Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Ver. Summary Created by Modification Content Size Created at Operation
1 + 998 word(s) 998 2021-11-26 03:56:40 |
2 format correct Meta information modification 998 2021-12-27 07:52:17 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Casà, C. The Multidisciplinary Management of Locally Advanced Vulvar Cancer. Encyclopedia. Available online: (accessed on 05 December 2023).
Casà C. The Multidisciplinary Management of Locally Advanced Vulvar Cancer. Encyclopedia. Available at: Accessed December 05, 2023.
Casà, Calogero. "The Multidisciplinary Management of Locally Advanced Vulvar Cancer" Encyclopedia, (accessed December 05, 2023).
Casà, C.(2021, December 27). The Multidisciplinary Management of Locally Advanced Vulvar Cancer. In Encyclopedia.
Casà, Calogero. "The Multidisciplinary Management of Locally Advanced Vulvar Cancer." Encyclopedia. Web. 27 December, 2021.
The Multidisciplinary Management of Locally Advanced Vulvar Cancer

Locally advanced vulvar cancer (LAVC) requires a multidisciplinary management. Based on the available evidence, radiotherapy, with or without concurrent chemotherapy, has a relevant role in neoadjuvant, adjuvant or exclusive treatments. A multidisciplinary and multidimensional assessment can also be useful to identify the most suitable approach, in view of a better treatment personalization.

vulvar cancer radiotherapy review

1. Introduction

Vulvar cancer (VC) is an uncommon disease, usually affecting elderly women and representing about 5% of gynecological cancers [1][2][3].
VC patients require a multidisciplinary evaluation for primary surgery and inguinal lymph node assessment, and potentially adjuvant radiation and/or chemotherapy [4][5][6][7][8]. Radiotherapy (RT) and/or chemotherapy may be considered for primary treatment instead of surgery in cases that would otherwise require radical surgery such as abdominal-perineal resection or exenterative procedures.
As there is no standard treatment algorithm that fits all patients, multimodal clinical approaches, especially in VC involving perineal tissues, have been proposed [8][9][10].
Groin and pelvic adjuvant RT should be administered for any nodal metastasis and/or close/involved margins unfit for further surgery. Large tumors, or those at high risk of surgical morbidity, are candidates for primary (chemo) radiation treatment, and multidisciplinary teams play an important role in the evaluation phase [11][12][13][14][15].
In recent decades, RT has benefited from major technological improvements, with image-guided and intensity-modulated treatments. The use of computed tomography (CT) and magnetic resonance imaging (MRI) for treatment planning allows for the precise delineation of the tumor and surrounding organs (OARs), improving target dose coverage. Modern techniques allow the delivery of comparatively higher doses to the tumor, while minimizing doses to healthy tissue. In several cancers, these improvements lead to a better outcome, in terms of both local control and toxicity rates [16][17][18].

2. The Multidisciplinary Management of Locally Advanced Vulvar Cancer

The 30% of VC patients presenting with locally advanced disease (T3/T4) may represent a problem regarding the treatment. Ultraradical surgery alone (radical vulvar operation combined with a partial or total pelvic exenterative-type procedure) is associated with a 4.3% mortality rate and 46% disease-free survival [19]. However, although this is not well reported in the literature, there is significant physical and psychological morbidity resulting from these procedures due to a permanent colostomy, urostomy or both [19][20]. In comparison with radical surgery, chemotherapy has been shown to be associated with poor survival and significant treatment-related toxicity [21][22]. RT combined with chemotherapy, followed by organ-sparing surgery has shown efficacy in preventing stoma, but is also associated with significant wound-healing problems and treatment-related mortality [23][24][25]. High-quality evidence on neoadjuvant RT was difficult to collect for several reasons, such as a small sample size, the heterogeneity of studies, and the use of different radio-chemotherapy schedules, RT dose fractionation, techniques, and target definitions. There was no evidence of a survival advantage or reduction in toxicity when neoadjuvant radio-chemotherapy was compared to primary surgery for women with locally advanced VC [26]. In patients with large tumours that can only be treated with anterior and/or posterior exenteration, the complications of neo-adjuvant therapy might outweigh the complications of exenterative surgery. Neoadjuvant therapy is not justified in patients with tumours that can be adequately treated with radical vulvectomy and bilateral groin node dissection alone [27].

