Monocyte infiltration is an independent positive prognostic biomarker in vulvar squamous cell carcinoma.

BACKGROUND: Vulvar squamous cell carcinoma (VSCC) arises after an HPV infection or the mutation of p53 or other driver genes and is treated by mutilating surgery and/or (chemo) radiation, with limited success and high morbidity. In-depth information on the immunological make up of VSCC is pivotal to assess whether immunotherapy may form an alternative treatment. METHODS: A total of 104 patient samples, comprising healthy vulva (n = 27) and VSCC (n = 77), were analyzed. Multispectral immunofluorescence (15 markers) was used to study both the myeloid and lymphoid immune cell composition, and this was linked to differences in transcriptomics (NanoString nCounter, 1258 genes) and in survival (Kaplan-Meier analyses). RESULTS: Healthy vulva and VSCC are both well infiltrated but with different subpopulations of lymphoid and myeloid cells. In contrast to the lymphoid cell infiltrate, the density and composition of the myeloid cell infiltrate strongly differed per VSCC molecular subtype. A relative strong infiltration with epithelial monocytes (HLADR-CD11c-CD14+CD68-CD163-CD33-) was prognostic for improved survival, independent of T cell infiltration, disease stage or molecular subtype. A strong infiltration with T cells and/or monocytes was associated with drastic superior survival: 5-year survival > 90% when either one is high, versus 40% when both are low (p < 0.001). CONCLUSION: A hot myeloid and/or lymphoid infiltrate predicts excellent survival in VSCC. Based on the response of similarly high-infiltrated other tumor types, we have started to explore the potential of neoadjuvant checkpoint blockade in VSCC.

Single-cell analysis of the cellular landscape of vulvar melanoma provides new insight for immunotherapy administration.

BACKGROUND: Vulvar and vaginal melanoma (VuM & VaM) is a rare gynecologic malignancy with high mortality but low effectiveness to checkpoint immunotherapy compared to cutaneous melanoma. This article aims to elucidate the role of the disordered immune microenvironment in cancer progression in VuM. METHODS: At first, this article applied single-cell RNA sequencing (scRNA-seq) to the VuM obtained from a 68-year-old female patient, and constructed a single-cell atlas of VuM consist of 12,243 single cells. Then this article explores the genomic complexity and core signal channel in VuM microenvironment. RESULTS: This article provides new insights about the pathogenesis of VuM based on single-cell resolution data. It was found that the activation of CD8+ T cell contributed to induce tumor angiogenesis and immune escape, and the activation of the antigen-presenting molecular function participated in melanoma metastasis. CONCLUSION: This article provided new insights into underlining VuM molecular regulation and potential signaling involved in immunotherapy, which would benefit the clinical practice and administration.

Management of inguinal lymph nodes in locally advanced, surgically unresectable, squamous cell carcinoma of the vulva.

OBJECTIVE: To assess clinical outcomes of inguinal lymph node surgical resection compared to primary groin radiotherapy for locally advanced, surgically unresectable vulvar cancer. METHODS: All patients treated with radiation for vulvar cancer were identified between Jan 1, 2000 - Dec 31, 2020 at 2 academic centres. Inclusion criteria were those treated with curative intent primary radiotherapy +/- chemotherapy, tumors >4 cm, and surgically unresectable squamous cell vulvar carcinoma. Groin recurrence-free survival (RFS) was compared for groin surgery and primary groin radiotherapy using the Kaplan Meier method and log rank test. Groin failures are described by treatment modality, radiation dose and lymph node size. RESULTS: Of 476 patients treated with radiation for vulvar cancer, 112 patients (23.5%) met inclusion and exclusion criteria. The median (95% CI) follow up was 1.9 (1.4-2.5) years. Complete clinical response was significantly higher (80.0%) in patients with surgical groin resection compared to patients treated with primary groin radiotherapy (58.2%) (p = 0.04). On multivariable analysis, after adjusting for clinical and/or radiologically abnormal lymph nodes (p = 0.67), surgical groin resection was significantly associated with lower groin recurrence (HR 0.2 (95%CI 0.05-0.92), p = 0.04). The 3-year groin recurrence-free survival (RFS) was significantly higher at 94.4% (87.1-100) in patients with surgical groin resection compared to 79.2% (69.1-90.9) in patients treated with primary radiation (p = 0.02). CONCLUSIONS: In locally advanced squamous cell vulvar cancer, surgical groin management improves groin RFS compared to radiotherapy alone.

