Vaginal Cancer

The most common presenting symptom of vaginal cancers is abnormal vaginal bleeding.[16] This is followed by nondescript symptoms such as vaginal discharge or dysuria. Pelvic pain is often indicative of advanced disease. One of the most important aspects of the patient history is the preexistence of cervical cancer. In a retrospective study, vaginal cancer was the most common type of metachronous malignancy.[17] Evaluation for suspected vaginal cancer requires a thorough physical exam, which can include a digital exam, a rectovaginal exam, a speculum exam, palpation of inguinal nodes, and colposcopy with biopsies.

Biopsy remains the gold standard to diagnose vaginal cancer. This can be best accomplished by an examination under anesthesia with inspection of the vaginal fornices as well as biopsies of the cervix. However, clinical evaluation can also be performed if the patient is comfortable. Furthermore, if a patient has a history of preinvasive or invasive cervical cancer, it is necessary to offer a vaginoscopy following abnormal cytology after hysterectomy or radiation therapy. No specific lab abnormalities exist in diagnosing vaginal cancer. Elevated liver function tests can suggest metastatic disease but are nonspecific. MRI of the pelvis is useful in the staging of vulval and vaginal neoplasms to assess tumor size, local tumor extent, and presence of lymph node metastases. Further indications for MRI are the diagnosis of post-therapeutic changes and tumor recurrence.[18] 

PET-CT scans have limited utility in the diagnosis of vaginal cancer, and FIGO encourages the use of advanced imaging modalities, such as computed tomography, magnetic resonance imaging (MRI), and positron emission tomography (PET), to guide therapy. However, the imaging findings may not be used to change or reassign the stage.[19] In one study, FIGO evaluated the use of PET/CT for the assessment of suspected or known disease (primary or recurrent). They reported a change in prognostic impression and intended patient management, in 51% and 36% of studies performed respectively.[20]

Early vaginal carcinomas are generally treated with either surgery or radiation therapy. Advanced cancers are treated with radiation therapy and the simultaneous administration of combined chemotherapy.[16] A study from the National Cancer Database showed that the use of CCRT (combined chemoradiation therapy) for patients with vaginal cancer has increased, and it is associated with a significant improvement. CCRT should be incorporated into treatment guidelines for vaginal cancer.[21] 

The primary treatment options in Stage I vaginal carcinoma are surgery and/or radiation therapy. For a small tumor, a wide excision can be used. For high-risk patients, more aggressive surgery is mandatory. From a surgical standpoint, radical surgery for stage I and II cancers have very good outcomes. A retrospective study was conducted on eleven patients aged 35 to 78 years. All the patients in the study received radical surgery for vaginal carcinoma from April 2010 until June 2015. The mean age of the patients in the study was 53.2 years. Using the FIGO staging system, ten patients diagnosed with vaginal cancer stage I vaginal cancer, whereas one had stage II vaginal cancer. The majority of the patients had squamous cell histology; however, a small number (2) had neuroendocrine tumors. The carcinoma is confined to the upper two-thirds of the vagina in eight cases, and the lower one-third of the vagina in three cases. All the patients received radical pelvic surgery. Nine of the patients had lymph node dissection performed; of these patients, three had positive nodes. These patients, along with those who had positive surgical margins, received adjuvant treatment. Six patients did not receive adjuvant therapy, five who did not require due to not meeting the prior stated criteria, and one patient deferred treatment. Complications and local recurrence were minimal, with one patient developing a vesicovaginal fistula and another having local recurrence over a follow-up of 5 to 67 months. One patient was lost to follow-up at 15 months. The 12-month disease-free survival was 88.9%, and 12-month overall survival was 100%.[22] 

The most frequently used treatment strategy for stage II is a combination of brachytherapy and external beam radiation therapy (EBRT). Highly selective patients may be treated by radical surgery. Neoadjuvant chemotherapy, followed by radical surgery, is a valid alternative to the standard treatment in terms of survival. A combination of EBRT and brachytherapy is utilized most often for stages III-IV A and, in selected patients, pelvic exenteration or a combination of irradiation can be used.[23]

The differential diagnosis for vaginal cancer is diverse, and it can include lesions not typical of the reproductive system. Sexually transmitted infections, such as herpes simplex and syphilis, can cause lesions that can mimic cancer. Vaginal trauma can also present with similar bleeding to that of vaginal cancers. Vaginal atrophy can also present with vaginal bleeding. Benign vaginal masses include but are not limited to, polyps, Gartner duct cysts, Bartholin gland cysts or vaginal adenosis. From an oncologic perspective, cervical cancer and vulvar cancer must be ruled out when determining if a lesion is a primary vaginal carcinoma. Metastatic lesions from colorectal cancer have been reported as well.[24]

