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Gracia M, Alonso-Espías M, Zapardiel I. Current Limitations of Sentinel Node Biopsy in Vulvar Cancer. Curr Oncol 2025; 32:215. [PMID: 40277771 PMCID: PMC12026259 DOI: 10.3390/curroncol32040215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2025] [Revised: 04/03/2025] [Accepted: 04/07/2025] [Indexed: 04/26/2025] Open
Abstract
Background: Vulvar cancer is a rare gynecologic malignancy with increasing incidence. Lymph node status is the most critical prognostic factor, traditionally assessed through inguinofemoral lymphadenectomy, a procedure associated with significant morbidity. Sentinel lymph node biopsy (SLNB), in selected cases, has emerged as a less invasive alternative with favorable oncologic outcomes. Objective: This review summarizes current evidence on the indications, technique, safety, and oncologic outcomes of SLNB in vulvar cancer, with a focus on controversial scenarios such as recurrent and larger tumors. Methods: A narrative review of PubMed-indexed studies published in English over the last 35 years was conducted. Eligible studies included original research, systematic reviews, meta-analyses, randomized controlled trials, and case-control studies. Results: SLNB is recommended for unifocal vulvar tumors < 4 cm with stromal invasion > 1 mm and clinically negative nodes. Landmark trials, including GROINSS-V-I and GOG-173, confirmed its accuracy and lower morbidity compared to lymphadenectomy. SLNB utilization has increased since its inclusion in guidelines, with a concurrent decline in lymphadenectomy rates. Combined detection techniques are mandatory, while indocyanine green (ICG) is an emerging option. Future studies should focus on refining patient selection criteria, improving detection techniques, and clarifying the implications of low-volume nodal disease to further optimize outcomes for patients with vulvar cancer. Conclusion: SLNB is a validated, minimally invasive staging approach in early-stage vulvar cancer. Further research is needed to refine its role in high-risk cases and optimize detection methods.
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Affiliation(s)
- Myriam Gracia
- Gynecologic Oncology Unit, La Paz University Hospital, 28015 Madrid, Spain; (M.A.-E.); (I.Z.)
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Mulugeta-Gordon L, Gysler S, Latif NA, Ko EM, Giuntoli RL, Kim SH, Nasioudis D. Quality of adjuvant radiation therapy and impact on the survival of patients with lymph node-positive squamous cell carcinoma of the vulva. Int J Gynecol Cancer 2025:101748. [PMID: 40199647 DOI: 10.1016/j.ijgc.2025.101748] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2025] [Revised: 02/13/2025] [Accepted: 02/17/2025] [Indexed: 04/10/2025] Open
Abstract
OBJECTIVE Patients with squamous cell carcinoma of the vulva with inguinal lymph node metastases undergo adjuvant treatment to reduce the risk of recurrence. We examined the patterns of adjuvant treatment delivery and their impact on overall survival. METHODS Patients diagnosed between January 2004 and December 2015 with apparent early-stage squamous cell carcinoma of the vulva, who underwent surgical resection with lymph node sampling/dissection, had at least 1 positive lymph node, and received adjuvant radiation therapy were identified. A total of 3 quality metrics associated with improved survival were evaluated: utilization of radiosensitizing chemotherapy, receipt of radiation therapy within 8 weeks of surgery, and completion of radiation therapy within 8 weeks of initiation. Overall survival was examined after the generation of Kaplan-Meier curves and compared using the log-rank test. A Cox model was constructed to control for the a priori confounding factors. RESULTS A total of 1181 patients were identified, with a median number of positive lymph of 2 (range; 1-14). All 3 quality metrics were met by 238 patients (20.2%). These patients were younger (median age, 59 vs 67 years, p<.001), more likely to have private insurance (52.1% vs 33.4%, p<.001), and less likely to have medical co-morbidities (22.7% vs 30.5%; p=.017). Patients who received adjuvant radiotherapy meeting all quality metrics had better overall survival than those who did not (p<.001); the 5-year overall survival rates were 62.6% and 42.8%, respectively. After controlling for patient age, race, insurance status, presence of medical co-morbidities, tumor size, performance of comprehensive lymphadenectomy, and number of positive lymph nodes, adjuvant radiation therapy meeting all quality metrics was associated with better overall survival (HR 0.56, 95% CI 0.44 to 0.72). CONCLUSIONS Approximately 1 in 5 patients with lymph node-positive vulvar cancer received adjuvant treatment that met all quality metrics associated with improved survival.
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Affiliation(s)
- Lakeisha Mulugeta-Gordon
- University of Pennsylvania, Penn Medicine, Division of Gynecologic Oncology, Philadelphia, PA, USA
| | - Stefan Gysler
- University of Pennsylvania, Penn Medicine, Division of Gynecologic Oncology, Philadelphia, PA, USA
| | - Nawar A Latif
- University of Pennsylvania, Penn Medicine, Division of Gynecologic Oncology, Philadelphia, PA, USA
| | - Emily M Ko
- University of Pennsylvania, Penn Medicine, Division of Gynecologic Oncology, Philadelphia, PA, USA
| | - Robert L Giuntoli
- University of Pennsylvania, Penn Medicine, Division of Gynecologic Oncology, Philadelphia, PA, USA
| | - Sarah H Kim
- University of Pennsylvania, Penn Medicine, Division of Gynecologic Oncology, Philadelphia, PA, USA
| | - Dimitrios Nasioudis
- University of Pennsylvania, Penn Medicine, Division of Gynecologic Oncology, Philadelphia, PA, USA.
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Tzur Y, Magri A, Meyer R, Brodeur MN, Salvador S, Lau S, Gotlieb W, Levin G. Association between body mass index, obesity, and vulvar cancer recurrence. Int J Gynaecol Obstet 2025. [PMID: 39861991 DOI: 10.1002/ijgo.16182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 12/24/2024] [Accepted: 01/13/2025] [Indexed: 01/27/2025]
Abstract
OBJECTIVE The objective of this paper is to study the association between obesity and tumor recurrence in patients with vulvar cancer. METHODS This is a retrospective study including vulvar cancer patients from 2003 to 2022. Our primary outcome was progression-free survival (PFS) stratified by status of obesity, defined as body mass index (BMI) >30.0 kg/m2. RESULTS Overall, 48 patients were included in the study, with 32 (66.7%) diagnosed at early stages (I-II). The median BMI was 28.0 kg/m2 [interquartile range 24.9-32.3 kg/m2]. There were 13 obese patients (27%), and the median follow-up time was 55 months [interquartile range 14-102]. Most patients (80%) were HPV-independent of human papilloma virus. Surgical intervention was the primary treatment modality for 88% (n = 42) of the cohort, and 26 patients (54%) received adjuvant chemoradiation. Disease recurrence was identified in 28 patients (58%). The median PFS was 68 months, and the median overall survival was 109 months. There was no difference in the median PFS between obese patients and non-obese patients (P = 0.370). In a Cox regression analysis, after adjusting for patient age, margin-free distance, and stage of disease, BMI was not associated with PFS hazard ratio 1.06 (0.99-1.12). CONCLUSION Obesity is not associated with PFS in patients with vulvar cancer, and BMI might not be considered a risk factor for recurrence.
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Affiliation(s)
- Yossi Tzur
- Division of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
| | - Angela Magri
- School of Medicine, McGill University, Montreal, Quebec, Canada
| | - Raanan Meyer
- Division of Minimally Invasive Gynecologic Surgery, Department of Obstetrics and Gynecology, Cedars Sinai Medical Center, California, Los Angeles, USA
| | | | - Shannon Salvador
- Division of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
| | - Susie Lau
- Division of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
| | - Walter Gotlieb
- Division of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
| | - Gabriel Levin
- Division of Gynecologic Oncology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
- The Department of Gynecologic Oncology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem,, Jerusalem, Israel
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Chae YK, Corthell L, Patel SP, Edwards R, Scalici JM, Kim HS, Chung LIY, Othus M, McLeod CM, Chen HX, Sharon E, Streicher H, Ryan CW, Blanke CD, Kurzrock R. A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors SWOG S1609: Vulvar Cancers. Clin Cancer Res 2025; 31:308-315. [PMID: 39561273 PMCID: PMC11804806 DOI: 10.1158/1078-0432.ccr-24-1957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 09/17/2024] [Accepted: 11/14/2024] [Indexed: 11/21/2024]
Abstract
PURPOSE Dual PD-1/CTLA-4 inhibition shows promise in various malignancies. The SWOG S1609 Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART) trial presents initial results of ipilimumab/nivolumab in vulvar cancers. PATIENTS AND METHODS DART is a prospective/open-label/multicenter (1,016 US sites)/multicohort phase II clinical trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks). The primary endpoint was objective response rate [ORR; confirmed complete response and partial response (PR)] per RECISTv1.1, whereas progression-free survival (PFS), overall survival, clinical benefit rate (CBR; ORR plus stable disease ≥6 months), and toxicity were secondary endpoints. RESULTS Sixteen evaluable patients (median age, 55.5 years; 0-6 prior therapies; no prior immunotherapy) were analyzed, all of whom had squamous cell carcinoma histology. The ORR was 18.8% (3/16), CBR was 25% (4/16), and CBR plus unconfirmed PR rate was 31% (5/16); the PFS was 34.1, 16.7. 15.5, 7.2, and 7.0 months for these five patients, respectively. The median PFS and overall survival were 2.2 and 7.6 months, respectively. The most common adverse events were diarrhea, fatigue, pruritus, anorexia, and nausea (25%, n = 4 each). Grade 3 to 4 adverse events occurred in 25% of patients (n = 4). There was one grade 1 to 2 adverse event (6.7%) that led to discontinuation and one (6.7%) grade 5 death adverse event. CONCLUSIONS Ipilimumab plus nivolumab in vulvar cancers resulted in an objective response in 3 of 16 patients, all of whom had durable responses lasting over 1 year. Notably, two additional patients experienced durable stable disease and unconfirmed PR. Correlative studies to determine response and resistance markers are ongoing.
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Affiliation(s)
| | - Lucy Corthell
- SWOG Statistics and Data Management Center, Seattle, WA
| | | | - Robert Edwards
- University of Pittsburgh Medical Center Magee-Womens Hospital, Pittsburgh, PA
| | | | - Hye Sung Kim
- Northwestern University, Chicago, IL
- Temple University Hospital, Philadelphia, PA
| | | | - Megan Othus
- SWOG Statistics and Data Management Center, Seattle, WA
| | | | - Helen X. Chen
- National Cancer Institute, Investigational Drug Branch, Cancer Therapy Evaluation Program, Bethesda, MD
| | - Elad Sharon
- National Cancer Institute, Investigational Drug Branch, Cancer Therapy Evaluation Program, Bethesda, MD
| | - Howard Streicher
- National Cancer Institute, Investigational Drug Branch, Cancer Therapy Evaluation Program, Bethesda, MD
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Burt L, Jarboe E, Gaffney D, Suneja G, DeCesaris C, Bedell S, Brower J. Vulvar Cancer: Histopathologic Considerations and Nuances to Management. Pract Radiat Oncol 2025; 15:86-92. [PMID: 39209108 DOI: 10.1016/j.prro.2024.07.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 07/15/2024] [Accepted: 07/17/2024] [Indexed: 09/04/2024]
Abstract
Vulvar cancer, although rare, poses significant challenges in diagnosis and treatment because of its histopathologic complexities and nuances. This paper reviewed key aspects of the management of vulvar cancer, focusing on histopathologic diagnosis, margin status interpretation, lymph node involvement assessment, and ongoing clinical trials.
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Affiliation(s)
- Lindsay Burt
- University of Utah Health, Huntsman Cancer Institute, Department of Radiation Oncology, Salt Lake City, Utah.
| | - Elke Jarboe
- Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah
| | - David Gaffney
- University of Utah Health, Huntsman Cancer Institute, Department of Radiation Oncology, Salt Lake City, Utah
| | - Gita Suneja
- University of Utah Health, Huntsman Cancer Institute, Department of Radiation Oncology, Salt Lake City, Utah
| | - Cristina DeCesaris
- University of Utah Health, Huntsman Cancer Institute, Department of Radiation Oncology, Salt Lake City, Utah
| | - Sabrina Bedell
- Department of Obstetrics and Gynecology, University of Utah Health, Huntsman Cancer Institute, Salt Lake City, Utah
| | - Jeffrey Brower
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; Radiation Oncology Associates-New England, Manchester, New Hampshire
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Hussaini MA, Abuhijlih R, Mohamad I, Al-Ani A, Abuhijla F. Role of hematological biomarkers in predicting oncological outcomes of definitive chemoradiation in locally advanced vulvar carcinoma. J Biol Methods 2024; 12:e99010044. [PMID: 40200950 PMCID: PMC11973051 DOI: 10.14440/jbm.2025.0104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 11/14/2024] [Accepted: 11/21/2024] [Indexed: 04/10/2025] Open
Abstract
Background The systemic inflammatory response triggered by the carcinogenic process induces significant changes in a wide range of hematological biomarkers, impacting their levels, functions, and overall roles in the body's physiological and pathological processes. Objective To evaluate the value of pre-treatment hematological parameters in the prediction of clinical and radiological responses of locally advanced vulvar cancer to definitive chemoradiation. Methods We retrospectively reviewed the medical records of patients treated at the King Hussein Cancer Center receiving definitive chemoradiation for pathologically confirmed locally advanced vulvar carcinoma. Response of the primary disease to treatment was classified as complete response (CR) if there was no clinically- or radiologically-confirmed residual disease at 12 weeks after completion of chemoradiation. Univariate analyses on complete response, progression-free survival (PFS), and overall survival (OS) were performed using clinical factors and pre-treatment hematological parameters. Results A total of 30 patients were included, with a median age of 57.5 years and a median follow-up of 21 months. Of these, 24 patients (80%) achieved CR. Disease progression occurred in 11 patients (36.7%) during the follow-up period, and 9 (30%) died. Kaplan-Meier analysis demonstrated that only the neutrophil-to-lymphocyte ratio (NLR) (p = 0.007) and basophil-to-lymphocyte ratio (BLR) (p = 0.05) were predictive of OS. Conversely, PFS was significantly associated with white blood cell count (p = 0.042) and BLR (p = 0.004). Receiver operating characteristic (ROC) analysis indicated that NLR and BLR had significant predictive power for survival at the following cutoffs: 3.4 and 0.035, respectively. When categorized by ROC values, BLR was significantly associated with response to treatment (p = 0.026). Moreover, both NLR and BLR were significantly associated with OS and PFS. Conclusion Pre-treatment NLR and BLR may be useful predictive markers for clinical and radiological response, as well as for oncological outcomes in locally advanced vulvar cancer treated with definitive chemoradiation.
