After a median follow-up of 74 months, the 6-year overall survival (OS) rate was 51% in the radiation arm versus 41% in the pelvic node dissection arm (hazard ratio [HR], 0.61; 95% CI, 0.3–1.3; P = .18). Vulvar cancer-specific mortality was statistically significantly lower in the radiation study arm: 29% versus 51% in the pelvic node resection arm (HR, 0.49; 95% CI, 0.28–0.87; P = .015) However, there were 14 intercurrent deaths in the radiation therapy arm versus two deaths in the pelvic dissection study arm. Late chronic lymphedema was similar in the radiation therapy and pelvic dissection groups arms (16% vs. 22%), respectively.[Level of evidence: 1iiB]
Radical radiation therapy can be used for patients unable to tolerate surgery or deemed unsuitable for surgery because of site or extent of disease.[11,12,13,14]
Role of Chemotherapy
There is no standard chemotherapy for vulvar cancer, and reports describing the use of this modality in the setting of metastatic or recurrent disease are anecdotal. Extrapolating from regimens used for anal or cervical squamous cell cancers, chemotherapy has been studied in combination with radiation in the neoadjuvant setting or as primary therapy in advanced disease. Chemotherapy regimens have included various combinations of 5-fluorouracil (5-FU), cisplatin, mitomycin-C, or bleomycin. There is no clear evidence of improvement in survival or palliation. Given the advanced age and comorbidity of many patients with advanced or recurrent vulvar cancer, patient tolerance is a major consideration in the use of these agents.
Systemic treatment for inoperable patients
A systematic review of the use of neoadjuvant chemoradiation in patients who were considered inoperable or who would have required extensive surgery, such as pelvic exenteration, colostomy, or urinary diversion revealed no randomized trials. Five nonrandomized studies that met the inclusion criteria of neoadjuvant chemoradiation administered in this population with an intent to permit curative surgery were reviewed.[16,17,18,19,20] The five studies used four different chemoradiation schedules and different radiation therapy dose-fractionation techniques. In the four studies using 5-FU + cisplatin or 5-FU + mitomycin-C, the operability rate after chemoradiation ranged from 63% to 92%.[16,17,18,19]
In the one study using bleomycin, the operability rate was only 20%. In summary, there is evidence that neoadjuvant chemoradiation with 5-FU plus either cisplatin or mitomycin-C may convert patients to more operable status, but the evidence base is limited by study design. In addition to a paucity of randomized trials, interpretation of these studies is complicated by the lack of a standard definition of inoperability.[Level of evidence: 3iiiDiv] Treatment-related toxicity is substantial.
Systemic treatment for operable patients
There is also limited evidence regarding the use of neoadjuvant chemoradiation in advanced operable cases of vulvar cancer, but the available data do not suggest an advantage to this approach. A systematic review found only one randomized trial that addressed this issue, and it was published only in abstract form.[4,21] In that trial, 68 patients with advanced vulvar cancer (T2 >4 cm, T3, any case with positive lymph nodes) were randomly assigned to receive preoperative neoadjuvant radiation therapy (50 Gy) concomitantly with 5-FU plus mitomycin-C versus primary surgery. Neoadjuvant therapy-related serious toxicity was high (13 of 24 patients; 10 patients had wound diastasis). After a mean follow-up of 42 months, the 5-year OS rates in the neoadjuvant and primary surgery groups were 30% and 49%, respectively (RR of death, 1.39; 95% CI, 0.94–2.06; P = .19).[4,21][Level of evidence 1iiA]
- Hacker NF, Van der Velden J: Conservative management of early vulvar cancer. Cancer 71 (4 Suppl): 1673-7, 1993.
- Thomas GM, Dembo AJ, Bryson SC, et al.: Changing concepts in the management of vulvar cancer. Gynecol Oncol 42 (1): 9-21, 1991.
