Laboratory Studies
CBC results can identify patients who are anemic secondary to bleeding from the primary tumor. Preoperative management of anemia is indicated because the average blood loss from an abdominal radical hysterectomy is 500-1000 mL. Some reports indicate a negative association between anemia and outcome in patients with cervical cancer. Whether correction of anemia before and during therapy improves survival rates and the progression-free interval is unclear.
Serum chemistries are helpful in determining renal function and nutritional status before surgery. An abnormal serum creatinine level may be an indication of ureteral obstruction due to advanced disease, which is a contraindication to surgical management. Low total body protein stores, low albumin level, and uncontrolled hyperglycemia should raise concern regarding the likelihood of successful wound healing after surgery.
Preoperative arterial blood gas and pulmonary function tests may be beneficial in risk assessment and in establishing a baseline before surgery in patients with significant pulmonary risk factors. Patients deemed high risk by pulmonary criteria might be better served by radiation therapy.
Urinalysis results may indicate preoperative urinary tract infection, which must be treated to avoid possible postoperative febrile morbidity. Additionally, gross or microscopic hematuria may reflect an advanced stage of disease due to bladder or ureter involvement.
Cone biopsy of the cervix is essential for the surgical planning for microscopic disease management. It is critical to establish the depth and width of invasion to delineate microscopic stage IA1, IA2, and IB1 in order to execute the correct surgical procedure (extrafascial hysterectomy, modified radical hysterectomy, and type III radical hysterectomy, respectively).
Imaging Studies
Chest radiographs help identify effusions or intraparenchymal lesions consistent with distal metastatic disease.
Historically, intravenous pyelography (IVP) has been used to identify hydroureter and hydronephrosis, which are indicative of stage III disease. Computed tomography (CT) scanning is now widely used in the preoperative evaluation and planning due to its ability to evaluate the above abnormalities and possible determination of significant lymphadenopathy. However, according to guidelines published by the International Federation of Gynecology and Obstetrics (FIGO), only information that could have been obtained by intravenous pyelography, barium enema, and a clinical examination should be used for the clinical staging of cervical cancer.
A barium enema can be of assistance in evaluating patients for disease outside the cervix; however, similar information may be obtained from CT scanning and proctoscopy.
Bipedal lymphangiography was one of the studies originally allowed in the FIGO staging scheme to look for advanced disease in the lymphatics of the pelvis and paraaortic region. Few radiology departments still offer or are proficient at this procedure.
CT scanning has been used as an adjunct to clinical staging because of its ability to simultaneously evaluate the urinary tract for obstruction and determine if the liver, bone, and lymph nodes contain metastatic disease. CT findings may also be helpful in delineating anatomic variances that alter surgical management, such as ureteral duplication or the presence of a pelvic kidney. CT scanning, lymphangiography, and MRI are equally accurate (~84%) in detecting paraaortic metastasis. [20] CT scanning is limited because it can only detect nodes larger than 1 cm. Nodes that are not pathologically enlarged but which contain microscopic tumor cannot be detected on CT scans. Additionally, lymph nodes may be enlarged because of inflammation related to tumor necrosis and may not contain metastatic disease.
While CT scanning and MRI are equal in their ability to detect pathologically enlarged lymph nodes, MRI is better at discriminating tumor-containing tissue from non–tumor-containing tissue. This is beneficial when evaluating the patient for factors that may militate against a radical hysterectomy. The patient may be evaluated for tumor size, depth of stromal invasion, and vaginal or parametrial extension as well as nodal involvement. [21, 22] MRI is particularly useful in evaluating pregnant patients diagnosed with cervical cancer because MRI has not been found to be detrimental to the fetus. An optimal treatment plan can be developed based on these findings.