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Affiliation(s)
- Maysa Al Hussaini
- Department of Pathology, King Hussein Cancer Center, Amman, 11941, Jordan
| | - Ramiz Abuhijlih
- Department of Radiation Oncology, King Hussein Cancer Center, Amman, 11941, Jordan
| | - Issa Mohamad
- Department of Radiation Oncology, King Hussein Cancer Center, Amman, 11941, Jordan
| | - Abdallah Al-Ani
- Department of Scientific Affairs and Research, King Hussein Cancer Center, Amman, 11941, Jordan
| | - Fawzi Abuhijla
- Department of Radiation Oncology, King Hussein Cancer Center, Amman, 11941, Jordan
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Kumar N, Nutakki S, Patel P, Lakhera KK, Sulaniya C, Kumar A, Babu A, Singhal P, Gora BS, Singh S. Survival Trends Following Surgical Management in Carcinoma Vulva Patients During Covid 19 Pandemic: A Tertiary Care Hospital Study. J Obstet Gynaecol India 2024; 74:513-522. [PMID: 39758564 PMCID: PMC11693637 DOI: 10.1007/s13224-023-01935-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 12/21/2023] [Indexed: 01/07/2025] Open
Abstract
Background Vulval cancers account for 0.25% of new cancer cases and 0.2% of new deaths of all sites worldwide making it an uncommon malignancy according to Global cancer Statistics 2020. Covid 19 for two years made the situation worse. Proper investigations, adjuvant therapy and follow-up for complications was a challenge. The present study is a prospective observational study on treatment outcome of Carcinoma Vulva at a tertiary care hospital during COVID-19 pandemic. Methods Twenty patients of non-metastatic carcinoma vulva were recruited over 22 months of Covid 19 pandemic. Surgery was individualized as wide local excision or radical vulvectomy. Inguinal nodes were addressed as per location of tumour. All cases were followed 2 monthly with virtual/physical meetings till 18 months. Changes in accordance with ongoing COVID 19 pandemic were made in carcinoma vulva diagnostic tests, preoperative work up, intra operatively, post-op complication management and follow-up. Results The mean age of the study participants was 59.85 ± 10.32 years. In the sample population analysed, menopause was experienced on average at the age of 49.47 ± 4.29 years. Thirty five percent (7) of patients had positive lymph nodes during surgery. All 3 patients who died had positive lymph nodes. Also, all three had no taken adjuvant treatment advised to them by the tumour board. Phased resumption of complex surgeries and adaptation to better PPEs helps in the staff acclimatization to the new normal of operating under constant threat of COVID. In our study, 85% patients were disease free at 18 months follow-up. This is similar to outcomes of carcinoma vulva cases in non-Covid times. There was no difference amongst re-exploration, morbidity and mortality rates for cancer surgeries in COVID and non-COVID years highlighting the fact that effective implementation of cancer surgery and peri operative care guidelines is crucial for good surgical outcomes. Conclusion This study sheds light on good prognosis of carcinoma vulva with proper treatment and follow-up. Covid times were managed with virtual meets and talking with local practitioners. Screening programs, rural awareness camps and more studies are needed in this field. Supplementary Information The online version contains supplementary material available at 10.1007/s13224-023-01935-9.
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Affiliation(s)
- Naina Kumar
- Department of Surgical Oncology, SMS Medical College and Attached Group of Hospitals, B 31 Prabhu Marg Tilak Nagar, Jaipur, 302004 India
| | - Srikanth Nutakki
- Department of Surgical Oncology, SMS Medical College and Attached Group of Hospitals, B 31 Prabhu Marg Tilak Nagar, Jaipur, 302004 India
- Department of GynaecOncology, SMS Medical College and Attached Group of Hospitals, Jaipur, India
- Department of Internal Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Pinakin Patel
- Department of Surgical Oncology, SMS Medical College and Attached Group of Hospitals, B 31 Prabhu Marg Tilak Nagar, Jaipur, 302004 India
| | - Kamal Kishore Lakhera
- Department of Surgical Oncology, SMS Medical College and Attached Group of Hospitals, B 31 Prabhu Marg Tilak Nagar, Jaipur, 302004 India
| | - Chandrakanta Sulaniya
- Department of GynaecOncology, SMS Medical College and Attached Group of Hospitals, Jaipur, India
| | - Arjun Kumar
- Department of Internal Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Agil Babu
- Department of Surgical Oncology, SMS Medical College and Attached Group of Hospitals, B 31 Prabhu Marg Tilak Nagar, Jaipur, 302004 India
| | - Pranav Singhal
- Department of Surgical Oncology, SMS Medical College and Attached Group of Hospitals, B 31 Prabhu Marg Tilak Nagar, Jaipur, 302004 India
| | - Bhoopendra Singh Gora
- Department of Surgical Oncology, SMS Medical College and Attached Group of Hospitals, B 31 Prabhu Marg Tilak Nagar, Jaipur, 302004 India
| | - Suresh Singh
- Department of Surgical Oncology, SMS Medical College and Attached Group of Hospitals, B 31 Prabhu Marg Tilak Nagar, Jaipur, 302004 India
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Proppe L, Jaeger A, Goy Y, Petersen C, Kruell A, Prieske K, Schmalfeldt B, Mueller V, Woelber L. Systematic review - Adjuvant radiotherapy of the vulva in primary vulvar cancer. Gynecol Oncol 2024; 190:264-271. [PMID: 39265464 DOI: 10.1016/j.ygyno.2024.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 08/30/2024] [Accepted: 09/02/2024] [Indexed: 09/14/2024]
Abstract
OBJECTIVE Adjuvant radiotherapy to the vulva in vulvar squamous cell carcinoma (VSCC) is frequently performed albeit strong evidence is lacking. This systematic review aims to summarize the current literature on this topic. METHODS 19 retrospective studies were included and analyzed, focusing on the primary outcome of local recurrence. RESULTS The publications present conflicting results. While the benefit of adjuvant radiotherapy to the groins in case of node-positive VSCC is well established, the indication criteria and effectiveness of adjuvant radiotherapy to the vulva remain unclear. Based on the studies included in this review, the current evidence suggests that adjuvant radiotherapy to the vulva might not significantly reduce the risk of recurrence or only in certain subgroups. CONCLUSION Most of the studies do not consider individual risk factors such as HPV status, resection margin, lymph node stage, grading and others. As a result, the comparability and reliability of these findings are limited. This review aims to highlight the need of further research addressing the risk stratification, considering both oncologic risk factors and adverse events.
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Affiliation(s)
- L Proppe
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Germany
| | - A Jaeger
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Germany
| | - Y Goy
- Department of Radiooncology, University Medical Center Hamburg-Eppendorf, Germany
| | - C Petersen
- Department of Radiooncology, University Medical Center Hamburg-Eppendorf, Germany
| | - A Kruell
- Department of Radiooncology, University Medical Center Hamburg-Eppendorf, Germany
| | - K Prieske
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Germany; Dysplasia Center at the Krankenhaus Jerusalem, Hamburg, Germany
| | - B Schmalfeldt
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Germany
| | - V Mueller
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Germany
| | - L Woelber
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Germany; Dysplasia Center at the Krankenhaus Jerusalem, Hamburg, Germany.
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Li W, Zhai L, Zhu Y, Lou F, Liu S, Li K, Chen L, Wang H. Review effects of radiation treatment on HPV-related vulvar cancer: a meta-analysis and systematic review. Front Oncol 2024; 14:1400047. [PMID: 39324004 PMCID: PMC11422069 DOI: 10.3389/fonc.2024.1400047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 05/17/2024] [Indexed: 09/27/2024] Open
Abstract
Objective Vulvar carcinoma exhibits a robust correlation alongside HPV infection; however, the impact of HPV rank on the prognostic outcomes of radiation therapy within vulvar malignancies stays ambiguous. In the present study, we performed a comprehensive examination as well as meta-analysis to assess the influence of infection with HPV upon the long-term outlook as well as sensitivity of individuals with vulvar cancer undergoing radiation therapy. Methods A meticulous examination of the existing research was conducted in accordance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A thorough search was conducted in the PubMed, Embase, Web of Science, as well as Cochrane Library databases, covering the entire available literature till April 1, 2023. The studies that met the inclusion criteria contained data about HPV infection and oncological outcomes in patients with vulvar cancer who received radiation therapy. This study was registered in PROSPERO (CRD42023417957). Results We identified 12 retrospective studies meeting our inclusion criteria, which included a total of 3967 patients. Patients with HPV-associated vulvar cancer achieved a better overall survival rate after radiotherapy (HR=0.71, 95%CI: 0.54-0.93, P=0.01), and showed a significant improvement in disease-free survival (HR=0.75, 95%CI: 0.58-0.97, P=0.09) and progression-free survival (HR=0.31, 95%CI: 0.22-0.45, P,<0.01). Meanwhile, the complete remission rate after radiotherapy was higher for HPV-associated vulvar cancer patients (M-H=4.02, 95% CI: 1.87-8.61, P=0.0003), and the local control rate was better (HR=1.90, 95% CI: 1.15-3.15, P=0.01), exhibiting a reduced incidence of relapse within the field of study (HR=0.21, 95% CI: 0.10-0.42, P<0.001). Conclusion In comparison to HPV-independent vulvar squamous cell carcinoma, patients with HPV-associated vulvar cancer exhibit higher sensitivity to radiotherapy, with a significant difference in prognosis. Further research should investigate the mechanisms underlying this high sensitivity to radiotherapy caused by HPV, and should be evaluated using high-quality randomized controlled trials.
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Affiliation(s)
- Wei Li
- Department of Radiation Oncology, The Third People's Hospital of Dalian, Dalian Municipal Cancer Hospital, Affiliated Dalian Third People's Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Lijun Zhai
- Department of Radiation Oncology, The Third People's Hospital of Dalian, Dalian Municipal Cancer Hospital, Affiliated Dalian Third People's Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Yinju Zhu
- Department of Radiation Oncology, The Third People's Hospital of Dalian, Dalian Municipal Cancer Hospital, Affiliated Dalian Third People's Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Fengjun Lou
- Department of Radiation Oncology, The Third People's Hospital of Dalian, Dalian Municipal Cancer Hospital, Affiliated Dalian Third People's Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Shiyu Liu
- Department of Radiation Oncology, The Third People's Hospital of Dalian, Dalian Municipal Cancer Hospital, Affiliated Dalian Third People's Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Ke Li
- Department of Radiation Oncology, The Third People's Hospital of Dalian, Dalian Municipal Cancer Hospital, Affiliated Dalian Third People's Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Liang Chen
- Department of Radiation Oncology, The Third People's Hospital of Dalian, Dalian Municipal Cancer Hospital, Affiliated Dalian Third People's Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Huankun Wang
- Department of Radiation Oncology, The Third People's Hospital of Dalian, Dalian Municipal Cancer Hospital, Affiliated Dalian Third People's Hospital of Dalian Medical University, Dalian, Liaoning, China
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Wölber L, Soergel P, Hampl M. Lymphknotenstaging beim Vulva- und Vaginalkarzinom. DIE ONKOLOGIE 2024; 30:671-682. [DOI: 10.1007/s00761-024-01548-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 05/23/2024] [Indexed: 01/03/2025]
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Brassetti A, Chiacchio G, Anceschi U, Bove A, Ferriero M, D'Annunzio S, Misuraca L, Guaglianone S, Tuderti G, Mastroianni R, Tedesco F, Cacciatore L, Proietti F, Flammia SR, De Nunzio C, Cozzi G, Leonardo C, Galosi AB, Simone G. Robot-assisted inguinal lymphadenectomy to treat penile and vulvar cancers: a scoping review. Minerva Urol Nephrol 2024; 76:278-285. [PMID: 38920009 DOI: 10.23736/s2724-6051.24.05532-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/27/2024]
Abstract
INTRODUCTION Inguinal lymph nodes dissection (ILND) is recommended in patients presenting with high-risk penile (PC) or vulvar cancers (VC). Though, this surgical procedure is underused because of its anticipated morbidity. Minimally invasive approaches were proposed to minimize complications associated with open surgery. In this review, we analyze current available data exploring intra and perioperative outcomes of robot-assisted ILND (RAIL). EVIDENCE ACQUISITION On April 9th, 2023, a literature search was conducted using the PubMed and Scopus databases. The search employed the combination of the following terms: ("robotic assisted" OR "robot-assisted" OR "robotic") AND ("inguinal lymph node dissection" OR "lymphadenectomy") AND ("penile cancer" OR "vulvar cancer"). Out of the 404 identified articles, 18 were used for the present scoping review and their results were reported according to the PRISMA statement. EVIDENCE SYNTHESIS Data on 171 patients, ranging in age from 32 to 85 years, were obtained. Most of them (90.6%) harbored a penile squamous cell carcinoma and presented with no palpable nodes (85%). Operation time (OT) ranged between 45 and 300 min. Estimated blood loss varied from 10 to 300 mL. One single intra-operative complication was reported and one conversion to open was recorded. The lymph nodes (LNs) count spanned from 3 to 26 per groin, with 17 studies reporting a median yield >7 nodes. Hospital stay was 1-7 days, while the duration of drainage ranged from 4 to 72 days. Post-operative complications included lymphocele (22.2%; 0-100%), lymphedema (13.4%; 0-40%), cellulitis (11.1%; 0-25%), skin necrosis (8.7%; 0-15.4%). seroma (3.5%; 0-20%) and wound breakdown/wound infection (2.9%; 0-10%). Out of the included studies, 7 provided at least a 12-month follow-up, with recurrence-free rates ranging from 50% to 100% in patients affected by penile cancer and from 92% to 100% in vulvar cancer patients. CONCLUSIONS The available evidence on RAIL for the treatment of PC and VC is limited. The approach appears to be safe and effective, as it provides an adequate lymph node yield while ensuring a minimally morbid postoperative course and a short hospital stay.
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Affiliation(s)
- Aldo Brassetti
- Department of Urology, IRCCS - "Regina Elena" National Cancer Institute, Rome, Italy
| | - Giuseppe Chiacchio
- Urology Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Università Politecnica delle Marche, Ancona, Italy -
| | - Umberto Anceschi
- Department of Urology, IRCCS - "Regina Elena" National Cancer Institute, Rome, Italy
| | - Alfredo Bove
- Department of Urology, IRCCS - "Regina Elena" National Cancer Institute, Rome, Italy
| | | | - Simone D'Annunzio
- Department of Urology, IRCCS - "Regina Elena" National Cancer Institute, Rome, Italy
| | - Leonardo Misuraca
- Department of Urology, IRCCS - "Regina Elena" National Cancer Institute, Rome, Italy
| | - Salvatore Guaglianone
- Department of Urology, IRCCS - "Regina Elena" National Cancer Institute, Rome, Italy
| | - Gabriele Tuderti
- Department of Urology, IRCCS - "Regina Elena" National Cancer Institute, Rome, Italy
| | - Riccardo Mastroianni
- Department of Urology, IRCCS - "Regina Elena" National Cancer Institute, Rome, Italy
| | - Francesco Tedesco
- Department of Urology, Fondazione Policlinico Universitario Campus Bio-Medico di Roma, Rome, Italy
| | - Loris Cacciatore
- Department of Urology, Fondazione Policlinico Universitario Campus Bio-Medico di Roma, Rome, Italy
| | - Flavia Proietti
- Department of Urology, IRCCS - "Regina Elena" National Cancer Institute, Rome, Italy
| | - Simone R Flammia
- Department of Urology, IRCCS - "Regina Elena" National Cancer Institute, Rome, Italy
| | | | - Gabriele Cozzi
- Division of Urology, European Institute of Oncology, IRCCS, Milan, Italy
| | - Costantino Leonardo
- Department of Urology, IRCCS - "Regina Elena" National Cancer Institute, Rome, Italy
| | - Andrea B Galosi
- Urology Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Università Politecnica delle Marche, Ancona, Italy
| | - Giuseppe Simone
- Department of Urology, IRCCS - "Regina Elena" National Cancer Institute, Rome, Italy
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Ferrari F, Ismail L, Sabbagh A, Hardern K, Owens R, Gozzini E, Soleymani Majd H. Adjuvant Radiotherapy for Groin Node Metastases Following Surgery for Vulvar Cancer: A Systematic Review. Oncol Rev 2024; 18:1389035. [PMID: 38774492 PMCID: PMC11107452 DOI: 10.3389/or.2024.1389035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 04/04/2024] [Indexed: 05/24/2024] Open
Abstract
Background: Lymph node metastasis in vulvar cancer is a critical prognostic factor associated with higher recurrence and decreased survival. A survival benefit is reported with adjuvant radiotherapy but with potential significant morbidity. We aim to clarify whether there is high-quality evidence to support the use of adjuvant radiotherapy in this setting. Objectives: The aim of the study was to assess the effectiveness and safety of adjuvant radiotherapy to locoregional metastatic nodal areas. Search Methods: We conducted a comprehensive and systematic literature search of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Google Scholar, ClinicalTrials.gov, and the National Cancer Institute. We considered only randomized controlled trials (RCTs). Main Results: We identified 1,760 records and finally retrieved only one eligible RCT (114 participants with positive inguinofemoral lymph nodes). All women had undergone radical vulvectomy and bilateral inguinal lymphadenectomy and had been randomized to adjuvant radiotherapy or to intraoperative ipsilateral pelvic lymphadenectomy without adjuvant radiotherapy. At 6 years, the overall survival (OS) was 51% versus 41% in favor of radiotherapy (HR 0.61; 95% CI 0.30-1.3) without significance and with very low certainty of evidence. At 6 year, the cumulative incidence of cancer-related deaths was 29% versus 51% in favor of adjuvant radiotherapy (HR 0.49; 95% CI 0.28-0.87). Recurrence-free survival at 6 years was 59% after adjuvant radiotherapy versus 48% after pelvic lymphadenectomy (HR 0.39; 95% CI 0.17-0.88). Three (5.3%) versus 13 (24.1%) groin recurrences were noted, respectively, in the adjuvant radiotherapy and pelvic lymphadenectomy groups. There was no significant difference in acute toxicities for pelvic lymphadenectomy compared to radiotherapy. In women with positive pelvic lymph nodes (20%), the OS at 6 year was 36% compared with 13% in favor of adjuvant radiotherapy. Late cutaneous toxicity rate appeared to be greater after radiotherapy (19% vs. 15%) but with less chronic lymphedema (16% vs. 22%). Conclusion: There is only very low-quality evidence on administering adjuvant radiotherapy for inguinal lymph node metastases. Although the identified study was a multicenter RCT, there was a reasonable imprecision and inconsistency because of small study numbers, wide confidence intervals in the data, and early trial closure, resulting in downgrading of the evidence.
