Vaginal Cancer

Content written by Don S. Dizon, MD

OVERVIEW: SEXUAL DYSFUNCTION IN VAGINAL CANCER SURVIVORS

Primary vaginal cancer is one of the rarest malignancies of the female genital tract. It accounts for less than 1% of these tumors, and has an incidence of 0.7 per 100,000 women.[i] [Hellman K, Lundell M, Silfversward C, et al. Int J Gynecol Cancer. 2006; 16:1201–11] The American Cancer Society estimates that in the year 2009, about 2,160 new cases of vaginal cancer will be diagnosed in the United States; 770 women are expected to die of this cancer.[ii] [American Cancer Society. Atlanta: American Cancer Society, 2009] For all cases of vaginal cancer combined (squamous, adenocarcinoma, and melanoma), the relative 5-year survival is about 50%.

Treatment for vaginal cancer is dependent upon the location, size, and clinical stage of the tumor; surgical and radiotherapy decisions are based upon the proximity of the tumor to the bladder, urethra, and rectum, as well as the patient’s desire to maintain a functional vagina. Pre-cancers of the vagina (vaginal intraepithelial neoplasia, VAIN), are treated with wide surgical excision, loop diathermy, carbon dioxide laser ablation, and the topical application of chemotherapeutics. Radiation is the mainstay of treatment for actual vaginal cancers, which entails the use of external beam radiation and/or intracavitary brachytherapy. As tumor cells are not exclusively radiosensitive, damage to surrounding normal vaginal tissue and adjacent organs is expected. Stage I cancers are sometimes treated with surgery, which can range from local excision and vaginectomy to trachelectomy and hysterectomy. Surgery is also used in cases of radiation failure where pelvic exenteration is required. If all or most of the vagina must be removed, it can be reconstructed surgically out of skin or intestinal tissue. Patients whose bladders must be removed require urinary diversions that connect to skin with external collection bags. Cases in which the rectum and colon are affected further require resection of affected areas and sometimes the use of a colostomy bag connected to the abdominal wall.

Because of the rarity of invasive vaginal cancer, there are numerous conflicting recommendations regarding definitive treatment modalities that provide the best outcomes. Several studies have indicated that radiotherapy should be the primary treatment for vaginal cancer, while others have recommended surgery.[iii] [Samant R, Tam T, Dahrouge S, et al. Radiotherapy and Oncology. Nov 2005; 77(2): 133-136] Sacrifice of vaginal function is the requisite expectation of both modalities with radiation leading to generalized scarring and stenosis and surgery often requiring near total vaginectomy in order to achieve clear surgical margins. However with most vaginal cancers occurring in the upper third of the vagina, surgery runs high risk of damaging the bladder anteriorly and the sigmoid colon posteriorly. Radiation therapy has therefore become the preferred primary treatment for vaginal cancer, with surgery reserved as salvage for cases uncontrolled by radiation.

Nevertheless these studies have prioritized the eradication of cancer over quality of life in survivorship as their treatment goals, with any decline in sexual function often inappropriately assumed to be due to the old age and collective co-morbidities of most patients. Consequently there are few studies comparing the two modalities with respect to sexual function in survivorship. Little quantitative data on sexual impact is available per modality in general. With this consideration in mind, it may be appropriate to consider alternative therapies or alterations to current regimens that may allow for improved sexual function outcomes. For example, there may be a larger role for surgery in early stage cancers in place of radiation therapy, as surgery may prevent progressive vaginal contraction.[iv] [Al-Kurdi M, Monaghan JM. Br J Obstet Gynaecol. 1981; 88: 1145-50] Where patients receiving surgery can expect their post-surgical vaginal scarring to improve after the first year of treatment, patients receiving radiation therapy may experience chronic fibrotic changes in the pelvic tissues for 2-5 years post-treatment. [v],[vi]

[Frumovitz M, Sun CC, Schover LR, et al. Journal of Clinical Oncology. 20 Oct 2005; 23(30):7428-7436], [Denton A, et al. Clinical Oncology. 2000; 12(1): 347-353]

As squamous cell carcinoma is the most common variant of vaginal cancer as well as the latest presenting, most patients are postmenopausal at treatment. As a result, radiation therapy that damages the ovaries does not affect the hormone status of these patients nor does it then lead to the more dramatic changes in sexual function experienced by premenopausal patients. Approximately 20-30% of vaginal cancer patients are under the age of 60, the majority of those patients with adenocarcinoma of the vagina presenting before the age of 30.[vii] [Herbst AL. Am J Obstet Gynecol 1999;181:1576-9] These patients are more likely to suffer from premature ovarian failure with radiation therapy and encounter a steeper decline in sexual function, only compounded by infertility. Radiation-sparing surgery should be considered in these cases where possible.[viii] [Carter J, Rowland K, Chi D, et al. Gynecol Oncol. 2005; 97:90–95]

