High concordance of molecular subtyping between pre-surgical biopsy and surgical resection specimen (matched-pair analysis) in patients with vulvar squamous cell carcinoma using p16- and p53-immunostaining.

OBJECTIVE: Vulvar squamous cell carcinoma (VSCC) can be stratified into three molecular subtypes based on the immunoexpression of p16 and p53: HPV-independent p53-abnormal (p53abn) (most common, biologically aggressive), HPV-associated, with p16-overexpression (second most common, prognostically more favourable) and more recently recognised HPV-independent p53-wildtype (p53wt) (rarest subtype, prognostically intermediate). Our aim was to determine whether molecular subtypes can be reliably identified in pre-operative biopsies and whether these correspond to the subsequent vulvectomy specimen. METHODS: Matched-paired pre-surgical biopsies and subsequent resection specimen of 57 patients with VSCC were analysed for the immunohistochemical expression of p16 and p53 by performing a three-tiered molecular subtyping to test the accuracy rate. RESULTS: Most cases 36/57 (63.2%) belonged to the HPV-independent (p53-abn) molecular subtype, followed by HPV-associated 17/57 (29.8%) and HPV-independent (p53wt) 4/57 (7.0%). The overall accuracy rate on biopsy was 91.2% (52/57): 97.3% for p53-abnormal, 94.1% for p16-overexpression and 50% for p16-neg/p53-wt VSCC. Incorrect interpretation of immunohistochemical p53 staining pattern was the reason for discordant results in molecular subtyping in all five cases. In one case there was an underestimation of p53 pattern (wildtype instead of abnormal/aberrant) and in one case an overestimation of the p53 staining pattern (abnormal/aberrant instead of wildtype). In 3/5 there was a "double positive" staining result (p16 overexpression and abnormal/aberrant p53 staining pattern). In that cases additional molecular workup is required for correct molecular subtyping, resulting in an overall need for molecular examination of 3/57 (3.5%). CONCLUSIONS: Compared to the final resections specimen, the three-tiered molecular classification of VSCC can be determined on pre-surgical biopsies with a high accuracy rate. This enables more precise surgical planning, prediction of the response to (chemo) radiation, selection of targeted therapies and planning of the optimal follow-up strategy for patients in the age of personalised medicine.

Update on the Sentinel Node Procedure in Vulvar Cancer.

Early-stage vulvar cancer is managed by a local excision of the primary tumor and, if indicated, a sentinel node (SN) biopsy to assess the need for further groin treatment. With the SN procedure, many patients can be treated less radically and will experience less complications and morbidity compared with an inguinofemoral lymphadenectomy (IFL). Still, the SN procedure can be further optimized. Different tracers for detecting the SN are being investigated, aiming to optimize detection rates and decrease the burden of the procedure and short-term complications. Until now, no standardized protocols exist for the pathologic workup of the SN, possibly leading to discrepancies in detection of metastases between institutes using different methods. New techniques, such as one-step nucleic amplification, seem to have potential in accurately detecting metastases in other cancers, but have not yet been investigated in vulvar squamous cell carcinoma (VSCC). Furthermore, several studies have investigated the possibility to broaden the indications for the SN procedure, such as its use in recurrent disease, larger tumors, or multifocal tumors. Although these studies show encouraging results, cohorts are small and further studies are needed. Prospective studies are currently investigating these subgroups. Lastly, several studies investigated optimization of groin treatment of patients with a metastatic SN. Inguinofemoral radiotherapy is a good alternative to IFL in patients with micrometastases in the SN, with comparable efficacy and less treatment-related morbidity. Reduction of the radicality of groin treatment is also possible in other ways, such as omitting contralateral IFL in patients with lateralized tumors and a unilateral metastatic SN. In conclusion, the SN procedure is an established procedure in early-stage VSCC, although optimization of the technique, pathologic workup, indications, and treatment in the setting of metastatic disease are the subject of ongoing research.

