Role of Radiotherapy in Vulvar Squamous Cell Carcinoma: 
Review of the Literature

Yildiz, Ferah; Beduk Esen, Caglayan Selenge; Gultekin, Melis

doi:10.5505/tjo.2021.3327

Role of Radiotherapy in Vulvar Squamous Cell Carcinoma: Review of the Literature

Çağlayan Selenge BEDÜK ESEN, (Hacettepe Üniversitesi, Tıp Fakültesi, Radyasyon Onkolojisi Anabilim Dalı, Ankara, Türkiye)

Melis GÜLTEKİN, (Hacettepe Üniversitesi, Tıp Fakültesi, Radyasyon Onkolojisi Anabilim Dalı, Ankara, Türkiye)

Ferah YILDIZ (Hacettepe Üniversitesi, Tıp Fakültesi, Radyasyon Onkolojisi Anabilim Dalı, Ankara, Türkiye)

Türk Onkoloji Dergisi

2 0

Yıl: 2021 Cilt: 36 Sayı: 4 Sayfa Aralığı: 529 - 537 Metin Dili: İngilizce DOI: 10.5505/tjo.2021.3327 İndeks Tarihi: 15-06-2022

Role of Radiotherapy in Vulvar Squamous Cell Carcinoma: Review of the Literature

Öz:

En bloc radical vulvectomy with bilateral inguinofemoral lymph node dissection was the standard approach for patients diagnosed with vulvar cancer, regardless of disease extent in the past. This radical surgical approach was with high rates of morbidity and adverse psychological effects and led to insufficient locoregional control rates in patients with locally advanced-stage disease. In recent years, multimodal treatment approaches have been introduced to decrease treatment-related morbidity and increase the locoregional control rates. Radiotherapy (RT) has a major role in the treatment of vulvar cancer. It has been successfully used as an adjuvant approach in patients with high risk of local recurrence after surgery and as a sole local treatment with concomitant chemotherapy in locally advanced disease. In this current review, we will discuss the rationale of RT and provide up-to-date information about the role of RT in the treatment of vulvar cancer.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Derleme Erişim Türü: Erişime Açık

