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).

Radiation therapy for vulvar cancer: consensus guidelines of the GINECOR working group of the Spanish Society of Radiation Oncology. Part 1: clinical recommendations

Purpose The present consensus statement was developed by the GINECOR working group on behalf of the Spanish Society of Radiation Oncology (SEOR). Given the lack of prospective data on the management of vulvar carcinoma, this document provides an up-to-date review of radiotherapy treatment in vulvar cancer and a series of consensus-based recommendations from a group of experts. Methods A two-round, online modified Delphi study was conducted to reach consensus treatment recommendations in three clinical settings: 1) adjuvant treatment, 2) locally-advanced vulvar cancer (LAVC), and 3) recurrent disease. After the first round, we comprehensively reviewed the available medical literature from peer-reviewed journals to assess and define the evidence-based treatment options. In the second round, participants were asked to indicate their level of agreement with the preliminary recommendations according to the GRADE (Grade of Recommendation, Assessment, Development, and Evaluation) criteria, as follows: strongly agree; agree; neither agree nor disagree; disagree; strongly disagree. Results The main recommendations were as follows: 1) following surgical resection, adjuvant radiotherapy is recommended with the presence of adverse risk factors (primarily positive margins and lymph node involvement); 2) radiotherapy (with or without chemotherapy) should be considered in LAVC; and 3) in recurrent disease, radiotherapy should be individualised on a case-by-case basis. A high level of agreement over 80% was reached. Conclusions In the absence of robust clinical data, these final recommendations may help to select the optimal radiotherapy approach for this relatively rare cancer (AU)

Radiation therapy for vulvar cancer: consensus technical guidelines of the GINECOR working group of the Spanish Society of Radiation Oncology. Part 2: radiotherapy recommendations

Purpose The present consensus statement was developed by the GINECOR working group on behalf of the Spanish Society of Radiation Oncology (SEOR). This document provides an up-to-date review of the technical aspects in radiation treatment of vulvar cancer. Methods A two-round modified Delphi study was conducted to reach consensus on the appropriateness of technical aspects of external beam radiotherapy and brachytherapy. Three clinical scenarios were proposed: adjuvant treatment of vulvar cancer, radiation treatment of locally advanced vulvar carcinoma and locoregional recurrences. After the first round, an extensive analysis of current medical literature from peer-reviewed journal was performed to define evidence-based treatment options. In the second round, participants were asked to indicate their level of agreement with the preliminary recommendations according to the GRADE (Grade of Recommendation, Assessment, Development, and Evaluation) criteria, as follows: strongly agree; agree; neither agree nor disagree; disagree and strongly disagree. Results The main recommendations on external beam radiotherapy and brachytherapy, both in adjuvant setting and local advanced disease are summarized. Recommendations include treatment technique, treatment volume, and doses in target and organs at-risk. Taking into consideration the different clinical scenarios of recurrent disease, the radiation treatment should be individualized. Conclusions In the absence of robust clinical data, these recommendations may help to select the optimal radiotherapy approach for this relatively rare cancer (AU)

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.

Fluorescence imaging of lymphangioma circumscriptum of the vulva with aminolevulinic acid and target-type narrow band ultraviolet light.

Lymphangioma circumscriptum of the vulva is a rare lymphatic disorder. Defining the precise location of the lesion is required to select an appropriate treatment. Herein we present photodynamic diagnosis of lymphangioma circumscriptum of the vulva with aminolevulinic acid and target-type narrow band ultraviolet light device.

Radiation therapy for vulvar cancer: consensus guidelines of the GINECOR working group of the Spanish Society of Radiation Oncology. Part 1: clinical recommendations.

PURPOSE: The present consensus statement was developed by the GINECOR working group on behalf of the Spanish Society of Radiation Oncology (SEOR). Given the lack of prospective data on the management of vulvar carcinoma, this document provides an up-to-date review of radiotherapy treatment in vulvar cancer and a series of consensus-based recommendations from a group of experts. METHODS: A two-round, online modified Delphi study was conducted to reach consensus treatment recommendations in three clinical settings: 1) adjuvant treatment, 2) locally-advanced vulvar cancer (LAVC), and 3) recurrent disease. After the first round, we comprehensively reviewed the available medical literature from peer-reviewed journals to assess and define the evidence-based treatment options. In the second round, participants were asked to indicate their level of agreement with the preliminary recommendations according to the GRADE (Grade of Recommendation, Assessment, Development, and Evaluation) criteria, as follows: strongly agree; agree; neither agree nor disagree; disagree; strongly disagree. RESULTS: The main recommendations were as follows: 1) following surgical resection, adjuvant radiotherapy is recommended with the presence of adverse risk factors (primarily positive margins and lymph node involvement); 2) radiotherapy (with or without chemotherapy) should be considered in LAVC; and 3) in recurrent disease, radiotherapy should be individualised on a case-by-case basis. A high level of agreement over 80% was reached. CONCLUSIONS: In the absence of robust clinical data, these final recommendations may help to select the optimal radiotherapy approach for this relatively rare cancer.