Treatment of vulvar cancer recurrence with electrochemotherapy: a case-control study.

BACKGROUND: Electrochemotherapy (ECT) is a combined treatment method based on electroporation and simultaneous chemotherapy. In cases where radiotherapy has previously been used, surgery is often the only treatment option for vulvar cancer recurrence with potential resection of clitoris, vagina, urethra or anal sphincter. The unique advantage of ECT is its selectivity for cancer cells while sparing the surrounding healthy tissue. The aim of the study was to compare the ECT treatment of vulvar cancer recurrence for non-palliative purposes with surgical treatment. MATERIALS AND METHODS: Eleven patients with single vulvar cancer recurrence were treated with ECT and followed up for 12 months. As a control group, 15 patients with single vulvar cancer recurrence were treated with wide local excision. The following data were collected, analyzed and compared: Age, body mass index, comorbidities, histological type, location and size of vulvar cancer recurrence, treatment history, details of procedures and hospital stay. RESULTS: The probability curves for local tumor control did not differ between the ECT group and the surgical group (p = 0.694). The mean hospital stay and the mean duration of procedure were statistically significantly shorter in the ECT group (p < 0.001). There were no statistically significant differences between the ECT and surgical groups in terms of mean body mass index, associated diseases, previous treatments, presence of lichen sclerosus, p16 status, gradus, anatomical site of the tumor, and type of anesthesia. CONCLUSION: In this case-control study, treatment of vulvar cancer recurrence with ECT for non-palliative purposes was comparable to surgical treatment in terms of effectiveness. The results need to be confirmed in larger randomized trials.

Feasibility study of focused ultrasound in the treatment of vulvar low-grade squamous intraepithelial lesions with persistent symptoms.

OBJECTIVE: This study aimed to investigate the feasibility, efficacy, and safety of focused ultrasound (FUS) for the treatment of vulvar low-grade squamous intraepithelial lesions (VLSIL) with persistent symptoms. METHODS: This retrospective analysis included 24 VLSIL patients who underwent FUS treatment. At each follow-up visit, the clinical response was assessed including changes in symptoms and signs. In addition, the histological response was assessed based on the vulvar biopsy results of the 3rd follow-up. Clinical and histological response were assessed to elucidate the efficacy. RESULTS: A total of 22 patients completed follow-up and post-treatment pathological biopsies. After treatment, the clinical scores of itching decreased from 2.55 ± 0.51 to 0.77 ± 0.81 (p < 0.05). Furthermore, the clinical response rate and histological response rate were 86.4% and 81.8%, respectively. Only two cured patients indicated recurrence in the 3rd and 4th year during the follow-up period and achieved cure after re-treatment. In terms of adverse effects, only one patient developed ulcers after treatment, which healed after symptomatic anti-inflammatory treatment without scarring, and no other treatment complications were found in any patients. None of the patients developed a malignant transformation during the follow-up period. CONCLUSION: This study revealed that FUS is feasible, effective, and safe for treating VLSIL patients with persistent symptoms, providing a new solution for the noninvasive treatment of symptomatic VLSIL.

Genetics and beyond: Precision Medicine Real-World Data for Patients with Cervical, Vaginal or Vulvar Cancer in a Tertiary Cancer Center.