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Affiliation(s)
- Federico Ferrari
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Lamiese Ismail
- Department of Obstetrics and Gynaecology, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
| | - Ahmad Sabbagh
- Department of Clinical Oncology, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
| | - Kieran Hardern
- Department of Anaesthetics, University Hospital Bristol and Western Hospital, Bristol, United Kingdom
| | - Robert Owens
- Department of Clinical Oncology, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
| | - Elisa Gozzini
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Hooman Soleymani Majd
- Department of Gynaecology Oncology, Oxford University Hospitals NHS Trust, Oxford, United Kingdom
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13
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Harari CM, Brower JV, Gaffney DK, Bradley KA. Navigating the Complexities of Lymph Node Management in Vulvar Cancer: Insights and Perspectives. Pract Radiat Oncol 2024; 14:e220-e225. [PMID: 38336276 DOI: 10.1016/j.prro.2024.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 01/30/2024] [Accepted: 01/30/2024] [Indexed: 02/12/2024]
Affiliation(s)
- Colin M Harari
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
| | - Jeffery V Brower
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin; Radiation Oncology Associates, Manchester, New Hampshire
| | - Dave K Gaffney
- Department of Radiation Oncology, Huntsman Cancer Hospital, University of Utah, Salt Lake City, Utah
| | - Kristin A Bradley
- Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
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14
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Chen J, Ln H. A review of prognostic factors in squamous cell carcinoma of the vulva: Evidence from the last decade. Semin Diagn Pathol 2024; 41:140-153. [PMID: 32988675 DOI: 10.1053/j.semdp.2020.09.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 09/17/2020] [Indexed: 12/24/2022]
Abstract
Squamous cell carcinoma of the vulva is a rare gynecologic cancer that is associated with significant patient morbidity and mortality, particularly for recurrent disease. This review summarizes the evidence and continued challenges, regarding the traditional clinicopathologic factors used to prognosticate vulvar squamous cell carcinoma. Articles published within the last 10 years (2010-2020) were identified. Relevant articles concerning the following fifteen prognostic factors were reviewed: HPV/p16 status, vulvar intraepithelial neoplasia, patient age, tumor stage, tumor grade, tumor size, depth of invasion, stromal changes, histologic patterns of invasion, lymphovascular space invasion (LVSI), perineural invasion, lymph node metastases, tumour focality, margin status and lichen sclerosus (LS). The relationship between each prognostic factor and progression-free survival (PFS) and overall survival (OS), including hazard ratios, 95% confidence intervals and p-values, were extracted.
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Affiliation(s)
- Julia Chen
- Medical Undergraduate Program, Faculty of Medicine, University of British Columbia, BC, Canada
| | - Hoang Ln
- Department of Pathology, Vancouver General Hospital and University of British Columbia, BC, Canada; Genetic Pathology Evaluation Center (GPEC), BC, Canada.
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15
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Chargari C, Wasserman J, Gabro A, Canlobre G, Spano JP, Uzan C, Maingon P. Vulvar Carcinoma: Standard of Care and Perspectives. J Clin Oncol 2024; 42:961-972. [PMID: 38315939 DOI: 10.1200/jco.23.01187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2023] [Revised: 09/24/2023] [Accepted: 11/14/2023] [Indexed: 02/07/2024] Open
Abstract
PURPOSE Treatment of vulvar carcinoma (VC) is challenging. The objectives of this review were to describe for clinicians the epidemiologic and clinical aspects of VC, the standard of care in terms of primary local treatment and systemic therapies, and the recent innovations and perspectives emerging from translational research in immuno-oncology. DESIGN We conducted a comprehensive review outlying the clinical aspects and biologic background of vulvar cancer, highlighting modern treatment strategies on the basis of a personalized approach. RESULTS Epidemiologic data showed a recent rise in incidence of VC, attributed to human papillomavirus. Surgery is the mainstay of primary treatment, but multimodal approaches are frequently required in the presence of adverse prognosis histopathologic factors. Chemoradiation is indicated when organ-sparing surgery is not feasible. However, inability to achieve high locoregional control rates in advanced cases and the morbidity associated with local treatments are still key issues. Recent clinical data showed the benefit of individualized strategies combining organ-sparing surgical strategies, less invasive lymph node staging procedures, and refinement in radiotherapy modalities. Among the most important research area, there is a sound rationale for testing modern systemic approaches such as immune checkpoint inhibitors in selected patients with recurrent and/or metastatic tumors. Although no specific data exist for VC, the role of supportive care and post-treatment rehabilitation strategies is also crucial. CONCLUSION There are still insufficient studies dedicated to patients with VC. Public health programs for prevention, screening, and early diagnosis are required, and clinical research should be strengthened to provide high-quality clinical evidence and improve patients' oncologic and functional outcomes.
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Affiliation(s)
- Cyrus Chargari
- Service d'oncologie radiothérapie, Hôpital Universitaire Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP) Sorbonne Université, Paris, France
- Institut Universitaire de Cancérologie (IUC), Sorbonne Université, Paris, France
| | - Johanna Wasserman
- Institut Universitaire de Cancérologie (IUC), Sorbonne Université, Paris, France
- Service d'oncologie médicale, Hôpital Universitaire Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP) Sorbonne Université, Paris, France
| | - Alexandra Gabro
- Service d'oncologie radiothérapie, Hôpital Universitaire Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP) Sorbonne Université, Paris, France
- Institut Universitaire de Cancérologie (IUC), Sorbonne Université, Paris, France
| | - Geoffroy Canlobre
- Institut Universitaire de Cancérologie (IUC), Sorbonne Université, Paris, France
- Service de chirurgie et cancérologie gynécologique et mammaire, Assistance Publique-Hôpitaux de Paris (AP-HP) Sorbonne Université, Paris, France
- INSERM UMR S938, Biologie et Thérapeutique des cancers, Paris, France
| | - Jean-Philippe Spano
- Institut Universitaire de Cancérologie (IUC), Sorbonne Université, Paris, France
- Service d'oncologie médicale, Hôpital Universitaire Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP) Sorbonne Université, Paris, France
| | - Catherine Uzan
- Institut Universitaire de Cancérologie (IUC), Sorbonne Université, Paris, France
- Service de chirurgie et cancérologie gynécologique et mammaire, Assistance Publique-Hôpitaux de Paris (AP-HP) Sorbonne Université, Paris, France
- INSERM UMR S938, Biologie et Thérapeutique des cancers, Paris, France
| | - Philippe Maingon
- Service d'oncologie radiothérapie, Hôpital Universitaire Pitié Salpêtrière, Assistance Publique-Hôpitaux de Paris (AP-HP) Sorbonne Université, Paris, France
- Institut Universitaire de Cancérologie (IUC), Sorbonne Université, Paris, France
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16
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Gies S, Melchior P, Stroeder R, Tänzer T, Theobald L, Pohlers M, Glombitza B, Sester M, Solomayer EF, Walch-Rückheim B. Immune landscape of vulvar cancer patients treated with surgery and adjuvant radiotherapy revealed restricted T cell functionality and increased IL-17 expression associated with cancer relapse. Int J Cancer 2024; 154:343-358. [PMID: 37786948 DOI: 10.1002/ijc.34745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 08/31/2023] [Accepted: 09/01/2023] [Indexed: 10/04/2023]
Abstract
For vulvar cancers, radiotherapy is targeting cancer cells, but also affects the host immune system. As this may affect treatment outcome, in this prospective study, we characterized the individual T cell immune milieu induced by surgery and adjuvant radio +/- chemotherapy (aRT) systemically in the blood of vulvar cancer patients and found increased frequencies of Interleukin (IL)-17-producing CD4+ and CD8+ T cells after aRT while frequencies of Th1 and perforin-producing CD8+ killer cells were strongly diminished. Phenotypic characterization revealed enhanced expression of the ectonucleotidase CD39 on Th17 and Tc17 cells as well as CD8+ perforin+ cells after aRT. Furthermore, the aRT cohort exhibited increased proportions of Programmed Cell Death Protein (PD-1) expressing cells among Th1 and CD8+ perforin+ cells, but not among Th17 and Tc17 cells. High post-therapeutic levels of Th17 and Tc17 cells and low proportions of Th1 and CD8+ perforin+ cells expressing PD-1 was associated with reduced recurrence free survival on follow-up. In conclusion, our study defines individual therapy-induced changes in the cellular immune milieu of patients and their association with cancer relapse. Our results may help to explain differences in the individual courses of disease of vulvar cancer patients and suggest PD-1 and IL-17 as targets for immunotherapy in vulvar cancer.
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Affiliation(s)
- Selina Gies
- Center of Human and Molecular Biology (ZHMB), Institute of Virology, Saarland University, Homburg, Saar, Germany
| | - Patrick Melchior
- Department of Radiation Oncology, Saarland University Medical Center, Homburg, Saar, Germany
| | - Russalina Stroeder
- Department of Obstetrics and Gynecology, Saarland University Medical Center, Homburg, Saar, Germany
| | - Tanja Tänzer
- Center of Human and Molecular Biology (ZHMB), Institute of Virology, Saarland University, Homburg, Saar, Germany
| | - Laura Theobald
- Center of Human and Molecular Biology (ZHMB), Institute of Virology, Saarland University, Homburg, Saar, Germany
| | - Maike Pohlers
- Center of Human and Molecular Biology (ZHMB), Institute of Virology, Saarland University, Homburg, Saar, Germany
| | - Birgit Glombitza
- Center of Human and Molecular Biology (ZHMB), Institute of Virology, Saarland University, Homburg, Saar, Germany
| | - Martina Sester
- Department of Transplant and Infection Immunology, Saarland University, Homburg, Saar, Germany
| | - Erich-Franz Solomayer
- Department of Obstetrics and Gynecology, Saarland University Medical Center, Homburg, Saar, Germany
| | - Barbara Walch-Rückheim
- Center of Human and Molecular Biology (ZHMB), Institute of Virology, Saarland University, Homburg, Saar, Germany
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Morrison J, Baldwin P, Hanna L, Andreou A, Buckley L, Durrant L, Edey K, Faruqi A, Fotopoulou C, Ganesan R, Hillaby K, Taylor A. British Gynaecological Cancer Society (BGCS) vulval cancer guidelines: An update on recommendations for practice 2023. Eur J Obstet Gynecol Reprod Biol 2024; 292:210-238. [PMID: 38043220 DOI: 10.1016/j.ejogrb.2023.11.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 11/10/2023] [Indexed: 12/05/2023]
Affiliation(s)
- Jo Morrison
- Department of Gynaecological Oncology, GRACE Centre, Musgrove Park Hospital, Somerset NHS Foundation Trust, Taunton TA1 5DA, UK.
| | - Peter Baldwin
- Addenbrooke's Hospital, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
| | - Louise Hanna
- Department of Oncology, Velindre Cancer Centre, Whitchurch, Cardiff CF14 2TL, UK
| | - Adrian Andreou
- Department of Radiology, Royal United Hospitals Bath NHS Foundation Trust, Combe Park, Bath BA1 3NG, UK
| | - Lynn Buckley
- Department of Gynae-Oncology, Castle Hill Hospital, Hull University Teaching Hospitals NHS Trust, East Yorkshire HU16 5JQ, UK; Perci Health Ltd, 1 Vincent Square, London SW1P 2PN, UK. https://www.percihealth.com/
| | - Lisa Durrant
- Radiotherapy Department, Beacon Centre, Musgrove Park Hospital, Somerset NHS Foundation Trust, Taunton TA1 5DA, UK
| | - Katharine Edey
- Centre for Women's Health Royal Devon and Exeter NHS Foundation Trust, Barrack Road, Exeter EX2 5DW, UK
| | - Asma Faruqi
- Department of Cellular Pathology, The Royal London Hospital, Barts Health NHS Trust, London E1 2ES, UK
| | - Christina Fotopoulou
- Department of Cellular Pathology, The Royal London Hospital, Barts Health NHS Trust, London E1 2ES, UK; Gynaecologic Oncology, Imperial College London Faculty of Medicine, London SW7 2DD, UK
| | - Raji Ganesan
- Department of Cellular Pathology, Birmingham Women's Hospital, Birmingham B15 2TG, UK
| | - Kathryn Hillaby
- Department Gynaecological Oncology, Cheltenham General Hospital, Gloucestershire, Hospitals NHS Foundation Trust, GL53 7AN, UK
| | - Alexandra Taylor
- The Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ, UK
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18
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Nishio S. Current status of vulvar cancer in Japan: analysis of the Japanese Gynecologic Oncology Group nationwide survey study. Jpn J Clin Oncol 2023; 53:1003-1008. [PMID: 37551024 DOI: 10.1093/jjco/hyad089] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Accepted: 07/12/2023] [Indexed: 08/09/2023] Open
Abstract
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.
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Affiliation(s)
- Shin Nishio
- Department of Obstetrics and Gynecology, Kurume University School of Medicine, Fukuoka, Japan
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19
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Katsanevakis E, Joshi A, Ong ZZ, O'Connor R, Nunns D, Gajjar K. A study of recurrence, complication and survival rates in patients with early stage vulval cancer undergoing sentinel lymph node sampling: a single-centre experience. Arch Gynecol Obstet 2023; 308:561-567. [PMID: 36854984 DOI: 10.1007/s00404-023-06968-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 02/05/2023] [Indexed: 03/02/2023]
Abstract
PURPOSE Groin sentinel lymph node (SLN) identification and removal has become a standard of care for women with clinical early stage vulval cancer. There is evidence to support safe detection of the SLN with minimal morbidity. The purpose of this study is to report our experience of managing patients focusing on patient selection, adverse events, quality assurance of the procedure and any benefits and/or disadvantages to patients. METHODS This was a retrospective study of patients with clinical early stage vulval cancer in a cancer centre over 5 years. Notes and hospital data were reviewed including admissions to emergency departments. Statistical software was used for the statistical analysis and the Kaplan Meier survival curve was generated to present survival rates. RESULTS 61 cases were analysed. A total of 156 nodes have been removed and positive nodes were identified in 14 cases. In total, 9 women (14.75%) had disease recurrence within 5 years from primary surgery. Overall, 4 patients (6.5%) developed groin recurrence. In 3 of these patients there was isolated groin recurrence (4.9%). The median length of admission was 3 days and 6 cases were managed as day cases. CONCLUSIONS Since the closure of the GROINNS-2 trial we have continued the procedure of SLN identification for women with clinical early stage vulval cancer. We have shown high level of adherence to our protocol and survival and complication rates comparable to other studies on the same field. There were a few patients managed as day-case which was of benefit to the patients.