- Homesley HD, Bundy BN, Sedlis A, et al.: Radiation therapy versus pelvic node resection for carcinoma of the vulva with positive groin nodes. Obstet Gynecol 68 (6): 733-40, 1986.
- Shylasree TS, Bryant A, Howells RE: Chemoradiation for advanced primary vulval cancer. Cochrane Database Syst Rev (4): CD003752, 2011.
- Eifel PJ, Berek JS, Markman MA: Cancer of the cervix, vagina, and vulva. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1311-44.
- Ansink A, van der Velden J: Surgical interventions for early squamous cell carcinoma of the vulva. Cochrane Database Syst Rev (2): CD002036, 2000.
- Van der Zee AG, Oonk MH, De Hullu JA, et al.: Sentinel node dissection is safe in the treatment of early-stage vulvar cancer. J Clin Oncol 26 (6): 884-9, 2008.
- Stehman FB, Bundy BN, Thomas G, et al.: Groin dissection versus groin radiation in carcinoma of the vulva: a Gynecologic Oncology Group study. Int J Radiat Oncol Biol Phys 24 (2): 389-96, 1992.
- van der Velden J, Fons G, Lawrie TA: Primary groin irradiation versus primary groin surgery for early vulvar cancer. Cochrane Database Syst Rev (5): CD002224, 2011.
- Kunos C, Simpkins F, Gibbons H, et al.: Radiation therapy compared with pelvic node resection for node-positive vulvar cancer: a randomized controlled trial. Obstet Gynecol 114 (3): 537-46, 2009.
- Petereit DG, Mehta MP, Buchler DA, et al.: Inguinofemoral radiation of N0,N1 vulvar cancer may be equivalent to lymphadenectomy if proper radiation technique is used. Int J Radiat Oncol Biol Phys 27 (4): 963-7, 1993.
- Slevin NJ, Pointon RC: Radical radiotherapy for carcinoma of the vulva. Br J Radiol 62 (734): 145-7, 1989.
- Perez CA, Grigsby PW, Galakatos A, et al.: Radiation therapy in management of carcinoma of the vulva with emphasis on conservation therapy. Cancer 71 (11): 3707-16, 1993.
- Kumar PP, Good RR, Scott JC: Techniques for management of vulvar cancer by irradiation alone. Radiat Med 6 (4): 185-91, 1988 Jul-Aug.
- van Doorn HC, Ansink A, Verhaar-Langereis M, et al.: Neoadjuvant chemoradiation for advanced primary vulvar cancer. Cochrane Database Syst Rev 3: CD003752, 2006.
- Eifel PJ, Morris M, Burke TW, et al.: Prolonged continuous infusion cisplatin and 5-fluorouracil with radiation for locally advanced carcinoma of the vulva. Gynecol Oncol 59 (1): 51-6, 1995.
- Landoni F, Maneo A, Zanetta G, et al.: Concurrent preoperative chemotherapy with 5-fluorouracil and mitomycin C and radiotherapy (FUMIR) followed by limited surgery in locally advanced and recurrent vulvar carcinoma. Gynecol Oncol 61 (3): 321-7, 1996.
- Montana GS, Thomas GM, Moore DH, 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 48 (4): 1007-13, 2000.
- Moore DH, Thomas GM, Montana GS, et al.: Preoperative chemoradiation for advanced vulvar cancer: a phase II study of the Gynecologic Oncology Group. Int J Radiat Oncol Biol Phys 42 (1): 79-85, 1998.
- Scheiströen M, Tropé C: Combined bleomycin and irradiation in preoperative treatment of advanced squamous cell carcinoma of the vulva. Acta Oncol 32 (6): 657-61, 1993.
- Maneo A, Landoni F, Colombo A, et al.: Randomised study between neoadjuvant chemoradiotherapy and primary surgery for the treatment of advanced vulvar cancer. [Abstract] Int J Gynecol Cancer 13 (Suppl 1): A-PL19, 6, 2003.