Advances in molecular tumor diagnostics have transformed cancer care. However, it remains unclear whether precision oncology has the same impact and transformative nature across all malignancies. We conducted a retrospective analysis of patients with human papillomavirus (HPV)-related gynecologic malignancies who underwent comprehensive molecular profiling and subsequent discussion at the interdisciplinary Molecular Tumor Board (MTB) of the University Hospital, LMU Munich, between 11/2017 and 06/2022. We identified a total cohort of 31 patients diagnosed with cervical (CC), vaginal or vulvar cancer. Twenty-two patients (fraction: 0.71) harbored at least one mutation. Fifteen patients (0.48) had an actionable mutation and fourteen (0.45) received a recommendation for a targeted treatment within the MTB. One CC patient received a biomarker-guided treatment recommended by the MTB and achieved stable disease on the mTOR inhibitor temsirolimus for eight months. Factors leading to non-adherence to MTB recommendations in other patient cases included informed patient refusal, rapid deterioration, stable disease, or use of alternative targeted but biomarker-agnostic treatments such as antibody-drug conjugates or checkpoint inhibitors. Despite a remarkable rate of actionable mutations in HPV-related gynecologic malignancies at our institution, immediate implementation of biomarker-guided targeted treatment recommendations remained low, and access to targeted treatment options after MTB discussion remained a major challenge.

The intratumour microbiota and neutrophilic inflammation in squamous cell vulvar carcinoma microenvironment.

BACKGROUND: A causal link between microbiota composition (dysbiosis) and oncogenesis has been demonstrated for several types of cancer. Neutrophils play a role in both immune protection against bacterial threats and carcinogenesis. This study aimed to characterise intratumoral bacteria in vulvar squamous cell carcinoma (VSCC) and their putative effect on neutrophil recruitment and cancer progression. METHODS: Clinical material was obtained from 89 patients with VSCC. Next-generation sequencing (NGS) of 16S rRNA and quantitative polymerase chain reaction (qPCR) were used to detect bacterial species in VSCC. To verify neutrophil activation, CD66b expression in tumour specimens was analysed by immunohistochemistry (IHC). Subsequently, IHC was applied to detect the main neutrophil serine proteases (NSPs), cathepsin G (CTSG), neutrophil elastase (ELANE), and proteinase 3 (PRTN3) in VSCC. RESULTS: Fusobacterium nucleatum and Pseudomonas aeruginosa were identified as tumour-promoting bacteria, and their presence was found to be associated with a shorter time to progression in VSCC patients. Furthermore, high abundance of CD66b, the neutrophil activation marker, in VSCC samples, was found to relate to poor survival of patients with VSCC. The selected NSPs were shown to be expressed in vulvar tumours, also within microabscess. The increased numbers of microabscesess were correlated with poor survival in VSCC patients. CONCLUSIONS: Our results show that neutrophilic inflammation seem to be permissive for tumour-promoting bacteria growth in VSCC. The findings provide new therapeutic opportunities, such as based on shifting the balance of neutrophil populations to those with antitumorigenic activity and on targeting NSPs produced by activated neutrophils at the inflammation sites.

Vulvar squamous cell carcinoma in women 80 years and older: Treatment, survival and impact of comorbidities.

BACKGROUND: Despite being a disease of mainly older women, little is known about the clinical management of older women with vulvar squamous cell carcinoma (VSCC). We evaluated their daily clinical management compared with younger women, and established the prevalence of comorbidities and its impact on overall survival (OS). METHODS: All Dutch women diagnosed with VSCC from 2015 to 2020 (n = 2249) were selected from the Netherlands Cancer Registry. Women aged ≥80 years (n = 632, 28%) were defined as "older" patients, women <80 years were considered as "younger". Chi-square tests were performed to evaluate differences in treatment by age group and comorbidities. Differences in OS were evaluated using Kaplan-Meier Curves and log-rank test. RESULTS: The vast majority of both older (91%) and younger (99%) patients with FIGO IA VSCC received surgical treatment of the vulva. Older FIGO IB-IV VSCC patients were less likely to undergo groin surgery than younger patients (50% vs. 84%, p < 0.01). Performance of surgical treatment of the vulva and groin(s) was not associated with the number of comorbidities in older patients (p = 0.67 and p = 0.69). Older patients with ≥2 comorbidities did have poorer OS compared to women with one or no comorbidities (p < 0.01). CONCLUSION: The vast majority of older patients underwent vulvar/local surgery. Older patients less often received groin surgery compared to younger patients. The majority of older patients had at least one comorbidity, but this did not impact treatment choice. The poorer survival in older VSCC patients may therefore be due to death of competing risks instead of VSCC itself.

