reporting complications, quality of life, and long term follow-up. However, results for chemoradiation are encouraging enough to warrant further investigation.
CONCLUSIONS
There remains inadequate evidence to identify an optimal treatment for LAVC. However, there is sufficient evidence to support a trial of anovulvectomy versus chemoradiation. Discussions and consensus would be needed to determine trial criteria including the primary outcome measure. Neoadjuvant chemotherapy or radiotherapy alone may be best reserved for the palliative setting or metastatic disease.
Topics: Adult; Aged; Aged, 80 and over; Chemoradiotherapy; Female; Humans; Intersectoral Collaboration; Middle Aged; Randomized Controlled Trials as Topic; Retrospective Studies; Vulva; Vulvar Neoplasms
PubMed: 28034465
DOI: 10.1016/j.ygyno.2016.12.007 -
European Journal of Surgical Oncology :... Dec 2022The prognostic role of perineural invasion (PNI) in vulvar squamous cell carcinoma (VSCC) has not been fully established since few studies on this topic are currently... (Meta-Analysis)
Meta-Analysis Review
The prognostic role of perineural invasion (PNI) in vulvar squamous cell carcinoma (VSCC) has not been fully established since few studies on this topic are currently available in the literature. In the present study, we conducted a systematic review and metanalysis of literature data in order to determine if PNI could be an independent prognostic predictor of patient's survival in VSCC. Four electronic databases (PubMed, ISI Web of Science, Scopus and Google Scholar) were searched from their inception to December 2021 for all studies assessing the prognostic value of PNI in VSCC. Multivariate hazard ratios (HRs) for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were pooled. Six studies with 1048 patients were included. PNI was significantly associated with decreased OS (HR = 2.687; p < 0.001), DSS (HR = 2.375; p = 0.014) and PFS (HR = 1.757; p = 0.001), with no statistical heterogeneity among studies and no significant risk of bias across studies. The present meta-analysis highlights that PNI is independently associated with unfavorable prognosis in patients with VSCC. Therefore, PNI should be included in the pathological report of VSCC and considered in combination with other risk factors as a possible criteria for prognostic assessment adjuvant treatment planning inclusion.
Topics: Female; Humans; Prognosis; Neoplasm Invasiveness; Vulvar Neoplasms; Carcinoma, Squamous Cell; Proportional Hazards Models
PubMed: 35811178
DOI: 10.1016/j.ejso.2022.06.031 -
Journal of Obstetrics and Gynaecology... Feb 2022The objectives of this study were to determine: 1) the prevalence of lichen sclerosus (LS) and lichen planus (LP) present in association with vulvar squamous cell... (Review)
Review
OBJECTIVES
The objectives of this study were to determine: 1) the prevalence of lichen sclerosus (LS) and lichen planus (LP) present in association with vulvar squamous cell carcinoma (VSCC), and 2) the incidence and absolute risk of developing VSCC in LS and LP.
METHODS
A search was performed of MEDLINE, EMBASE and CINAHL databases. Three independent reviewers screened articles published before September 1, 2020, first on title/abstract and then on the full text. Women with a history of VSCC, human papillomavirus, smoking, or autoimmune disease were excluded. Newcastle-Ottawa observational study scales were used to assess the risk of bias and methodological quality of the included studies. Of the 3132 studies assessed, 31 were selected for analysis. Due to study heterogeneity, a qualitative synthesis was conducted.
RESULTS
The prevalence of LS and LP in association with VSCC ranged from 0% (95% CI 0-5) to 83% (95% CI 36-100) and 1% (95% CI 0-7) to 33% (95% CI 4-78), respectively. The incidence of VSCC ranged from 1.16 (95% CI 0.03-6.44) to 13.67 (95% CI 5.50-28.17) per 1000 person-years for LS. The absolute risk of developing VSCC in patients ranged from 0.0% (95% CI 0.0-5.52) to 21.88% (95% CI 9.28-39.97) with LS and was 1.16% (95% CI 0.1-4.1) with LP. Incidence was not calculable for LP owing to study characteristics.
CONCLUSIONS
This review provides evidence that there is an increased risk of developing VSCC in women with LS, while associations with LP are less clear. Early identification, treatment, and long-term follow-up are essential to prevent potential malignant progression of these vulvar dermatoses.
Topics: Carcinoma, Squamous Cell; Female; Humans; Lichen Planus; Lichen Sclerosus et Atrophicus; Observational Studies as Topic; Vulva; Vulvar Neoplasms
PubMed: 34678521
DOI: 10.1016/j.jogc.2021.09.023 -
The Cochrane Database of Systematic... Jun 2019This is an updated version of the original Cochrane Review published in Issue 10, 2013.Extramammary Paget's disease is a rare form of superficial skin cancer. The most...