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Affiliation(s)
- Emmanouil Katsanevakis
- Department of Gynaecological Oncology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
| | - Anuja Joshi
- Department of Obstetrics and Gynaecology, University Hospitals of Derby and Burton NHS Trust, Derby, UK
| | - Zun Zhen Ong
- Department of Gynaecological Oncology, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Richard O'Connor
- Department of Clinical Radiology, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - David Nunns
- Department of Gynaecological Oncology, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Ketankumar Gajjar
- Department of Gynaecological Oncology, Nottingham University Hospitals NHS Trust, Nottingham, UK
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20
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Zhang T, Zhu Y, Luo J, Li J, Niu S, Chen H, Zhou F. An integrated model for prognosis in vulvar squamous cell carcinoma. BMC Cancer 2023; 23:534. [PMID: 37308869 DOI: 10.1186/s12885-023-11039-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 06/05/2023] [Indexed: 06/14/2023] Open
Abstract
BACKGROUND Vulvar squamous cell carcinoma (VSCC) is a relatively rare gynecologic cancer. Unlike cervical squamous cell carcinoma (CSCC), in which nearly all cases are caused by HPV infection, most VSCCs are HPV-independent. Patients with VSCC also have worse overall survival (OS) than those with CSCC. Unlike CSCC, the risk factors of VSCC have not been extensively studied. Here, we investigated the prognostic values of clinicopathological parameters as well as biomarkers in patients with VSCC. METHODS In total, 69 cases of VSCC accessions were selected for analysis between April 2010 and October 2020. The risk factors of VSCC were screened using Cox models to establish nomograms for predicting survival outcomes. RESULTS Following the multivariate COX model for OS, independent predictors including advanced age (hazard ratio [HR] 5.899, p = 0.009), HPV positivity (HR 0.092, p = 0.016), high Ki-67 index (HR 7.899, p = 0.006), PD-L1-positivity (HR 4.736, p = 0.077), and CD8 + tumor-infiltrating lymphocytes (TILs) (HR 0.214, p = 0.024) were included in the nomogram for OS; multivariate COX model for progression-free survival (PFS) was used to screen prognostic factors including advanced age (HR 2.902, p = 0.058), lymph node metastasis (HR 5.038, p = 0.056), HPV positivity (HR 0.116, p = 0.011), high Ki-67 index (HR 3.680, p = 0.042), PD-L1-positivity (HR 5.311, p = 0.045), and CD8 + TILs (HR 0.236, p = 0.014) to establish the PFS nomogram model. Based on the C-index (0.754 for OS and 0.754 for PFS) from our VSCC cohort and the corrected C-index (0.699 for OS and 0.683 for PFS) from an internal validation cohort, the nomograms demonstrated good predictive and discriminative ability. Kaplan-Meier curves also supported the excellent performance of the nomograms. CONCLUSION Our prognostic nomograms suggested that (1) shorter OS and PFS were associated with PD-L1-positivity, high Ki-67 index, and low CD8 + TILs; (2) HPV-independent tumors were associated with poorer survival outcome, and mutant p53 status showed no prognostic significance.
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Affiliation(s)
- Tao Zhang
- Department of Gynecology, Zhejiang University School of Medicine Women's Hospital, Hangzhou, 310006, China
| | - Yingfan Zhu
- Department of Gynecology, Zhejiang University School of Medicine Women's Hospital, Hangzhou, 310006, China
| | - Jie Luo
- Department of Gynecology, Zhejiang University School of Medicine Women's Hospital, Hangzhou, 310006, China
| | - Juanqing Li
- Department of Gynecology, Zhejiang University School of Medicine Women's Hospital, Hangzhou, 310006, China
| | - Shuang Niu
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Hao Chen
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
| | - Feng Zhou
- Department of Pathology, Zhejiang University School of Medicine Women's Hospital, Hangzhou, 310006, China.
- Department of Pathology, International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
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Rustetska N, Szczepaniak M, Goryca K, Bakuła-Zalewska E, Figat M, Kowalik A, Góźdź S, Kowalewska M. The intratumour microbiota and neutrophilic inflammation in squamous cell vulvar carcinoma microenvironment. J Transl Med 2023; 21:285. [PMID: 37118737 PMCID: PMC10141905 DOI: 10.1186/s12967-023-04113-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 04/09/2023] [Indexed: 04/30/2023] Open
Abstract
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.
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Affiliation(s)
- Natalia Rustetska
- Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781, Warsaw, Poland
| | - Magdalena Szczepaniak
- Department of Molecular Diagnostics, Holycross Cancer Centre, 25-734, Kielce, Poland
| | - Krzysztof Goryca
- Genomics Core Facility, Centre of New Technologies, University of Warsaw, 02-097, Warsaw, Poland
| | - Elwira Bakuła-Zalewska
- Department of Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781, Warsaw, Poland
| | - Małgorzata Figat
- Department of Gynecologic Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-097, Warsaw, Poland
| | - Artur Kowalik
- Department of Molecular Diagnostics, Holycross Cancer Centre, 25-734, Kielce, Poland
- Division of Medical Biology, Institute of Biology, Jan Kochanowski University, 25-406, Kielce, Poland
| | - Stanisław Góźdź
- Department of Clinical Oncology, Holycross Cancer Centre, 25-734, Kielce, Poland
- Collegium Medicum, Jan Kochanowski University, 25-317, Kielce, Poland
| | - Magdalena Kowalewska
- Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781, Warsaw, Poland.
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Cordoba Largo S, Rodriguez Rodriguez I, Rodriguez Villalba S, Najjari Jamal D, Anchuelo Latorre J, Celada Alvarez F, Garcia Cabezas S, de la Fuente Alonso C, Couselo Paniagua L, Martinez Montesinos I, Villafranca Iturre E, Belinchon Olmeda B, Farga Albiol D, Navarrete Solano PA, Sanchez Belda M. Radiation therapy for vulvar cancer: consensus technical guidelines of the GINECOR working group of the Spanish Society of Radiation Oncology. Part 2: radiotherapy recommendations. Clin Transl Oncol 2023:10.1007/s12094-023-03101-z. [PMID: 36961728 DOI: 10.1007/s12094-023-03101-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 01/22/2023] [Indexed: 03/25/2023]
Abstract
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.
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Affiliation(s)
- Sofia Cordoba Largo
- Department of Radiation Oncology, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain.
| | | | | | - Dina Najjari Jamal
- Department of Radiation Oncology, Catalan Institut of Oncology, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain
| | - Javier Anchuelo Latorre
- Department of Radiation Oncology, Marqués de Valdecilla University Hospital, Santander, Spain
| | | | - Sonia Garcia Cabezas
- Department of Radiation Oncology, Reina Sofía, University Hospital, Córdoba, Spain
| | | | - Luz Couselo Paniagua
- Department of Radiation Oncology, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
| | | | | | | | - Dolores Farga Albiol
- Department of Radiation Oncology, Consorcio Hospital General de Valencia, Valencia, Spain
| | | | - Maria Sanchez Belda
- Department of Radiation Oncology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
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23
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Cordoba Largo S, Rodriguez Rodriguez I, Rodriguez Villalba S, Najjari Jamal D, Anchuelo Latorre J, Celada Álvarez F, Garcia Cabezas S, de la Fuente Alonso C, Couselo Paniagua L, Martínez Montesinos I, Villafranca Iturre E, Belinchón Olmeda B, Farga Albiol D, Navarrete Solano PA, Sánchez Belda M. Radiation therapy for vulvar cancer: consensus guidelines of the GINECOR working group of the Spanish Society of Radiation Oncology. Part 1: clinical recommendations. Clin Transl Oncol 2023:10.1007/s12094-023-03095-8. [PMID: 36961727 DOI: 10.1007/s12094-023-03095-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 01/17/2023] [Indexed: 03/25/2023]
Abstract
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.
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Affiliation(s)
- Sofia Cordoba Largo
- Department of Radiation Oncology, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain.
| | | | | | - Dina Najjari Jamal
- Department of Radiation Oncology, Catalan Institut of Oncology, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain
| | - Javier Anchuelo Latorre
- Department of Radiation Oncology, Marqués de Valdecilla University Hospital, Santander, Spain
| | | | - Sonia Garcia Cabezas
- Department of Radiation Oncology, Reina Sofía, University Hospital, Córdoba, Spain
| | | | - Luz Couselo Paniagua
- Department of Radiation Oncology, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
| | | | | | | | - Dolores Farga Albiol
- Department of Radiation Oncology, La Fe, University Hospital and Politécnico, Valencia, Spain
| | | | - María Sánchez Belda
- Department of Radiation Oncology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain
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Abstract
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.
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Affiliation(s)
- Anjali Y Hari
- University of California, Irvine Division of Gynecologic Oncology, Orange, California, USA
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Wanka G, Jueckstock J, Wild CM, Vattai A, Fürst S, Heidegger HH, Kuhn C, Schmoeckel E, Jeschke U, Dannecker C. MTA1 as negative prognostic marker in vulvar carcinoma. J Cancer Res Clin Oncol 2023:10.1007/s00432-023-04579-4. [PMID: 36689059 PMCID: PMC10356867 DOI: 10.1007/s00432-023-04579-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 01/06/2023] [Indexed: 01/24/2023]
Abstract
PURPOSE Vulvar cancer is the fourth most common malignancy of the female genital tract after endometrial, ovarian, and cervical carcinoma and affects mainly elderly women. In 2020 there were registered more than 17,000 deaths worldwide related to vulvar carcinoma. Data about target-based therapies and predictive biomarkers for vulva carcinomas are rare so far. The metastasis-associated gene MTA1 is a transcriptional repressor with a potential effect on cancer. Expression of MTA1 was found to be significantly enhanced in gynecological malignancies as breast or ovarian cancer tissues with advanced cancer stages and higher FIGO grading, indicating an important role of MTA1 in the progression of those tumor entities. Due to the lack of information around MTA1 and its significance regarding vulvar carcinoma, this study focuses on the expression of MTA1 in vulvar carcinoma and its correlation to clinicopathological characteristics and prognosis. METHODS A total of 157 paraffin-embedded vulvar cancer tissues were immunohistochemically stained and examined for MTA1 expression by using the immunoreactive score. Subsequently, the values were correlated with clinicopathological parameters. RESULTS MTA1 was found to be expressed in 94% of the patients in the cytoplasm and 91% in the nucleus. Cytoplasmatic expression of MTA1 was significantly increased in non-keratinizing squamous cell carcinoma and in vulvar carcinoma of the condylomatous type, compared to keratinizing squamous cell carcinoma and vulvar carcinoma of the verrucous type. High MTA1 expression in the nucleus was associated with advanced tumor size as well as higher FIGO grading. In addition, p16 negative vulvar carcinomas showed a higher nuclear expression of MTA1 compared to p16 positive vulvar carcinomas. Suprisingly, Kaplan-Meier analysis showed a significantly lower disease-free survival in tumor samples without a nuclear expression of MTA1. CONCLUSIONS MTA1 was identified as a negative prognostic marker for vulvar carcinoma associated with advanced tumor stage and FIGO grading. A possible explanation could be that the antibody used for this study does not bind to a possible mutation in the C terminal region of MTA leading to negative immunohistochemical staining and this can be correlated with early recurrence in patients with vulvar carcinoma.
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Affiliation(s)
- Giulia Wanka
- Department of Obstetrics and Gynecology, University Hospital Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
| | - Julia Jueckstock
- Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany.,Department of Obstetrics and Gynecology, RoMed Clinic, Krankenhausstraße 2, 83512, Wasserburg am Inn, Germany
| | - Carl Mathis Wild
- Department of Obstetrics and Gynecology, University Hospital Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
| | - Aurelia Vattai
- Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany
| | - Sophie Fürst
- Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany
| | - Helene H Heidegger
- Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany
| | - Christina Kuhn
- Department of Obstetrics and Gynecology, University Hospital Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
| | - Elisa Schmoeckel
- Department of Pathology, LMU Munich, Thalkirchner Straße 142, 80337, Munich, Germany
| | - Udo Jeschke
- Department of Obstetrics and Gynecology, University Hospital Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany. .,Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany.
| | - Christian Dannecker
- Department of Obstetrics and Gynecology, University Hospital Augsburg, Stenglinstraße 2, 86156, Augsburg, Germany
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Macchia G, Casà C, Ferioli M, Lancellotta V, Pezzulla D, Pappalardi B, Laliscia C, Ippolito E, Di Muzio J, Huscher A, Tortoreto F, Boccardi M, Lazzari R, De Iaco P, Raspagliesi F, Gadducci A, Garganese G, Ferrandina G, Morganti AG, Tagliaferri L. Observational multicenter Italian study on vulvar cancer adjuvant radiotherapy (OLDLADY 1.2): a cooperation among AIRO Gyn, MITO and MaNGO groups. LA RADIOLOGIA MEDICA 2022; 127:1292-1302. [PMID: 36088437 DOI: 10.1007/s11547-022-01538-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 07/28/2022] [Indexed: 12/01/2022]
Abstract
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.
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Affiliation(s)
- Gabriella Macchia
- Radiation Oncology Unit, Gemelli Molise Hospital - Università Cattolica del Sacro Cuore, Campobasso, Italy
| | - Calogero Casà
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Martina Ferioli
- Radiation Oncology, Department of Experimental, Diagnostic and Specialty Medicine - DIMES, IRCCS Azienda Ospedaliero, Universitaria di Bologna - Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Valentina Lancellotta
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
| | - Donato Pezzulla
- Radiation Oncology Unit, Gemelli Molise Hospital - Università Cattolica del Sacro Cuore, Campobasso, Italy
| | - Brigida Pappalardi
- Radiotherapy Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Concetta Laliscia
- Department of New Technologies and Translational Research, Division of Radiation Oncology, University of Pisa, Pisa, Italy
| | - Edy Ippolito
- Radiation Oncology, Università Campus Bio-Medico, Rome, Italy
| | - Jacopo Di Muzio
- Dipartimento di Oncologia P.O. S. Anna - SS Radioterapia, A.O.U "Città della Salute e della Scienza", Turin, Italy
| | - Alessandra Huscher
- Fondazione Poliambulanza, U.O. di Radioterapia Oncologica "Guido Berlucchi", Brescia, Italy
| | - Francesca Tortoreto
- U.O.C. Radiotherapy, S. Giovanni Calibita Fatebenefratelli Hospital - Amethyst Radioterapia Italia, Rome, Italy
| | - Mariangela Boccardi
- Radiation Oncology Unit, Gemelli Molise Hospital - Università Cattolica del Sacro Cuore, Campobasso, Italy
| | - Roberta Lazzari
- Division of Radiotherapy, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Pierandrea De Iaco
- Division of Oncologic Gynecology, IRCCS Azienda Ospedaliero, Universitaria di Bologna - Alma Mater Studiorum University of Bologna, Bologna, Italy
| | | | - Angiolo Gadducci
- Department of Clinical and Experimental Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy
| | - Giorgia Garganese
- Gynecology and Breast Care Center, Mater Olbia Hospital, Olbia, Italy
| | - Gabriella Ferrandina
- Unità Operativa Complessa Ginecologia Oncologica, Dipartimento per la Salute della Donna e del Bambino e della Salute Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS - Università Cattolica del Sacro Cuore, Rome, Italy
| | - Alessio Giuseppe Morganti
- Radiation Oncology, Department of Experimental, Diagnostic and Specialty Medicine - DIMES, IRCCS Azienda Ospedaliero, Universitaria di Bologna - Alma Mater Studiorum University of Bologna, Bologna, Italy
| | - Luca Tagliaferri
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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Ni L, Sinha S, Rara M, Phuong C, Chen LM, Hsu ICJ, Yoshida EJ. The role of adjuvant radiation therapy in older patients with node-positive vulvar cancer: A national cancer database analysis. Gynecol Oncol 2022; 167:189-195. [PMID: 36150913 DOI: 10.1016/j.ygyno.2022.09.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 09/05/2022] [Accepted: 09/07/2022] [Indexed: 11/21/2022]
Abstract
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.
