Incidence Trends of Vulvar Cancer in the United States: A 20-Year Population-Based Study.

BACKGROUND: Despite being uncommon, vulvar cancer is a serious health concern with a 5-year relative survival rate of 71%. AIMS: The objective was to investigate the incidence rates of this disease across different racial, ethnic, and histological subgroups in the United States, as well as the effects of the COVID-19 pandemic on this cancer. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) 22 database. The International Classification of Diseases for Oncology Version 3 topologic code C51 was assigned for vulvar cancer. Average annual percent change (AAPC) and the pairwise comparison with the parallelism and coincidence were reported. Counts and age-adjusted incidence rates per 100 000 individuals with their corresponding 95% confidence intervals (CIs) were reported. RESULTS: The age-adjusted incidence rate of vulvar cancer was 2.40 (95% CI, 2.38-2.43) over the period 2000-2019, with an AAPC of 0.80 (95% CI, 0.63-0.99). By race/ethnicity, only non-Hispanic Whites had an increasing trend over 2000-2019 (AAPC: 1.30; 95% CI, 1.07-1.54). The highest age-adjusted incidence rate of vulvar cancer in the United States was for squamous cell carcinoma (SCC). There was a significant decrease in the age-standardized incidence rate of vulvar cancer in all races/ethnicities in all age groups (AAPC: -10.15; 95% CI, -15.35 to -4.94) over 2019-2020. Also, the incidence rates and incident numbers of vulvar cancer increased with aging and peaked at the 85+ age group. CONCLUSION: There was an increase in the incidence rate of vulvar cancer in all races, with a significantly increased trend in non-Hispanic White women from 2000 to 2019. SCC displayed the highest incidence rate among vulvar cancer histological types. It is recommended to conduct further research to identify the relevant risk factors of vulvar cancer in the United States.

Neoadjuvant chemotherapy with bevacizumab for locally advanced vulvar cancer.

OBJECTIVES: External beam radiation with sensitizing platinum is the recommended therapy for locally advanced vulvar cancers not amenable to curative surgery and is associated with considerable acute and chronic side effects. Radical vulvectomy post-radiation for persistent disease is often compromised with poor wound healing. We describe clinical outcomes for patients who received neoadjuvant chemotherapy plus bevacizumab followed by radical vulvectomy for locally advanced vulvar cancer. METHODS: We performed retrospective analyses of all patients at our institution who underwent radical vulvectomy from January 2015 to November 2023. Of 113 patients, 13 patients underwent neoadjuvant chemotherapy. Demographics and clinicopathologic data were extracted, and descriptive statistical analyses were performed. Cases with neoadjuvant chemotherapy plus bevacizumab were further evaluated for response, adverse effects, and survival. RESULTS: Neoadjuvant chemotherapy was administered to 13 patients with stage II-IV disease that involved the urethra, vagina, or anus. Lesion sizes ranged from 4 to 20 cm (median 7 cm). Patients received 2-6 cycles of carboplatin or cisplatin, paclitaxel, and bevacizumab. Nine (69.2%) patients had partial pathologic responses, and four patients had complete responses. All patients had negative surgical margins. Ten (76.9%) patients had radiographic evidence of inguinal lymph node metastasis prior to neoadjuvant chemotherapy, and four had residual nodal disease. Only one patient developed a superficial groin seroma. Three patients developed recurrence, two locally and one distant, and there was one death. The median follow-up was 23 months (range 6-84 months). CONCLUSIONS: Neoadjuvant chemotherapy using combination platinum/paclitaxel/bevacizumab was efficacious for locally advanced vulvar cancer, resulting in complete resections, negative margins, and excellent wound healing. A multi-institutional phase II trial is warranted to validate these findings.

Adenoid Cystic Carcinoma of the Vulva: A Case Report.

