miércoles, 13 de febrero de 2019

Vaginal Cancer Treatment (PDQ®)—Health Professional Version - National Cancer Institute

Vaginal Cancer Treatment (PDQ®)—Health Professional Version - National Cancer Institute



National Cancer Institute

Vaginal Cancer Treatment (PDQ®)–Health Professional Version

General Information About Vaginal Cancer

Incidence and Mortality

Estimated new cases and deaths from vaginal (and other female genital) cancer in the United States in 2019:[1]
  • New cases: 5,350.
  • Deaths: 1,430.
Carcinomas of the vagina are uncommon tumors comprising about 1% of the cancers that arise in the female genital system.[2,3]
Early-stage tumors are often curable with local modality therapies, but there is no standard treatment of proven efficacy for metastatic disease. A large proportion (30%–50%) of women with vaginal carcinomas have had a previous hysterectomy for benign, pre-malignant, or malignant disease.[2,4]
The American Joint Committee on Cancer (AJCC) staging system indicates that tumors in the vagina that involve the cervix of women with an intact uterus are classified as cervical cancers.[5] Therefore, tumors that may have actually originated in the apical vagina but extend to the cervix would be classified as cervical cancers. (Refer to the PDQ summary on Cervical Cancer Treatment for more information.)
Squamous cell cancer (SCC) accounts for approximately 85% of vaginal cancer cases.[6] SCC initially spreads superficially within the vaginal wall and later invades the paravaginal tissues and the parametria. Distant hematogenous metastases occur most commonly in the lungs, and less frequently in liver, bone, or other sites.[6] SCC of the vagina is associated with a high rate of infection with oncogenic strains of human papillomavirus (HPV) and has many risk factors in common with SCC of the cervix.[7-9] HPV infection has also been described in a case of vaginal adenocarcinoma.[9] (Refer to the PDQ summary on Cervical Cancer Treatment for more information.)

Risk Factors

Approximately 5% to 10% of vaginal cancer cases are adenocarcinomas. A rare form of adenocarcinoma (clear cell carcinoma, described below) occurs in association with in uteroexposure to diethylstilbestrol (DES), with a peak incidence at young ages (<30 years). However, adenocarcinomas that are not associated with DES exposure occur primarily during postmenopausal years.
The association between the clear cell carcinomas and in utero exposure to DES was first reported in 1971.[10] The incidence of this disease, which is highest for those exposed during the first trimester, peaked in the mid-1970s, reflecting the use of DES in the 1950s. It is extremely rare now.[6] However, women with a known history of in utero DES exposure should be carefully followed for possible presence of this tumor.
Vaginal adenosis is most commonly found in young women who had in utero exposure to DES and may coexist with a clear cell adenocarcinoma, though it rarely progresses to adenocarcinoma. Adenosis is replaced by squamous metaplasia, which occurs naturally, and requires follow-up but not removal.
Rarely, melanomas (often nonpigmented), sarcomas, or small-cell carcinomas have been described as primary vaginal cancers.

Prognostic Factors

Patient prognosis depends primarily on the stage of disease, but survival is reduced among those who are older than 60 years, are symptomatic at the time of diagnosis, have lesions of the middle and lower third of the vagina, or have poorly differentiated tumors.
In addition, the length of vaginal wall involvement has been found to be associated with survival and stage of disease in vaginal SCC patients.
Non–DES-associated adenocarcinomas generally have a worse prognosis than SCC tumors, but DES-associated clear cell tumors have a relatively good prognosis.[6] The natural history, prognosis, and treatment of other primary vaginal cancers (i.e., sarcoma, melanoma, lymphoma, and carcinoid tumors) are different and are not covered in this summary.