In a review of treatment outcomes from 1985-1994, women surgically treated for Stage I disease had a 5-year relative survival rate of 90% compared with 63% for Stage I patients treated with radiotherapy only and 79% for patients treated with both.[ix] [Creasman WT, Phillips JL, Menck HR. Cancer. 1998; 83: 1033– 40.] Tjalma et al. achieved similar results (91% at 5 years) with surgery alone for Stage I patients.[x] [Tjalma WA, Monaghan JM, de Barros Lopes A, et al. Gynecol Oncol. 2001; 81: 360–365] In both studies the majority of surgeries only required partial vaginectomy with lymph node dissection. These studies however did not directly examine sexual function. A 2006 that looked at sexual function as an outcome surveyed 4 women undergoing partial vaginectomy and lymphadenectomy for stage I vaginal cancer, finding survival of all 4 cases through 45 months without complaint of dyspareunia, vaginal dryness or loss of vaginal sensation. All reported a satisfying sexual relationship. [xi] [Cutillo G, Cignini P, Pizzi G, et al. Gynecol Oncol. Oct 2006; 103(1): 234-237]

Despite what benefit surgery may provide for young patients with respect to sexual dysfunction, treatment options are still limited by the stage of the disease. Radiation therapy is the mainstay for treatment of any vaginal cancers greater than Stage I. However modifications to radiation therapy regimens may be able to prevent sexual dysfunction by limiting damage to normal vaginal tissue. In a 23 year review of vaginal cancer radiotherapy, external beam therapy was combined with intracavitary brachytherapy (n=15) or interstitial brachytherapy (n=10) with resulting vaginal morbidity compared. As intracavitary brachytherapy incorporates the use of long cylinders that emit radiation across the entire length of the vaginal cavity, the entire circumference is irradiated, resulting in widespread fibrosis and shortening of the canal seen among 60% of those receiving this treatment. External beam radiation with interstitial therapy uses needles to target therapy to shorter segments of the vagina resulting in half the incidence of stenosis as compared to intracavitary brachytherapy.[xii] [Stryker JA. British J of Radiology. 2000; 73:1200-1205] In trying to decrease the area of vaginal mucosa exposed to radiation, Perez et al in 1999 analyzed the benefit of brachytherapy alone instead of brachytherapy with external irradiation in Stage I vaginal carcinomas. In a sample of 59 patients, the addition of external irradiation did not increase tumor control (78-92% with 5 year disease-free survival) compared to brachytherapy alone (80-100%).[xiii] [Perez CA, Grigsby PW, Garipagaoglu M, et al. April 1999; 44(1): 37-45] Nevertheless with such low sample population numbers, it is difficult to draw conclusions on how to balance radiation exposure with disease control. There exist multiple conflicting studies that would suggest the use of external beam radiation alone to control disease recurrence. Frank et al in 2003 reports the regimented initial use of EBRT in all cases of vaginal carcinoma, highlighting the notion that vaginal lymph drains to all lymph nodes in the pelvis, making external radiation therapy the better modality for treatment of possible micrometastases that may have not been captured when looking at 5 year survival, as was done in the Perez study. In examination of 10-year survival rates at their institution, Frank et al had an 18% treatment failure rate with brachytherapy alone. For the 11 patients who received external radiation with or without brachytherapy, no pelvic recurrence was encountered. [xiv] [Frank SJ, Jhingran A, Levenback C, et al. Int J Rad Oncol. May 2005; 62(1): 138-147] As their study did not assess vaginal morbidity or sexual function however, radiation therapy should continue to be individualized to patient outcome expectations.

As no studies have directly examined vaginal morbidities associated with treatment for vaginal cancer, studies on cervical cancer treatment can provide insight into risk factors for sexual dysfunction. Brand et al reviewed 10 years of data on 188 patients treated for cervical cancer primarily with pelvic radiation, finding that where stage of the cancer was not a predictive factor for vaginal stenosis after treatment, age greater than 50 years was.[xv] [Brand AH, Bull CA, Cakir B. Int J Rad Oncol. 2006; 16(1): 288–293] This finding is significant in that the increased risk of developing vaginal stenosis in peri/postmenopausal women may be related to lack of estrogen and/or lack of sexual activity in older women. This finding would highlight the value of using vaginal estrogens, if not contraindicated, as well as vaginal dilators to prevent treatment complications.

TREATMENT FOR SEXUAL DYSFUNCTION

Though survivors of vaginal cancers are generally satisfied with their cancer care, more than half feel that their sexuality after treatment is seldom addressed by the physician. In one study, 62% of vaginal cancer survivors reported that a doctor had never initiated a conversation about the effects of genital cancer or its treatments on sexuality. The study further showed that a conversation with a physician about the sexual effects of vaginal cancer treatment was associated with significantly less sexual morbidity.[xvi] [Lindau ST, Gavrilova N, Anderson D. Gynecol Oncol. Aug 2007; 106(2):413-418]