Sentinel Lymph Node Evaluation in Early-Stage Vulvar Cancer.

OPINION STATEMENT: Sentinel lymph node mapping (SLNM) and dissection (SLND) should be used as an alternative to full inguinofemoral lymph node dissection (IFLND) in select patients with early-stage vulvar cancer. IFLND is associated with high postoperative complications such as wound breakdown, lymphedema, lymphocyst formation, and infection. SLND in select patients offers a safe, effective, and less morbid alternative. Candidates for SLND include patients with a unifocal vulvar tumor less than four centimeters, clinically negative lymph nodes, and no prior inguinofemoral surgeries. SLND should ideally be performed by a high-volume SLN surgeon. Most commonly, SLND is performed using both radiocolloid lymphoscintigraphy (e.g., Technetium-99) and a visual tracer such as blue dye; however, near infrared imaging with indocyanine green injection is becoming more widely adopted. Further prospective studies are needed to examine the safety and efficacy of various techniques for SLND. SLND has been demonstrated to be cost-effective, especially when including perioperative complications. Further studies are needed to demonstrate quality of life differences between IFLND and SLND.

Unusual Presentation of Lymphangioma Circumscriptum of the Vulva: In Association With Crohn Disease.

ABSTRACT: Lymphangioma circumscriptum (LC) is a rare benign condition, with marked dilation of surface lymphatic vessels in the deep and subcutaneous layers. Vulvar LC can become a highly disabling condition with vulvar discomfort, itching, burning and lymph seeping being the dominant symptoms. Biopsy is mandatory for the diagnosis. There is no consensus on the standard treatment for vulvar LC and recurrence is frequent. In complex cases with wide disease location, combination of different treatment options, such as abrasive methods and surgery, may lead to the best clinical and aesthetical result, with extended disease-free periods. We present a patient with a long history of Crohn disease with multiple pelvic surgeries who developed an extensive vulvar LC.

Prevalence of prescribing topical corticosteroids to patients with lichen sclerosus following surgery for vulvar cancer: a survey among gynaecologic oncologists in The Netherlands.

BACKGROUND: Vulvar lichen sclerosus (LS) is a chronic inflammatory dermatosis which can progress to precursor lesion differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar squamous cell carcinoma (VSCC). The risk of developing recurrent vulvar cancer following LS-associated VSCC is high. Evidence suggests that treatment of LS with topical corticosteroids (TCS) can prevent progression to dVIN, VSCC and recurrences. However, current guidelines do not give any recommendation on the management of LS following surgery for VSCC. The aim of this study was to conduct a survey among all registered gynaecologic oncologists (GOs) in the Netherlands to evaluate the current management of LS patients without a history of VSCC (LSnoVSCC) and patients with LS following surgery for VSCC (LSVSCC). METHODS: An online survey was distributed to all registered GOs in the Netherlands. Primary outcome measures were the frequency, type and duration of TCS treatment prescribed for LSnoVSCC and LSVSCC patients, separately. As a secondary outcome measure, reasons for treating or not treating patients with LSnoVSCC and LSVSCC with TCS were analysed. RESULTS: Forty-four GOs completed the survey, resulting in a response rate of 75%. TCS were prescribed more often to patients with LSnoVSCC as compared to patients with LSVSCC (86% versus 52%, respectively, p < 0.001). If treatment was initiated, ultra-potent (class IV) TCS were most commonly prescribed for an indefinite period of time for both patient groups. The most reported reason for treating patients in both groups with TCS was symptoms, followed by clinical aspects of the lesion and prevention of progression to dVIN and VSCC. CONCLUSION: The majority of GOs who participated in our study endorse the utilisation of long-term ultra-potent TCS therapy in both patients with LSnoVSCC and LSVSCC. Nevertheless, Dutch GOs are currently prescribing TCS more frequently to patients with LSnoVSCC than to patients with LSVSCC.