Adenoid cystic carcinoma (ACC) of the vulva represents a highly uncommon type of female malignancy. Due to the absence of specific treatment guidelines, such cases are typically managed by the treatment protocols for vulvar cancer. Here, we report the case of a 52-year-old woman who presented with a painful right vulvar mass, leading to a diagnosis of ACC of the vulva after biopsy and immunohistochemical analysis. She underwent vulvectomy, bilateral inguinal lymphadenectomy, and targeted radiotherapy, and no evidence of recurrence has been found for three years, with ongoing monitoring for post-radiation effects. This case adds valuable insights into the management of ACC of the vulva and underscores the need for further research and guideline development to optimize care for future patients.

Evaluation of the impact of a protocol for immediate vulvar reconstruction after vulvectomy.

Vulvar cancers are usually diagnosed at an advanced stage and require wide surgical resections in the form of vulvectomy. Immediate vulvar reconstruction can potentially reduce the reoperation rate and postoperative complications. With this objective, we introduced a protocol for immediate vulvar reconstruction. This study, five years after its introduction, assesses the impact of this intervention on the postoperative evolution of vulvectomy patients. In January 2017 we introduced a protocol for immediate vulvar reconstruction that considered four criteria of high risk for postoperative dehiscence. Patients who meet the criteria were reconstructed at the time of the vulvectomy. To assess the impact of the protocol, we prospectively registered all included patients over a 5 years period (2017-2022). As a control group, we reviewed the vulvectomised patients at our centre from January 2012 to January 2017 (5 years) who would have met the protocol. No statistically significant differences were found in the epidemiological data (age, diabetes mellitus diagnosis, and obesity diagnosis) or in the tumour characteristics (tumour size). We obtained a statistically significant difference in the incidence of complications and need for reintervention, in favour of the reconstruction group. Our study shows the medical and economic benefits for vulvar cancer patients of immediate vulvar reconstruction.

Surgery as primary treatment improved overall survival in vulvar squamous cancer: A single center study with 108 women.

OBJECTIVE: To describe a single-center experience managing women with vulvar squamous cancer and analyze factors influencing their survival. STUDY DESIGN: It is an observational longitudinal retrospective study that reviewed medical records of patients admitted for treatment at the University of Campinas between 2010 and 2019, followed up until June 2022. The final sample was 108 cases. The main outcomes were disease-free survival (DFS) and overall survival (OS). Other variables were age, stage, relapse, and race. Vital status was accessed by medical records, active search, or public online register. Survival analysis was performed by the Kaplan-Meier method and Log-rank Test, and Regression Cox-Model assessed risks. RESULTS: The mean age in stages IA and IB were 65.0 years, and in stages II + III + IVA 71.1 years. Women 70 years or older were more related to diagnosis in stages II + III + IVA (p = 0.019). Progression was observed in 7 (16.7 %) patients in stage IB and 30 (65.2 %) in stage II + III + IVA. Both five-year (5y) DFS and OS were significantly different in stage IB and II + III + IVA (5y-DFS 70.5 % and 39.3 %, p = 0.024; 65.1 % and 24.3 %, p < 0.001). In stages II + III + IVA, most deaths happened before 24 months of follow-up. The primary treatment was surgery in 81.0 % of stage IB and 47.8 % of stage II + III + IVA. A higher OS was observed in patients treated primarily by surgery compared to radiotherapy in stage IB (p = 0.008), and in stages II + III + IVA (p = 0.013). Surgery followed or not by adjuvant radiotherapy was independently associated with a 60 % adjusted death protection compared to radiotherapy alone as primary treatment (0.40, 0.23;0.70). CONCLUSIONS: Half of the patients have been diagnosed in stage I. The progression rate was high in the advanced stages of the disease. Overall survival by stage was improved when surgery was the primary treatment. Surgery was independently associated with death.

From existential uncertainty to a new mindset promoting recovery: Exploring the development of uncertainty experience in women with vulvar neoplasia - A qualitative longitudinal study.