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Affiliation(s)
- Lisa Ni
- University of California San Francisco, Department of Radiation Oncology, 1600 Divisadero St, Suite H1031, Box 1708, San Francisco, CA 94115, United States of America
| | - Sumi Sinha
- University of California San Francisco, Department of Radiation Oncology, 1600 Divisadero St, Suite H1031, Box 1708, San Francisco, CA 94115, United States of America
| | - Marianne Rara
- University of California San Francisco, Department of Radiation Oncology, 1600 Divisadero St, Suite H1031, Box 1708, San Francisco, CA 94115, United States of America
| | - Christina Phuong
- University of California San Francisco, Department of Radiation Oncology, 1600 Divisadero St, Suite H1031, Box 1708, San Francisco, CA 94115, United States of America
| | - Lee-May Chen
- University of California San Francisco, Department of Obstetrics and Gynecology and Reproductive Sciences, 1825 Fourth St, Sixth Floor, San Francisco, CA 94158, United States of America
| | - I-Chow J Hsu
- University of California San Francisco, Department of Radiation Oncology, 1600 Divisadero St, Suite H1031, Box 1708, San Francisco, CA 94115, United States of America
| | - Emi J Yoshida
- University of California San Francisco, Department of Radiation Oncology, 1600 Divisadero St, Suite H1031, Box 1708, San Francisco, CA 94115, United States of America.
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Benmoulay-Rigollot C, Karpathiou G, Prevot-Bitot N, Heinemann M, Trombert-Paviot B, Barjat T, Chauleur C. Performance of Indocyanine Green Compared to 99mTc-Nanocolloids for Sentinel Lymph Node Detection in Early Vulvar Cancer. Curr Oncol 2022; 29:8084-8092. [PMID: 36354698 PMCID: PMC9688937 DOI: 10.3390/curroncol29110638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 10/23/2022] [Accepted: 10/25/2022] [Indexed: 01/14/2023] Open
Abstract
STUDY OBJECTIVE The aim of this study was to evaluate the performance of indocyanine green (ICG) compared to that of the gold standard 99mtechnetium (99mTc-nanocolloids) in detecting sentinel lymph nodes (SLN) in early vulvar cancer. MATERIAL AND METHODS A single-center retrospective cohort study comparing SLN detection by 99mTc-nanocolloids and ICG was performed in patients presenting early vulvar cancer (T1/2), with clinically negative nodes. All SLN showing a radioactive and/or fluorescent signal were resected. The primary endpoints were the sensitivity, positive predictive value (PPV) and false negative (FN) rate of ICG in detecting SLN compared to 99mTc-nanocolloids. RESULTS Thirty patients were included and 99 SLN were identified in 43 groins. Compared to 99mTc-nanocolloids, ICG had a sensitivity of 80.8% (95% CI [72.6; 88.6%]), a PPV of 96.2% (95% CI [91.8; 100%]) and a FN rate of 19.1% in detecting SLN. Seventeen (17.1%) infiltrated (positive) SLN were identified out of the 99 SLN detected. Compared to 99mTc-nanocolloids, ICG showed a sensitivity of 82.3% (95% CI [73.1; 91.5%]), a PPV of 100% and a FN rate of 17.6% (3/17) in detecting infiltrated SLN. CONCLUSION Despite its many advantages, ICG cannot be used as the sole tracer for the detection of SLN in early vulvar cancer and should be employed in conjunction with 99mTc-nanocolloids.
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Affiliation(s)
| | - Georgia Karpathiou
- Department of Pathology, University Hospital, 42023 Saint Etienne, France
| | - Nathalie Prevot-Bitot
- Department of Gynecology and Obstetrics, University Hospital, 42055 Saint Etienne, France
- Department of Nuclear Medicine, University Hospital, 42023 Saint Etienne, France
| | - Mellie Heinemann
- Department of Gynecology, LEON BERARD Center, 69008 Lyon, France
| | - Beatrice Trombert-Paviot
- Department of Gynecology and Obstetrics, University Hospital, 42055 Saint Etienne, France
- INSERM U1059, 42023 Saint Etienne, France
| | - Tiphaine Barjat
- Department of Gynecology and Obstetrics, University Hospital, 42055 Saint Etienne, France
- INSERM U1059, 42023 Saint Etienne, France
| | - Céline Chauleur
- Department of Gynecology and Obstetrics, University Hospital, 42055 Saint Etienne, France
- INSERM U1059, 42023 Saint Etienne, France
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29
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T-Cell Density at the Invasive Margin and Immune Phenotypes Predict Outcome in Vulvar Squamous Cell Cancer. Cancers (Basel) 2022; 14:cancers14174246. [PMID: 36077784 PMCID: PMC9454842 DOI: 10.3390/cancers14174246] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 08/25/2022] [Accepted: 08/25/2022] [Indexed: 11/29/2022] Open
Abstract
Background: Although quantification of tumor infiltrating lymphocytes (TILs) has become of increasing interest in immuno-oncology, only little is known about TILs infiltration in the tumor microenvironment and its predictive value in vulvar cancer. Methods: Immunohistochemistry and automated digital image analysis was applied to measure the densities of CD3+ (DAKO, #IR503) and CD8+ (DAKO, #IR623) TILs at the invasive margin and in the center of 530 vulvar squamous cell cancers. Results: An elevated density of CD3+ T-cell at the invasive margin was significantly associated with low tumor stage (p = 0.0012) and prolonged survival (overall survival [OS] p = 0.0027, progression free survival [PFS] p = 0.024) and was independent from tumor stage, nodal stage, grade, and HPV-status in multivariate analysis (p < 0.05). The prognostic impact of CD3+ cells in the center of the tumor was weaker compared to the invasive margin (OS p = 0.046, PFS p = 0.031) and lacking for CD8+ T-cell densities at any location (p ≥ 0.14 each). Unsupervised clustering of CD3+ and CD8+ T-cell densities identified three major subgroups corresponding to the immune desert (137 patients), immune excluded (220 patients) and immune inflamed phenotypes (133 patients). Survival analysis revealed a particular poor prognosis for the immune desert phenotype for OS (p = 0.0071) and PFS (p = 0.0027). Conclusion: Our data demonstrate a high prognostic value of CD3+ T-cells at the invasive margin and immune phenotypes in vulvar squamous cell cancer.
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Pedrão PG, Guimarães YM, Godoy LR, Possati-Resende JC, Bovo AC, Andrade CEMC, Longatto-Filho A, dos Reis R. Management of Early-Stage Vulvar Cancer. Cancers (Basel) 2022; 14:cancers14174184. [PMID: 36077719 PMCID: PMC9454625 DOI: 10.3390/cancers14174184] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 07/21/2022] [Accepted: 07/25/2022] [Indexed: 11/22/2022] Open
Abstract
Simple Summary Vulvar cancer is a rare gynecological malignancy that affects mainly postmenopausal women. Recently, however, an alarming increase in the rates among young women has been observed due to human papillomavirus infection. The standard treatment for vulvar cancer is surgery with or without radiotherapy as adjuvant treatment. In recent decades, sentinel lymph node biopsy has been included as part of the surgical treatment. Thus, our objective was to review and discuss the advances found in the literature about early-stage vulvar cancer. For this, we searched PubMed for publications in the English language. Relevant articles, such as the GROINS-V studies, and the GOG protocols, are presented in this review exhibiting the evolution of early-stage vulvar cancer treatment and the decrease in surgical morbidity rates. Abstract Vulvar cancer is a rare gynecological malignancy since it represents 4% of all cancers of the female genital tract. The most common histological type is squamous cell carcinoma (90%). This type can be classified into two clinicopathological subtypes according to the etiology. The first subtype is associated with persistent human papillomavirus infection and is usually diagnosed in younger women. The second subtype is associated with lichen sclerosus condition, and in most cases is diagnosed in postmenopausal women. Currently, an increase in first subtype cases has been observed, which raised the concern about associated mortality and treatment morbidity among young women. Vulvar cancer treatment depends on histopathology grade and staging, but surgery with or without radiotherapy as adjuvant treatment is considered the gold standard. In recent decades, sentinel lymph node biopsy has been incorporated as part of the treatment. Therefore, we sought to review and discuss the advances documented in the literature about vulvar cancer focusing on the treatment of early-stage disease. Relevant articles, such as the GROINS-V studies and the GOG protocols, are presented in this review. Additionally, we discuss key points such as the evolution of treatment from invasive surgery with high morbidity, to more conservative approaches without compromising oncologic safety; the role of sentinel lymph node mapping in the initial staging, since it reduces the complications caused by inguinofemoral lymphadenectomy; the recurrences rates, since local recurrence is common and curable, however, groin-associated, or distant recurrences have a poor prognosis; and, finally, the long-term follow-up that is essential for all patients.
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Affiliation(s)
- Priscila Grecca Pedrão
- Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo 14784-400, Brazil
| | | | - Luani Rezende Godoy
- Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo 14784-400, Brazil
| | | | - Adriane Cristina Bovo
- Department of Prevention Oncology, Barretos Cancer Hospital, Mato Grosso do Sul 79085-040, Brazil
| | - Carlos Eduardo Mattos Cunha Andrade
- Department of Gynecologic Oncology, Barretos Cancer Hospital, São Paulo 14784-400, Brazil
- Barretos School of Health Sciences, Dr. Paulo Prata-FACISB, Barretos, São Paulo 14785-002, Brazil
| | - Adhemar Longatto-Filho
- Molecular Oncology Research Center, Barretos Cancer Hospital, São Paulo 14784-400, Brazil
- Medical Laboratory of Medical Investigation (LIM) 14, Department of Pathology, Medical School, University of São Paulo, São Paulo 01246-903, Brazil
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, 4710-057 Braga, Portugal
- ICVS/3B’s—PT Government Associate Laboratory, 4805-017 Guimarães, Portugal
| | - Ricardo dos Reis
- Department of Gynecologic Oncology, Barretos Cancer Hospital, São Paulo 14784-400, Brazil
- Correspondence: ; Tel.: +55-3321-6600 (ext. 7126)
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Mokhtech M, Gao SJ, Kassick M, Menderes G, Damast S. Declining use of inguinofemoral lymphadenectomy in the treatment of clinically negative, pathologic node positive vulvar cancer. Gynecol Oncol 2022; 166:61-68. [PMID: 35550710 DOI: 10.1016/j.ygyno.2022.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 04/25/2022] [Accepted: 05/01/2022] [Indexed: 11/04/2022]
Abstract
PURPOSE The management of vulvar cancer with clinically negative groin lymph nodes but with positive sentinel lymph node biopsy (SLNB) is controversial, with options including inguinofemoral lymphadenectomy (IFL) and/or adjuvant chemotherapy and radiotherapy. We used the National Cancer Database (NCDB) to examine trends in the management of clinically node negative, pathologically node positive (cN-/pN+) patients. METHODS The NCDB was used to identify cN-/pN+ vulvar cancer patients. Demographic and clinical data were compared with chi-squared and Wilcoxon rank-sum tests. OS was analyzed with the Kaplan-Meier method and log-rank test. Cox proportional hazards regression was used to determine factors associated with OS. RESULTS A total of 885 cN-/pN+ vulvar cancer patients were identified between 2012 and 2016, during which the rate of SLNB alone increased from 3.6% to 11.7%, while the rate of IFL +/- SLNB decreased from 89.7% to 78.1% (p < 0.05). Radiation was used in 68.5% and 64.6% of the SLNB-alone and IFL +/- SLNB cohorts, respectively, with chemoradiation in 37.1% and 33.6%, respectively. OS was not different between patients who received SLNB-alone vs. IFL +/- SLNB (p = 0.644). Receipt of chemotherapy and radiation was associated with improved OS (p < 0.001). CONCLUSIONS Among cN-/pN+ vulvar cancer patients in the NCDB, the practice of performing IFL decreased over time as SLNB-alone became more common and the majority received radiation +/- chemotherapy. There was no difference in OS between SLNB-alone vs. IFL +/- SLNB. Patients treated with adjuvant chemoradiation had improved survival. Whether the favorable outcomes in the SLNB-alone cohort may be attributed to radiotherapy dose escalation or use of chemotherapy warrants further study.
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Affiliation(s)
- Meriem Mokhtech
- Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, United States of America.
| | - Sarah J Gao
- Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, United States of America.
| | - Megan Kassick
- Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, United States of America
| | - Gulden Menderes
- Department of Obstetrics, Gynecology, & Reproductive Sciences, Yale School of Medicine, New Haven, CT, United States of America
| | - Shari Damast
- Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, United States of America
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Lukovic J, Han K. Postoperative management of vulvar cancer. Int J Gynecol Cancer 2022; 32:338-343. [PMID: 35256421 DOI: 10.1136/ijgc-2021-002463] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 12/06/2021] [Indexed: 11/03/2022] Open
Abstract
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.
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Affiliation(s)
- Jelena Lukovic
- Radiation Oncology, Princess Margaret Hospital Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Kathy Han
- Radiation Oncology, Princess Margaret Hospital Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada
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Brunette LL, Khetan VU, Deshpande RR, Nusbaum DJ, Klar M, Roman LD, Wright JD, Matsuo K. Population-level trends and outcomes of sentinel lymph node biopsy in vulvar cancer surgery in the United States. Gynecol Oncol 2022; 164:651-657. [PMID: 35031190 DOI: 10.1016/j.ygyno.2022.01.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Revised: 12/15/2021] [Accepted: 01/03/2022] [Indexed: 11/29/2022]
Abstract
OBJECTIVE To examine population-level trends, characteristics, and outcomes related to nodal assessment for vulvar cancer surgery in the United States. METHODS This is a retrospective cohort study querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population was 5604 women with T1b or T2-smaller(≤4 cm) squamous cell carcinoma of the vulva who underwent primary vulvectomy from 2003 to 2018. The exposure allocation was based on nodal evaluation type: lymphadenectomy (LND; n = 3319, 59.2%), sentinel lymph node (SLN) biopsy (n = 751, 13.4%), or no surgical nodal evaluation (n = 1534, 27.4%). The main outcomes were (i) trends and characteristics related to SLN biopsy assessed by multinomial regression model, and (ii) vulvar cancer-specific survival assessed by competing risk analysis and inverse probability of treatment weighting propensity score. Sensitivity analysis included evaluation of external cohort with T1a disease (n = 1291). RESULTS The utilization of SLN biopsy increased from 5.7% to 23.3% in 2006-2018, while the proportion of LND decreased from 64.1% to 48.8% in 2010-2018, and these associations remained independent in multivariable analysis (adjusted-P < 0.05). In the propensity score weighted model, 5-year cumulative rate for vulvar cancer-specific mortality was 15.2% (interquartile range 12.1-18.9) for the SLN biopsy group and 16.9% (interquartile range 15.6-18.3) for the LND group (subdistribution-hazard ratio 0.90, 95% confidence interval 0.76-1.06, P = 0.217). The increasing SLN biopsy use was also observed in T1a disease from 1.3% to 7.3% during the study period (P < 0.001). CONCLUSION The landscape of surgical nodal evaluation is shifting from lymphadenectomy to SLN biopsy in vulvar cancer surgery in the United States. SLN biopsy-incorporated treatment approach was not associated with worse survival compared to LND.