Vulvar lichen sclerosus (LS) is a chronic skin condition which may progress to vulvar squamous cell carcinoma (VSCC) through differentiated vulvar intraepithelial neoplasia (dVIN). LS symptoms are treated with topical corticosteroids (TCS), which can also prevent progression to dVIN and VSCC. However, current international guidelines do not give any recommendation on the treatment of LS following surgery for VSCC. To evaluate the current management of LS patients without a history of VSCC (LS^noVSCC) and patients with LS following surgery for VSCC (LS^VSCC), a survey study was conducted among all gynaecologic oncologists (GOs) in The Netherlands. The findings of this study demonstrate that Dutch GOs prescribed TCS more often to patients with LS^noVSCC as compared to patients with LS^VSCC. However, when deciding to prescribe TCS, the majority of Dutch GOs prescribed ultra-potent TCS for an indefinite period of time for both LS^noVSCC and LS^VSCC patients.

Transmissible venereal tumor of the uterine stump following successful chemotherapy in a 5-year-old mixed-breed dog.

A 5-year-old spayed female mixed-breed dog was referred to the Atlantic Veterinary College (Charlottetown, Prince Edward Island) because of a 7-month history of intermittent pink, mucoid, vulvar discharge. The dog was imported from the Bahamas at 3.5 y of age and had a history of transmissible venereal tumor (TVT) of the vulva that was successfully treated with a course of vincristine chemotherapy. Complete remission was achieved with a disease-free interval of 6 mo before clinical signs recurred. Abdominal ultrasound and CT scan identified a large caudal abdominal mass thought to arise from the uterine stump. An exploratory laparotomy was performed and the mass grossly excised. Histopathology was consistent with a poorly differentiated round cell tumor, and immunohistochemical analysis confirmed TVT as the most likely diagnosis. No further treatment was carried out. Repeat abdominal ultrasound at 4 mo after surgery showed no evidence of mass recurrence. At 8 mo after surgery, the dog was reported to be doing well clinically. Key clinical message: Transmissible venereal tumor should be considered as a differential diagnosis for masses arising from the deep genital tissues of dogs in cases where there is a history of previous TVT. Transmissible venereal tumor should be considered even in dogs that have had complete resolution of a primary mass after chemotherapy.

Tumeur vénérienne transmissible du moignon utérin à la suite d'une chimiothérapie réussie chez un chien croisé de 5 ans.Une chienne de race mixte de 5 ans, stérilisée, a été référée au Atlantic Veterinary College (Charlottetown, Île-du-Prince-Édouard) en raison d'antécédents de pertes vulvaires roses, mucoïdes et intermittentes depuis 7 mois. Le chien a été importé des Bahamas à l'âge de 3,5 ans et avait des antécédents de tumeur vénérienne transmissible (TVT) de la vulve qui a été traitée avec succès par une chimiothérapie à la vincristine. Une rémission complète a été obtenue avec un intervalle sans maladie de 6 mois avant la réapparition des signes cliniques. L'échographie abdominale et la tomodensitométrie ont identifié une grosse masse abdominale caudale qui proviendrait du moignon utérin. Une laparotomie exploratoire a été réalisée et la masse excisée. L'histopathologie était compatible avec une tumeur à cellules rondes peu différenciée et l'analyse immunohistochimique a confirmé la TVT comme le diagnostic le plus probable. Aucun autre traitement n'a été effectué. Une échographie abdominale répétée 4 mois après la chirurgie n'a montré aucun signe de récidive massive. Huit mois après l'opération, la chienne se portait bien cliniquement.Message clinique clé:Les tumeurs vénériennes transmissibles doivent être considérées comme un diagnostic différentiel pour les masses provenant des tissus génitaux profonds des chiens dans les cas où il existe des antécédents de TVT. Une tumeur vénérienne transmissible doit être envisagée même chez les chiens dont la masse primaire a complètement disparu après chimiothérapie.(Traduit par Dr Serge Messier).