Radiation therapy for vulvar cancer: consensus technical guidelines of the GINECOR working group of the Spanish Society of Radiation Oncology. Part 2: radiotherapy recommendations.

PURPOSE: The present consensus statement was developed by the GINECOR working group on behalf of the Spanish Society of Radiation Oncology (SEOR). This document provides an up-to-date review of the technical aspects in radiation treatment of vulvar cancer. METHODS: A two-round modified Delphi study was conducted to reach consensus on the appropriateness of technical aspects of external beam radiotherapy and brachytherapy. Three clinical scenarios were proposed: adjuvant treatment of vulvar cancer, radiation treatment of locally advanced vulvar carcinoma and locoregional recurrences. After the first round, an extensive analysis of current medical literature from peer-reviewed journal was performed to define evidence-based treatment options. In the second round, participants were asked to indicate their level of agreement with the preliminary recommendations according to the GRADE (Grade of Recommendation, Assessment, Development, and Evaluation) criteria, as follows: strongly agree; agree; neither agree nor disagree; disagree and strongly disagree. RESULTS: The main recommendations on external beam radiotherapy and brachytherapy, both in adjuvant setting and local advanced disease are summarized. Recommendations include treatment technique, treatment volume, and doses in target and organs at-risk. Taking into consideration the different clinical scenarios of recurrent disease, the radiation treatment should be individualized. CONCLUSIONS: In the absence of robust clinical data, these recommendations may help to select the optimal radiotherapy approach for this relatively rare cancer.

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.

Comparison of cisplatin and mitomycin C/5-FU as radiosensitisers in the treatment of locally advanced vulvar cancer: results of a retrospective, observational, single-institutional cohort study.

PURPOSE: We retrospectively investigated the widely used radiosensitisers cisplatin and mitomycin C/5-fluorouracil (5-FU) in patients with locally advanced vulvar cancer for outcome and toxicity. METHODS: We screened the archive for patients treated with chemoradiation for vulvar cancer diagnosed between 01/2010 and 08/2021 at our institution. The impact of both radiosensitisers on prognosis was compared using Kaplan-Meier method and Cox-regression analysis. RESULTS: One hundred and forty-three patients with vulvar cancer were screened. Twenty-nine patients received chemoradiation (mitomycin C/5-FU n = 14; cisplatin n = 12; others n = 3) as a primary, neoadjuvant or adjuvant treatment. Median follow-up was 15.5 months. Patients in the cisplatin group were older (mean age 54.4 vs. 70.7; p = 0.004). However, the mitomycin C/5-FU group had more advanced tumour stages. The 2-year recurrence-free survival (RFS) was comparable (44.5% vs. 33.3%; p = 0.932). The 2-year overall survival (OS) showed a numerical but not statistically significant difference in favour of the mitomycin C/5-FU group (59.7% vs. 31.7%; p = 0.37). 64.3% (9 out of 14) patients, who received mitomycin C/5-FU achieved clinical complete response (cCR) compared to 41.7% (5 out of 12) who received cisplatin (p = 0.505). Radiodermatitis was the most common adverse event in both groups (81%) and more severe in the mitomycin C/5-FU cohort. Myelotoxicity was frequently observed in both groups. Eighteen patients received an additional radiation boost with 10.0 (9-16) Gy and showed a significantly prolonged RFS (p = 0.027) and OS (p = 0.003). CONCLUSION: Mitomycin C/5-FU may be considered in the treatment of young and healthy patients with locally advanced vulvar cancer.

Coverage probability planning for simultaneously integrated boosts of inguinal lymph nodes in vulvar cancer.

BACKGROUND AND PURPOSE: Strategies for minimizing irradiation of organs at risk (OARs) from pathological inguinal lymph node (PILN) boosting are needed to minimize the risk of morbidity. Coverage probability (CovP) is a conformal planning strategy for simultaneously integrated boost (SIB). Our aim was to investigate if SIB of PILN using CovP can be delivered safely in vulvar cancer. MATERIALS AND METHODS: Ten consecutive patients treated with definitive radiotherapy (RT) including SIB of PILN and with daily cone beam CT (CBCT) were included. Dose prescription was 51.2/32 fx to the elective target and 64 Gy/32 fx to the gross disease at the vulva and to positive lymph nodes (LN). PILN were contoured on both planning CT and MRI (GTV-N) and combined to form ITV-N. Each PILN GTV-N was contoured on every third CBCT, in total 11 CBCT for each patient. OARs were subcutaneous tissue (SC), inguinal vessels, skin rim, bowel, and body contour. Three plans were created for every patient: A) Standard CT-based planning; PTV-N based on GTV-NCT with a 10 mm isotropic margin. B) CT and MRI-based planning with smaller margins: PTV-N based on ITV-N with a 5 mm isotropic margin. C) CovP. The total delivered dose to GTV-Ns was estimated by accumulating dose across all fractions based on GTV-Ns contoured on CBCT. RESULTS: Thirty-five PILNs were boosted. There was no significant difference in accumulated GTV-N D98% between the three plans. CovP delivered a higher mean dose to the GTV-N D50% and D2% (p < 0.001). The planned mean doses to the OARs were reduced when applying CovP. CONCLUSIONS: SIB of PILN in vulvar cancer based on CovP and a 5 mm PTV margin does not compromise target coverage during RT and reduces the dose to normal tissues in the groin.