Current status of vulvar cancer in Japan: analysis of the Japanese Gynecologic Oncology Group nationwide survey study.

This review provides an overview of the current status of vulvar cancer in Japan, focusing specifically on the findings from the Japanese Gynecologic Oncology Group nationwide survey study. The author offers a comprehensive summary of the current status of vulvar cancer in Japan, along with an exploration of the molecular mechanisms underlying the disease. Notably, the review highlights the concerning upward trend of vulvar cancer in older age groups and advanced stages in Japan. The author concludes that addressing these challenges may require the centralization of resources and expertise. By bridging knowledge gaps and identifying areas for improvement, this review contributes to enhancing the understanding and management of vulvar cancer in Japan.

Role of immunotherapy for lymph node positive vulvar melanoma: utilization and outcomes.

OBJECTIVE: To investigate the utilization and outcomes of adjuvant immunotherapy for patients with vulvar melanoma and inguinal lymph node metastases. METHODS: The National Cancer Database was accessed and patients with vulvar melanoma diagnosed between 2004 and 2015 who did not have distant metastases, underwent inguinal lymphadenectomy, had positive lymph nodes, and at least 1 month of follow-up were identified. Administration of immunotherapy was evaluated and clinicopathological characteristics were compared. Median overall survival was compared with the log-rank test. Stratified analysis based on clinical status of lymph nodes was performed. A Cox model was constructed to evaluate survival after controlling for confounders. RESULTS: A total of 300 patients were identified; the rate of immunotherapy use was 25% (75 patients). Patients who received immunotherapy were younger (median 58 vs 70 years, p<0.001); however, the two groups were comparable in terms of clinical lymph node status, rate of positive tumor margins, presence of tumor ulceration, tumor size, Breslow thickness, and performance of comprehensive lymphadenectomy. There was no overall survival difference between patients who did (median 31.08 months) and did not (median 22.77 months) receive immunotherapy (p=0.18). Following stratification by clinical lymph node status, immunotherapy did not improve overall survival of patients with clinically negative (median 35.35 vs 33.22, p=0.75) or positive lymph nodes (median 23.33 vs 16.99, p=0.64). After controlling for confounders, administration of immunotherapy was not associated with better overall survival (HR 0.81, 95% CI 0.57 to 1.14). CONCLUSIONS: In this study approximately one in four patients received adjuvant immunotherapy. Immunotherapy was not associated with improved overall survival.

European Society of Gynaecological Oncology Guidelines for the Management of Patients with Vulvar Cancer - Update 2023.

BACKGROUND: As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) first published in 2017 evidence-based guidelines for the management of patients with vulvar cancer. OBJECTIVE: To update the ESGO guidelines based on the new evidence addressing the management of vulvar cancer and to cover new topics in order to provide comprehensive guidelines on all relevant issues of diagnosis and treatment of vulvar cancer. METHODS: The ESGO Council nominated an international development group comprised of practicing clinicians who provide care to vulvar cancer patients and have demonstrated leadership through their expertize in clinical care and research, national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (18 experts across Europe). To ensure that the statements were evidence-based, new data identified from a systematic search were reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 206 international practitioners in cancer care delivery and patient representatives. RESULTS: The updated guidelines cover comprehensively diagnosis and referral, staging, pathology, pre-operative investigations, surgical management (local treatment, groin treatment, sentinel lymph node procedure, reconstructive surgery), (chemo)radiotherapy, systemic treatment, treatment of recurrent disease (vulvar, inguinal, pelvic, and distant recurrences), and follow-up. Management algorithms are also defined.

Impaired sexual health among women treated for vulvar cancer: An integrated review.