1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin 2021;71(1):7–33.
2. Schuurman MS, van den Einden LC, Massuger LF, Kiemeney LA, van der Aa MA, de Hullu JA. Trends in incidence and survival of Dutch women with vulvar squamous cell carcinoma. Eur J Cancer 2013;49:3872– 80.
3. Bethesda M. SEER Cancer Statistics Factsheets: Vulvar Cancer. Tamil Nadu: NIH; 2021.
4. Bornstein J, Bogliatto F, Haefner HK, Stockdale CK, Preti M, Bohl TG, et al. The 2015 international society for the study of vulvovaginal disease (ISSVD) terminology of vulvar squamous intraepithelial lesions. J Low Genit Tract Dis 2016;20(2):11–4.
5. Madsen BS, Jensen HL, van den Brule AJ, Wohlfahrt J, Frisch M. Risk factors for invasive squamous cell carcinoma of the vulva and vagina--populationbased case-control study in Denmark. Int J Cancer 2008;122(12):2827–34.
6. Zapardiel I, Iacoponi S, Coronado PJ, Zalewski K, Chen F, Fotopoulou C, et al. Prognostic factors in patients with vulvar cancer: The VULCAN study. Int J Gynecol Cancer 2020;30(9):1285–91.
7. Yap J, O’Neill D, Nagenthiran S, Dawson CW, Luesley DM. Current insights into the aetiology, pathobiology, and management of local disease recurrence in squamous cell carcinoma of the vulva. BJOG 2017;124(6):946–54.
8. Cheng X, Zang R, Wu X, Li Z, Cai S, Zhang Z. Recurrence patterns and prognostic factors in Chinese patients with squamous cell carcinoma of the vulva treated with primary surgery. Int J Gynecol Cancer 2009;19(1):158–62.
9. Way S. Carcinoma of the vulva. Am J Obstet Gynecol 1960;79:692–7.
10.Soliman AA, Heubner M, Kimmig R, Wimberger P. Morbidity of inguinofemoral lymphadenectomy in vulval cancer. ScientificWorldJournal 2012;2012:341253.
11.Rouzier R, Haddad B, Dubernard G, Dubois P, Paniel BJ. Inguinofemoral dissection for carcinoma of the vulva: Effect of modifications of extent and technique on morbidity and survival. J Am Coll Surg 2003;196(3):442–50.
12.Ansink A, van der Velden J. Surgical interventions for early squamous cell carcinoma of the vulva. Cochrane Database Syst Rev 2000;2000(2):CD002036.
13. van der Velden J, Schilthuis MS, Hyde SE, Ten Kate FJ, Burger MP. Squamous cell cancer of the vulva with occult lymph node metastases in the groin: The impact of surgical technique on recurrence pattern and survival. Int J Gynecol Cancer 2004;14(4):633–8.
14.Burke TW, Levenback C, Coleman RL, Morris M, Silva EG, Gershenson DM. Surgical therapy of T1 and T2 vulvar carcinoma: Further experience with radical wide excision and selective inguinal lymphadenectomy. Gynecol Oncol 1995;57(2):215–20.
15.National Comprehensive Cancer Network. NCCN Guidelines Version 3.2021 Vulvar Cancer (Squamous Cell Carcinoma). United States: National Comprehensive Cancer Network; 2021.
16.Jolly S, Soni P, Gaffney DK, Biagioli M, Elshaikh MA, Jhingran A, et al. ACR appropriateness criteria(R) adjuvant therapy in vulvar cancer. Oncology (Williston Park) 2015;29(11):867–72.
17.Iversen T, Aas M. Lymph drainage from the vulva. Gynecol Oncol 1983;16(2):179–89.
18.Sedlis A, Homesley H, Bundy BN, Marshall R, Yordan E, Hacker N, et al. Positive groin lymph nodes in superficial squamous cell vulvar cancer. A gynecologic oncology group study. Am J Obstet Gynecol 1987;156(5):1159–64.
19.Rutledge F, Smith JP, Franklin EW. Carcinoma of the vulva. Am J Obstet Gynecol 1970;106:1117–30.
20.Homesley HD, Bundy BN, Sedlis A, Yordan E, Berek JS, Jahshan A, et al. Prognostic factors for groin node metastasis in squamous cell carcinoma of the vulva (a Gynecologic Oncology Group study). Gynecol Oncol 1993;49(3):279–83.
21.Van der Zee AG, Oonk MH, De Hullu JA, Ansink AC, Vergote I, Verheijen RH, et al. Sentinel node dissection is safe in the treatment of early-stage vulvar cancer. J Clin Oncol 2008;26(6):884–9.
22.Te Grootenhuis NC, van der Zee AG, van Doorn HC, van der Velden J, Vergote I, Zanagnolo V, 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(1):8–14.
23.Levenback CF, Ali S, Coleman RL, Gold MA, Fowler JM, Judson PL, et al. Lymphatic mapping and sentinel lymph node biopsy in women with squamous cell carcinoma of the vulva: A gynecologic oncology group study. J Clin Oncol 2012;30(31):3786–91.
24.Brian Slomovitz MO, Monk BJ, Van Driel WJ, Cibula D, DiSilvestro PA, Covens AL, et al. Validation of sentinel lymph biopsy in patients with early stage vulvar cancer: A prospective trial of 1552 women (GROINSV2/ GOG270). In: Annual Meeting on Women’s Cancer. Vol. 159. Toronto: Gynecologic Oncology; 2020.
25. van Der Zee AL, de Hullu JA, van Dorst E, Hermans R, Nunns D, Cibula D, et al. Radiotherapy as an alternative treatment for inguinofemoral lymphadenectomy in vulvar cancer patients with a metastatic sentinel node: Results of groinss-v II. In: Annual Meeting on Women’s Cancer. Vol. 159. Toronto: Gynecologic Oncology; 2020.
26.Viswanathan AN, Pinto AP, Schultz D, Berkowitz R, Crum CP. Relationship of margin status and radiation dose to recurrence in post-operative vulvar carcinoma. Gynecol Oncol 2013;130(3):545–9.
27.Ignatov T, Eggemann H, Burger E, Costa SD, Ignatov A. Adjuvant radiotherapy for vulvar cancer with close or positive surgical margins. J Cancer Res Clin Oncol 2016;142(2):489–95.
28.Heaps JM, Fu YS, Montz FJ, Hacker NF, Berek JS. Surgical-pathologic variables predictive of local recurrence in squamous cell carcinoma of the vulva. Gynecol Oncol 1990;38(3):309–14.
29.Chan JK, Sugiyama V, Pham H, Gu M, Rutgers J, Osann K, et al. Margin distance and other clinico-pathologic prognostic factors in vulvar carcinoma: A multivariate analysis. Gynecol Oncol 2007;104(3):636–41.
30.Woelber L, Griebel LF, Eulenburg C, Sehouli J, Jueckstock J, Hilpert F, et al. Role of tumour-free margin distance for loco-regional control in vulvar cancer-a subset analysis of the arbeitsgemeinschaft gynakologische onkologie CaRE-1 multicenter study. Eur J Cancer 2016;69:180–8.
31.Woelber L, Choschzick M, Eulenburg C, Hager M, Jaenicke F, Gieseking F, et al. Prognostic value of pathological resection margin distance in squamous cell cancer of the vulva. Ann Surg Oncol 2011;18(13):3811–8.