Treatment Options

Therapeutic options depend on tumor stage; surgery and radiation therapy are highly effective in early stages, whereas radiation therapy is the primary treatment of more advanced stages. Chemotherapy has not been shown to be curative for advanced vaginal cancer, and there are no standard drug regimens.
References
  1. American Cancer Society: Cancer Facts and Figures 2019. Atlanta, Ga: American Cancer Society, 2019. Available online. Last accessed January 23, 2019.
  2. 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.
  3. American Cancer Society: Cancer Facts and Figures 2017. Atlanta, Ga: American Cancer Society, 2017. Available online. Last accessed February 7, 2019.
  4. Stock RG, Chen AS, Seski J: A 30-year experience in the management of primary carcinoma of the vagina: analysis of prognostic factors and treatment modalities. Gynecol Oncol 56 (1): 45-52, 1995. [PUBMED Abstract]
  5. Vagina. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 387-9.
  6. Eifel P, Berek J, Markman M: Cancer of the cervix, vagina, and vulva. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. Vols. 1 & 2. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2008, pp 1496-1543.
  7. Daling JR, Madeleine MM, Schwartz SM, et al.: A population-based study of squamous cell vaginal cancer: HPV and cofactors. Gynecol Oncol 84 (2): 263-70, 2002. [PUBMED Abstract]
  8. Parkin DM: The global health burden of infection-associated cancers in the year 2002. Int J Cancer 118 (12): 3030-44, 2006. [PUBMED Abstract]
  9. Ikenberg H, Runge M, Göppinger A, et al.: Human papillomavirus DNA in invasive carcinoma of the vagina. Obstet Gynecol 76 (3 Pt 1): 432-8, 1990. [PUBMED Abstract]
  10. Herbst AL, Ulfelder H, Poskanzer DC: Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N Engl J Med 284 (15): 878-81, 1971. [PUBMED Abstract]

Stage Information for Vaginal Cancer

If the cervix is intact, biopsies are mandatory to rule out a primary carcinoma of the cervix. Carcinoma of the vulva should also be ruled out.

Definitions: FIGO

The Féderation Internationale de Gynécologie et d’Obstétrique (FIGO) and the American Joint Committee on Cancer (AJCC) have designated staging to define vaginal cancer; the FIGO system is most commonly used.[1,2] The definitions of the AJCC's T, N, and M categories correspond to the stages accepted by FIGO.

FIGO staging system (and modified World Health Organization [WHO] prognostic scoring system)

The FIGO staging system is as follows:[1]
Table 1. Carcinoma of the Vaginaa
FIGO Nomenclature
FIGO = Féderation Internationale de Gynécologie et d’Obstétrique.
aAdapted from FIGO Committee on Gynecologic Oncology.[1]
Stage IThe carcinoma is limited to the vaginal wall.
Stage IIThe carcinoma has involved the subvaginal tissue but has not extended to the pelvic wall.
Stage IIIThe carcinoma has extended to the pelvic wall.
Stage IVThe carcinoma has extended beyond the true pelvis or has involved the mucosa of the bladder or rectum; bullous edemas as such does not permit a case to be allotted to stage IV.
IVa - Tumor invades bladder and/or rectal mucosa and/or direct extension beyond the true pelvis.
IVb - Spread to distant organs.
In addition, the FIGO staging system incorporates a modified WHO prognostic scoring system. The scores from the eight risk factors are summed and incorporated into the FIGO stage, separated by a colon (e.g., Stage II:4, Stage IV:9, etc.). Unfortunately, a variety of risk scoring systems have been published, making comparisons of results difficult.
References
  1. FIGO Committee on Gynecologic Oncology: Current FIGO staging for cancer of the vagina, fallopian tube, ovary, and gestational trophoblastic neoplasia. Int J Gynaecol Obstet 105 (1): 3-4, 2009. [PUBMED Abstract]
  2. Vagina. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 641–7.