BACKGROUND
This is an updated version of the original Cochrane Review published in Issue 10, 2013.Extramammary Paget's disease is a rare form of superficial skin cancer. The most common site of involvement is the vulva. It is seen mainly in postmenopausal white women. Paget's disease of the vulva often spreads in an occult fashion, with margins extending beyond the apparent edges of the lesion. There is a range of interventions from surgical to non-invasive techniques or treatments. The challenges of interventions are to remove or treat disease that may not be visible, without overtreatment and with minimisation of morbidity from radical surgery. There is little consensus regarding treatment. Surgery, by default, is the most common treatment, but it is challenging to excise the disease adequately, and recurrence is common, leading to repeated operations, and destruction of anatomy. Alternative treatments of photodynamic therapy, laser therapy, radiotherapy, topical treatments or even chemotherapy have been mooted, and it is important to evaluate the available evidence. It is essential to assess whether newer cell-specific treatments, such as photodynamic therapy and imiquimod, can reduce the need for radical surgery.
OBJECTIVES
To evaluate the benefits and harms of different treatment modalities for the management of Paget's disease of the vulva.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via Ovid) and Embase (via Ovid) up to 8 May 2018. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of review articles.
SELECTION CRITERIA
We searched for randomised controlled trials (RCTs) and well-designed non-randomised studies that compared different interventions in women with Paget's disease of the vulva, DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. We found no trials and, therefore, analysed no data.
MAIN RESULTS
The search for the original version of the review identified 635 unique references. We found 31 references (which reported on 30 studies) in full text after inspection of titles and abstracts, but we excluded them all as they did not meet the inclusion criteria. However, we have included a comprehensive narrative account of studies where we identified an analysis of more than 10 women, as this forms the only evidence base in this rare disease. Surgery continues to be the mainstay of treatment in the current literature, with other treatments limited to case reports or treatment of inoperable or recurrent disease.This update between September 2013 and May 2018 identified 35 new studies. None of these met the inclusion criteria. There was only one prospective study of 5% imiquimod in recurrent Paget's disease of the vulva, which although of good quality only included eight women.
AUTHORS' CONCLUSIONS
Since the last version of the review was published there are many more cases in the literature reporting a clinical response to 5% imiquimod cream. There is one prospective study of eight women treated with 5% imiquimod for recurrent Paget's disease of the vulva, and one prospective trial of 20 women was due to be reported. This increasing evidence for the safety and efficacy of 5% imiquimod will be helpful for women and clinicians alike. Ideally, a multicentre RCT of reasonable size is needed, but ongoing publications of high-quality non-randomised prospective studies will enhance the current available literature.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Female; Humans; Imiquimod; Laser Therapy; Middle Aged; Paget Disease, Extramammary; Photochemotherapy; Randomized Controlled Trials as Topic; Vulvar Neoplasms
PubMed: 31167037
DOI: 10.1002/14651858.CD009245.pub3 -
PloS One 2015To systematically review previous studies and to evaluate the feasibility and safety of video endoscopic inguinal lymphadenectomy (VEIL) in vulvar cancer. (Review)
Review
OBJECTIVE
To systematically review previous studies and to evaluate the feasibility and safety of video endoscopic inguinal lymphadenectomy (VEIL) in vulvar cancer.
METHODS
We conducted a comprehensive review of studies published through September 2014 to retrieve all relevant articles. The PubMed, EMBASE, Web of Science, Cochrane Library, Wan Fang Data and Chinese National Knowledge Infrastructure databases were systematically searched for all relevant studies published in English or Chinese through September 2014. Data were abstracted independently by two reviewers, and any differences were resolved by consensus.
RESULTS
A total of 9 studies containing 249 VEIL procedures involving 138 patients were reviewed. Of the 249 VEIL procedures, only 1 (0.4%) was converted to an open procedure for suturing because of injury to the femoral vein. The range of operative time was 62 to 110 minutes, and the range of estimated blood loss was 5.5 to 22 ml. The range of the number of harvested lymph nodes was 7.3 to 16. The length of hospital stay varied from 7 to 13.6 days across reports. The incidence of lymph node metastasis was 19.7% (27/138), and the recurrence rate was 4.3% (3/70) within 3 to 41 months of follow-up. One or more short-term complications were documented in 18 of 138 (13.0%) patients. Complications after VEIL were observed in 14 (10.13%) patients and in 15 (6.0%) of the VEIL cases, including major lymphocyst formation in 9 (3.6%), lymphorrhea in 2 (0.8%), inguinal wound infection without wound breakdown in 3 (1.2%) and lymphedema in 1 (0.4%).
CONCLUSIONS
VEIL appears to be a feasible procedure in the management of vulvar cancer. There may be potential benefits that result in lower morbidity compared to traditional methods, but this has yet to be objectively proven.