Surgical management can be considered in stage I lesions that are amenable to hysterectomy with upper vaginectomy and lymph node dissection. Ideally, these lesions would be present in the apex of the posterior fornix of the vagina. Lower lesions could be approached with vulvovaginectomy, but due to the complex nature and complications associated with it, this procedure is not common. For young women with vaginal cancer requiring radiation as primary treatment, ovarian transposition can be offered before definitive radiation treatment to prevent the adverse effects of radiation-induced menopause. In selected cases, laparoscopic or extraperitoneal removal of bulky lymph nodes can be offered as part of staging and treatment planning.[1]

In the majority of cases and particularly in advanced stages, radiation constitutes the cornerstone of treatment for this disease. Radiation therapy is a combination of external beam radiation (EBRT) and intracavitary radiotherapy or brachytherapy (ICRT). The principal advantage of radiation is organ preservation. EBRT to the pelvis includes the external iliac and obturator nodes as per the standard of care. Additionally, the inguinal nodes may be included if the tumor is in the distal vagina.[1] 

The optimal or lower threshold dose is 70 Gy, which has been shown to improve outcomes.[25] The Korean Radiation Oncology Group conducted a retrospective study examining primary radiation therapy for vaginal cancer. The study examined those treated with primary radiation with or without chemotherapy. A total of 138 patients met the inclusion criteria, and of those, none received surgery to excise the lesion. The median follow-up time of the patients who survive in the study was 77.6 months, and the median survival time was 46.9 months. Overall 5-year survival rate was 68%, cancer-specific survival (CSS) rate was 80%, and progression-free survival (PFS) rates were 68.7%. Having had a hysterectomy and an early FIGO stage diagnosis were both positive indicators of CSS.

Additionally, the analysis showed that diagnosis before the year 2000 was associated with a positive prognostic factor of PFS. Subgroup analysis did not show any importance of HPV status and rates of recurrence. advanced vaginal cancer grade 3 or 4 acute and late toxicity were seen in 16 and 9 patients, respectively. The volume of tumor and FIGO stage were foreboders of severe late toxicity. Ultimately, the data showed that a later stage of disease was associated with a worse survival outcome and more toxicity from treatment. Therefore, radiation therapy and strict observation are crucial in advanced vaginal cancer. Despite HPV status not relating to survival outcome, more study is needed in this particular area.[26]

Due to the rarity of primary vaginal cancer, there are currently no randomized trials determining treatment for vaginal cancer. 

The use of chemotherapy in vaginal cancer is relatively new, and most of the research has been extrapolated from data of cervical cancer treatment. In many cases, treatment with cisplatin or 5-fluorouracil has demonstrated some efficacy.[27] Chemoradiation can be consider in the management plan of vaginal cancer following a recent retrospective review suggesting an encouraging improvement in both overall and disease-free survival rates.[28] Although it was a small review of 71 patients, it displayed a significant difference in both overall survival and disease-free survival rates between women who received radiation alone versus those who received chemoradiation as initial treatment (three-year overall survival of 56% versus 79% and three-year disease-free survival of 43% versus 73%).[28]

The Federation Internationale de Gynecologie et d'Obstetrique (FIGO) staging of vaginal cancer (2009) is performed in a similar manner to cervical cancer; Clinical staging is done with routine investigative modalities for staging such as certain imaging techniques as well as procedures such as proctoscopy and cystoscopy.[19]

• Stage I - limited to the vaginal mucosa
• Stage II - involvement of the subvaginal tissue without extension to the pelvic sidewall
• Stage III - extension to the pelvic sidewall
• Stage IVA - spread to adjacent organs
• Stage IVB - spread to distant organs

Many prognostic factors can influence the management plan. Lymph node metastasis an important prognostic factor. Other factors include histology, size, and age. In a recent SEER analysis of more than 2000 patients, the 5-year disease-specific survival was 84% for stage I, 75% for stage II, and 57% for advanced tumors.[16]

Complications from treatment of vaginal cancer depend on many factors. The factors can be divided into treatment-based and patient-based. Treatment-based factors include the intensity of radiation, type of surgery, and type of chemotherapy. Patient-based factors include age, hormonal status, and personal hygiene. The complications from radiation include edema, erythema, and mucositis with or without ulceration. Usually, these effects resolve within a few months after treatment. 

A cross-sectional survey of outpatient visits showed female cancer patients have unmet sexual and vaginal health needs. Preferences for receiving sexual health information vary by age. Improved physician-patient communication, awareness, and educational resources using proven sexual health promotion strategies can help women cope with treatment side effects.[29]

Vaginal cancer is rare, so an important aspect of diagnosing vaginal cancer is ruling out other carcinomas of gynecologic origin, specifically cervical cancer. Managing routine cytology screening for cervical cancer has undoubtedly saved many lives. Yet, it is not without its difficulties. Recordkeeping, follow-up treatment, and unnecessary repeat procedures have made cervical cytology an imperfect science. However, a team-based approach that emphasizes obtaining outside records and communication with nursing staff can mitigate some of these issues. Once the diagnosis of vaginal carcinoma is made, coordinated care needs to be prompt. The involvement of social workers, nurse navigators, radiation oncologists, and gynecologic oncologists is critical.[16]