The changing role for extended resections in an era of advanced radiotherapy techniques and novel therapies in gynaecological malignancy.

Pelvic exenteration, first described in 1948 and subsequently refined, may be offered as a last hope of cure to patients with recurrent or locally advanced pelvic tumours, where radiotherapy is not an option. It is a complex, morbid, ultra-radical procedure involving en-bloc resection of the female reproductive organs, lower urinary tract, and a portion of the rectosigmoid. This article discusses the evolution of and current indications for pelvic exenteration in gynaecologic oncology as well as the reasons for its decline: primary and secondary prevention of cervical cancer (the recurrence of which is the most common indication for exenteration); improvements in treatment of cervical, endometrial, vaginal and vulvar cancer in the primary and recurrent setting; and the advent of novel therapies.

The role of adjuvant radiation therapy in older patients with node-positive vulvar cancer: A national cancer database analysis.

OBJECTIVE: We sought to evaluate whether the survival benefit of adjuvant radiotherapy in patients with node-positive vulvar cancer is maintained in older patients, who comprise a large subgroup of patients with vulvar cancer. METHODS: The National Cancer Database (NCDB) was queried for patients aged 65 years or older, who were diagnosed with vulvar squamous cell carcinoma from 2004 to 2017 and underwent surgery with confirmed node-positive disease. Statistical analysis was performed with propensity-score matching, chi-square test, log-rank test, Kaplan-Meier, and multivariable Cox proportional regression. RESULTS: A total of 2396 patients were analyzed, and 1517 (63.3%) received adjuvant radiotherapy. Median follow-up was 73 months. Median age at diagnosis was 77 years (range 65-90). In the propensity score-matched cohort, five-year overall survival (OS) was 29%. Five-year OS was 33% in patients who received surgery followed by adjuvant radiotherapy and 26% in patients who received surgery alone (p < 0.0001). Multivariable analysis continued to demonstrate a survival benefit associated with the addition of adjuvant radiotherapy (OR 0.77 [95% CI 0.69-00.87], p < 0.001). Adjuvant radiotherapy was associated with improved OS among patients aged 65-84 (5-year OS 35% vs 29%, p = 0.0004), but not in patients aged 85 years and older (5-year OS 20% vs 19%, p = 0.32). CONCLUSION: This NCDB study suggests that in older patients with node-positive vulvar cancer, radiotherapy continues to be a vital component of multimodality therapy. However, a comprehensive and geriatrics-specific approach is crucial for treating older adults with node-positive vulvar cancer, as the benefit of adjuvant radiotherapy may be compromised by treatment-related morbidity/toxicity.

Time to completion of radiation treatment in locally advanced squamous cell carcinoma of the vulva and the impact on survival.

OBJECTIVE: To assess whether radiation completion within a planned timeframe in locally advanced squamous cell vulvar cancer impacts overall survival (OS). METHODS: The National Cancer Database from 2004 to 2017 was used to identify women ≥18 years old with stage II-IVA squamous cell vulvar cancer. We included women who received radiation alone (RT) or concurrent chemoradiation (CRT) for initial vulvar cancer treatment. Primary outcome was overall survival associated with time of delay in radiation completion. RESULTS: There were 2378 women identified (n = 856 RT and n = 1522 CRT). Median age was 67 (IQR 56-78), majority (88.35%) were white with advanced stage III or IVA (72.29%) disease. Median radiation dose was 5720 c-Gray (IQR 5040-6300). Radiation completion with delay ≥7 days resulted in reduction in survival compared to delay of <7 days (unadjusted HR 1.183 [95%CI: 1.066-1.313], p = 0.0016). When delays extended to ≥14 days compared to <14 days there was increased hazard of death (unadjusted HR: 1.263 [95%CI:1.126-1.416], p < 0.0001). Survival improved for patients with <7 versus ≥7 days delay whether treatment was with RT (median OS: 34.9 months versus 21.6 months, p < 0.01) or CRT (Median OS:58 months versus 41.3 months, p < 0.01). Stage IVA disease was associated with the greatest increase in hazard of death (HR 1.759 [95%CI 1.517-2.039], p < 0.0001) compared to stage II. CONCLUSION: Radiation completion with <7 days delay is associated with improved overall survival, independent of concurrent chemotherapy. This suggest that strategies to minimize delays in radiation are crucial in locally advanced vulvar cancer.