Topics: Bacterial Infections; Blood Loss, Surgical; Female; Humans; Length of Stay; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Lymphocele; Operative Time; Postoperative Complications; Treatment Outcome; Video-Assisted Surgery; Vulva; Vulvar Neoplasms
PubMed: 26496391
DOI: 10.1371/journal.pone.0140873 -
Medicine Nov 2017Lower limb lymphedema (LLL) is an important concern for patients with vulvar cancer. Studies of the incidence of vulvar cancer-related lymphedema and its risk factors... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lower limb lymphedema (LLL) is an important concern for patients with vulvar cancer. Studies of the incidence of vulvar cancer-related lymphedema and its risk factors have substantially increased in the new millennium.
OBJECTIVES
This article is a meta-analysis that aimed to systematically evaluate the incidence of LLL and its risk factors related to vulvar cancer.
DATA SOURCES
Data were collected from eligible studies from PubMed, ScienceDirect, and Web of Science.
SYNTHESIS METHODS
Random effects models were used to calculate a pooled overall estimate of LLL incidence, and subgroup analyses were performed to assess the effects of different study designs, countries of study origin, diagnostic methods, and extent of lymph node surgery. Risk factors for lymphedema were also evaluated.
RESULTS
Twenty-seven studies met the inclusion criteria for the assessment of lymphedema incidence with a pooled estimate of 28.8% [95% confidence interval (CI) 22.1-35.5]. The estimate was 16.7% (95% CI 9.7-23.7) when data were restricted to prospective cohort studies (7 studies). The incidence of LLL was increased by approximately 5-fold in women who underwent inguinofemoral lymph node dissection compared to those who underwent sentinel lymph node biopsy. The reported risk factors included wound infection, inguinofemoral lymphadenectomy, older age, body mass index (BMI), and radiation therapy.
CONCLUSIONS
Approximately 3 in 10 women who survive vulvar cancer will develop lower limb lymphedema. More studies are needed to improve the understanding of its risk factors and to develop prevention and management strategies to alleviate this distressing disorder.
Topics: Female; Humans; Incidence; Lower Extremity; Lymphedema; Risk Factors; Vulvar Neoplasms
PubMed: 29145314
DOI: 10.1097/MD.0000000000008722 -
Gynecologic Oncology Mar 2018In patients treated for early-stage squamous cell vulvar carcinoma local recurrence is reported in up to 40% after ten years. Knowledge on prognostic factors related to... (Review)
Review
BACKGROUND
In patients treated for early-stage squamous cell vulvar carcinoma local recurrence is reported in up to 40% after ten years. Knowledge on prognostic factors related to local recurrences should be helpful to select high risk patients and/or to develop strategies to prevent local recurrences.
OBJECTIVE
This systematic review aims to evaluate the current knowledge on the incidence of local recurrences in vulvar carcinoma related to clinicopathologic and cell biologic variables.
DATA SOURCES
Relevant studies were identified by an extensive online electronic search in July 2017.
STUDY ELIGIBILITY CRITERIA
Studies reporting prognostic factors specific for local recurrences of vulvar carcinoma were included.
STUDY APPRAISAL AND SYNTHESIS METHODS
Two review authors independently performed data selection, extraction and assessment of study quality. The risk difference was calculated for each prognostic factor when described in two or more studies.
RESULTS
Twenty-two studies were included; most of all were retrospective and mainly reported pathologic prognostic factors. Our review indicates an estimated annual local recurrence rate of 4% without plateauing. The prognostic relevance for local recurrence of vulvar carcinoma of all analyzed variables remains equivocal, including pathologic tumor free margin distance <8mm, presence of lichen sclerosus, groin lymph node metastases and a variety of primary tumor characteristics (grade of differentiation, tumor size, tumor focality, depth of invasion, lymphovascular space invasion, tumor localization and presence of human papillomavirus).
CONCLUSIONS
Current quality of data on prognostic factors for local recurrences in vulvar carcinoma patients does not allow evidence-based clinical decision making. Further research on prognostic factors, applying state of the art methodology is needed to identify high-risk patients and to develop alternative primary and secondary prevention strategies.
Topics: Carcinoma, Squamous Cell; Female; Groin; Gynecologic Surgical Procedures; Humans; Lymph Nodes; Lymphatic Metastasis; Margins of Excision; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Papillomavirus Infections; Prognosis; Risk Factors; Vulvar Lichen Sclerosus; Vulvar Neoplasms
PubMed: 29137809
DOI: 10.1016/j.ygyno.2017.11.006 -
Journal of Clinical Medicine Jun 2023The most important causative agent of neoplasms in the anogenital area is the human papillomavirus (HPV). Due to the anatomical proximity of the genital and anus area... (Review)
Review
BACKGROUND
The most important causative agent of neoplasms in the anogenital area is the human papillomavirus (HPV). Due to the anatomical proximity of the genital and anus area and the ease with which HPV infection is transmitted, it seems that patients after the treatment of HPV-related gynecological diseases may have an increased risk of developing a second HPV-related neoplasm anal cancer. The aim of this study was to determine the risk of anal intraepithelial neoplasia (AIN) and anal cancer (AC) among patients after the treatment of HPV-related gynecological diseases.