Treatment Option Overview

Roles of Radiation, Surgery, and Chemotherapy

Given the rarity of vaginal carcinoma, studies are limited to retrospective case series that may span a number of years, usually from single-referral institutions.[Level of evidence 3iiiD] Comparison of different treatment approaches is further complicated by the frequent failure of investigators to provide precise staging criteria (particularly for stage I vs. stage II disease) or criteria for the choice of treatment modality. This has led to a broad range of reported disease control and survival rates for any given stage and treatment modality.[1] In addition, given the long time span covered by these case series, there are often changes within a given case series in the available staging tests and radiation techniques, including the shift to high-energy accelerators and conformal- and intensity-modulated radiation.[2,3]
Factors to be considered in planning therapy for vaginal cancer include:
  • Stage and size of the lesion.
  • Proximity to radiosensitive organs or organs that preclude radical resection without unacceptable functional deficits (e.g., bladder, rectum, urethra).
  • Ability to retain a functional vagina.
  • Presence or absence of the uterus.
  • Whether there has been previous pelvic radiation therapy.
In a series of 100 women studied retrospectively over 30 years, 50% had undergone hysterectomy before the diagnosis of vaginal cancer.[4] In this posthysterectomy group, 31 of 50 (62%) women developed cancers limited to the upper third of the vagina. In women who had not previously undergone hysterectomy, upper vaginal lesions were found in only 17 of 50 (34%) women.
The lymphatics may drain to pelvic or inguinal nodes or both, depending on tumor location, and consideration should be given to these areas in treatment planning.
Radiation-induced damage to nearby organs may include:[2,3]
  • Rectovaginal fistulas.
  • Vesicovaginal fistulas.
  • Rectal or vaginal strictures.
  • Cystitis.
  • Proctitis.
  • Premature menopause from ovarian damage.
  • Soft tissue or bone necrosis.
The proximity of the vagina to the bladder or rectum also limits surgical treatment options and increases short- and long-term surgical complications and functional deficits involving these organs.
For patients with carcinoma of the vagina in its early stages, radiation or surgery or a combination of these treatments are standard treatment. Data from randomized trials are lacking and the choice of therapy is generally determined by institutional experience and the factors listed above. For patients with stages III and IVA disease, radiation therapy is standard and includes external-beam radiation, alone or with brachytherapy. Regional lymph nodes are included in the radiation portal. When used alone, external-beam radiation involves a 60 Gy to 70 Gy tumor dose, using shrinking fields, delivered within 6 to 7 weeks. Intracavitary brachytherapy provides insufficient dose penetration for locally advanced tumors, so interstitial brachytherapy (75 Gy–85 Gy) is used if brachytherapy is employed.[1,5]
Local control is a problem with bulky tumors. In recent years, some investigators have also used concurrent chemotherapy with agents such as cisplatin, bleomycin, mitomycin-C, floxuridine, and vincristine; but this practice has not been proven to improve outcomes.[2] It is an extrapolation from treatment approaches used in cervical cancer, based on shared etiologic and risk factors.
For patients with stage IVB or recurrent disease that cannot be managed with local treatments, current therapy is inadequate. No established anticancer drugs can be considered of proven clinical benefit, although patients are often treated with regimens used to treat cervical cancer. (Refer to the PDQ summary on Cervical Cancer Treatment for more information.)
Concurrent chemotherapy, using 5-fluorouracil or cisplatin-based therapy, and radiation are sometimes advocated, based solely on extrapolation from cervical cancer management strategies.[6-8] Experience is limited to small case series and the incremental impact on survival and local control is not well defined.[Level of evidence 3iiiDiv] Because of the rarity of these patients, they should be considered candidates for clinical trials of anticancer drugs and/or radiosensitizers to attempt to improve survival or local control.
Management of the extremely rare vaginal clear cell carcinoma is generally similar to the management of squamous cell carcinoma, though techniques that preserve vaginal and ovarian function are given strong consideration in treatment planning, given the young average age at diagnosis.[9]
In light of the many uncertainties about the relative efficacy of treatment approaches, ongoing clinical trials should be discussed with patients if they are eligible. Information about ongoing clinical trials is available from the NCI website.

Post-therapy Surveillance

Similarly to other gynecologic malignancies, the evidence base for surveillance after initial management of vaginal cancer is weak because of a lack of randomized, or even prospective, clinical studies.[10] There is no reliable evidence that routine cytologic or imaging procedures in patients improve health outcomes beyond what is achieved by careful physical examination and assessment of new symptoms. Therefore, outside the investigational setting, imaging procedures may be reserved for patients in whom physical examination or symptoms raise clinical suspicion of a recurrence or progression.
References
  1. 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.
  2. Frank SJ, Jhingran A, Levenback C, et al.: Definitive radiation therapy for squamous cell carcinoma of the vagina. Int J Radiat Oncol Biol Phys 62 (1): 138-47, 2005. [PUBMED Abstract]
  3. Tran PT, Su Z, Lee P, et al.: Prognostic factors for outcomes and complications for primary squamous cell carcinoma of the vagina treated with radiation. Gynecol Oncol 105 (3): 641-9, 2007. [PUBMED Abstract]
  4. Stock RG, Chen AS, Seski J: A 30-year experience in the management of primary carcinoma of the vagina: analysis of prognostic factors and treatment modalities. Gynecol Oncol 56 (1): 45-52, 1995. [PUBMED Abstract]
  5. Chyle V, Zagars GK, Wheeler JA, et al.: Definitive radiotherapy for carcinoma of the vagina: outcome and prognostic factors. Int J Radiat Oncol Biol Phys 35 (5): 891-905, 1996. [PUBMED Abstract]
  6. Grigsby PW: Vaginal cancer. Curr Treat Options Oncol 3 (2): 125-30, 2002. [PUBMED Abstract]
  7. Dalrymple JL, Russell AH, Lee SW, et al.: Chemoradiation for primary invasive squamous carcinoma of the vagina. Int J Gynecol Cancer 14 (1): 110-7, 2004 Jan-Feb. [PUBMED Abstract]
  8. Samant R, Lau B, E C, et al.: Primary vaginal cancer treated with concurrent chemoradiation using Cis-platinum. Int J Radiat Oncol Biol Phys 69 (3): 746-50, 2007. [PUBMED Abstract]
  9. Senekjian EK, Frey KW, Anderson D, et al.: Local therapy in stage I clear cell adenocarcinoma of the vagina. Cancer 60 (6): 1319-24, 1987. [PUBMED Abstract]
  10. Salani R, Backes FJ, Fung MF, et al.: Posttreatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations. Am J Obstet Gynecol 204 (6): 466-78, 2011. [PUBMED Abstract]