BACKGROUND: Women with vulvar neoplasia continue to experience uncertainty up to six months post-surgery. Uncertainty in illness is considered a significant psychosocial stressor, that negatively influences symptom distress, self-management strategies and quality of life. According to the Reconceptualized Uncertainty in Illness Theory, the appraisal of uncertainty changes positively over time in chronic illness. We aimed at exploring whether and how the experience of uncertainty develops in women with vulvar neoplasia. METHODS: We selected a purposive sample of seven women diagnosed with vulvar neoplasia in four Swiss and one Austrian women's clinic. By means of a qualitative longitudinal study, we conducted 30 individual interviews at five points of time during one year after diagnosis. We applied Saldaña's analytical questions for longitudinal qualitative research. RESULTS: First, participants experienced uncertainty as an existential threat, then an inherent part of their illness, and finally a certainty. Women initially associated the existential threat with a high risk for suffering from severe health deteriorations. Participants that could reduce their individually assessed risk by adopting health promoting behaviors, accepted the remaining uncertainty. From now on they reframed uncertainty into a certainty. This new mindset was based on a belief of promoting recovery and reducing the risk of recurrence. CONCLUSIONS: The long-lasting and oscillating nature of uncertainty should receive attention in supportive oncology care. Uncertainty concerning existential issues is of special importance since it can inhibit a positive development of uncertainty experience.

Vulvar cancer incidence and net survival in Sweden 1960 to 2019: A population-based national study.

INTRODUCTION: Vulvar cancer is a rare gynecological cancer affecting mostly older women. The aim of this population-based study was to investigate the incidence and net survival of vulvar cancer in Swedish women from 1960 to 2019. MATERIAL AND METHODS: Data were retrieved from the mandatory Swedish Cancer Registry consisting of all women diagnosed with vulvar cancer between 1960 and 2019. Only women with a morphologically verified diagnosis of vulvar cancer were included. The individuals were then further matched with the Swedish Death Registry up until May 31, 2020. RESULTS: In total, 8499 women were included with the following morphologies: squamous cell carcinoma 7250 (85.8%), malignant melanoma 539 (6.4%), adenocarcinoma 401 (4.8%) and other: 259 (3.1%). More than 50% of vulvar cancer cases occurred in women aged between 65 and 84 years of age. The 5-year age-standardized net survival increased from 53.0% (95% confidence interval [CI] 48.9-57.5) in 1960 to 72.1% (95% CI 68.8-75.5) in 2019. The proportion of adenocarcinoma among all cases increased from 2.0% to 8.7% between the 1960s and 2010s and an increase in age-standardized 5-year net survival was found for adenocarcinoma. CONCLUSIONS: The age-standardized incidence of vulvar cancer cases in Sweden was stable between 1960 and 2019. During the study period, an increase in adenocarcinoma and a decrease in malignant melanoma cases was found. Five-year net survival increased by 20 percent units during the study period. For squamous cell carcinoma, an increased age-specific 5-year net survival was observed for all age groups, apart for women aged ≥85.

Time to extend the indication for sentinel node biopsy in vulvar cancer? Results from a prospective nationwide Swedish study.

OBJECTIVE: To assess detection rates and negative predictive values of sentinel node biopsy in vulvar squamous cell carcinoma with tumors ≥4 cm, multifocal tumors, and in locally recurrent disease. METHODS: Between December 2019 and December 2022, patients with vulvar squamous cell carcinoma with tumors ≥4 cm (group 1), multifocal tumors (group 2), or a first local recurrence without or with previous groin treatment (groups 3 and 4, respectively) were included in a prospective, nationwide multicenter interventional pilot study. The participants underwent a sentinel node biopsy followed by inguinofemoral lymph node dissection. Detection rates, negative predictive values, the proportion of micrometastases, and isolated tumor cells were determined separately for each group. RESULTS: In all, 64 women were included, 36 women in group 1 (56%), and 17 women in group 2 (27%). Due to the small number and heterogeneity of the 11 women in groups 3 and 4, they were excluded from further analyses. In groups 1 and 2, 25 women (47%) were diagnosed with node-positive disease, and in 16 women (64%) only in the sentinel nodes. The detection rates varied between 94.1-100% per patient and 84.1-85.3% per groin. No false-negative sentinel nodes were identified, giving a negative predictive value of 100% for group 1 (95% CI 91.2% to 100%) and for group 2 (95% CI 83.9% to 100%). Of the node-positive patients, 32% had micrometastasis or isolated tumor cells only. One third of the metastases were detected by ultrastaging. In 27% of the non-mapping groins, metastases were found in the lymphadenectomy specimen, and in 75% the metastases showed extranodal growth. CONCLUSION: In this small cohort of patients, we provide further data that may widen the indication of the sentinel node technique to women with tumors ≥4 cm and multifocal tumors. TRIAL REGISTRATION NUMBER: NCT04147780.