BACKGROUND: Although gynaecological cancer's negative effects on sexual function are well known, most studies on the subject have not included vulvar cancer patients or a multidimensional perspective on sexual health. Therefore, this review aimed to address this research gap and explored the impact of vulvar cancer on women's sexual health from a multidimensional perspective. METHODOLOGY: An integrated review was conducted, as described by Whittemore and Knafl. The PubMed, CINAHL, PsycINFO and Embase databases were searched in March 2021 and updated in August 2022 and March 2023. The data were thematically analysed using NVivo, and the PRISMA-ScR and ENTREQ guidelines were followed. FINDINGS: The following themes were identified in the 28 reviewed articles: impact of a changed female body, impact on women's sexual identity, consequences for women's sexual relationships and unmet needs and loneliness caused by taboos about sexual health. DISCUSSION: Women's impaired sexual health after vulvar cancer points to a great need to understand and holistically investigate sexual health. In addition, healthcare professionals have an obligation to care for the sexual health issues of patients with vulvar cancer. However, most questionnaires used in the selected studies revealed a narrow understanding of sexual health and focused on sexuality as a genital activity. CONCLUSION: The sexual health of women with vulvar cancer was tabooed and stigmatised for patients and healthcare professionals. Consequently, women received sparse sexual guidance, felt isolated and had unmet needs. IMPLICATIONS FOR CLINICAL PRACTICE: Healthcare professionals need knowledge and training on how to break taboos and address the sexual needs of vulvar cancer patients. Systematic screenings for sexual health needs should be conducted using a multidimensional perspective. TRIAL AND PROTOCOL REGISTRATION: The protocol was preregistered at the Open Science Framework (www.osf.io), registration DOI: https://doi.org/10.17605/OSF.IO/YDA2Q PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Cervical, vaginal and vulvar cancer incidence and survival trends in Denmark, Finland, Norway and Sweden with implications to treatment.

BACKGROUND: Incidence of cervical cancer has been reduced by organized screening while for vaginal and vulvar cancers no systematic screening has been implemented. All these cancers are associated with human papilloma virus (HPV) infection. We wanted to analyze incidence trends and relative survival in these cancers with specific questions about the possible covariation of incidence, survival changes coinciding with incidence changes and the role of treatment in survival. We used nationwide cancer registry data for Denmark (DK), Finland (FI), Norway (NO) and Sweden (SE) to address these questions. METHODS: We use the NORDCAN database for the analyses: incidence data were available from 1943 in DK, 1953 in FI and NO and 1960 in SE, through 2016. Survival data were available from 1967 through 2016. World standard population was used in age standardization. RESULTS: In each country the incidence of cervical cancer declined subsequent to rolling out of screening activities. The attained plateau incidence was lowest at 4/100,000 in FI and highest at 10/100,000 in DK and NO. The incidence of vaginal and vulvar cancer remained relatively constant at about 2/100,000. Relative 1-year survival in cervical cancer improved in all countries from low 80%s to high 80%s in the 50-year period, and 5-year survival improved also but at 20% units lower level. Survival gains were found only in patients diagnosed before age 60 years. Survival in vaginal and vulvar cancer followed the same patterns but at a few % units lower level. CONCLUSION: Cervical cancer screening appeared to have reached its limits in the Nordic countries by year 2000. Novel treatments, such as immunotherapy, would be needed to improve survival until HPV vaccination will reach population coverage and boost the global fight against these cancers.

Clinical impact of SARS-CoV-2 infection among patients with vulvar cancer: the Gemelli Vul.Can multidisciplinary team.

BACKGROUND: 'Severe acute respiratory syndrome coronavirus-2' (SARS-CoV-2) infection has dramatically affected the management of patients with cancer, who are most vulnerable to the consequences of the infection. Patients with vulvar cancer are frequently elderly and affected by multiple co-morbidities, thus representing a particularly frail population. OBJECTIVE: To assess the clinical impact of the SARS-CoV-2 infection among patients scheduled for treatment for active vulvar cancer. METHODS: Data on patients with vulvar tumors referred to Fondazione Policlinico Universitario Agostino Gemelli IRCCS between February 2020 and July 2021 were retrospectively analyzed. Patients with a positive reverse transcription polymerase chain reaction in nasopharyngeal swab were considered as positive for SARS-Cov-2. RESULTS: One hundred and ninety-one patients with vulvar cancer were evaluated and scheduled for treatment. The median age was 72 years (range 35-94). Seven (3.7%) patients were diagnosed with SARS-Cov-2 infection: three (42.9%) had their treatment delayed, with no apparent consequences, two (28.6%) had their treatment delayed and later abandoned because of clinical worsening due to oncologic disease progression, and two (28.6%) contracted the infection in the post-operative period and died due to respiratory complications. CONCLUSIONS: In most cases the infection had major clinical implications, being associated with significant delays in oncologic treatments and extremely high mortality when contracted in the post-operative period.