Genitocrural Island Perforator Flap (GIP-Flap): An ideal surgical technique for covering uni- or bilateral vulvar loss tissue.

Vulvar loss of soft tissue leads to urinary, sexual and morphological dysfunctions. Most patients affected are comorbid making it difficult to perform a flap, which is the most appropriate way to reconstruct. Our multidisciplinary plastic and gynecologic surgery team has developed a new technique using a pedicled internal pudendal island flap. Reconstruction is reliable, quick and applicable to all patients, with a highly satisfactory final appearance.

Incidence of inguinofemoral lymph node metastases at the first local recurrence of vulvar cancer: a Dutch nationwide study.

BACKGROUND: Up to 40% of vulvar cancer patients present with local recurrence within 10 years of follow-up. An inguinofemoral lymphadenectomy (IFL) is indicated if not performed at primary treatment. The incidence and risk factors for lymph node metastases (LNM) at first local recurrence, however, are unclear. Our aim was to determine the incidence of LNM at first local recurrence, in relation to previous groin treatment and clinicopathological factors. METHODS: A multicenter cohort study including vulvar cancer patients with a first macroinvasive local recurrence after primary surgical treatment between 2000 and 2015 was conducted in the Netherlands. Groin status at local recurrence was defined as positive (N+), negative (N-) or unknown (N?) and based on histology, imaging and follow-up. Patient-, tumour- and treatment characteristics of primary and recurrent disease were analysed. RESULTS: Overall, 16.3% (66/404) had a N+ groin status at first local recurrence, 66.4% (268/404) N- and 17.3% (70/404) N? groin status. The incidence of a N+ groin status was comparable after previous SLN and IFL, 11.5% and 13.8%, respectively. A N+ groin status was related to tumour size (25 vs.12 mm; P < 0.001), depth of invasion (5 vs. 3 mm; P < 0.001) and poorly differentiated tumours (22.9 vs. 11.9%; P = 0.050) at local recurrence. CONCLUSIONS: The incidence of LNM at first local recurrence in vulvar cancer patients was 16.3%, and independent of previous type of groin surgery. In accordance with primary diagnosis, tumour size, depth of invasion, and tumour grade were significantly associated with a positive groin status.

Topical imiquimod versus surgery for vulvar intraepithelial neoplasia: a multicentre, randomised, phase 3, non-inferiority trial.

BACKGROUND: The optimal management of vulvar high-grade squamous intraepithelial lesions (vHSILs) is challenging. Surgery is the standard treatment, but recurrences are observed in half of patients. Medical treatment with imiquimod is an effective alternative, but the two modalities have not been compared in a randomised trial. The aim of this study was to compare the clinical effectiveness, histological response, human papillomavirus (HPV) clearance, acceptance, and psychosexual morbidity of primary imiquimod treatment versus surgical treatment in women with vHSIL. METHODS: This study was a multicentre, randomised, phase 3, non-inferiority clinical trial done by the Austrian Gynaecological Oncology group at six hospitals in Austria. We recruited female patients aged 18-90 years with histologically confirmed vHSIL with visible unifocal or multifocal lesions. Main exclusion criteria were clinical suspicion of invasion, a history of vulvar cancer or severe inflammatory dermatosis of the vulva, and any active treatment for vHSIL within the previous 3 months. Women with known immunodeficiency, who were pregnant, or who were lactating were excluded. Patients were randomly assigned (1:1) by block randomisation to imiquimod or surgery, and stratified by unifocal or multifocal disease. Treatment with imiquimod was self-administered in a slowly escalating dosage scheme up to three times per week for a period of 4-6 months. Surgery consisted of excision or ablation. Patients were assessed with vulvoscopy, vulvar biopsy, HPV tests, and patient-reported outcomes at baseline and after 6 months and 12 months. The primary endpoint was complete clinical response (CCR) at 6 months after local imiquimod treatment or one surgical intervention. Primary analysis was per protocol with a non-inferiority margin of 20%. This trial is registered at ClinicalTrials.gov, NCT01861535. FINDINGS: 110 patients with vHSIL (78% with unifocal vHSIL and 22% with multifocal vHSIL) were randomly assigned between June 7, 2013, and Jan 8, 2020. Clinical response to treatment could be assessed in 107 patients (54 in the imiquimod group and 53 in the surgery group), and 98 patients (46 in the imiquimod group and 52 in the surgery group) completed the study per protocol. 37 (80%) of 46 patients using imiquimod had CCR, compared with 41 (79%) of 52 patients after one surgical intervention, showing non-inferiority of the new treatment (difference in proportion -0·016, 95% CI -0·15 to -0·18; p=0·0056). Invasive disease was found in five patients at primary or secondary surgery, but not in patients with per-protocol imiquimod treatment. There was no significant difference in HPV clearance, adverse events, and treatment satisfaction between study groups. INTERPRETATION: Imiquimod is a safe, effective, and well accepted alternative to surgery for women with vHSIL and can be considered as first-line treatment. FUNDING: Austrian Science Fund and Austrian Gynaecological Oncology group.