Clinical experiences with online adaptive radiotherapy of vulvar carcinoma.

BACKGROUND AND PURPOSE: Radiotherapy for vulvar carcinoma is challenging due to relatively high risk of locoregional disease recurrence, a technically challenging target, and postoperative lymphocele, and a high risk radiation sequelae. We aim to explore, if it is possible to reduce dose to normal tissue, while maintaining CTV coverage for this patient group with online adaptive radiotherapy. MATERIALS AND METHODS: 20 patients with vulvar carcinoma (527 fractions) were treated with online adaptation on a Varian Ethos accelerator. Setup CBCTs were acquired daily for adaptive planning. Verification CBCTs were acquired immediately prior to dose delivery. CTV dose coverage and dose to bladder and rectum were extracted from the scheduled and adapted plans as well as from adapted plans recalculated based on verification CBCTs. In addition, analysis of the decision of the adaptive procedure was performed for 17 patients (465 fractions). RESULTS: Mean CTV D95% and standard deviation was 98% ± 5% for the scheduled plan compared to 100.0 ± 0.3% and 100.0 ± 0.8% for the adapted plan on the setup and verification CBCT respectively. Dose to OARs varied substantially and did not show any benefit from adaption itself, however a margin reduction was implemented after the first patients treated. The adapted plan was chosen for 63.5% of the fractions and dominant reasons for not adapting were 'no significant dosimetric gain' (75 fractions, 14%) and 'Medical doctor (MD) not available for treatment' (50 fractions, 9.5%). The median adaption time was 15 min and the 25th and 75th percentile was 12 and 17 min, respectively. CONCLUSION: CTVs and PTVs dose coverage were significantly improved with adaptation compared to image-guided RT. This gain was robust during the treatment time.

Fibroma mole gigante vulvar: relato de caso / Giant soft vulvar fibroma: case report

Fibroma mole, ou pólipo fibroepitelial, é uma lesão de proporções geralmente reduzidas, de cor hiperpigmentada ou igual à da pele, localizando-se frequentemente na face, pescoço, tronco e regiões intertriginosas. É um tumor classificado como benigno e pode acometer tanto homens quanto mulheres em idade reprodutiva e depois da quarta década de vida. Ocorre principalmente em obesos, diabéticos e durante a gestação. Com menor frequência, podem alcançar dimensões que excedem 5 cm. Seu crescimento pode ser lento ou rápido e comumente são assintomáticos, mas podem promover sangramentos por conta de ulcerações decorrentes de traumas repetidos. Apresentamos neste relato um fibroma mole, gigante, de localização vulvar, com 11 cm de comprimento, 11 cm de largura e 5 cm de espessura, pesando 500 g.

Giant soft vulvar fibroma is a fibroepithelial polyp lesion with generally reduced proportions, with a hyperpigmented color or similar to that of the skin, frequently located on the face, neck, trunk and intertriginous regions. It is a tumor classified as benign, can affect both men and women, of reproductive age and after the fourth decade, mainly obese, diabetic and during pregnancy. However, less frequently, they can reach dimensions that exceed 5 cm, may have a slow or accelerated evolution. They are commonly asymptomatic, but bleeding may be present due to ulcerations resulting from repeated trauma. In the current study, we describe a giant soft fibroma with a vulvar location measuring 11 cm in length, 11 cm in width, 5 cm in thickness and weighing 500 grams.