Age was a significant predictor of Overall Survival (OS) [28][24][29][30][31]. When patients younger than the median age of 64 were compared to those >65 years, significant improvements in OS and Progression-Free Survival (PFS) were observed [28][24][29][30][31]. Furthermore, age > 60 - 68 years had a negative impact on the entire response rate [24].

Adjuvant RT is indicated in patients with high risk factors, such as close/involved margins or inguinal lymph node involvement, to decrease the rate of recurrence, and thus improve OS, as shown in our results. Statistically significant improvements in OS and DFS according to low-stage and negative nodal status [32] were found, together with an improved LC in patients with close/involved surgical margins after adjuvant RT [30]. Even in the adjuvant setting, we recorded high clinical outcome rates [33][30][34]. These results, particularly in terms of LC, favorably compare with surgery alone. In fact, even in patients with early VC, surgical resection is associated with local recurrence rates of up to 40%. [35]. Moreover, after surgery that affect tissues worsening tolerance, severe acute/late toxicity was reported in about one third of patients, mainly in terms of skin side effects.

The treatment with Interventional Radiotherapy (IRT) that allows for the delivery of a high radiation dose to the tumor, while sparing the surrounding, at-risk organs, with a very sharp dose fall-off, deserves special attention. It is well known that IRT is an effective treatment option for primary and recurrent VC, especially in patients with severe comorbidities and contraindications for surgery [1]. Our analysis confirmed previous findings, which reported encouraging 5-year clinical outcomes, especially considering the preferential selection of most frail patients for IRT [36][21][22][27][37]. Despite these positive data, IRT is rarely considered among the therapeutic options for locally advanced VC patients. It is likely that the rarity of this tumor, lack of widespread experience and expertise, and complexities in performing this treatment technique limit the use of IRT in the majority of RT centers [38][39]. IRT could theoretically also be used as a boost after concurrent radio-chemotherapy to improve LC rates, especially in larger VCs. However, the role and real efficacy of IRT-based boost is largely unproven, with no prospective or randomized controlled trials available in this setting [40].

3. Conclusions

Most of the evidence on RT of VCs is low-level, based on retrospective studies. However, in different treatment settings, RT results are quite homogeneously encouraging even if there is clearly room for further improvements, in terms of both treatment outcomes and late sequelae and patient selection. These improvements may derive from prospective and possibly randomized studies, even if the rarity of VCs severely limits their feasibility. In parallel, or alternatively, the design of large databases could allow for the development of predictive models, which are particularly useful for defining individualized treatments based on tumors and patients’ characteristics. To date, the multidisciplinary management of these patients, based on tumor board discussion, represents the broader and more fruitful cooperation possible when choosing the best treatment for each patient.