Vulvar cancer survival by primary treatment modality: A retrospective cohort study.

OBJECTIVE: To compare survival and complications for women with vulvar cancer treated with primary radiation vs surgery. METHODS: Retrospective cohort study of Kaiser Permanente members diagnosed with vulvar squamous cell carcinoma (SCC) between 2008 and 2018 and treated with primary surgery (PS only), surgery with adjuvant radiation (PS + RT), or primary radiation (PRT). Primary outcomes were 1- and 3-year overall (OS) and progression-free (PFS) survival. Multivariable regression adjusted for age, stage, comorbidities, and smoking. RESULTS: We included 201 women: 114 PS only (56.7%), 36 PS + RT (17.9%), and 51 PRT (25.4%). PS only patients had less advanced disease. Crude 1- and 3-year OS were 96.5% and 82.6% for PS only compared to 72.2% and 48.3% for PS + RT and 72.6% and 53.9% for PRT (p < 0.001). There were no statistical differences in hazard of death when controlling for stage and other covariates (PRT vs PS only: aHR 1.35, 95% CI 0.61-2.99; PS + RT vs PS only: aHR 1.28, 95% CI 0.60-2.75; PS + RT vs PRT: aHR 0.95, CI 0.48-1.90). Older age and stage III disease were poor prognostic factors. Risk of lymphedema was elevated with PS + RT (36.1% vs 20.2% for PS only and 9.8% for PRT, p = 0.011). Wound infection was more likely in surgical groups, whereas hospital readmission and blood transfusion were more common with PRT. CONCLUSIONS: Vulvar cancer survival was not statistically different among women treated with primary radiation compared to primary surgery when controlling for stage. Surgery followed by adjuvant radiation demonstrated elevated rates of lymphedema. Primary radiation therapy may be an acceptable alternative to primary surgery in women who are likely to need adjuvant therapy.

Association of hospital-level factors with utilization of sentinel lymph node biopsy in patients with early-stage vulvar cancer.