Trends in Net Survival from Vulvar Squamous Cell Carcinoma in Italy (1990-2015).

(1) Objective: In many Western countries, survival from vulvar squamous cell carcinoma (VSCC) has been stagnating for decades or has increased insufficiently from a clinical perspective. In Italy, previous studies on cancer survival have not taken vulvar cancer into consideration or have pooled patients with vulvar and vaginal cancer. To bridge this knowledge gap, we report the trend in survival from vulvar cancer between 1990 and 2015. (2) Methods: Thirty-eight local cancer registries covering 49% of the national female population contributed the records of 6274 patients. Study endpoints included 1- and 2-year net survival (NS) calculated using the Pohar-Perme estimator and 5-year NS conditional on having survived two years (5|2-year CNS). The significance of survival trends was assessed with the Wald test on the coefficient of the period of diagnosis, entered as a continuous regressor in a Poisson regression model. (3) Results: The median patient age was stable at 76 years. One-year NS decreased from 83.9% in 1990-2001 to 81.9% in 2009-2015 and 2-year NS from 72.2% to 70.5%. Five|2-year CNS increased from 85.7% to 86.7%. These trends were not significant. In the age stratum 70-79 years, a weakly significant decrease in 2-year NS from 71.4% to 65.7% occurred. Multivariate analysis adjusting for age group at diagnosis and geographic area showed an excess risk of death at 5|2-years, of borderline significance, in 2003-2015 versus 1990-2002. (4) Conclusions: One- and 2-year NS and 5|2-year CNS showed no improvements. Current strategies for VSCC control need to be revised both in Italy and at the global level.

The modified 5-item frailty index is a predictor of post-operative complications in vulvar cancer: a National Surgical Quality Improvement Program (NSQIP) analysis.

OBJECTIVE: To determine whether frailty is associated with post-operative complications following surgery for vulvar cancer. METHODS: This retrospective study used a multi-institutional dataset from the National Surgical Quality Improvement Program (NSQIP) database (2014-2020) to analyze the relationship between frailty, procedure type, and post-operative complications. Frailty was determined using the modified frailty index-5 (mFI-5). Univariate and multivariable-adjusted logistic regression analyses were performed. RESULTS: Of 886 women, 49.9% underwent radical vulvectomy alone, and 19.5% and 30.6% underwent concurrent unilateral or bilateral inguinofemoral lymphadenectomy, respectively; 24.5% had mFI ≥2 and were considered frail. Compared with non-frail women, those with an mFI ≥2 were more likely to have an unplanned readmission (12.9% vs 7.8%, p=0.02), wound disruption (8.3% vs 4.2%, p=0.02), and deep surgical site infection (3.7% vs 1.4%, p=0.04). On multivariable-adjusted models, frailty was a significant predictor for minor (OR 1.58, 95% CI 1.09 to 2.30) and any complications (OR 1.46, 95% CI 1.02 to 2.08). Specifically, for radical vulvectomy with bilateral inguinofemoral lymphadenectomy, frailty was significantly associated with major (OR 2.13, 95% CI 1.03 to 4.40) and any complications (OR 2.10, 95% CI 1.14 to 3.87). CONCLUSION: In this analysis of the NSQIP database, nearly 25% of women undergoing radical vulvectomy were considered frail. Frailty was associated with increased post-operative complications, especially in women concurrently undergoing bilateral inguinofemoral lymphadenectomy. Frailty screening prior to radical vulvectomy may assist in patient counseling and improve post-operative outcomes.

Phase II activity trial of high-dose radiation and chemosensitization in patients with macrometastatic lymph node spread after sentinel node biopsy in vulvar cancer: GROningen INternational Study on Sentinel nodes in Vulvar cancer III (GROINSS-V III/NRG-GY024).