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Affiliation(s)
- Laurie L Brunette
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA
| | - Varun U Khetan
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA
| | - Rasika R Deshpande
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA
| | | | - Maximilian Klar
- Department of Obstetrics and Gynecology, University of Freiburg Faculty of Medicine, Freiburg, Germany
| | - Lynda D Roman
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
| | - Jason D Wright
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY, USA
| | - Koji Matsuo
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Southern California, Los Angeles, CA, USA; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
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Khullar K, Patrich T, Jabbour SK, Hathout L. Adjuvant Radiation in Early Stage Vulvar Cancer: A Review of Indications and Optimal Dose. APPLIED RADIATION ONCOLOGY 2022; 11:14-20. [PMID: 35445143 PMCID: PMC9017798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Vulvar cancer is a relatively rare gynecologic malignancy for which surgery remains the cornerstone of treatment. A wide local excision is the goal for treatment with curative intent in patients with early stage vulvar cancer, given that there are adverse pathologic features shown to increase risk of local recurrence. Specifically, the presence of positive or close margins of < 8 mm or 2 or more positive nodes have been shown to significantly increase the risk of recurrence and have informed guidelines for risk-adapted adjuvant radiation, although the optimal dose for adjuvant radiation is yet to be established. Given the rarity of vulvar cancer, guidelines regarding the indications and dose for adjuvant radiation are based largely on retrospective studies. The purpose of this review is to summarize the evidence underlying the current indications for adjuvant radiation in early stage vulvar cancer as well as to determine the optimal dose for adjuvant radiation.
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Affiliation(s)
- Karishma Khullar
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA
| | - Tomas Patrich
- Rutgers Robert Wood Johnson Medical School, Piscataway, NJ
| | - Salma K Jabbour
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA
| | - Lara Hathout
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA
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Woelber L, Hampl M, zu Eulenburg C, Prieske K, Hambrecht J, Fuerst S, Klapdor R, Heublein S, Gass P, Rohner A, Canzler U, Becker S, Bommert M, Bauerschlag D, Denecke A, Hanker L, Runnebaumn I, Forner DM, Schochter F, Klar M, Schwab R, Koepke M, Kalder M, Hantschmann P, Ratiu D, Denschlag D, Schroeder W, Tuschy B, Baumann K, Mustea A, Soergel P, Bronger H, Bauerschmitz G, Kosse J, Koch MC, Ignatov A, Sehouli J, Dannecker C, Mahner S, Jaeger A. Risk for Pelvic Metastasis and Role of Pelvic Lymphadenectomy in Node-Positive Vulvar Cancer-Results from the AGO-VOP.2 QS Vulva Study. Cancers (Basel) 2022; 14:cancers14020418. [PMID: 35053582 PMCID: PMC8773532 DOI: 10.3390/cancers14020418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 01/05/2022] [Accepted: 01/10/2022] [Indexed: 02/05/2023] Open
Abstract
Simple Summary In node-positive vulvar squamous cell cancer, questions of when and how to perform pelvic lymphadenectomy (LAE) as well as the optimal extent of pelvic treatment in general have been surrounded by considerable controversy. In Germany, systematic pelvic LAE is currently recommended as a staging procedure in patients at risk for pelvic nodal involvement in order to prevent morbidity caused by pelvic radiotherapy (RT) in patients without histologically-confirmed pelvic involvement. However, the population at risk for pelvic metastases remains insufficiently described, resulting in the potential overtreatment of a considerable proportion of patients with groin-positive disease. This applies to the indication to perform surgical staging but also to adjuvant RT of the pelvis without previous pelvic staging. Our study aims to describe the risk for pelvic lymph node metastasis with regard to positive groin nodes and to clarify the indication criteria for pelvic treatment in node-positive vulvar cancer. Abstract The need for pelvic treatment in patients with node-positive vulvar cancer (VSCC) and the value of pelvic lymphadenectomy (LAE) as a staging procedure to plan adjuvant radiotherapy (RT) is controversial. In this retrospective, multicenter analysis, 306 patients with primary node-positive VSCC treated at 33 gynecologic oncology centers in Germany between 2017 and 2019 were analyzed. All patients received surgical staging of the groins; nodal status was as follows: 23.9% (73/306) pN1a, 23.5% (72/306) pN1b, 20.4% (62/306) pN2a/b, and 31.9% (97/306) pN2c/pN3. A total of 35.6% (109/306) received pelvic LAE; pelvic nodal involvement was observed in 18.5%. None of the patients with nodal status pN1a or pN1b and pelvic LAE showed pelvic nodal involvement. Taking only patients with nodal status ≥pN2a into account, the rate of pelvic involvement was 25%. In total, adjuvant RT was applied in 64.4% (197/306). Only half of the pelvic node-positive (N+) patients received adjuvant RT to the pelvis (50%, 10/20 patients); 41.9% (122/291 patients) experienced recurrent disease or died. In patients with histologically-confirmed pelvic metastases after LAE, distant recurrences were most frequently observed (7/20 recurrences). Conclusions: A relevant risk regarding pelvic nodal involvement was observed from nodal status pN2a and higher. Our data support the omission of pelvic treatment in patients with nodal status pN1a and pN1b.
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Affiliation(s)
- Linn Woelber
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg—Eppendorf, 20246 Hamburg, Germany; (K.P.); (J.H.); (A.J.)
- Colposcopy Center at the Jerusalem Hospital Hamburg, 20357 Hamburg, Germany
- Correspondence:
| | - Monika Hampl
- Department of Gynecology, University Medical Center Duesseldorf, 40225 Duesseldorf, Germany;
| | - Christine zu Eulenburg
- Department of Epidemiology, UMCG, Universität Groningen, 9713 Groningen, The Netherlands;
| | - Katharina Prieske
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg—Eppendorf, 20246 Hamburg, Germany; (K.P.); (J.H.); (A.J.)
- Colposcopy Center at the Jerusalem Hospital Hamburg, 20357 Hamburg, Germany
- Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg—Eppendorf, 20251 Hamburg, Germany
| | - Johanna Hambrecht
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg—Eppendorf, 20246 Hamburg, Germany; (K.P.); (J.H.); (A.J.)
| | - Sophie Fuerst
- Department of Obstetrics and Gynecology, University Hospital, LMU—University of Munich, 80377 Munich, Germany; (S.F.); (S.M.)
| | - Ruediger Klapdor
- Department of Obstetrics and Gynecology, Hannover Medical School, 30625 Hannover, Germany;
| | - Sabine Heublein
- Department of Obstetrics and Gynecology, University Hospital Heidelberg, 69120 Heidelberg, Germany;
| | - Paul Gass
- Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany;
| | - Annika Rohner
- Department of Gynecology, University Medical Center Tuebingen, 72076 Tuebingen, Germany;
| | - Ulrich Canzler
- Department of Gynecology and Obstetrics, University Hospital Dresden, Technische Universität Dresden, Dresden, Germany & National Center for Tumor Diseases (NCT), Partner Site Dresden, 01307 Dresden, Germany;
| | - Sven Becker
- Department of Gynecology and Obstetrics, University Medical Center Frankfurt, 60590 Frankfurt, Germany;
| | - Mareike Bommert
- Department of Gynecology and Gynecologic Oncology, Evang. Kliniken Essen-Mitte, 45136 Essen, Germany;
| | - Dirk Bauerschlag
- Department of Gynecology, University Medical Center Kiel, 24105 Kiel, Germany;
| | - Agnieszka Denecke
- Department of Gynecology, Medical Center Wolfsburg, 38440 Wolfsburg, Germany;
| | - Lars Hanker
- Department of Gynecology and Gynecologic Oncology, University Medical Center Luebeck, 23562 Luebeck, Germany;
| | - Ingo Runnebaumn
- Department of Gynecology, Jena University Hospital, 07743 Jena, Germany;
| | - Dirk M. Forner
- Department of Gynecology, Evangelisches Krankenhaus Kalk, 51103 Cologne, Germany;
| | - Fabienne Schochter
- Department of Obstetrics and Gynecology, University of Ulm Medical Center, 89081 Ulm, Germany;
| | - Maximilian Klar
- Department of Gynecology, University Medical Center Freiburg, 79106 Freiburg, Germany;
| | - Roxana Schwab
- Department of Gynecology, University Medical Center Mainz, 55131 Mainz, Germany;
| | - Melitta Koepke
- Department of Obstetrics and Gynaecology, University Hospital Augsburg, 86156 Augsburg, Germany; (M.K.); (C.D.)
| | - Matthias Kalder
- Department of Gynecology and Obstetrics, University Hospital Marburg, 35043 Marburg, Germany;
| | - Peer Hantschmann
- Department of Gynecology and Obstetrics, Medical Center Altoetting, 84503 Altoetting, Germany;
| | - Dominik Ratiu
- Department of Gynecology, University Medical Center Koeln, 50937 Koeln, Germany;
| | - Dominik Denschlag
- Department of Gynecology, Hochtaunuskliniken, 61352 Bad Homburg, Germany;
| | - Willibald Schroeder
- Department of Gynecology, Medical Center Gynaecologicum Bremen, 28209 Bremen, Germany;
| | - Benjamin Tuschy
- Department of Gynecology, University Medical Center Mannheim, 68167 Mannheim, Germany;
| | - Klaus Baumann
- Department of Gynecology, Medical Center Ludwigshafen, 67063 Ludwigshafen, Germany;
| | - Alexander Mustea
- Department of Gynecology and Gynecologic Oncology, University Medical Center Bonn, 53127 Bonn, Germany;
| | - Philipp Soergel
- Department of Gynecology, University Medical Center Minden, 32429 Minden, Germany;
| | - Holger Bronger
- Department of Gynecology and Obstetrics, Technical University of Munich, 81675 Munich, Germany;
| | - Gerd Bauerschmitz
- Department of Gynecology, University Medical Center Goettingen, 37075 Goettingen, Germany;
| | - Jens Kosse
- Department of Gynecology, Sana Klinikum Offenbach, 63069 Offenbach am Main, Germany;
| | - Martin C. Koch
- Department of Gynecology, Medical Center Ansbach, 91522 Ansbach, Germany;
| | - Atanas Ignatov
- Department of Obstetrics and Gynecology, University Hospital Magdeburg, 39120 Magdeburg, Germany;
| | - Jalid Sehouli
- Department of Gynecology with Center for Oncological SurgeryNOGGO e.V., Charite Universitatsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Virchow Campus Clinic, Charité Medical University, 13353 Berlin, Germany;
| | - Christian Dannecker
- Department of Obstetrics and Gynaecology, University Hospital Augsburg, 86156 Augsburg, Germany; (M.K.); (C.D.)
| | - Sven Mahner
- Department of Obstetrics and Gynecology, University Hospital, LMU—University of Munich, 80377 Munich, Germany; (S.F.); (S.M.)
| | - Anna Jaeger
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg—Eppendorf, 20246 Hamburg, Germany; (K.P.); (J.H.); (A.J.)
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Garganese G, Inzani F, Fragomeni SM, Mantovani G, Della Corte L, Piermattei A, Santoro A, Angelico G, Giacò L, Corrado G, Fagotti A, Zannoni GF, Scambia G. The Vulvar Immunohistochemical Panel (VIP) Project: Molecular Profiles of Vulvar Squamous Cell Carcinoma. Cancers (Basel) 2021; 13:cancers13246373. [PMID: 34944993 PMCID: PMC8699435 DOI: 10.3390/cancers13246373] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 11/25/2021] [Accepted: 12/13/2021] [Indexed: 02/06/2023] Open
Abstract
Simple Summary This study investigated the immunohistochemical expression of 14 biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma, comparing 53 node-negative (Group A) and 48 node-positive (Group B) patients. Our results show a significantly higher p16 expression (surrogate of HPV-related tumors) in the vulvar samples of non-metastatic patients. In Group B, PD-L1 positivity and high EGFR expression were found in the vast majority of vulvar and/or nodal specimens. VEGF showed strong/moderate-diffuse expression in almost 14% of all vulvar samples. A mutated p53 and over-expressed PD-L1 showed a significant association with nodal metastasis. Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs, especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expression. Abstract Introduction: The study’s aim was to investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC). Methodology: A series of 101 patients surgically treated at our center from 2016 to 2020 were retrospectively enrolled: 53 node-negative (Group A) and 48 node-positive (Group B). A total of 146 samples, 101 from primary tumor (T) and 45 from nodal metastases (N), were investigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF, and CD31. The reactions were evaluated on qualitative and semi-quantitative scales. Generalized Linear Model (GLM) and cluster analysis were performed in R statistical environment. A distance plot compared the IHC panel of T with the correspondent N. Results: In Group A: p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs. 6.2%, p = 0.04). In Group B: PD-L1 positivity and high EGFR expression were found, respectively, in 77.1% and 97.9% patients (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups: tumoral immune infiltration (CD3 expression) was mainly moderate/intense (80% vs. 95%); VEGF showed strong/moderate-diffuse expression in 13.9% of T samples; CD31, related to tumoral microvessel density (MVD), showed no difference between groups; a mutated p53 and over-expressed PD-L1 showed significant association with nodal metastasis, with Odds Ratios (OR) of 4.26 (CI 95% = 1.14–15.87, p = 0.03) and 2.68 (CI 95% = 1.0–7.19, p < 0.05), respectively; since all mismatch repair proteins (MMR) showed a retained expression and ER, PR, and HER2/neu were negative, they were excluded from further analysis. The cluster analysis identified three and four sub-groups of molecular profiles, respectively, in Group A and B, with no difference in prognosis. The molecular signature of each N and corresponding T diverged significantly in 18/41 (43.9%) cases. Conclusions: Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expression.
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Affiliation(s)
- Giorgia Garganese
- Dipartimento Scienze della Vita e Sanità Pubblica, Sezione Ginecologia e Ostetricia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (G.G.); (A.F.); (G.S.)
- Gynecology and Breast Care Center, Mater Olbia Hospital, 07026 Olbia, Italy
| | - Frediano Inzani
- Unità di Gineco-Patologia e Patologia Mammaria, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (F.I.); (A.P.); (A.S.); (G.A.); (G.F.Z.)
| | - Simona Maria Fragomeni
- Unità di Ginecologia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (S.M.F.); (L.D.C.); (G.C.)
| | - Giulia Mantovani
- Department of Obstetrics and Gynaecology, Gynaecologic Oncology and Minimally-Invasive Pelvic Surgery, International School of Surgical Anatomy, IRCCS Sacro Cuore-Don Calabria Hospital, 37024 Negrar di Valpolicella, Italy
- Correspondence:
| | - Luigi Della Corte
- Unità di Ginecologia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (S.M.F.); (L.D.C.); (G.C.)
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, 80131 Naples, Italy
| | - Alessia Piermattei
- Unità di Gineco-Patologia e Patologia Mammaria, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (F.I.); (A.P.); (A.S.); (G.A.); (G.F.Z.)
| | - Angela Santoro
- Unità di Gineco-Patologia e Patologia Mammaria, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (F.I.); (A.P.); (A.S.); (G.A.); (G.F.Z.)
| | - Giuseppe Angelico
- Unità di Gineco-Patologia e Patologia Mammaria, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (F.I.); (A.P.); (A.S.); (G.A.); (G.F.Z.)
| | - Luciano Giacò
- Bioinformatics Facility Core Research, Gemelli Science and Technology Park, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy;
| | - Giacomo Corrado
- Unità di Ginecologia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (S.M.F.); (L.D.C.); (G.C.)
| | - Anna Fagotti
- Dipartimento Scienze della Vita e Sanità Pubblica, Sezione Ginecologia e Ostetricia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (G.G.); (A.F.); (G.S.)