Prevalence and Treatment of Vulvar Cancer From 2014-2018: A Nationwide Population-Based Study in Korea.

BACKGROUND: Vulvar cancer is one of the rare gynecologic malignancies. Despite the recent increasing trend of vulvar cancer in western countries due to the increased infection of human papillomavirus, there has been no study for population-based incidence of vulvar cancer in Korea. We aimed to investigate the prevalence and treatment of vulvar cancer in South Korea between 2014 and 2018. METHODS: Data from patients diagnosed and treated with vulvar cancer between 2014 and 2018 were obtained from the Health Insurance Review and Assessment Service/National Inpatient Sample (National In-Patient Sample) in South Korea. RESULTS: A total of 4,636,542 women were identified through the HIRA-NIS database from 2014 to 2018, of which 259 patients were diagnosed and treated for vulvar cancer. The mean age diagnosed with vulvar cancer was 62.82 (± 14.30) years in 2014, 64.19 (± 16.79) years in 2015, and 67.40 (± 14.41) years in 2016. In terms of treatment modalities, the most frequent treatment was surgery only without chemotherapy or radiation therapy. In the age-specific prevalence analysis, vulvar cancer was the most prevalent among those over 70 years old. According to multiple regression analysis, patients' age was significantly associated with the prevalence of vulvar cancer. Vulvar cancer was more prevalent in women with low socioeconomic status (SES) compared to those with high SES in 2018 (OR, 4.242; P < 0.001). CONCLUSION: Considering the high prevalence of vulvar cancer in the elderly, it is necessary to establish a new strategy for early screening and treatment.

Phase II study of definitive chemoradiation for locally advanced squamous cell cancer of the vulva: An efficacy study.

OBJECTIVE: To evaluate feasibility of chemoradiation as alternative for extensive surgery in patients with locally advanced vulvar cancer and to report on locoregional control, toxicity and survival. METHODS: In a multicenter, prospective phase II trial patients with locally advanced vulvar cancer were treated with locoregional radiotherapy combined with sensitizing chemotherapy (capecitabine). Treatment feasibility, percentage locoregional control, survival and toxicity were evaluated. RESULTS: 52 patients with mainly T2/T3 disease were treated according to the study protocol in 10 centers in the Netherlands from 2007 to 2019. Full dose radiotherapy (tumor dose of 64.8Gy) was delivered in 92% and full dose capecitabine in 69% of patients. Most prevalent acute ≥ grade 3 toxicities were regarding skin/mucosa and pain (54% and 37%). Late ≥grade 3 toxicity was reported for skin/mucosa (10%), fibrosis (4%), GI incontinence (4%) and stress fracture or osteoradionecrosis (4%). Twelve weeks after treatment, local clinical complete response (cCR) and regional control (RC) rates were 62% and 75%, respectively. After 2 years, local cCR persisted in 22 patients (42%) and RC was 58%. Thirty patients (58%) had no evidence of disease at end of follow-up (median 35 months). In 9 patients (17%) extensive surgery with stoma formation was needed. Progression free survival was 58%, 51% and 45% and overall survival was 76%, 66%, 52% at 1,2, and 5 years. CONCLUSIONS: Definitive capecitabine-based chemoradiation as alternative for extensive surgery is feasible in locally advanced vulvar cancer and results in considerable locoregional control with acceptable survival rates with manageable acute and late toxicity.

Patient reported outcome measures among patients with vulvar cancer at various stages of treatment, recurrence, and survivorship.