32.Groenen SM, Timmers PJ, Burger CW. Recurrence rate in vulvar carcinoma in relation to pathological margin distance. Int J Gynecol Cancer 2010;20(5):869–73.
33.Yoonessi M, Goodell T, Satchidanand S, Fett W, Solis F. Microinvasive squamous carcinoma of the vulva. J Surg Oncol 1983;24:315–21.
34.Bogani G, Cromi A, Serati M, Uccella S, Donato VD, Casarin J, et al. Predictors and patterns of local, regional, and distant failure in squamous cell carcinoma of the vulva. Am J Clin Oncol 2017;40(3):235–40.
35.Te Grootenhuis NC, Pouwer AW, de Bock GH, Hollema H, Bulten J, van der Zee AG, et al. Prognostic factors for local recurrence of squamous cell carcinoma of the vulva: A systematic review. Gynecol Oncol 2018;148(3):622–31.
36.Farias-Eisner R, Cirisano FD, Grouse D, Leuchter RS, Karlan BY, Lagasse LD, et al. Conservative and individualized surgery for early squamous carcinoma of the vulva: The treatment of choice for stage I and II (T1- 2N0-1M0) disease. Gynecol Oncol 1994;53(1):55–8.
37.Homesley HD, Bundy BN, Sedlis A, Adcock L. Radiation therapy versus pelvic node resection for carcinoma of the vulva with positive groin nodes. Obstet Gynecol 1986;68(6):733–40.
38.Mahner S, Jueckstock J, Hilpert F, Neuser P, Harter P, de Gregorio N, et al. Adjuvant therapy in lymph nodepositive vulvar cancer: The AGO-CaRE-1 study. J Natl Cancer Inst 2015;107(3):426.
39. van der Velden J, Pleunis N, Barlow E, Zijlmans H, de Hullu J, Hacker NF, et al. Radiotherapy is not indicated in patients with vulvar squamous cell carcinoma and only one occult intracapsular groin node metastasis. Gynecol Oncol 2021;160(1):128–33.
40.Parthasarathy A, Cheung MK, Osann K, Husain A, Teng NN, Berek JS, et al. The benefit of adjuvant radiation therapy in single-node-positive squamous cell vulvar carcinoma. Gynecol Oncol 2006;103(3):1095–9.
41.Serre E, Raimond E, Diguisto C, Bendifallah S, Body G, Touboul C, et al. Inguino-femoral radiotherapy in vulvar squamous cell carcinoma: Clues to revised indications in patients with only one intracapsular lymph node metastasis. Acta Oncol 2020;59(5):518–24.
42.Gill BS, Bernard ME, Lin JF, Balasubramani GK, Rajagopalan MS, Sukumvanich P, et al. Impact of adjuvant chemotherapy with radiation for node-positive vulvar cancer: A National Cancer Data Base (NCDB) analysis. Gynecol Oncol 2015;137(3):365–72.
43.Gaffney DK, King B, Viswanathan AN, Barkati M, Beriwal S, Eifel P, et al. Consensus recommendations for radiation therapy contouring and treatment of vulvar carcinoma. Int J Radiat Oncol Biol Phys 2016;95(4):1191–200.
44.Gadducci A, Cionini L, Romanini A, Fanucchi A, Genazzani AR. Old and new perspectives in the management of high-risk, locally advanced or recurrent, and metastatic vulvar cancer. Crit Rev Oncol Hematol 2006;60(3):227–41.
45.Boronow RC. Combined therapy as an alternative to exenteration for locally advanced vulvo-vaginal cancer: Rationale and results. Cancer 1982;49:1085–91.
46.Bartelink H, Roelofsen F, Eschwege F, Rougier P, Bosset JF, Gonzalez DG, et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: Results of a phase III randomized trial of the European organization for research and treatment of cancer radiotherapy and gastrointestinal cooperative groups. J Clin Oncol 1997;15(5):2040–9.
47.Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med 1999;340:1137–43.
48.Moore DH, Thomas GM, Montana GS, Saxer A, Gallup DG, 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(5):79–85.
49.Montana GS, Thomas GM, Moore DH, Saxer A, Mangan CE, Lentz SS, et al. Preoperative chemo-radiation for carcinoma of the vulva with N2/N3 nodes: A gynecologic oncology group study. Int J Radiat Oncol Biol Phys 2000;48(4):1007–13.
50.Moore DH, Ali S, Koh WJ, Michael H, Barnes MN, McCourt CK, et al. A phase II trial of radiation therapy and weekly cisplatin chemotherapy for the treatment of locally-advanced squamous cell carcinoma of the vulva: A gynecologic oncology group study. Gynecol Oncol 2012;124(3):529–33.
51.Natesan D, Hong JC, Foote J, Sosa JA, Havrilesky L, Chino J. Primary versus preoperative radiation for locally advanced vulvar cancer. Int J Gynecol Cancer 2017;27(4):794–804.
52.Kim CH, Olson AC, Kim H, Beriwal S. Contouring inguinal and femoral nodes; how much margin is needed around the vessels? Pract Radiat Oncol 2012;2(4):274– 8.
53.Chapman BV, Gill BS, Viswanathan AN, Balasubramani GK, Sukumvanich P, Beriwal S. Adjuvant radiation therapy for margin-positive vulvar squamous cell carcinoma: Defining the ideal dose-response using the national cancer data base. Int J Radiat Oncol Biol Phys 2017;97(1):107–17.
54.D’Souza DP, Rumble RB, Fyles A, Yaremko B, Warde P, Members of the IIEP. Intensity-modulated radiotherapy in the treatment of gynaecological cancers. Clin Oncol (R Coll Radiol) 2012;24(7):499–507.
55.Beriwal S, Heron DE, Kim H, King G, Shogan J, Bahri S, et al. Intensity-modulated radiotherapy for the treatment of vulvar carcinoma: A comparative dosimetric study with early clinical outcome. Int J Radiat Oncol Biol Phys 2006;64(5):1395–400.
56.Rao YJ, Chundury A, Schwarz JK, Hassanzadeh C, DeWees T, Mullen D, et al. Intensity modulated radiation therapy for squamous cell carcinoma of the vulva: Treatment technique and outcomes. Adv Radiat Oncol 2017;2(2):148–58.
57.Beriwal S, Shukla G, Shinde A, Heron DE, Kelley JL, Edwards RP, et al. Preoperative intensity modulated radiation therapy and chemotherapy for locally advanced vulvar carcinoma: analysis of pattern of relapse. Int J Radiat Oncol Biol Phys 2013;85(5):1269–74.
58.Beriwal S, Coon D, Heron DE, Kelley JL, Edwards RP, Sukumvanich P, et al. Preoperative intensitymodulated radiotherapy and chemotherapy for locally advanced vulvar carcinoma. Gynecol Oncol 2008;109(2):291–5.
59.Bloemers MC, Portelance L, Ruo R, Parker W, Souhami L. A dosimetric evaluation of dose escalation for the radical treatment of locally advanced vulvar cancer by intensity-modulated radiation therapy. Med Dosim 2012;37(3):310–3.