OBJECTIVE: To evaluate utilization of sentinel lymph node biopsy (SLNB) for early-stage vulvar cancer at minority-serving hospitals and low-volume facilities. METHODS: Between 2012-2018, individuals with T1b vulvar squamous cell carcinoma were identified using the National Cancer Database. Patient, facility, and disease characteristics were compared between patients undergoing SLNB or inguinofemoral lymph node dissection (IFLD). Multivariable logistic regression, adjusted for patient, facility, and disease characteristics, was used to evaluate factors associated with SLNB. Kaplan-Meier survival analysis using log rank test and Cox regression was performed. RESULTS: Of the 3,532 patients, 2,406 (68.1%) underwent lymph node evaluation, with 1,704 (48.2%) undergoing IFLD and 702 (19.8%) SLNB. In a multivariable analysis, treatment at minority-serving hospitals (OR 0.39, 95% CI 0.19-0.78) and low-volume hospitals (OR 0.44, 95% CI 0.28-0.70) were associated with significantly lower odds of undergoing SLNB compared to receiving care at non-minority-serving and high-volume hospitals, respectively. While SLNB utilization increased over time for the entire cohort and stratified subgroups, use of the procedure did not increase at minority-serving hospitals. After controlling for patient and tumor characteristics, SLNB was not associated with worse OS compared to IFLD in patients with positive (HR 1.02, 95% CI 0.63-1.66) or negative (HR 0.92, 95% CI 0.70-1.21) nodal pathology. CONCLUSIONS: For patients with early-stage vulvar cancer, treatment at minority-serving or low-volume hospitals was associated with significantly decreased odds of undergoing SLNB. Future efforts should be concentrated toward ensuring that all patients have access to advanced surgical techniques regardless of where they receive their care.

Feasibility of intraoperative injection of radioactive tracer and blue dye for sentinel lymph node biopsy in vulvar cancer.

OBJECTIVE: The objective of this study was to examine the feasibility and success rate of intraoperative injection of radiotracer and blue dye performed by the surgeon without the use of preoperative lymphoscintigraphy for the detection of sentinel lymph nodes in clinically early stage vulvar cancer. METHODS: All patients with clinically early stage vulvar cancer who underwent attempted sentinel lymph node biopsy using intraoperative injection of Technetium-99 m (99mTc) tracer and blue dye performed by the surgeon after induction of anesthesia at single academic institution from 12/2009 to 5/2022 were identified. Demographic and clinicopathologic variables were collected. Data were compared using descriptive statistics. RESULTS: One hundred sixty-four patients (median age 66.4 years) underwent intraoperative injection of radioactive tracer and dye for sentinel lymph node biopsy. Most patients (n = 156, 95.1%) were white. Squamous cell carcinoma accounted for 138 cases (84.1%), melanoma for 10 (6.1%), extra-mammary invasive Paget's disease for 11 (6.7%), and other histologies for 5 (3%). A majority of cases were stage I disease on final pathology (n = 119, 72.6%). Most patients (n = 117, 71%) had tumors located within 2 cm of the midline and underwent planned bilateral groin assessment, while 47 (29%) had well lateralized lesions and underwent unilateral groin assessment. For the patients undergoing unilateral groin assessment, 44 of 47 (93.6%) had successful unilateral mapping. Of the patients who underwent bilateral groin assessment, 87 of 117 (74.4%) had successful bilateral mapping, and 26 of 117 (22.2%) had successful unilateral mapping. Of the 26 patients who underwent bilateral assessment but only had unilateral mapping, 19 had unilateral mapping to ipsilateral groin but failed contralateral mapping, six had midline lesions with successful mapping to one groin but failed mapping to the other groin, and one had unilateral mapping to the contralateral groin but not ipsilateral groin. The total successful sentinel lymph node mapping rate in this cohort was 86.5% (243/281 total sentinel lymph node attempts). CONCLUSION: In this cohort, the overall success rate of sentinel lymph node mapping and biopsy was 86.5%. The high rate of successful sentinel lymph node mapping supports the use of intraoperative radiotracer and blue dye injection by trained providers.

Treatment patterns and outcomes of patients with locally advanced vulvar or vaginal cancer in British Columbia.