BACKGROUND: Standard treatment of early-stage vulvar cancer is a radical, wide, local excision of the primary tumor and a sentinel lymph node (SLN) procedure for the groins. An inguinofemoral lymphadenectomy is no longer necessary for patients who have a negative SLN or micrometastasis (≤2 mm). When there is macrometastasis (>2 mm) in the SLN, an inguinofemoral lymphadenectomy is indicated; however, this procedure is associated with major morbidity, such as wound healing, lymphoceles, and lymphedema. PRIMARY OBJECTIVE: To investigate the safety of replacing inguinofemoral lymphadenectomy by chemoradiation in patients with early-stage vulvar cancer with a macrometastasis (>2 mm) and/or extracapsular extension in the sentinel node. STUDY HYPOTHESIS: Combination of 56 Gy of radiation to the inguinal site and concurrent cisplatin chemotherapy without completion inguinofemoral lymphadenectomy will be feasible and safe, with low groin recurrence rates. TRIAL DESIGN: This is a single-arm, prospective phase II treatment trial with stopping rules for unacceptable groin recurrences. Eligible patients will receive 56 Gy of radiation to the involved inguinal site and chemotherapy with concurrent cisplatin. MAJOR INCLUSION/EXCLUSION CRITERIA: Eligible patients undergoing sentinel node procedure will have stage I, unifocal, invasive (>1 mm depth of invasion) squamous cell carcinoma of the vulva with tumor size <4 cm, and no suspicious nodes on imaging. Those eligible for the trial are those with a metastasis >2 mm in the sentinel node and/or extracapsular extension, or more than one sentinel node with micrometastasis ≤2 mm. PRIMARY ENDPOINT: Groin recurrence rate in the first 2 years after primary treatment. SAMPLE SIZE: 157 patients with macrometastases in their SLN. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: January 1, 2029. TRIAL REGISTRATION NUMBER: NCT05076942.

Detection of sentinel lymph node in vulvar cancer using 99mTc-labeled colloid lymphoscintigraphy, blue dye, and indocyanine-green fluorescence: a meta-analysis of studies published in 2010-2020.

OBJECTIVES: Sentinel lymph node (SLN) biopsy is widely accepted in the surgical staging of early vulvar cancer, although the most accurate method for its identification is not yet defined. This meta-analysis aimed to determine the technique with the highest pooled detection rate (DR) for the identification of SLN and compare the average number of SLNs detected by planar lymphoscintigraphy (PL), single-photon emission computed tomography/computed tomography (SPECT/CT), blue dye and indocyanine green (ICG) fluorescence. METHODS: The meta-analysis was conducted according to the PRISMA guideline. The search string was: "sentinel" and "vulv*", with date restriction from 1st January 2010 until Dec 31st, 2020. Three investigators selected studies based on: (1) a study cohort or a subset of a minimum of 10 patients with vulvar cancer undergoing either PL, SPECT/CT, blue-dye, or ICG fluorescence for the identification of SLN; (2) the possibility to extrapolate the DR or the average number of SLNs detected by a single technique (3) no evidence of other malignancies in the patient history. RESULTS: A total of 30 studies were selected. In a per-patient and a per-groin analysis, the DR for SLN of PL was respectively 96.13% and 92.57%; for the blue dye was 90.44% and 66.21%; for the ICG, the DR was 91.90% and 94.80%. The pooled DR of SPECT/CT was not calculated, since only two studies were performed in this setting. At a patient-based analysis, no significant difference was documented among PL, blue dye, and ICG (p = 0.28). At a per-groin analysis, PL and ICG demonstrated a significantly higher DR compared to blue dye (p < 0.05). The average number of SLNs, on a per-patient analysis, was available only for PL and ICG with a median number of 2.61 and 1.78 lymph nodes detected, respectively, and no significant statistical difference. CONCLUSIONS: This meta-analysis favors the use of ICG and PL alone and in combination over blue dye for the identification of the SLN in vulvar cancer. Future studies may investigate whether the combined approach allows the highest DR of SLN in patients with vulvar cancer.