Stage 0 Vaginal Cancer

Vaginal Intraepithelial Neoplasia (VAIN) Including Squamous Cell Carcinoma In Situ

Squamous cell carcinoma in situ of the vagina is a lesion that falls within the more general category known as vaginal intraepithelial neoplasia (VAIN). VAIN, the presence of noninvasive squamous cell atypia, is associated with a high rate of human papillomavirus (HPV) infection and is thought to have a similar etiology as cervical intraepithelial neoplasia (CIN).[1-3] VAIN is classified by the degree of involvement of the epithelium: VAIN 1, 2, and 3 denote involvement of the upper one-third, two-thirds, and more than two-thirds of the epithelial thickness, respectively. Carcinoma in situ denotes VAIN 3 lesions that involve the full thickness of the epithelium. The FIGO staging system no longer includes vaginal carcinoma in situ (Stage 0) in its staging system, but it is retained in the AJCC staging system.[4] Vaginal carcinoma in situ is often multifocal and commonly occurs at the vaginal vault. Because it is associated with other genital neoplasia, and in some cases may be an extension of CIN, the cervix (when present) and vulva should be carefully evaluated. (Refer to the PDQ summary on Cervical Cancer Treatment for more information.)
Women with VAIN 1 can usually be observed carefully without ablative or surgical treatment because the lesions often regress spontaneously. The natural history of VAIN is not known with precision because of its rarity, but patients with VAIN 3 are felt to be at substantial risk of progression to invasive cancer and are treated immediately. The intermediate grade, VAIN 2, is variously managed by careful observation or initial treatment. The treatments listed below have not been compared directly in randomized trials, so their relative efficacy is uncertain.[Level of evidence 3iiiDiv] The selection of treatment depends on patient factors, anatomic location, evidence of multifocality, and local expertise (e.g., anatomical distortion of the vaginal vault related to wall closure at the time of previous hysterectomy requires excision for technical reasons to exclude the possibility of invasion by buried disease). Lesions with hyperkeratosis respond better to excision or laser vaporization than to fluorouracil.[5]
Standard treatment options:
  1. Laser therapy.[6] The lesions should first be sampled adequately to rule out invasive components that could be missed with this treatment approach.
  2. Wide local excision with or without skin grafting.[7]
  3. Partial or total vaginectomy, with skin grafting for multifocal or extensive disease.[8]
  4. Intravaginal chemotherapy with 5% fluorouracil cream. This option may be useful in the setting of multifocal lesions.[6,9]
  5. Intracavitary radiation therapy.[10,11] Because of its attendant toxicity and inherent carcinogenicity, this treatment is primarily used in the setting of multifocal or recurrent disease, or when the risk of surgery is high.[1] The entire vaginal mucosa is usually treated.[12]
Imiquimod cream 5%, an immune stimulant used to treat genital warts, is an additional topical therapy that has a reported complete clinical response rate of 50% to 86% in small case series of patients with multifocal high-grade HPV-associated VAIN 2 and 3.[13] However, it is investigational, and it may have only short-lived efficacy.[14]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References
  1. 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.
  2. Daling JR, Madeleine MM, Schwartz SM, et al.: A population-based study of squamous cell vaginal cancer: HPV and cofactors. Gynecol Oncol 84 (2): 263-70, 2002. [PUBMED Abstract]
  3. Smith JS, Backes DM, Hoots BE, et al.: Human papillomavirus type-distribution in vulvar and vaginal cancers and their associated precursors. Obstet Gynecol 113 (4): 917-24, 2009. [PUBMED Abstract]
  4. Vagina. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 387-9.
  5. Wright VC, Chapman W: Intraepithelial neoplasia of the lower female genital tract: etiology, investigation, and management. Semin Surg Oncol 8 (4): 180-90, 1992 Jul-Aug. [PUBMED Abstract]
  6. Krebs HB: Treatment of vaginal intraepithelial neoplasia with laser and topical 5-fluorouracil. Obstet Gynecol 73 (4): 657-60, 1989. [PUBMED Abstract]
  7. Cheng D, Ng TY, Ngan HY, et al.: Wide local excision (WLE) for vaginal intraepithelial neoplasia (VAIN). Acta Obstet Gynecol Scand 78 (7): 648-52, 1999. [PUBMED Abstract]
  8. Indermaur MD, Martino MA, Fiorica JV, et al.: Upper vaginectomy for the treatment of vaginal intraepithelial neoplasia. Am J Obstet Gynecol 193 (2): 577-80; discussion 580-1, 2005. [PUBMED Abstract]
  9. Stefanon B, Pallucca A, Merola M, et al.: Treatment with 5-fluorouracil of 35 patients with clinical or subclinical HPV infection of the vagina. Eur J Gynaecol Oncol 17 (6): 534, 1996. [PUBMED Abstract]
  10. Chyle V, Zagars GK, Wheeler JA, et al.: Definitive radiotherapy for carcinoma of the vagina: outcome and prognostic factors. Int J Radiat Oncol Biol Phys 35 (5): 891-905, 1996. [PUBMED Abstract]
  11. Graham K, Wright K, Cadwallader B, et al.: 20-year retrospective review of medium dose rate intracavitary brachytherapy in VAIN3. Gynecol Oncol 106 (1): 105-11, 2007. [PUBMED Abstract]
  12. Perez CA, Garipagaoglu M: Vagina. In: Perez CA, Brady LW, eds.: Principles and Practice of Radiation Oncology. 3rd ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1998, pp 1891-1914.
  13. Iavazzo C, Pitsouni E, Athanasiou S, et al.: Imiquimod for treatment of vulvar and vaginal intraepithelial neoplasia. Int J Gynaecol Obstet 101 (1): 3-10, 2008. [PUBMED Abstract]
  14. Haidopoulos D, Diakomanolis E, Rodolakis A, et al.: Can local application of imiquimod cream be an alternative mode of therapy for patients with high-grade intraepithelial lesions of the vagina? Int J Gynecol Cancer 15 (5): 898-902, 2005 Sep-Oct. [PUBMED Abstract]