APA	Beduk Esen C, Gultekin M, Yildiz F (2021). Role of Radiotherapy in Vulvar Squamous Cell Carcinoma: Review of the Literature. , 529 - 537. 10.5505/tjo.2021.3327
Chicago	Beduk Esen Caglayan Selenge,Gultekin Melis,Yildiz Ferah Role of Radiotherapy in Vulvar Squamous Cell Carcinoma: Review of the Literature. (2021): 529 - 537. 10.5505/tjo.2021.3327
MLA	Beduk Esen Caglayan Selenge,Gultekin Melis,Yildiz Ferah Role of Radiotherapy in Vulvar Squamous Cell Carcinoma: Review of the Literature. , 2021, ss.529 - 537. 10.5505/tjo.2021.3327
AMA	Beduk Esen C,Gultekin M,Yildiz F Role of Radiotherapy in Vulvar Squamous Cell Carcinoma: Review of the Literature. . 2021; 529 - 537. 10.5505/tjo.2021.3327
Vancouver	Beduk Esen C,Gultekin M,Yildiz F Role of Radiotherapy in Vulvar Squamous Cell Carcinoma: Review of the Literature. . 2021; 529 - 537. 10.5505/tjo.2021.3327
IEEE	Beduk Esen C,Gultekin M,Yildiz F "Role of Radiotherapy in Vulvar Squamous Cell Carcinoma: Review of the Literature." , ss.529 - 537, 2021. 10.5505/tjo.2021.3327
ISNAD	Beduk Esen, Caglayan Selenge vd. "Role of Radiotherapy in Vulvar Squamous Cell Carcinoma: Review of the Literature". (2021), 529-537. https://doi.org/10.5505/tjo.2021.3327

