Vaginal cancer medical therapy: Difference between revisions
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==Medical therapy== | ==Medical therapy== | ||
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. | 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. 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. | ||
Factors to be considered in planning therapy for vaginal cancer include: | Factors to be considered in planning therapy for vaginal cancer include: | ||
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Whether there has been prior pelvic radiation therapy. | Whether there has been prior pelvic radiation therapy. | ||
In a series of 100 women studied retrospectively over 30 years, 50% had undergone hysterectomy prior to the diagnosis of vaginal cancer. | In a series of 100 women studied retrospectively over 30 years, 50% had undergone hysterectomy prior to the diagnosis of vaginal cancer. 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. | 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: | Radiation-induced damage to nearby organs may include: | ||
Rectovaginal fistulas. | Rectovaginal fistulas. | ||
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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. | 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. | 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. | ||
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. | 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. 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.) | 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, again based solely on extrapolation from cervical cancer management strategies. | Concurrent chemotherapy, using 5-fluorouracil or cisplatin-based therapy, and radiation are sometimes advocated, again based solely on extrapolation from cervical cancer management strategies. 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. | 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. | ||
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.==Therapies based on stage== | 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.==Therapies based on stage== | ||
Revision as of 18:38, 2 September 2015
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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Overview
Therapeutic alternatives depend on stage; surgery or radiation therapy is highly effective in early stages, while 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.
Medical therapy
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. 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.
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 prior pelvic radiation therapy.
In a series of 100 women studied retrospectively over 30 years, 50% had undergone hysterectomy prior to the diagnosis of vaginal cancer. 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:
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.
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. 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, again based solely on extrapolation from cervical cancer management strategies. 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.
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.==Therapies based on stage==
Stage 0 Vaginal Cancer
Squamous Cell Carcinoma In Situ
This disease is usually multifocal and commonly occurs at the vaginal vault. Because vaginal intraepithelial neoplasia (VAIN) is associated with other genital neoplasias, the cervix (when present) and vulva should be carefully examined. The treatments listed below produce equivalent cure rates. The selection of treatment depends on patient factors and local expertise (e.g., anatomical distortion of the vaginal vault [related to wall closure at the time of 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.
Standard treatment options:
- Wide local excision with or without skin grafting.
- Partial or total vaginectomy with skin grafting for multifocal or extensive disease.
- Intravaginal chemotherapy with 5% fluorouracil cream. Instillation of 1.5 g weekly for 10 weeks has been found to be as effective as more frequent use.
- Laser therapy.
- Intracavitary radiation therapy delivering 60 Gy to 70 Gy to the mucosa. The entire vaginal mucosa should be treated.
Stage I Vaginal Cancer
Squamous Cell Carcinoma
The treatments listed below produce equivalent cure rates. The selection of treatment depends on patient factors and local expertise.
Standard treatment options for superficial lesions less than 0.5 cm thick:
- Intracavitary radiation therapy. In most instances, 60 Gy to 70 Gy prescribed to 0.5 cm is delivered to the tumor for 5 to 7 days (external-beam radiation therapy [EBRT] is required for bulky lesions). For lesions of the lower third of the vagina, elective radiation therapy of 45 Gy to 50 Gy is given to pelvic and/or inguinal lymph nodes.
- Surgery. 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 should be considered.
Standard treatment options for lesions greater than 0.5 cm thick:
- Surgery. 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. 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.
- Radiation therapy. Combination of interstitial (single-plane implant) and intracavitary therapy to a dose of at least 75 Gy to the primary tumor. In addition to brachytherapy, EBRT is advocated for poorly differentiated or infiltrating tumors that may have a higher probability of lymph node metastasis. 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.
Adenocarcinoma
Standard treatment options:
- 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. In cases with close or positive surgical margins, adjuvant radiation therapy should be considered.
- Intracavitary and interstitial radiation as previously described for squamous cell cancer. 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.
- Combined local therapy in selected cases, which may include wide local excision, lymph node sampling, and interstitial therapy.
Stage II Vaginal Cancer
Squamous Cell Carcinoma
Radiation therapy is the standard treatment for patients with stage II vaginal carcinoma.
Standard treatment options:
- 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. 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.
- Radical surgery (radical vaginectomy or pelvic exenteration) with or without radiation therapy.
Adenocarcinoma
Standard treatment options:
- Combination of brachytherapy and EBRT to deliver a combined dose of 70 Gy to 80 Gy to the primary tumor. 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.
- Radical surgery (radical vaginectomy or pelvic exenteration) with or without radiation therapy.
Stage III Vaginal Cancer
Squamous Cell Carcinoma
Standard treatment options:
- Combination of interstitial, intracavitary, and external-beam radiation therapy (EBRT). EBRT for a period of 5 to 6 weeks (including 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.
- Rarely, surgery may be combined with the above.
Adenocarcinoma
Standard treatment options:
- Combination of interstitial, intracavitary, and EBRT as described for squamous cell cancer.
- Rarely, surgery may be combined with the above.
Stage IVA Vaginal Cancer
Squamous Cell Carcinoma
Standard treatment options:
- Combination of interstitial, intracavitary, and external-beam radiation therapy (EBRT).
- Rarely, surgery may be combined with the above.
Adenocarcinoma
Standard treatment options:
- Combination of interstitial, intracavitary, and EBRT.
- Rarely, surgery may be combined with the above.
Stage IVB Vaginal Cancer
Squamous Cell Carcinoma
Patients should be considered candidates for one of the ongoing clinical trials to improve therapeutic results. Standard treatment is inadequate.
Standard treatment options:
- Radiation (for palliation of symptoms) with or without chemotherapy.
Adenocarcinoma
Patients should be considered candidates for one of the ongoing clinical trials to improve therapeutic results.
Standard treatment options:
- Radiation (for palliation of symptoms) with or without chemotherapy.
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 failed in the central pelvis. Most recurrences are in the first 2 years after treatment. In centrally recurrent vaginal cancers, some patients may be candidates for pelvic exenteration or radiation therapy. Neither cisplatin nor mitoxantrone has significant activity in recurrent or advanced squamous cell cancer. There is no standard chemotherapy.