OBJECTIVE: Our goal was to pragmatically describe patient reported outcomes (PROs) in a typical clinic population of vulvar cancer patients, as prior studies of vulvar cancer PROs have examined clinical trial participants. METHODS: A prospective PRO program was implemented in the Gynecologic Oncology clinic of a tertiary academic institution in January 2018. Vulvar cancer patients through September 2019 were administered the European Organization for the Research and Treatment of Cancer Quality of life Questionnaire, the Patient Reported Outcome Measurement Information System Instrumental and Emotional Support Scales, and the Functional Assessment of Cancer Therapy-Vulvar questionnaire. Binary logistic regressions were performed to determine adjusted odds ratios for adverse responses to individual questions by insurance, stage, age, time since diagnosis, recurrence, radiation, and surgical radicality. RESULTS: Seventy vulvar cancer patients responded to PROs (85.4% response rate). Seventy-one percent were > 1 year since diagnosis, 61.4% had stage I disease, and 28.6% recurred. Publicly insured women had less support and worse quality of life (QOL, aOR 4.15, 95% CI 1.00-17.32, p = 0.05). Women who recurred noted more interference with social activities (aOR 4.45, 95% CI 1.28-15.41, p = 0.019) and poorer QOL (aOR 5.22 95% CI 1.51-18.10, p = 0.009). There were no major differences by surgical radicality. Those >1 year since diagnosis experienced less worry (aOR 0.17, 95% CI 0.04-0.63, p = 0.008). CONCLUSIONS: Surgical radicality does not affect symptoms or QOL in vulvar cancer patients, whereas insurance, recurrence, and time since diagnosis do. This data can improve counseling and awareness of patient characteristics that would benefit from social services referral.

Age, treatment and prognosis of patients with squamous cell vulvar cancer (VSCC) - analysis of the AGO-CaRE-1 study.

BACKGROUND: Despite an increasing incidence with simultaneous decreasing age of onset, vulvar squamous cell carcinoma (VSCC) is still a disease that mainly effects the elderly population. Data on the association of age with prognosis and treatment patterns in VSCC are sparse. METHODS: This is an analysis of the AGO-CaRE-1 cohort. Patients with VSCC (FIGO stage ≥1B), treated at 29 cancer centers in Germany from 1998 to 2008, were included in a centralized database (n = 1618). In this subgroup analysis patients were analyzed according to age [<50 yrs. (n = 220), 50-69 yrs. (n = 506), ≥70 yrs. (n = 521)] with regard to treatment patterns and prognosis. Only patients with documented age, surgical groin staging and known nodal status were included (n = 1247). Median follow-up was 27.5 months. RESULTS: At first diagnosis, women ≥70 yrs. presented with more advanced tumor stages (<0.001), larger tumor diameter (<0.001), poorer ECOG status (<0.001), more frequent HPV negative tumors (p = 0.03) as well as a higher rate of nodal involvement (<0.001). Disease recurrence occurred significantly more often in elderly patients (p = 0.001) and age as well as ECOG status, microscopic residual resection, tumor stage, grading, and (chemo)radiation were independent prognostic factors for death or recurrence in multivariate analysis. 2-year disease-free survival rates were 59.3% (≥70 yrs), 65.8% (50-69 yrs) and 81.1% (<50 yrs), respectively (p < 0.001). CONCLUSIONS: Older women with VSCC present with advanced tumor stages at first diagnosis and have an increased risk of recurrence as well as a decreased 2-year DFS in comparison to younger patients. Potential reasons could be self-awareness and/or more aggressive tumor biology due to HPV independent disease.

Evaluation of treatment, prognostic factors, and survival in 198 vulvar melanoma patients: Implications for clinical practice.

OBJECTIVE: To identify clinicopathological characteristics, treatment patterns, clinical outcomes and prognostic factors in patients with vulvar melanoma (VM). MATERIALS & METHODS: This retrospective multicentre cohort study included 198 women with VM treated in eight cancer centres in the Netherlands and UK between 1990 and 2017. Clinicopathological features, treatment, recurrence, and survival data were collected. Overall and recurrence-free survival was estimated with the Kaplan-Meier method. Prognostic parameters were identified with multivariable Cox regression analysis. RESULTS: The majority of patients (75.8%) had localized disease at diagnosis. VM was significantly associated with high-risk clinicopathological features, including age, tumour thickness, ulceration, positive resection margins and involved lymph nodes. Overall survival was 48% (95% CI 40-56%) and 31% (95% CI 23-39%) after 2 and 5 years respectively and did not improve in patients diagnosed after 2010 compared to patients diagnosed between 1990 and 2009. Recurrence occurred in 66.7% of patients, of which two-third was non-local. In multivariable analysis, age and tumour size were independent prognostic factors for worse survival. Prognostic factors for recurrence were tumour size and tumour type. Only the minority of patients were treated with immuno- or targeted therapy. CONCLUSION: Our results show that even clinically early-stage VM is an aggressive disease associated with poor clinical outcome due to distant metastases. Further investigation into the genomic landscape and the immune microenvironment in VM may pave the way to novel therapies to improve clinical outcomes in these aggressive tumours. Clinical trials with immunotherapy or targeted therapy in patients with high-risk, advanced or metastatic disease are highly needed.