- Unità di Ginecologia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (S.M.F.); (L.D.C.); (G.C.)
| | - Gian Franco Zannoni
- Unità di Gineco-Patologia e Patologia Mammaria, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (F.I.); (A.P.); (A.S.); (G.A.); (G.F.Z.)
- Dipartimento Scienze della Vita e Sanità Pubblica, Sezione Anatomia Patologica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Giovanni Scambia
- Dipartimento Scienze della Vita e Sanità Pubblica, Sezione Ginecologia e Ostetricia, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (G.G.); (A.F.); (G.S.)
- Unità di Ginecologia Oncologica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (S.M.F.); (L.D.C.); (G.C.)
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Transcriptome Analysis in Vulvar Squamous Cell Cancer. Cancers (Basel) 2021; 13:cancers13246372. [PMID: 34944992 PMCID: PMC8699756 DOI: 10.3390/cancers13246372] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Revised: 12/09/2021] [Accepted: 12/16/2021] [Indexed: 01/06/2023] Open
Abstract
Simple Summary The number of women, especially younger women, diagnosed with vulvar cancer, has been rising mainly due to the infection with human papilloma virus (HPV) over the last years. In contrast to other tumor entities, limited information on the underlying genetic changes is available, and thus treatment advances, especially the development of personalized treatments, are hampered. We aimed to explore the RNA expression profiles in a group of 24 vulvar cancer samples in order to detect potential prognostic markers and therapeutic targets in order to establish to a more profound understanding of vulvar cancer carcinogenesis. Abstract To date, therapeutic strategies in vulvar squamous cell carcinoma (VSCC) are lacking molecular pathological information and targeted therapy hasn’t been approved in the treatment of VSCC, yet. Two etiological pathways are widely accepted: HPV induced vs. HPV independent, associated with chronic skin disease, often harboring TP53 mutations (mut). The aim of this analysis was to analyze the RNA expression patterns for subtype stratification on VSCC samples that can be integrated into the previously performed whole exome sequencing data for the detection of prognostic markers and potential therapeutic targets. We performed multiplex gene expression analysis (NanoString) with 770 genes in 24 prior next generation sequenced samples. An integrative data analysis was performed. Here, 98 genes were differentially expressed in TP53mut vs. HPV+ VSCC, in the TP53mut cohort, where 56 genes were upregulated and 42 were downregulated in comparison to the HPV+ tumors. Aberrant expression was primarily observed in cell cycle regulation, especially in HPV+ disease. Within the TP53mut group, a distinct cluster was identified that was correlated to a significantly worse overall survival (p = 0.017). The RNA expression profiles showed distinct patterns with regard to the known VSCC subtypes and could potentially enable further subclassification in the TP53mut groups
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Chargari C, Petit A, Escande A, Peignaux K, Lafond C, Peiffert D, Hannoun-Lévi JM, Durdux C, Haie-Méder C. Role of radiotherapy in the management of vulvar cancer: Recommendations of the French society for radiation oncology. Cancer Radiother 2021; 26:286-291. [PMID: 34953710 DOI: 10.1016/j.canrad.2021.08.014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Primary vulvar carcinomas are rare gynaecological cancers, for which surgery is the mainstay of treatment. There is however a major place for external beam radiotherapy in the situation of inoperable locally advanced tumours and/or as adjuvant therapy, when there are risk factors for locoregional relapse. We present the recommendations of the French society for radiation oncology on the indications and techniques for radiotherapy in the treatment of primary vulvar cancer.
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Affiliation(s)
- C Chargari
- Département d'oncologie radiothérapie, Gustave-Roussy Cancer Campus, 114, rue Édouard-Vaillant, 94800 Villejuif, France.
| | - A Petit
- Département de radiothérapie, centre régional de lutte contre le cancer institut Bergonié, 229, cours de l'Argonne, 33000 Bordeaux, France
| | - A Escande
- Département de radiothérapie, centre Oscar-Lambret, avenue Frédéric-Combemale, 59000 Lille, France
| | - K Peignaux
- Département d'oncologie radiothérapie, centre Georges-François-Leclerc, 1, avenue Professeur-Marion, 21000 Dijon, France
| | - C Lafond
- Département de radiothérapie, centre Eugène-Marquis, avenue de la Bataille-Flandres-Dunkerque, 35000 Rennes, France
| | - D Peiffert
- Département de radiothérapie, Institut de cancérologie de Lorraine Alexis-4 Vautrin, 54511 Vandœuvre-lès-Nancy, France
| | - J-M Hannoun-Lévi
- Département de radiothérapie, centre Antoine-Lacassagne, avenue de Valombrose, 06000 Nice, France
| | - C Durdux
- Département d'oncologie radiothérapie, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France
| | - C Haie-Méder
- Département d'oncologie radiothérapie, Centre de cancérologie, Charlebourg la Défense, 65, avenue Foch, 92250 La Garenne-Colombes, France
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Li JY, Arkfeld CK, Tymon-Rosario J, Webster E, Schwartz P, Damast S, Menderes G. An evaluation of prognostic factors, oncologic outcomes, and management for primary and recurrent squamous cell carcinoma of the vulva. J Gynecol Oncol 2021; 33:e13. [PMID: 34910394 PMCID: PMC8899873 DOI: 10.3802/jgo.2022.33.e13] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 08/30/2021] [Accepted: 11/14/2021] [Indexed: 11/30/2022] Open
Abstract
OBJECTIVE To evaluate prognostic factors, outcomes, and management patterns of patients treated for squamous cell carcinoma of the vulva. METHODS One hundred sixty-four women were retrospectively identified with primary squamous cell carcinoma of the vulva treated at our institution between 1/1996-12/2018. Descriptive statistics were performed on patient, tumor, and treatment characteristics. The χ² tests and t-tests were used to compare categorical variables and continuous variables, respectively. Recurrence free survival (RFS), overall survival (OS), and disease-specific survival (DSS) were analyzed with Kaplan-Meier estimates, the log-rank test, and Cox proportional hazards. RESULTS Median follow-up was 52.5 months. Five-year RFS was 67.9%, 60.0%, 42.1%, and 20.0% for stage I-IV, respectively. Five-year DSS was 86.2%, 81.6%, 65.0%, and 42.9% for stage I-IV, respectively. On multivariate analysis, positive margins predicted overall RFS (hazard ratio [HR]=3.55; 95% confidence interval [CI]=1.18-10.73; p=0.025), while presence of lichen sclerosus on pathology (HR=2.78; 95% CI=1.30-5.91; p=0.008) predicted local RFS. OS was predicted by nodal involvement (HR=2.51; 95% CI=1.02-6.13; p=0.043) and positive margins (HR=5.19; 95% CI=2.03-13.26; p=0.001). Adjuvant radiotherapy significantly improved RFS (p=0.016) and DSS (p=0.012) in node-positive patients. Median survival after treatment of local, groin, and pelvic/distant recurrence was 52, 8, and 5 months, respectively. CONCLUSION For primary treatment, more conservative surgical approaches can be considered with escalation of treatment in patients with concurrent precursor lesions, positive margins, and/or nodal involvement. Further studies are warranted to improve risk stratification in order to optimize treatment paradigms for vulvar cancer patients.
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Affiliation(s)
- Jessie Y. Li
- Yale University School of Medicine, New Haven, CT, USA
| | - Christopher K. Arkfeld
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
| | - Joan Tymon-Rosario
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
| | - Emily Webster
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
| | - Peter Schwartz
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
| | - Shari Damast
- Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA
| | - Gulden Menderes
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
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Tagliaferri L, Lancellotta V, Casà C, Fragomeni SM, Ferioli M, Gentileschi S, Caretto AA, Corrado G, Gui B, Colloca GF, Gambacorta MA, Morganti AG, Garganese G, Macchia G. The Radiotherapy Role in the Multidisciplinary Management of Locally Advanced Vulvar Cancer: A Multidisciplinary VulCan Team Review. Cancers (Basel) 2021; 13:5747. [PMID: 34830901 PMCID: PMC8616490 DOI: 10.3390/cancers13225747] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Revised: 11/05/2021] [Accepted: 11/11/2021] [Indexed: 02/07/2023] Open
Abstract
Locally advanced vulvar cancer (LAVC) is a challenging disease, requiring multidisciplinary management. The aim of this review is to propose an integrated clinical approach including radiotherapy (RT) in the multidisciplinary management of LAVC to customize the treatment. A review of the literature was conducted on PubMed, Scopus, and Cochrane library to acquire all relevant studies on RT in LAVC. Based on the available evidence, RT, with or without concurrent chemotherapy, has a relevant role as adjuvant and exclusive treatment or in the neoadjuvant setting. However, multicentric prospective trials are needed to define the best treatment options based on tumor and patient characteristics. A multidisciplinary and multidimensional assessment can also be useful to identify the most suitable approach, considering patients' age and comorbidities, in view of a better treatment personalization.
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Affiliation(s)
- Luca Tagliaferri
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia—Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (L.T.); (V.L.); (B.G.); (G.F.C.); (M.A.G.)
| | - Valentina Lancellotta
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia—Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (L.T.); (V.L.); (B.G.); (G.F.C.); (M.A.G.)
| | - Calogero Casà
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia—Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (L.T.); (V.L.); (B.G.); (G.F.C.); (M.A.G.)
| | - Simona Maria Fragomeni
- Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (S.M.F.); (S.G.); (G.C.)
| | - Martina Ferioli
- Radiation Oncology Center, IRCCS Azienda Ospedaliero Universitaria di Bologna, DIMES, Alma Mater Studiorum—Bologna University, 40138 Bologna, Italy; (M.F.); (A.G.M.)
| | - Stefano Gentileschi
- Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (S.M.F.); (S.G.); (G.C.)
| | | | - Giacomo Corrado
- Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (S.M.F.); (S.G.); (G.C.)
| | - Benedetta Gui
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia—Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (L.T.); (V.L.); (B.G.); (G.F.C.); (M.A.G.)
| | - Giuseppe Ferdinando Colloca
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia—Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (L.T.); (V.L.); (B.G.); (G.F.C.); (M.A.G.)
| | - Maria Antonietta Gambacorta
- Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia—Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (L.T.); (V.L.); (B.G.); (G.F.C.); (M.A.G.)
| | - Alessio Giuseppe Morganti
- Radiation Oncology Center, IRCCS Azienda Ospedaliero Universitaria di Bologna, DIMES, Alma Mater Studiorum—Bologna University, 40138 Bologna, Italy; (M.F.); (A.G.M.)
| | - Giorgia Garganese
- Gynecology and Breast Care Center, Mater Olbia Hospital, 07026 Olbia, Italy;
- Dipartimento Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Gabriella Macchia
- Unità Operativa di Radioterapia, Ospedale Gemelli Molise, Università Cattolica del Sacro Cuore, 86100 Campobasso, Italy;
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Adjuvant radiotherapy and local recurrence in vulvar cancer - a subset analysis of the AGO-CaRE-1 study. Gynecol Oncol 2021; 164:68-75. [PMID: 34794839 DOI: 10.1016/j.ygyno.2021.11.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 10/29/2021] [Accepted: 11/04/2021] [Indexed: 11/24/2022]
Abstract
BACKGROUND The impact of adjuvant radiotherapy (RT) to the vulva with regard to prognosis and local recurrence in patients with vulvar squamous cell cancer (VSCC) is poorly described. PATIENTS AND METHODS In the AGO-CaRE-1 study 1618 patients with primary VSCC FIGO stage ≥ IB, treated between 1998-2008, were documented. In this retrospective subanalysis, 360 patients were included based on the following criteria: nodal involvement (pN+), known RT treatment and known radiation fields. RESULTS The majority had pT1b/pT2 tumors (n=299; 83.1%). In 76.7%, R0 resection was achieved. 57/360 (15.8%) N+ patients were treated with adjuvant RT to the groins/pelvis and 146/360 (40.5%) received adjuvant RT to the vulva and groins/pelvis. 157/360 (43.6%) patients did not receive any adjuvant RT. HPV status was available in 162/360 patients (45.0%), 75/162 tumors were HPV+(46.3%), 87/162 (53.7%) HPV-. During a median follow-up of 17.2 months, recurrence at the vulva only occurred in 25.5% of patients without adjuvant RT, in 22.8% of patients with adjuvant RT to groins/pelvis and in 15.8% of patients with adjuvant RT to the vulva and groins/pelvis respectively. The risk reducing effect of local RT was independent of the resection margin status. 50% disease free survival time (50% DFST) indicated a stronger impact of adjuvant RT to the vulva in HPV+ compared to HPV- patients (50% DFST 20.7 months vs. 17.8 months). CONCLUSION Adjuvant RT to the vulva was associated with a lower risk for local recurrence in N+ VSCC independent of the resection margin status. This observation was more pronounced in patients with HPV+ tumors in comparison to HPV- tumors.
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Heeren AM, Rotman J, Samuels S, Zijlmans HJMAA, Fons G, van de Vijver KK, Bleeker MCG, Kenter GG, Jordanova EJ, de Gruijl TD. Immune landscape in vulvar cancer-draining lymph nodes indicates distinct immune escape mechanisms in support of metastatic spread and growth. J Immunother Cancer 2021; 9:jitc-2021-003623. [PMID: 34697217 PMCID: PMC8547515 DOI: 10.1136/jitc-2021-003623] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/01/2021] [Indexed: 12/12/2022] Open
Abstract
Background Therapeutic immune intervention is highly dependent on the T-cell priming and boosting capacity of tumor-draining lymph nodes (TDLN). In vulvar cancer, in-depth studies on the immune status of (pre)metastatic TDLN is lacking. Methods We have phenotyped and enumerated various T-cell and myeloid subsets in tumor-free (LN−, n=27) and metastatic TDLN (LN+, n=11) using flow cytometry. Additionally, we studied chemokine and cytokine release profiles and assessed expression of indoleamine 2,3-dioxygenase (IDO) in relation to plasmacytoid dendritic cell (pDC) or myeloid subsets. Results Metastatic involvement of TDLN was accompanied by an inflamed microenvironment with immune suppressive features, marked by hampered activation of migratory DC, increased cytokine/chemokine release, and closely correlated elevations of pDC and LN-resident conventional DC (LNR-cDC) activation state and frequencies, as well as of terminal CD8+ effector-memory T-cell (TemRA) differentiation, regulatory T-cell (Treg) rates, T-cell activation, and expression of cytotoxic T-lymphocyte protein-4 (CTLA-4) and programmed cell death protein-1 (PD-1) immune checkpoints. In addition, high indoleamine 2,3-dioxygenase (IDO) expression and increased frequencies of monocytic myeloid-derived suppressor cells (mMDSC) were observed. Correlation analyses with primary and metastatic tumor burden suggested respective roles for Tregs and suppression of inducible T cell costimulator (ICOS)+ T helper cells in early metastatic niche formation and for CD14+ LNR-cDC and terminal T-cell differentiation in later stages of metastatic growth. Conclusions Metastatic spread in vulvar TDLN is marked by an inflamed microenvironment with activated effector T cells, which are likely kept in check by an interplay of suppressive feedback mechanisms. Our data support (neoadjuvant) TDLN-targeted therapeutic interventions based on CTLA-4 and PD-1 blockade, to reinvigorate memory T cells and curb early metastatic spread and growth.