  1. Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2020. CA Cancer J. Clin. 2020, 70, 7–30.
  2. Eifel, P.J.; Berek, J.S.; Markman, M.A. Cancer of the cervix, vagina and vulva. In Cancer: Principles and Practice of Oncology, 9th ed.; DeVita, V.T., Hellman, S., Rosenberg, S.A., Eds.; Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2011; pp. 1172–1210.
  3. Pejovic, T.; Krieg, J.A.; Odunsi, K. Molecular Biology of Gynecologic Cancers. In Cancer: Principles & Practice of Oncology, 9th ed.; DeVita, V.T., Hellman, S., Rosenberg, S.A., Eds.; Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2011; pp. 1163–1171.
  4. Garganese, G.; Fragomeni, S.M.; Pasciuto, T.; Leombroni, M.; Moro, F.; Evangelista, M.T.; Bove, S.; Gentileschi, S.; Tagliaferri, L.; Paris, I.; et al. Ultrasound morphometric and cytologic preoperative assessment of inguinal lymph-node status in women with vulvar cancer: MorphoNode study. Ultrasound Obstet. Gynecol. 2019, 55, 401–410.
  5. Rufini, V.; Garganese, G.; Ieria, F.P.; Pasciuto, T.; Fragomeni, S.M.; Gui, B.; Florit, A.; Inzani, F.; Zannoni, G.F.; Scambia, G.; et al. Diagnostic performance of preoperative (18F)FDG-PET/CT for lymph node staging in vulvar cancer: A large single-centre study. Eur. J. Nucl. Med. Mol. Imaging 2021, 48, 3303–3314.
  6. Collarino, A.; Garganese, G.; Fragomeni, S.M.; Bouda, L.M.P.A.; Ieria, F.P.; Boellaard, R.; Rufini, V.; de Geus-Oei, L.-F.; Scambia, G.; Olmos, R.A.V.; et al. Radiomics in vulvar cancer: First clinical experience using 18F-FDG PET/CT images. J. Nucl. Med. 2018, 60, 199–206.
  7. Garganese, G.; Tagliaferri, L.; Fragomeni, S.M.; Lancellotta, V.; Colloca, G.; Corrado, G.; Gentileschi, S.; Macchia, G.; Tamburrini, E.; Gambacorta, M.A.; et al. Personalizing vulvar cancer workflow in COVID-19 era: A proposal from Vul. Can MDT. J. Cancer Res. Clin. Oncol. 2020, 146, 2535–2545.
  8. Tagliaferri, L.; Garganese, G.; D′Aviero, A.; Lancellotta, V.; Fragomeni, S.M.; Fionda, B.; Casà, C.; Gui, B.; Perotti, G.; Gentileschi, S.; et al. Muldisciplinary personalized approach in the management of vulvar cancer—The Vul. Can Team experience. Int. J. Gynecol. Cancer 2020, 30, 932–938.
  9. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Vulvar Cancer Version 1. 2020. Available online: (accessed on 6 January 2020).
  10. Tagliaferri, L.; Casà, C.; Macchia, G.; Pesce, A.; Garganese, G.; Gui, B.; Perotti, G.; Gentileschi, S.; Inzani, F.; Autorino, R.; et al. The role of radiotherapy in extramammary paget disease: A systematic review. Int. J. Gynecol. Cancer 2018, 28, 829–839.
  11. Parthasarathy, A.; Cheung, M.K.; Osann, K.; Husain, A.; Teng, N.N.; Berek, J.S.; Kapp, D.S.; Chan, J.K. The benefit of adjuvant radiation therapy in single-node-positive squamous cell vulvar carcinoma. Gynecol. Oncol. 2006, 103, 1095–1099.
  12. Xanthopoulos, E.P.; Grover, S.; Puri, P.M.; Corradetti, M.N.; Heilbroner, S.P.; Mitra, N.; Simone, C.B.; Lin, L.L. Survival benefit of adjuvant radiation therapy in node-positive vulvar cancer. Am. J. Clin. Oncol. 2018, 41, 845–850.
  13. Swanick, C.W.; Eifel, P.J.; Huo, J.; Meyer, L.A.; Smith, G.L. Challenges to delivery and effectiveness of adjuvant radiation therapy in elderly patients with node-positive vulvar cancer. Gynecol. Oncol. 2017, 146, 87–93.
  14. Fons, G.; Groenen, S.; Oonk, M.; Ansink, A.; van der Zee, A.; Burger, M.; Stalpers, L.; van der Velden, J. Adjuvant radiotherapy in patients with vulvar cancer and one intra capsular lymph node metastasis is not beneficial. Gynecol. Oncol. 2009, 114, 343–345.