Impact of Medicaid expansion on women with gynecologic cancer: a difference-in-difference analysis.

BACKGROUND: Women with gynecologic cancer face socioeconomic disparities in care that affect survival outcomes. The Affordable Care Act offered states the option to expand Medicaid enrollment eligibility criteria as a means of improving timely and affordable access to care for the most vulnerable. The variable uptake of expansion by states created a natural experiment, allowing for quasi-experimental methods that offer more unbiased estimates of treatment effects from retrospective data than the traditional regression adjustment. OBJECTIVE: To use a quasi-experimental, difference-in-difference framework to create unbiased estimates of impact of Medicaid expansion on women with gynecologic cancer. STUDY DESIGN: We performed a quasi-experimental retrospective cohort study from the National Cancer Database files for women with invasive cancers of the uterus, ovary and fallopian tube, cervix, vagina, and vulva diagnosed from 2008 to 2016. Using a marker for state Medicaid expansion status, we created difference-in-difference models to assess the impact of Medicaid expansion on the outcomes of access to and timeliness of care. We excluded women aged <40 years owing to the suppression of the state Medicaid expansions status in the data and women aged ≥65 years owing to the universal Medicare coverage availability. Our primary outcome was the rate of uninsurance at diagnosis. Secondary outcomes included Medicaid coverage, early-stage diagnosis, treatment at an academic facility, and any treatment or surgery within 30 days of diagnosis. Models were run within multiple subgroups and on a propensity-matched cohort to assess the robustness of the treatment estimates. The assumption of parallel trends was assessed with event study time plots. RESULTS: Our sample included 335,063 women. Among this cohort, 121,449 were from nonexpansion states and 213,614 were from expansion states, with 79,886 posttreatment cases diagnosed after the expansion took full effect in expansion states. The groups had minor differences in demographics, and we found occasional preperiod event study coefficients diverging from the mean, but the outcome trends were generally similar between the expansion and nonexpansion states in the preperiod, satisfying the necessary assumption for the difference-in-difference analysis. In a basic difference-in-difference model, the Medicaid expansion in January 2014 was associated with significant increases in insurance at diagnosis, treatment at an academic facility, and treatment within 30 days of diagnosis (P<.001 for all). In an adjusted model including all states and accounting for variable expansion implementation time, there was a significant treatment effect of Medicaid expansion on the reduction in uninsurance at diagnosis (-2.00%; 95% confidence interval, -2.3 to -1.7; P<.001), increases in early-stage diagnosis (0.80%; 95% confidence interval, 0.2-1.4; P=.02), treatment at an academic facility (0.83%; 95% confidence interval, 0.1-1.5; P=.02), treatment within 30 days (1.62%; 95% confidence interval, 1.0-2.3; P<.001), and surgery within 30 days (1.54%; 95% confidence interval, 0.8-2.3; P<.001). In particular, large gains were estimated for women living in low-income zip codes, Hispanic women, and women with cervical cancer. Estimates from the subgroup and propensity-matched cohorts were generally consistent for all outcomes besides early-stage diagnosis and treatment within 30 days. CONCLUSION: Medicaid expansion was significantly associated with gains in the access and timeliness of treatment for nonelderly women with gynecologic cancer. The implementation of Medicaid expansion could greatly benefit women in nonexpansion states. Gynecologists and gynecologic oncologists should advocate for Medicaid expansion as a means of improving outcomes and reducing socioeconomic and racial disparities.