Stage I Vaginal Cancer

The treatments listed below have not been directly compared in randomized trials.[Level of evidence 3iiiD] Because of differences in patient selection, local expertise, and staging criteria, it is difficult to determine whether there are differences in disease control rates.

Squamous Cell Carcinoma

Standard treatment options for superficial lesions less than 0.5 cm thick:
  1. Radiation therapy.[1-4] These tumors may be amenable to intracavitary brachytherapy alone,[1] but some centers nearly always begin with external-beam radiation therapy (EBRT).[2] EBRT is required for bulky lesions or lesions that encompass the entire vagina).[1] For lesions of the lower third of the vagina, elective radiation therapy is often administered to the patient's pelvic and/or inguinal lymph nodes.[1,2]
  2. Surgery.[5] Wide local excision or total vaginectomy with vaginal reconstruction, especially in lesions of the upper vagina. In cases with close or positive surgical margins, adjuvant radiation therapy is often added.[6]
Standard treatment options for lesions greater than 0.5 cm thick:
  1. Surgery.[5] In lesions of the upper third of the vagina, radical vaginectomy and pelvic lymphadenectomy should be performed. Construction of a neovagina may be performed if feasible and if desired by the patient.[6,7] In lesions of the lower third, inguinal lymphadenectomy should be performed. In cases with close or positive surgical margins, adjuvant radiation therapy should be considered.[6]
  2. Radiation therapy.[1-4] EBRT [2] and/or combination of interstitial and intracavitary therapy to a dose of at least 75 Gy to the primary tumor.[1,8] For lesions of the lower third of the vagina, elective radiation therapy of 45 Gy to 50 Gy is given to the pelvic and/or inguinal lymph nodes.[1,2]