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Affiliation(s)
- Anne Marijne Heeren
- Cancer Center Amsterdam - Medical Oncology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
| | - Jossie Rotman
- Cancer Center Amsterdam - Medical Oncology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.,Center for Gynecologic Oncology (CGOA), Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
| | - Sanne Samuels
- Center for Gynecologic Oncology Amsterdam (CGOA), AVL NKI, Amsterdam, The Netherlands
| | | | - Guus Fons
- Center for Gynecologic Oncology (CGOA), Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
| | | | - Maaike C G Bleeker
- Department of Pathology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands.,Department of Pathology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
| | - Gemma G Kenter
- Center for Gynecologic Oncology (CGOA), Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.,Center for Gynecologic Oncology Amsterdam (CGOA), AVL NKI, Amsterdam, The Netherlands.,Center for Gynecologic Oncology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands
| | - Ekaterina J Jordanova
- Department of Obstetrics and Gynecology, Center for Gynecological Oncology Amsterdam (CGOA), Amsterdam UMC - Locatie VUMC, Amsterdam, The Netherlands
| | - Tanja D de Gruijl
- Cancer Center Amsterdam - Medical Oncology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
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Abstract
Vulvar cancer is an uncommon gynecological malignancy primarily affecting postmenopausal women. There is no specific screening and the most effective strategy to reduce vulvar cancer incidence is the opportune treatment of predisposing and preneoplastic lesions associated with its development. While vulvar cancer may be asymptomatic, most women present with vulvar pruritus or pain, or have noticed a lump or ulcer. Therefore, any suspicious vulvar lesion should be biopsied to exclude invasion. Once established, the most common subtype is squamous cell carcinoma. Treatment of vulvar cancer depends primarily on histology and surgical staging. Treatment is predominantly surgical, particularly for squamous cell carcinoma, although concurrent chemoradiation is an effective alternative, particularly for advanced tumors. Management should be individualized and carried out by a multidisciplinary team in a cancer center experienced in the treatment of these tumors. A useful update for trainees and specialists regarding the diagnosis, staging, treatment, and some controversies in the management of vulvar neoplasms.
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Affiliation(s)
- Alexander B Olawaiye
- Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Mauricio A Cuello
- Department of Gynecology, Division of Obstetrics and Gynecology, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Linda J Rogers
- Division of Gynecological Oncology, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.,South African Medical Research Council University of Cape Town Gynecological Cancer Research Centre (SA MRC UCT GCRC, Cape Town, South Africa
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Garganese G, Romito A, Scambia G, Fagotti A. New developments in rare vulvar and vaginal cancers. Curr Opin Oncol 2021; 33:485-492. [PMID: 34319290 DOI: 10.1097/cco.0000000000000757] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW To provide the latest insight on the rare vulvar and vaginal malignancies, able to impact on clinical practice, and to outline new potential research developments. RECENT FINDINGS Many efforts are being made to produce technical and scientific advances in the fields of vulvar and vaginal carcinoma, including imaging work-up, interventional procedures and minimally invasive surgical approach, as well as molecular profiling and identification of new target treatments. SUMMARY In the evaluation of lymph node status, ultrasound has demonstrated promising results because of high predictive value, low risk and low cost. Positron Emission Tomography-Computed Tomography is confirmed to be reliable and should be prospectively investigated for its potential applications in radiomics, whilst Fusion-US could allow a precision guidance in diagnostics and interventional procedures. Regarding interventional procedure, surgery is becoming less invasive with the aim to increase quality of life; in carefully selected patients it would be possible to overcome the current strict criteria in the use of sentinel node biopsy. Future research should focus on potential target therapy, on the basis of tumor-specific biological features.Rare cancers should be referred to experienced centers with a high case flow, able to offer a full range of diagnostic and therapeutical options and a multidisciplinary approach. Networking should be encouraged to promote research opportunities and enable data sharing and multicenter trials.
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Affiliation(s)
- Giorgia Garganese
- Gynecology and Breast Care Center, Mater Olbia Hospital, Olbia
- Dipartimento Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore
| | - Alessia Romito
- Gynecology and Breast Care Center, Mater Olbia Hospital, Olbia
| | - Giovanni Scambia
- Dipartimento Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore
- Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
| | - Anna Fagotti
- Dipartimento Scienze della Vita e Sanità Pubblica, Università Cattolica del Sacro Cuore
- Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A Gemelli IRCCS, Rome, Italy
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Jaeger A, Prieske K, Mathey S, Fischer I, Vettorazzi E, Kuerti S, Reuter S, Dieckmann J, Schmalfeldt B, Woelber L. Pelvic lymphadenectomy in vulvar cancer and its impact on prognosis and outcome. Arch Gynecol Obstet 2021; 305:233-240. [PMID: 34387725 PMCID: PMC8782795 DOI: 10.1007/s00404-021-06156-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Accepted: 07/21/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND The value of pelvic lymphadenectomy (LAE) has been subject of discussions since the 1980s. This is mainly due to the fact that the relation between lymph node involvement of the groin and pelvis is poorly understood and therewith the need for pelvic treatment in general. PATIENTS AND METHODS N = 514 patients with primary vulvar squamous cell cancer (VSCC) FIGO stage ≥ IB were treated at the University Medical Center Hamburg-Eppendorf between 1996 and 2018. In this analysis, patients with pelvic LAE (n = 21) were analyzed with regard to prognosis and the relation of groin and pelvic lymph node involvement. RESULTS The majority had T1b/T2 tumors (n = 15, 78.9%) with a median diameter of 40 mm (11-110 mm). 17/21 patients showed positive inguinal nodes. Pelvic nodal involvement without groin metastases was not observed. 6/17 node-positive patients with positive groin nodes also had pelvic nodal metastases (35.3%; median number of affected pelvic nodes 2.5 (1-8)). These 6 patients were highly node positive with median 4.5 (2-9) affected groin nodes. With regard to the metastatic spread between groins and pelvis, no contralateral spread was observed. Five recurrences were observed after a median follow-up of 33.5 months. No pelvic recurrences were observed in the pelvic nodal positive group. Patients with pelvic metastasis at first diagnosis had a median progression-free survival of only 9.9 months and overall-survival of 31.1 months. CONCLUSION A relevant risk for pelvic nodal involvement only seems to be present in highly node-positive disease, therefore pelvic staging (and radiotherapy) is probably unnecessary in the majority of patients with node-positive VSCC.
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Affiliation(s)
- A Jaeger
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - K Prieske
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.,Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - S Mathey
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - I Fischer
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - E Vettorazzi
- Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - S Kuerti
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - S Reuter
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - J Dieckmann
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - B Schmalfeldt
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany
| | - L Woelber
- Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
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Fokdal L, Jensen PT, Wulff C, Sanggaard MA, Hae M, Niemann I, Hansen ES, Lindegaard JC. Lichen Sclerosis is Associated With a High Rate of Local Failure After Radio(chemo)therapy for Vulvar Cancer. Clin Oncol (R Coll Radiol) 2021; 34:3-10. [PMID: 34392994 DOI: 10.1016/j.clon.2021.07.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 06/24/2021] [Accepted: 07/21/2021] [Indexed: 11/28/2022]
Abstract
AIMS Radio(chemo)therapy plays an important role in the treatment of vulvar cancer, either as postoperative treatment or as definitive treatment in patients who present with inoperable disease. Only limited data are available regarding outcome after modern state of the art radio(chemo)therapy and more information regarding prognostic factors are warranted. The aim of this study was to evaluate disease outcomes after radio(chemo)therapy in patients with vulvar cancer with special emphasis on the impact of lichen sclerosis on local control. MATERIALS AND METHODS All consecutive patients (n = 109) from the western half of Denmark who were treated with definitive (n = 52) or postoperative (n = 57) radio(chemo)therapy between January 2013 and January 2020 were included. Local control, cause-specific survival and overall survival, as well as morbidity, were analysed using Kaplan-Meier statistics. Prognostic factors for local control were analysed in univariate and multivariate analysis. RESULTS At a median follow-up of 35 (4-95) months, 46 (42.0%) patients were diagnosed with recurrence. Eighty per cent of the recurrences were located to the vulva region, leading to a 5-year local control of 58.9% (confidence interval 47.9-69.9). Cause-specific survival was 62.9% (confidence interval 53.1-72.7), whereas overall survival was 58.0% (confidence interval 47.6-68.5). Grade 3-4 morbidity was diagnosed in 10 (9%) patients. Lichen sclerosis (hazard ratio 3.89; confidence interval 1.93-7.79) was an independent risk factors for local recurrence. Patients without lichen sclerosis had a 5-year local control rate of 83.6% (confidence interval 67.2-99.0) and 62.6% (confidence interval 43.2-82.0) after postoperative and definitive radio(chemo)therapy, respectively. In patients with lichen sclerosis, the local control rate was 44.0% (confidence interval 19.3-69.0) and 17.6% (confidence interval 0-30.0) after postoperative and definitive radio(chemo)therapy, respectively. CONCLUSION Radio(chemo)therapy plays an important role in the treatment of vulvar cancer. However, despite dose escalation, a substantial proportion of patients experienced local relapse. Pre-existing lichen sclerosis seems to have a significant impact on the risk of recurrence. This should influence surveillance programmes for these patients.
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Affiliation(s)
- L Fokdal
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
| | - P T Jensen
- Department of Gynaecology, Aarhus University Hospital, Aarhus, Denmark
| | - C Wulff
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - M A Sanggaard
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - M Hae
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - I Niemann
- Department of Gynaecology, Aarhus University Hospital, Aarhus, Denmark
| | - E S Hansen
- Department of Pathology, Aarhus University Hospital, Aarhus, Denmark
| | - J C Lindegaard
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
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Bhatla N, Tomar S, Meena J, Sharma DN, Kumar L. Adjuvant treatment in cervical, vaginal and vulvar cancer. Best Pract Res Clin Obstet Gynaecol 2021; 78:36-51. [PMID: 34426088 DOI: 10.1016/j.bpobgyn.2021.07.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Accepted: 07/14/2021] [Indexed: 11/19/2022]
Abstract
Primary surgical management is successful as the sole therapeutic modality in the majority of women with early-stage cervical, vaginal and vulvar cancer, but the presence of certain risk factors in the surgico-pathological specimen indicates a poorer prognosis. Adjuvant treatment can improve overall survival in such cases. Important risk factors in cervical cancer include intermediate-risk factors (large tumor size, deep cervical stromal invasion, lymph-vascular space invasion) and high-risk factors (positive or close margins, lymph nodes, or parametrial involvement). In vulvar cancer, positive margins and lymph nodes are the two most important factors for adjuvant therapy. Radiation therapy has been the mainstay of adjuvant therapy in these cancers, supplemented by chemotherapy. Recent advances have witnessed the inclusion of newer therapeutic modalities such as immunotherapy. This review addresses the current status of various adjuvant therapeutic modalities for these gynecological cancers.
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Affiliation(s)
- Neerja Bhatla
- Department of Obstetrics & Gynaecology, All India Institute of Medical Sciences, New Delhi, India.
| | - Swati Tomar
- Department of Obstetrics & Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Jyoti Meena
- Department of Obstetrics & Gynaecology, All India Institute of Medical Sciences, New Delhi, India
| | - Daya Nand Sharma
- Department of Radiation Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
| | - Lalit Kumar
- Department of Medical Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
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Marco A, Luca B, Andrea Alberto L, Francesca V, Serena N, Tommaso G, Alessandro B, Fabio L. Neoadjuvant chemotherapy followed by radical surgery in locally advanced vulvar carcinoma: a single-institution experience. TUMORI JOURNAL 2021; 108:495-501. [PMID: 34289750 DOI: 10.1177/03008916211027627] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Squamous cell carcinoma of the vulva is a rare malignancy that affects elderly women. About one-third of vulvar cancers are diagnosed in an advanced stage, requiring extensive surgery. Neoadjuvant chemotherapy (NACT) has been introduced to reduce local tumor burden. In this retrospective study, we analyze the efficacy and toxicity of NACT followed by radical surgery. METHODS Patients with locally advanced vulvar cancer (LAVC) treated at our institution with neoadjuvant platinum and paclitaxel-based chemotherapy ± ifosfamide followed by surgery at our institution were retrospectively identified. RESULTS Fourteen patients (93%) completed NACT with tolerable toxicities (G3-G4 toxicity: 30%). Thirteen patients (87%) underwent surgery. The overall clinical response rate on vulvar disease was 66% (20% complete response, 46% partial response), confirmed by histopathologic analysis, while on inguinal lymph nodes it was 69% (23% complete response, 46% partial response). At the pathologic examination, all patients had negative surgical margins. Three out of 9 patients (33%) with lesions infiltrating the urethral meatus and 4 patients out of 7 (57%) with anal involvement did not require urethral amputation or colostomy, respectively, after NACT. No severe postoperative complications were described. Overall survival at 5 years was 60%, and median overall survival was 76 months. CONCLUSION NACT followed by surgery in locally advanced vulvar cancer is well tolerated and allows surgical modulation.
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Affiliation(s)
- Adorni Marco
- Gynaecologic Oncology Surgical Unit, Obstetrics and Gynaecology Department, ASST-Monza, San Gerardo Hospital, Monza, Lombardia, Italy.,School of Medicine and Surgery, University of Milano-Bicocca, Milano, Lombardia, Italy
| | - Bazzurini Luca
- Gynaecologic Oncology Surgical Unit, Obstetrics and Gynaecology Department, ASST-Monza, San Gerardo Hospital, Monza, Lombardia, Italy
| | - Lissoni Andrea Alberto
- Gynaecologic Oncology Surgical Unit, Obstetrics and Gynaecology Department, ASST-Monza, San Gerardo Hospital, Monza, Lombardia, Italy
| | - Vecchione Francesca
- Gynaecologic Oncology Surgical Unit, Obstetrics and Gynaecology Department, ASST-Monza, San Gerardo Hospital, Monza, Lombardia, Italy
| | - Negri Serena
- Gynaecologic Oncology Surgical Unit, Obstetrics and Gynaecology Department, ASST-Monza, San Gerardo Hospital, Monza, Lombardia, Italy.,School of Medicine and Surgery, University of Milano-Bicocca, Milano, Lombardia, Italy
| | - Grassi Tommaso
- Gynaecologic Oncology Surgical Unit, Obstetrics and Gynaecology Department, ASST-Monza, San Gerardo Hospital, Monza, Lombardia, Italy
| | - Buda Alessandro
- Gynaecologic Onclogy Unit, Michele e Pietro Ferrero Hospital, Verduno, Piemonte, Italy
| | - Landoni Fabio
- Gynaecologic Oncology Surgical Unit, Obstetrics and Gynaecology Department, ASST-Monza, San Gerardo Hospital, Monza, Lombardia, Italy
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49
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Wölber L, Jaeger A. Vulvadysplasie und Vulvakarzinom. COLOPROCTOLOGY 2021. [DOI: 10.1007/s00053-021-00543-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Abstract
PURPOSE OF REVIEW To highlight the recent advances regarding molecular mechanisms and therapeutic strategies in vulvar squamous cell carcinoma (VSCC), a rare but continuously rising disease. RECENT FINDINGS Clinical research focuses on deescalation especially with regard to surgery. Recurrence patterns have been analyzed to further understand the course of disease showing a persistent risk for local recurrence even several years after the initial diagnosis. The main focuses of recent translational research are the distinct molecular mechanisms behind human papillomavirus (HPV)-positive and -negative VSCC. Next-generation sequencing analyses have highlighted TP53 as central driver mutation in HPV-negative disease. For HPV-independent VSCC, an impaired prognosis with limited disease-free and overall survival has been reported from a large multicenter analysis. Although no targeted agent has been granted approval, the impact of immunotherapy in vulvar cancer has been investigated in basket trials. Therapy response, however, was limited. SUMMARY Further clinical research should focus on deciphering the molecular mechanisms of tumor development further. Detailed understanding of the molecular landscape will help to find novel therapy targets, fight the disease in advanced stages and thereby improve the quality of life for affected patients.
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