  15. Rydzewski, N.R.; Kanis, M.J.; Donnelly, E.D.; Lurain, J.R.; Strauss, J.B. Role of adjuvant external beam radiotherapy and chemotherapy in one versus two or more node-positive vulvar cancer: A National Cancer Database study. Radiother. Oncol. 2018, 129, 534–539.
  16. Tanderup, K.; Fokdal, L.U.; Sturdza, A.; Haie-Meder, C.; Mazeron, R.; van Limbergen, E.; Jürgenliemk-Schulz, I.; Petric, P.; Hoskin, P.; Doerr, W.; et al. Effect of tumor dose, volume and overall treatment time on local control after radiochemotherapy including MRI guided brachytherapy of locally advanced cervical cancer. Radiother. Oncol. 2016, 120, 441–446.
  17. Berger, T.; Seppenwoolde, Y.; Pötter, R.; Assenholt, M.S.; Lindegaard, J.C.; Nout, R.A.; de Leeuw, A.; Jürgenliemk-Schulz, I.; Tan, L.T.; Georg, D.; et al. Importance of technique, target selection, contouring, dose prescription, and dose-planning in external beam radiation therapy for cervical cancer: Evolution of practice from EMBRACE-I to II. Int. J. Radiat. Oncol. 2019, 104, 885–894.
  18. Mazeron, R.; Castelnau-Marchand, P.; Dumas, I.; del Campo, E.R.; Kom, L.K.; Martinetti, F.; Farha, G.; Tailleur, A.; Morice, P.; Chargari, C.; et al. Impact of treatment time and dose escalation on local control in locally advanced cervical cancer treated by chemoradiation and image-guided pulsed-dose rate adaptive brachytherapy. Radiother. Oncol. 2015, 114, 257–263.
  19. Flam, M.; John, M.; Pajak, T.F.; Petrelli, N.; Myerson, R.; Doggett, S.; Quivey, J.; Rotman, M.; Kerman, H.; Coia, L.; et al. Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: Results of a phase III randomized intergroup study. J. Clin. Oncol. 1996, 14, 2527–2539.
  20. Domingues, A.P.; Mota, F.; Durão, M.; Frutuoso, C.; Amaral, N.; De Oliveira, C.F. Neoadjuvant chemotherapy in advanced vulvar cancer. Int. J. Gynecol. Cancer 2010, 20, 294–298.
  21. Niu, Y.; Yin, R.; Wang, D.; Li, Q.; Gao, X.; Huang, M. Clinical analysis of neoadjuvant chemotherapy in patients with advanced vulvar cancer: A STROBE-compliant article. Medicine 2018, 97, e11786.
  22. O’Donnell, R.L.; Verleye, L.; Ratnavelu, N.; Galaal, K.; Fisher, A.; Naik, R. Locally advanced vulva cancer: A single centre review of anovulvectomy and a systematic review of surgical, chemotherapy and radiotherapy alternatives. Is an international collaborative RCT destined for the “too difficult to do” box? Gynecol. Oncol. 2016, 144, 438–447.
  23. Han, S.C.; Kim, D.H.; Higgins, S.A.; Carcangiu, M.-L.; Kacinski, B.M. Chemoradiation as primary or adjuvant treatment for locally advanced carcinoma of the vulva. Int. J. Radiat. Oncol. 2000, 47, 1235–1244.
  24. Rishi, A.; Rollins, M.; Ahmed, K.A.; Hunt, D.C.; Sarkar, P.; Fernandez, D.C.; Hoffman, M.S.; Apte, S.M.; Shahzad, M.M.; Chon, H.S.; et al. High-dose intensity-modulated chemoradiotherapy in vulvar squamous cell carcinoma: Outcome and toxicity. Gynecol. Oncol. 2020, 156, 349–356.
  25. Rao, Y.J.; Chin, R.-I.; Hui, C.; Mutch, D.G.; Powell, M.A.; Schwarz, J.K.; Grigsby, P.W.; Markovina, S. Improved survival with definitive chemoradiation compared to definitive radiation alone in squamous cell carcinoma of the vulva: A review of the National Cancer Database. Gynecol. Oncol. 2017, 146, 572–579.
  26. Van Doorn, H.C.; Ansink, A.; Verhaar-Langereis, M.; Stalpers, L. Neoadjuvant chemoradiation for advanced primary vulvar cancer. Cochrane Database Syst. Rev. 2006, 3, CD003752.
  27. Shylasree, T.S.; Bryant, A.; Howells, R.E. Chemoradiation for advanced primary vulval cancer. Cochrane Database Syst. Rev. 2011, 4, CD003752.