Adenocarcinoma

Standard treatment options:
  1. Surgery. Because the tumor spreads subepithelially, total radical vaginectomy and hysterectomy with lymph node dissection are indicated. The deep pelvic nodes are dissected if the lesion invades the upper vagina, and the inguinal nodes are removed if the lesion originates in the lower vagina. Construction of a neovagina may be performed if feasible and if desired by the patient.[6] In cases with close or positive surgical margins, adjuvant radiation therapy is often given.[6,7]
  2. Intracavitary and interstitial radiation as previously described for squamous cell cancer.[1] For lesions of the lower third of the vagina, elective radiation therapy of 45 Gy to 50 Gy is given to the pelvic and/or inguinal lymph nodes.[1,9]
  3. Combined local therapy in selected cases, which may include wide local excision, lymph node sampling, and interstitial therapy.[10]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References
  1. Perez CA, Camel HM, Galakatos AE, et al.: Definitive irradiation in carcinoma of the vagina: long-term evaluation of results. Int J Radiat Oncol Biol Phys 15 (6): 1283-90, 1988. [PUBMED Abstract]
  2. Frank SJ, Jhingran A, Levenback C, et al.: Definitive radiation therapy for squamous cell carcinoma of the vagina. Int J Radiat Oncol Biol Phys 62 (1): 138-47, 2005. [PUBMED Abstract]
  3. Tran PT, Su Z, Lee P, et al.: Prognostic factors for outcomes and complications for primary squamous cell carcinoma of the vagina treated with radiation. Gynecol Oncol 105 (3): 641-9, 2007. [PUBMED Abstract]
  4. Lian J, Dundas G, Carlone M, et al.: Twenty-year review of radiotherapy for vaginal cancer: an institutional experience. Gynecol Oncol 111 (2): 298-306, 2008. [PUBMED Abstract]
  5. Tjalma WA, Monaghan JM, de Barros Lopes A, et al.: The role of surgery in invasive squamous carcinoma of the vagina. Gynecol Oncol 81 (3): 360-5, 2001. [PUBMED Abstract]
  6. Stock RG, Chen AS, Seski J: A 30-year experience in the management of primary carcinoma of the vagina: analysis of prognostic factors and treatment modalities. Gynecol Oncol 56 (1): 45-52, 1995. [PUBMED Abstract]
  7. Rubin SC, Young J, Mikuta JJ: Squamous carcinoma of the vagina: treatment, complications, and long-term follow-up. Gynecol Oncol 20 (3): 346-53, 1985. [PUBMED Abstract]
  8. Andersen ES: Primary carcinoma of the vagina: a study of 29 cases. Gynecol Oncol 33 (3): 317-20, 1989. [PUBMED Abstract]
  9. Chyle V, Zagars GK, Wheeler JA, et al.: Definitive radiotherapy for carcinoma of the vagina: outcome and prognostic factors. Int J Radiat Oncol Biol Phys 35 (5): 891-905, 1996. [PUBMED Abstract]
  10. Senekjian EK, Frey KW, Anderson D, et al.: Local therapy in stage I clear cell adenocarcinoma of the vagina. Cancer 60 (6): 1319-24, 1987. [PUBMED Abstract]

Stage II Vaginal Cancer

The treatments listed below have not been directly compared in randomized trials.[Level of evidence 3iiiD] As a result of differences in patient selection, local expertise, and staging criteria, it is difficult to determine whether there are differences in disease control rates. Radiation therapy is the most common treatment for patients with stage II vaginal cancer.

Squamous Cell Carcinoma

Standard treatment options:
  1. Combination of brachytherapy and external-beam radiation therapy (EBRT) to deliver a combined dose of 70 Gy to 80 Gy to the primary tumor volume.[1-4] For lesions of the lower third of the vagina, elective radiation therapy of 45 Gy to 50 Gy is given to the pelvic and/or inguinal lymph nodes.[1,5]
  2. Radical surgery (radical vaginectomy or pelvic exenteration) with or without radiation therapy.[6-8]