Observational multicenter Italian study on vulvar cancer adjuvant radiotherapy (OLDLADY 1.2): a cooperation among AIRO Gyn, MITO and MaNGO groups.

BACKGROUND: Adjuvant radiotherapy (aRT) has been shown to reduce the risk of local relapse in vulvar cancer (VC). In this multicentre study (OLDLADY-1.2), several Institutions have combined their retrospective data on VC patients to produce a real-world dataset aimed at collecting data on efficacy and safety of aRT. METHODS: The primary study end-point was the 2-year-local control, secondary end-points were the 2-year-metastasis free-survival, the 2-year-overall survival and the rate and severity of acute and late toxicities. Participating centres were required to fill data sets including age, stage, tumor diameter, type of surgery, margin status, depth of invasion, histology, grading as well technical/dosimetric details of radiotherapy. Data about response, local and regional recurrence, acute and late toxicities, follow-up and outcome measures were also collected. RESULTS: One hundred eighty-one patients with invasive VC from 9 Institutions were retrospectively identified. The majority of patients were stage III (63%), grade 2 (62.4%) squamous carcinoma (97.2%). Positive nodes were observed in 117 patients (64.6%), moreover tumor diameter > 4 cm, positive/close margins and depth of invasion deeper than 5 mm were found in 59.1%, 38.6%, 58% of patients, respectively. Sixty-one patients (33.7%) received adjuvant chemoradiation, and 120 (66.3%) received radiotherapy alone. aRT was started 3 months after surgery in 50.8% of patients. Prescribed volumes and doses heterogeneity was recorded according to margin status and nodal disease. Overall, 42.5% locoregional recurrences were recorded. With a median follow-up of 27 months (range 1-179), the 2-year actuarial local control rate, metastasis free and overall survival were 68.7%, 84.5%, and 67.5%, respectively. In term of safety, aRT leads to a prevalence of acute skin toxicity with a low incidence of severe toxicities. CONCLUSIONS: In the context of aRT for VC the present study reports a broad spectrum of approaches which would deserve greater standardization in terms of doses, volumes and drugs used.

Definitive chemoradiation or radiation therapy alone for the management of vulvar cancer.

Vulvar cancer is rare, and unresectable disease provides a therapeutic conundrum. Although definitive surgery remains the mainstay for curative treatment of vulvar cancer, a minority of patients present with advanced disease for which surgical resection would be extraordinarily morbid. Pre-operative and definitive radiation with radiosensitizing systemic therapy allows such patients an opportunity for cure. In this review, we explore the origins of pre-operative radiation, current treatment standards for pre-operative and definitive chemoradiation, and future directions.

Postoperative management of vulvar cancer.

The primary treatment for resectable vulvar cancer includes wide local excision of the primary tumor and surgical lymph node assessment. Following surgery, up to 40-50% of patients develop a local recurrence. Historically, the strongest predictor of local recurrence is a positive or close margin (defined as <8 mm), although recent studies question the importance of margin status. Post-operative radiotherapy to the vulva is recommended for all women with a positive margin where re-excision is not possible. Radiotherapy may also be considered in the setting of risk factors for local recurrence: close margin, lymphovascular invasion, large tumor size, and/or depth of invasion >5 mm. Nodal assessment is an important component of vulvar cancer management. A negative sentinel node is associated with a low false-negative predictive value (2% in patients with vulvar tumor <4 cm in GOG 173), 2-year groin recurrence rate of 2.3%, and 3-year disease-specific survival rate of 97% in patients with unifocal vulvar tumor <4 cm in the GROningen INternational Study on Sentinel nodes in Vulvar Cancer (GROINSS-V I) study. Thus, patients with tumor size <4 cm (without additional local risk factors) and negative sentinel node can be observed. Patients with sentinel node metastasis ≤2 mm can be treated with post-operative radiotherapy (2-year isolated groin recurrence rate of 1.6% in GROINSS-V II), as a safe alternative to lymphadenectomy. Patients with sentinel node metastasis >2 mm following sentinel node biopsy should undergo inguinofemoral lymphadenectomy followed by post-operative radiotherapy-based on the GROINSS-V II study, the 2-year isolated groin recurrence rate remains unacceptably high (22%) with radiotherapy alone. Retrospective studies suggest that the addition of concurrent chemotherapy to radiotherapy may improve survival. The ongoing GROINSS-V III study is investigating concurrent chemotherapy and radiotherapy dose escalation. The main goal of these post-operative treatments is to reduce the risk of local, and especially groin, recurrences, which are almost universally fatal.