OBJECTIVE: As vulvar and vaginal cancers are rare malignancies, treatment is extrapolated from the cervical cancer field. Further studies are necessary to evaluate whether surgery, radiotherapy (RT), or combined chemoRT is most beneficial. METHODS: A retrospective chart review was conducted on patients diagnosed with vulvar or vaginal cancer in 2000-2017. Descriptive statistics was used to summarize demographic factors. Kaplan-Meier curves, log-rank tests, multivariate analysis with hazard ratios (HR) were conducted to compare survival outcomes, including overall survival (OS), disease-free survival, and cancer-specific survival, between surgery, RT, and chemoRT. RESULTS: This study included 688 patients with either vulvar (n = 560, 81%) or vaginal cancer (n = 128, 19%). Median age of diagnosis was 68 (27-98) years. In multivariate survival analysis, vulvar cancer was associated with more likelihood of death (HR: 1.50, p = 0.042) compared to vaginal cancer. For patients who received definitive RT, median OS was 63.8 months with concurrent chemotherapy vs. 46.3 months without for vulvar cancer (p = 0.75); for vaginal, median OS 100.4 with chemotherapy vs. 66.6 months without (p = 0.31). For vulvar cancer patients who received RT (n = 224), adding chemotherapy (n = 100) was not associated with statistically significant OS improvement (HR: 0.989, p = 0.957). Similarly, vaginal cancer patients who received chemoRT (n = 51) did not have significant OS benefit (HR: 0.720, p = 0.331) over patients who received RT (n = 49). CONCLUSIONS: In this retrospective study, chemoRT was not associated with significant improvements in survival compared to RT in vulvar or vaginal cancer. Future studies investigating novel therapies to treat these cancers are needed to improve patient outcomes.

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.

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.

Sentinel lymphatic mapping for gynecologic malignancies.

PURPOSE OF REVIEW: To summarize the latest data in Gynecologic Oncology for the use of sentinel lymphatic mapping in vulvar, uterine, and cervical cancers. RECENT FINDINGS: To decrease morbidity and improve detection of lymphatic metastasis, lymphatic mapping with sentinel lymph node biopsy is emerging as standard of care over conventional systemic lymphadenectomy in the surgical management of gynecologic malignancies. SUMMARY: Sentinel lymph node mapping with biopsy is one of the most significant advances in cancer surgery. The presence of nodal metastasis is not only a prognostic factor for recurrence and survival in patients with gynecologic malignancies, but also guides assessment for adjuvant treatment. This review article discusses the most recent clinical updates in sentinel lymph node mapping, dissection, and management in vulvar cancer, endometrial cancer, and cervical cancer.

Assessment and Reporting of Perioperative Adverse Events and Complications in Patients Undergoing Inguinal Lymphadenectomy for Melanoma, Vulvar Cancer, and Penile Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Inguinal lymph node dissection (ILND) plays a crucial role in the oncological management of patients with melanoma, penile, and vulvar cancer. This study aims to systematically evaluate perioperative adverse events (AEs) in patients undergoing ILND and its reporting. METHODS: A systematic review was conducted according to PRISMA. PubMed, MEDLINE, Scopus, and Embase were queried to identify studies discussing perioperative AEs in patients with melanoma, penile, and vulvar cancer following ILND. RESULTS: Our search generated 3.469 publications, with 296 studies meeting the inclusion criteria. Details of 14.421 patients were analyzed. Of these studies, 58 (19.5%) described intraoperative AEs (iAEs) as an outcome of interest. Overall, 68 (2.9%) patients reported at least one iAE. Postoperative AEs were reported in 278 studies, combining data on 10.898 patients. Overall, 5.748 (52.7%) patients documented ≥1 postoperative AEs. The most reported ILND-related AEs were lymphatic AEs, with a total of 4.055 (38.8%) events. The pooled meta-analysis confirmed that high BMI (RR 1.09; p = 0.006), ≥1 comorbidities (RR 1.79; p = 0.01), and diabetes (RR 1.81; p = < 0.00001) are independent predictors for any AEs after ILND. When assessing the quality of the AEs reporting, we found 25% of studies reported at least 50% of the required criteria. CONCLUSION: ILND performed in melanoma, penile, and vulvar cancer patients is a morbid procedure. The quality of the AEs reporting is suboptimal. A more standardized AEs reporting system is needed to produce comparable data across studies for furthering the development of strategies to decrease AEs.