Adenocarcinoma

Standard treatment options:
  1. Combination of brachytherapy and EBRT to deliver a combined dose of 70 Gy to 80 Gy to the primary tumor.[1] For lesions of the lower third of the vagina, elective radiation therapy of 45 Gy to 50 Gy is given to the pelvic and/or inguinal lymph nodes.[1,5,9]
  2. Radical surgery (radical vaginectomy or pelvic exenteration) with or without radiation therapy.[7]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References
  1. Perez CA, Camel HM, Galakatos AE, et al.: Definitive irradiation in carcinoma of the vagina: long-term evaluation of results. Int J Radiat Oncol Biol Phys 15 (6): 1283-90, 1988. [PUBMED Abstract]
  2. Frank SJ, Jhingran A, Levenback C, et al.: Definitive radiation therapy for squamous cell carcinoma of the vagina. Int J Radiat Oncol Biol Phys 62 (1): 138-47, 2005. [PUBMED Abstract]
  3. Tran PT, Su Z, Lee P, et al.: Prognostic factors for outcomes and complications for primary squamous cell carcinoma of the vagina treated with radiation. Gynecol Oncol 105 (3): 641-9, 2007. [PUBMED Abstract]
  4. Lian J, Dundas G, Carlone M, et al.: Twenty-year review of radiotherapy for vaginal cancer: an institutional experience. Gynecol Oncol 111 (2): 298-306, 2008. [PUBMED Abstract]
  5. Andersen ES: Primary carcinoma of the vagina: a study of 29 cases. Gynecol Oncol 33 (3): 317-20, 1989. [PUBMED Abstract]
  6. Rubin SC, Young J, Mikuta JJ: Squamous carcinoma of the vagina: treatment, complications, and long-term follow-up. Gynecol Oncol 20 (3): 346-53, 1985. [PUBMED Abstract]
  7. Stock RG, Chen AS, Seski J: A 30-year experience in the management of primary carcinoma of the vagina: analysis of prognostic factors and treatment modalities. Gynecol Oncol 56 (1): 45-52, 1995. [PUBMED Abstract]
  8. Tjalma WA, Monaghan JM, de Barros Lopes A, et al.: The role of surgery in invasive squamous carcinoma of the vagina. Gynecol Oncol 81 (3): 360-5, 2001. [PUBMED Abstract]
  9. Chyle V, Zagars GK, Wheeler JA, et al.: Definitive radiotherapy for carcinoma of the vagina: outcome and prognostic factors. Int J Radiat Oncol Biol Phys 35 (5): 891-905, 1996. [PUBMED Abstract]

Stage III Vaginal Cancer

Squamous Cell Carcinoma

Standard treatment options:
  1. External-beam radiation therapy (EBRT) alone, or in combination with interstitial, intracavitary radiation.[1-4] For example, EBRT for a period of 5 to 6 weeks (including the pelvic nodes) followed by an interstitial and/or intracavitary implant for a total tumor dose of 75 Gy to 80 Gy and a dose to the lateral pelvic wall of 55 Gy to 60 Gy.[1,2,5]
  2. Rarely, surgery may be combined with the above.[6]

Adenocarcinoma

Standard treatment options:
  1. Combination of interstitial, intracavitary, and EBRT as described for squamous cell cancer.[1,5]
  2. Rarely, surgery may be combined with the above.[6]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References
  1. Perez CA, Camel HM, Galakatos AE, et al.: Definitive irradiation in carcinoma of the vagina: long-term evaluation of results. Int J Radiat Oncol Biol Phys 15 (6): 1283-90, 1988. [PUBMED Abstract]
  2. Frank SJ, Jhingran A, Levenback C, et al.: Definitive radiation therapy for squamous cell carcinoma of the vagina. Int J Radiat Oncol Biol Phys 62 (1): 138-47, 2005. [PUBMED Abstract]
  3. Tran PT, Su Z, Lee P, et al.: Prognostic factors for outcomes and complications for primary squamous cell carcinoma of the vagina treated with radiation. Gynecol Oncol 105 (3): 641-9, 2007. [PUBMED Abstract]
  4. Lian J, Dundas G, Carlone M, et al.: Twenty-year review of radiotherapy for vaginal cancer: an institutional experience. Gynecol Oncol 111 (2): 298-306, 2008. [PUBMED Abstract]
  5. Chyle V, Zagars GK, Wheeler JA, et al.: Definitive radiotherapy for carcinoma of the vagina: outcome and prognostic factors. Int J Radiat Oncol Biol Phys 35 (5): 891-905, 1996. [PUBMED Abstract]
  6. Boronow RC, Hickman BT, Reagan MT, et al.: Combined therapy as an alternative to exenteration for locally advanced vulvovaginal cancer. II. Results, complications, and dosimetric and surgical considerations. Am J Clin Oncol 10 (2): 171-81, 1987. [PUBMED Abstract]

Stage IVA Vaginal Cancer

Squamous Cell Carcinoma

Standard treatment options:
  1. Combination of interstitial, intracavitary, and external-beam radiation therapy (EBRT).[1-5]
  2. Rarely, surgery may be combined with the above.[6]

Adenocarcinoma

Standard treatment options:
  1. Combination of interstitial, intracavitary, and EBRT.[1,2]
  2. Rarely, surgery may be combined with the above.[7]