Prior to beginning conversation about sexual dysfunction after treatment for cancer however, physicians need understand baseline sexual dysfunction in these patients. Patients with vaginal carcinoma may initially present with postmenopausal or postcoital vaginal bleeding, malodorous vaginal discharge, a vaginal mass, urinary symptoms, complaints with defecation, or pelvic pain. Though never surveyed formally, sexual dysfunction may exist at baseline in these patients. Treating sexual dysfunction requires realistic expectations; consequently pre-treatment symptoms should be assessed prior to interventions that might affect function. Furthermore, women should be provided reassurance early on that despite significant sexual dysfunction entailed by treatment of vaginal cancer, long-term surveys of survivors still indicate high rates of marriage, sexual partnership and activity. Positive attitudes, partnership and behavior are often maintained.[xvii] [Lindau ST, Gavrilova N, Anderson D. Gynecol Oncol. Aug 2007; 106(2):413-418]

As most women with vaginal cancers will undergo radiation therapy, they should be made aware of its sexual side effects ahead of treatment. Radiation therapy generally takes 5-6 weeks and can lead to significant damage to the vaginal epithelium. Some patients even experience blistering, which can lead to pain with sitting. Patients need to have their pain controlled with medication, and should be recommended protective ointments such as Eucerin or A&D ointment, as well as sitz baths to cool and cleanse the area.

Such extensive damage to the epithelium requires anywhere from three to six months to heal. Yet visual inspection of epithelial regrowth is not sufficient, as the basal cell layer is likely to still be too thin to allow penetrative intercourse. Healing can be facilitated however by using topical estrogen to promote epithelial regeneration, decreasing dryness and tenderness.[xviii] [Denton AS, Maher EJ. Cochrane Review. 2006] In 1971, Pitkin and Van Voorhis compared the use of a vaginal cream with estrogen and a placebo, finding that patients treated with estrogen to have less dyspareunia and twice the likelihood of retaining normal vaginal caliber.[xix] [Pitkin RM, VanVoorhis LW. Radiology. 1971 May; 99(2):417-21] However more recent studies have not confirmed the benefit of estrogen and the use of topical estrogen is contraindicated in women who should not have systemic estrogen. Patients suffering from the immediate effects of radiation vaginitis after brachytherapy can use benzydamine, an anti-inflammatory which has been shown to decrease symptoms of pain, pruritis, tension, burning, and vaginal tenderness. [xx] [Volterrani F, Tana S, Trenti N. Int J Tissue React. 1987; 9(2):169-71]

Looking forward, women can prevent vaginal stenosis with the aide of vaginal dilators as a replacement for or adjunct to intercourse. Even for women without partners, dilation of the vagina continues to be important to ensure future possibilities and the physician’s ability to perform speculum vaginal exams for recurrence. Currently there is no clear research evidence concerning the optimum time to start vaginal dilatation. Some physicians encourage use during treatment; all women should be advised to start dilating regularly following treatment. Nevertheless, some researchers have suggested that vaginal dilators are inadequate for the complete prevention of dyspareunia. Dilators do not consistently reach the upper third of the vagina, leaving the upper third to continue stenosis. Decruze in 1999 studied the use of vaginal stents, finding that among women placing a vaginal stent once daily for one year, only 11% experienced stenosis compared to 54% in women not using any stent at 1 year post-treatment.[xxi]

More important than stents however, is ensuring compliance. Given the trauma to the vaginal vault from radiotherapy, the use of a dilator may induce fear. Robinson et al found that younger women were significantly more likely than older women to follow recommendations for vaginal dilation, likely due to their expectations to continue sexual relations.[xxii] [Robinson J, Faris P, Scott C. Int J Radiat Oncol. 1999; 44:497-506.] Women provided with dilators thus need to be provided with reassurance, rationale for treatment, as well as suggestions for ease of use.

Suggestions from the National Forum of Gynaecological Oncology Nurses:

Women who require vaginectomy for adequate control of their cancer or whose therapy leads to severe stenosis may opt for the creation of a neovagina. In this procedure, surgeons use other tissues from the patient’s body to create a functional vagina. Experimental tissues have included skin grafts, buccal mucosa grafts, bladder mucosa, peritoneum, and even bowel. There is no consensus on the best procedure for vaginal replacement. For patients who have vaginas reconstructed from myocutaneous flaps harvested from the muscle and skin from the leg, stimulation of the vagina may make a woman feel as if her thigh is being stroked. This phenomenon is due to the preservation of nerve supply to the transplanted flap. Over time however the patient may adapt to the feeling and associate it with sexuality. A more promising result that may leave fewer surgical scars and may be more adaptable uses laparoscopy to enter the abdomen and isolate a section of the ileum for anastomosis to the vaginal cuff and conversion into a new vaginal vault.[xxiv] [Wu JX, Li B, Li WZ, Jiang YG, et al. Int J of Gynecol & Obstet. Dec 2009; 107(3): 258-261] Unfortunately, a reconstructed vagina produces little or no natural lubricant when a woman becomes sexually excited. Sexual intercourse cannot be as spontaneous as might be preferred and couples have to lubricate ahead of time. Regardless of case reports of success, surgeries of this type are not recommended for patients who have been irradiated due to the compromised tissue healing.

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