METHODS
We conducted a comprehensive review of the available literature from multiple databases. The study was performed following and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 guidelines. Moreover, we assessed the quality of each study using QUADAS-2.
RESULTS
Twenty-five studies were included in the final analysis. Patients after the treatment of HPV-related gynecological diseases have a significantly higher risk of AC (mean standardized incidence ratio (SIR) = 5.387, mean incidence risk (IR) = 0.096%, mean IR per 100,000 person-years = 10.37) and AIN (mean IR = 23.683%) compared to the population risk.
CONCLUSIONS
patients with HPV-related gynecological diseases should constitute a group for which an appropriate primary and secondary screening for AC should be introduced.
PubMed: 37445251
DOI: 10.3390/jcm12134216 -
International Journal of Gynecological... May 2018Vulva cancer (VC) treatment carries a high risk of severe late effects that may have a negative impact on quality of life (QoL). Patient-reported outcome measures...
OBJECTIVES
Vulva cancer (VC) treatment carries a high risk of severe late effects that may have a negative impact on quality of life (QoL). Patient-reported outcome measures (PROMs) are increasingly used when evaluating disease- and treatment-specific effects. However, the adequacy of measures used to assess sequelae and QoL in VC remains unclear. The aims of the present study were to evaluate disease- and treatment-related effects as measured by PROMs in VC patients and to identify available VC-specific PROMs.
METHODS/MATERIALS
A systematic literature search from 1990 to 2016 was performed. The inclusion criterion was report of disease- and treatment-related effects in VC patients using PROMs in the assessment. Methodological and reporting quality was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. This systematic review was performed as part of phase 1 of the development of a European Organisation for Research and Treatment of Cancer QoL questionnaire for VC patients.
RESULTS
The search revealed 2299 relevant hits, with 11 articles extracted including a total of 535 women with VC; no randomized controlled trials were identified. The selected studies exhibited great heterogeneity in terms of PROMs use. Twenty-one different instruments assessed QoL. Most of the questionnaires were generic. Different issues (sexuality, lymphedema, body image, urinary and bowel function, vulva-specific symptoms) were reported as potentially important, but the results were not systematically collected. Only one VC-specific questionnaire was identified but did not allow for assessment and reporting on a scale level.
CONCLUSIONS
Vulva cancer treatment is associated with considerable morbidity deteriorating QoL. To date, there is no validated PROM available that provides adequate coverage of VC-related issues. The study confirms the need for a VC-specific QoL instrument with sensitive scales that allows for broad cross-cultural application for use in clinical trials.
Topics: Female; Humans; Patient Reported Outcome Measures; Quality of Life; Vulvar Neoplasms
PubMed: 29420364
DOI: 10.1097/IGC.0000000000001211 -
Gynecologic and Obstetric Investigation 2017Extramammary Paget's disease of the vulva (EPDV) is a rare adenocarcinoma in situ of the vulvar skin and is often resected with involved margins due to its reticular... (Review)
Review
BACKGROUND
Extramammary Paget's disease of the vulva (EPDV) is a rare adenocarcinoma in situ of the vulvar skin and is often resected with involved margins due to its reticular growth pattern. Adjuvant treatment with the immunomodulator imiquimod may be suitable to avoid repeated and mutilating surgery.
CASE PRESENTATION
We present the case of a 73-year-old woman with EPDV, initially treated with surgical resection and re-resection for involved margins. Final histology revealed Paget's disease of the left vulva with 8 cm in the largest diameter and again involved margins. Subsequently, topical therapy with imiquimod 5% cream twice weekly was applied for 3 months. Vulvoscopy and local biopsies confirmed complete remission (CR). Based on a literature search using PubMed and the Cochrane Central Register of Controlled Trials, 21 reports on the therapeutic efficacy of imiquimod in 70 women with EPDV have been published. Pooled rates of CR and partial remission were 71% (50/70) and 16% (11/70), respectively. There were 4 cases of disease progression under imiquimod and the therapy was generally well tolerated with mild to moderate local reactions in >50% of cases.
CONCLUSION
EPDV is a rare genital neoplasia and may be successfully treated with the topical immunomodulator imiquimod. Specifically, adjuvant imiquimod is a feasible and efficacious treatment option for women with involved resection margins after surgery.
Topics: Adjuvants, Immunologic; Administration, Topical; Aminoquinolines; Antineoplastic Agents; Female; Humans; Imiquimod; Paget Disease, Extramammary; Skin Cream; Vulvar Neoplasms
PubMed: 27655036
DOI: 10.1159/000449158