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References
  1. Perez CA, Camel HM, Galakatos AE, et al.: Definitive irradiation in carcinoma of the vagina: long-term evaluation of results. Int J Radiat Oncol Biol Phys 15 (6): 1283-90, 1988. [PUBMED Abstract]
  2. Chyle V, Zagars GK, Wheeler JA, et al.: Definitive radiotherapy for carcinoma of the vagina: outcome and prognostic factors. Int J Radiat Oncol Biol Phys 35 (5): 891-905, 1996. [PUBMED Abstract]
  3. Frank SJ, Jhingran A, Levenback C, et al.: Definitive radiation therapy for squamous cell carcinoma of the vagina. Int J Radiat Oncol Biol Phys 62 (1): 138-47, 2005. [PUBMED Abstract]
  4. Tran PT, Su Z, Lee P, et al.: Prognostic factors for outcomes and complications for primary squamous cell carcinoma of the vagina treated with radiation. Gynecol Oncol 105 (3): 641-9, 2007. [PUBMED Abstract]
  5. Lian J, Dundas G, Carlone M, et al.: Twenty-year review of radiotherapy for vaginal cancer: an institutional experience. Gynecol Oncol 111 (2): 298-306, 2008. [PUBMED Abstract]
  6. Boronow RC, Hickman BT, Reagan MT, et al.: Combined therapy as an alternative to exenteration for locally advanced vulvovaginal cancer. II. Results, complications, and dosimetric and surgical considerations. Am J Clin Oncol 10 (2): 171-81, 1987. [PUBMED Abstract]
  7. Stock RG, Chen AS, Seski J: A 30-year experience in the management of primary carcinoma of the vagina: analysis of prognostic factors and treatment modalities. Gynecol Oncol 56 (1): 45-52, 1995. [PUBMED Abstract]

Stage IVB Vaginal Cancer

Current therapy is of unclear benefit for patients with Stage IVB disease. No established anticancer drugs can be considered of proven clinical benefit, although patients are often treated with regimens used to treat cervical cancer. (Refer to the PDQ summary on Cervical Cancer Treatment for more information.)
Concurrent chemotherapy using 5-fluorouracil or cisplatin-based therapy and radiation is sometimes advocated, and, again, this is based solely on extrapolation from cervical cancer management strategies. (Refer to the PDQ summary on Cervical Cancer Treatment for more information.)[1-3] Experience is limited to small case series and the incremental impact on survival and local control is not well defined.[Level of evidence 3iiiDiv] Considering the rarity of these patients, they should be considered candidates for clinical trials to improve survival or local control. Information about ongoing clinical trials is available from the NCI website.

Squamous Cell Carcinoma

Standard treatment options:
  • Radiation (for palliation of symptoms) with or without chemotherapy.

Adenocarcinoma

Standard treatment options:
  • Radiation (for palliation of symptoms) with or without chemotherapy.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References
  1. Grigsby PW: Vaginal cancer. Curr Treat Options Oncol 3 (2): 125-30, 2002. [PUBMED Abstract]
  2. Dalrymple JL, Russell AH, Lee SW, et al.: Chemoradiation for primary invasive squamous carcinoma of the vagina. Int J Gynecol Cancer 14 (1): 110-7, 2004 Jan-Feb. [PUBMED Abstract]
  3. Samant R, Lau B, E C, et al.: Primary vaginal cancer treated with concurrent chemoradiation using Cis-platinum. Int J Radiat Oncol Biol Phys 69 (3): 746-50, 2007. [PUBMED Abstract]

Recurrent Vaginal Cancer

Recurrence carries a grave prognosis. In a large series, only five of fifty patients with recurrence were salvaged by surgery or radiation therapy. All five of these salvaged patients originally presented with stage I or II disease and had tumor recurrence in the central pelvis.[1] Most recurrences occur in the first 2 years after treatment. In centrally recurrent vaginal cancers, some patients may be candidates for pelvic exenteration or radiation therapy.
No established anticancer drugs can be considered of proven clinical benefit, although patients are often treated with regimens used to treat cervical cancer. (Refer to the PDQ summary on Cervical Cancer Treatment for more information.) If eligible, patients should be offered the option of participation in one of the ongoing clinical trials. Information about ongoing clinical trials is available from the NCI website.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
References
  1. Stock RG, Chen AS, Seski J: A 30-year experience in the management of primary carcinoma of the vagina: analysis of prognostic factors and treatment modalities. Gynecol Oncol 56 (1): 45-52, 1995. [PUBMED Abstract]

Changes to This Summary (02/07/2019)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Updated statistics with estimated new cases and deaths for 2019 (cited American Cancer Society as reference 1).
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

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