  28. Sakanaka, K.; Itasaka, S.; Ishida, Y.; Fujii, K.; Horimatsu, T.; Mizowaki, T.; Sakai, Y.; Hiraoka, M. Dosimetric advantages and clinical outcomes of simultaneous integrated boost intensity-modulated radiotherapy for anal squamous cell carcinoma. Radiat. Oncol. J. 2017, 35, 368–379.
  29. Logar, H.B.Z. Long term results of radiotherapy in vulvar cancer patients in Slovenia between 1997–2004. Radiol. Oncol. 2017, 51, 447–454.
  30. Mahner, S.; Jueckstock, J.; Hilpert, F.; Neuser, P.; Harter, P.; de Gregorio, N.; Hasenburg, A.; Sehouli, J.; Habermann, A.; Hillemanns, P.; et al. Adjuvant therapy in lymph node–positive vulvar cancer: The AGO-CaRE-1 study. J. Natl. Cancer Inst. 2015, 107, dju426.
  31. Laliscia, C.; Gadducci, A.; Fabrini, M.G.; Barcellini, A.; Parietti, E.; Pasqualetti, F.; Morganti, R.; Mazzotti, V.; Cafaro, I.; Paiar, F. Definitive radiotherapy for recurrent vulvar carcinoma after primary surgery: A two-institutional Italian experience. Tumori J. 2019, 105, 225–230.
  32. Kunos, C.; Simpkins, F.; Gibbons, H.; Tian, C.; Homesley, H. Radiationtherapy compared with pelvic noderesection for node positive vulv cancer: A randomized controlled trial. Obstet. Gynecol. 2009, 114, 537–546.
  33. Gill, B.S.; Bernard, M.E.; Lin, J.F.; Balasubramani, G.K.; Rajagopalan, M.S.; Sukumvanich, P.; Krivak, T.C.; Olawaiye, A.B.; Kelley, J.L.; Beriwal, S. Impact of adjuvant chemotherapy with radiation for node-positive vulvar cancer: A National Cancer Data Base (NCDB) analysis. Gynecol. Oncol. 2015, 137, 365–372.
  34. Laliscia, C.; Fabrini, M.G.; Cafaro, I.; Barcellini, A.; Baldaccini, D.; Miniati, M.; Parietti, E.; Morganti, R.; Paiar, F.; Gadducci, A. Adjuvant radiotherapy in high-risk squamous cell carcinoma of the vulva: A two-institutional Italian experience. Oncol. Res. Treat. 2017, 40, 778–783.
  35. Te Grootenhuis, N.C.; Van Der Zee, A.G.J.; Van Doorn, H.C.; van der Velden, J.; Vergote, I.; Zanagnolo, V.; Baldwin, P.J.; Gaarenstroom, K.N.; Van Dorst, E.B.; Trum, J.W.; et al. Sentinel nodes in vulvar cancer: Long-term follow-up of the GROningen INternational Study on Sentinel nodes in Vulvar cancer (GROINSS-V) I. Gynecol. Oncol. 2016, 140, 8–14.
  36. Moore, D.H.; Thomas, G.M.; Montana, G.S.; Saxer, A.; Gallup, D.G.; Olt, G. Preoperative chemoradiation for advanced vulvar cancer: A phase II study of the Gynecologic Oncology Group. Int. J. Radiat. Oncol. Biol. Phys. 1998, 42, 79–85.
  37. Cox, J.D.; Stetz, J.; Pajak, T.F. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int. J. Radiat. Oncol. Biol. Phys. 1995, 31, 1341–1346.
  38. Autorino, R.; Vicenzi, L.; Tagliaferri, L.; Soatti, C.; Kovacs, G.; Aristei, C. A national survey of AIRO (Italian Association of Radiation Oncology) brachytherapy (Interventional Radiotherapy) study group. J. Contemp. Brachyther. 2018, 10, 254–259.
  39. Tagliaferri, L.; Vavassori, A.; Lancellotta, V.; De Sanctis, V.; Barbera, F.; Fusco, V.; Vidali, C.; Fionda, B.; Colloca, G.; Gambacorta, M.; et al. Can brachytherapy be properly considered in the clinical practice? Trilogy project: The vision of the AIRO (Italian Association of Radiotherapy and Clinical Oncology) Interventional Radiotherapy study group. J. Contemp. Brachyther. 2020, 12, 84–90.
  40. Lancellotta, V.; Macchia, G.; Garganese, G.; Fionda, B.; Fragomeni, S.M.; D’Aviero, A.; Casà, C.; Gui, B.; Gentileschi, S.; Corrado, G.; et al. The role of brachytherapy (interventional radiotherapy) for primary and/or recurrent vulvar cancer: A Gemelli Vul. Can multidisciplinary team systematic review. Clin. Transl. Oncol. 2021, 23, 1611–1619.
Subjects: Oncology
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to :
View Times: 248
Revisions: 2 times (View History)
Update Date: 28 Dec 2021