Can late lymphoscintigraphy be omitted in the sentinel node procedure in early-stage vulvar cancer?

INTRODUCTION: In the Netherlands, the sentinel lymph node procedure protocol consists of preoperative lymphoscintigraphy combined with intraoperative blue dye for identifying sentinel lymph nodes in early vulvar squamous cell carcinoma. This study aimed at investigating the role of early and late lymphoscintigraphy. MATERIAL AND METHODS: From January 2015 to January 2019, early and late lymphoscintigraphies of 52 women were retrospectively analyzed. Lymphoscintigraphy was performed 30 minutes (early) and 2.5-4 hours (late) after vulvar injection of 99m Tc-labeled nanocolloid. We calculated the concordance correlation coefficient (CCC) between number of sentinel lymph nodes detected on both images using the Lins concordance coefficient and correlated with clinicopathological data. RESULTS: Thirty-four women had a midline tumor and 18 had a lateral tumor. Detection rates with early and late scintigraphy were 88.5% and 98.1%, respectively. Median number of detected nodes was 1.0 (0-7) and 2.0 (0-7). Good statistical correlation between number of sentinel lymph nodes detected on early and late imaging was found (CCC = 0.76) in most patients. In 18 women (35%) a mismatch occurred: a higher number of nodes was detected on late imaging. In 11 of 18 women re-injection was performed because no sentinel lymph nodes were visualized on early images. Late imaging and intraoperative detection showed a good statistical correlation (CCC = 0.61). One woman showed an isolated groin recurrence despite negative sentinel lymph nodes. CONCLUSIONS: This study showed good statistical correlations between early and late scintigraphy in most patients. However, in 35% of women late scintigraphy detected more nodes. In case of poor visualization after the first scintigraphy, re-injection should be considered. Late scintigraphy is probably helpful in confirming successful re-injection and in showing deviating lymph flow in women with failed mapping after the first injection and successful re-injection. Because missing metastatic sentinel lymph nodes often leads to a poor prognosis, we prefer optimal correlations between imaging and intraoperative identification. Hence, late scintigraphy cannot be safely omitted.

Prognostic value of postoperative radiotherapy in patients with vulvar squamous carcinoma: findings based on the SEER database.

INTRODUCTION: The role of postoperative radiotherapy in treating squamous cell carcinoma of the vulva remains controversial. This study evaluated the effect of radiotherapy on the survival of patients with postoperative squamous cell carcinoma of the vulva. METHODS: Clinical and prognostic information on patients diagnosed with vulvar squamous cell carcinoma from 2010 to 2015 was collected from the Surveillance, Epidemiology, and Prognosis (SEER) database. A propensity score matching (PSM) approach was used to balance the differences in clinicopathological characteristics between groups. The impact of postoperative radiotherapy on overall survival (OS) and disease-specific survival (DSS) was assessed. RESULTS: The study included 3571 patients with squamous cell carcinoma of the vulva, of whom 732 (21.1%) received postoperative radiotherapy. After propensity score matching, multivariate analysis showed that age, race, N stage, and tumor size were independent influences on overall survival and disease-specific survival of patients. Postoperative radiotherapy did not improve patients' overall survival or disease-specific survival. Further subgroup survival analysis showed that in patients with AJCC stage III, N1 stage, lymph node metastasis, and large tumor diameter (> 3.5 cm), postoperative radiotherapy resulted in a significant improvement in overall patient survival. CONCLUSION: Postoperative radiotherapy is not indicated for all patients with postoperative vulvar cancer and has improved survival outcomes only for patients with AJCC stage III, N1, lymph node metastases and large tumor diameter (> 3.5 cm).