APA	Beduk Esen C, Gultekin M, Yildiz F (2021). Role of Radiotherapy in Vulvar Squamous Cell Carcinoma: Review of the Literature. Türk Onkoloji Dergisi, 36(4), 529 - 537. 10.5505/tjo.2021.3327
Chicago	Beduk Esen Caglayan Selenge,Gultekin Melis,Yildiz Ferah Role of Radiotherapy in Vulvar Squamous Cell Carcinoma: Review of the Literature. Türk Onkoloji Dergisi 36, no.4 (2021): 529 - 537. 10.5505/tjo.2021.3327
MLA	Beduk Esen Caglayan Selenge,Gultekin Melis,Yildiz Ferah Role of Radiotherapy in Vulvar Squamous Cell Carcinoma: Review of the Literature. Türk Onkoloji Dergisi, vol.36, no.4, 2021, ss.529 - 537. 10.5505/tjo.2021.3327
AMA	Beduk Esen C,Gultekin M,Yildiz F Role of Radiotherapy in Vulvar Squamous Cell Carcinoma: Review of the Literature. Türk Onkoloji Dergisi. 2021; 36(4): 529 - 537. 10.5505/tjo.2021.3327
Vancouver	Beduk Esen C,Gultekin M,Yildiz F Role of Radiotherapy in Vulvar Squamous Cell Carcinoma: Review of the Literature. Türk Onkoloji Dergisi. 2021; 36(4): 529 - 537. 10.5505/tjo.2021.3327
IEEE	Beduk Esen C,Gultekin M,Yildiz F "Role of Radiotherapy in Vulvar Squamous Cell Carcinoma: Review of the Literature." Türk Onkoloji Dergisi, 36, ss.529 - 537, 2021. 10.5505/tjo.2021.3327
ISNAD	Beduk Esen, Caglayan Selenge vd. "Role of Radiotherapy in Vulvar Squamous Cell Carcinoma: Review of the Literature". Türk Onkoloji Dergisi 36/4 (2021), 529-537. https://doi.org/10.5505/tjo.2021.3327