Because tumors take up glucose at a higher rate than healthy tissues, positron emission tomography (PET) scanning, which uses a radionuclide-labeled glucose analogue, has been increasingly used for the evaluation of metastatic disease. [23] Rose and colleagues found a 75% positive predictive value and a 92% negative predictive value for PET scanning of the pelvic and para-aortic nodes before lymphadenectomy. [24] Thus, PET may be better able to delineate the presence of subclinical metastatic disease than a preoperative CT or intraoperative evaluation of high-risk regions that includes lymph nodes and parametrial tissue. PET scanning, or PET integrated with CT, has also proved valuable for assessing treatment response after completion of concurrent chemoradiation, documented recurrent cervical cancer, and unexplained elevation of tumor markers post treatment. [25]
Diagnostic Procedures
Physical examination
The physical examination should evaluate the primary lesion and potential sites of metastatic disease, such as the left supraclavicular fossa, lungs, groin, and abdomen. Close inspection of the distal vagina, vulva, urethra, and rectum is warranted to rule out locally advanced disease. Unilateral leg edema may be indicative of disease extending to the sidewall, which causes lymphatic or venous obstruction.
The size of the primary lesion and the presence of vaginal or parametrial extension are particularly important for determining the clinical stage and treatment modality. The ideal setting for a thorough evaluation of these areas is an examination under anesthesia.
Cystoscopy and proctoscopy
Although the ability to detect disease outside the cervix with a stage I tumor is low with these procedures, an evaluation under anesthesia may provide the physician with a better understanding of the clinical disease status and stage. The cervix and vagina can be visualized and palpated, as can the uterosacral ligaments and parametria, via rectovaginal examination.
Cystoscopy may reveal cancer that extends through the bladder mucosa directly from the primary lesion. Bullous edema of the bladder does not elevate the stage of disease based on FIGO clinical staging criteria, but it may alert the physician to the presence of lymphatic obstruction of nearby tissue by tumor.
Proctoscopy is performed to evaluate for tumor extension into the rectal mucosa.
Colposcopy
Colposcopy is indicated for patients with abnormal Pap smear results in order to search for the etiology of the abnormal result when no gross lesion has been visualized.
Ectocervical carcinomas are traditionally associated with abnormal vessels that vary in their caliber and have acute angles in their distribution. Endocervical lesions may occur in the presence of a normal-appearing ectocervix, and, therefore, the colposcopic appearance may be normal.
If an abnormal Pap smear result cannot be explained by a colposcopically detected lesion, then evaluation of the endocervical canal by endocervical curettage should be considered.
Cone biopsy
Cervical cone biopsy may be indicated if microinvasion is thought possible and the diagnostic biopsy is not deep enough to determine the depth of the lesion.
Cone biopsy is also indicated for the following situations:
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Evaluation of a discrepancy between Pap smear results and colposcopically directed biopsies
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Inability to visualize the entire lesion during colposcopy
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Inability to visualize the entire transformation zone at colposcopy
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Detection of dysplastic cells from endocervical curettage
Histologic Findings
The most common histologic type of cervical cancer is squamous cell carcinoma, which comprises approximately 85% of all cervical carcinomas. The remainder are usually adenocarcinomas (endocervical or mucinous). More rare epithelial subtypes include adenosquamous, glassy cell, adenoid cystic, adenoid basal, small cell, carcinoid, and undifferentiated.
Staging
FIGO criteria for staging of cervical cancer are based on clinical findings. The FIGO classification of cervical cancer is below. [26]
Stage I: Cervical carcinoma is confined to the cervix.
Stage IA: Invasive carcinoma is diagnosed only by microscopy, with deepest stromal invasion of less than or equal to 5 mm and largest horizontal of spread less than or equal to 7 mm; substages are as follows:
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Stage IA1: Stromal invasion less than or equal to 3 mm in depth and horizontal spread less than or equal to 7 mm
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Stage IA2: Stromal invasion greater than 3 mm but less than or equal to 5 mm in depth and horizontal spread less than or equal to 7 mm
Stage IB: Clinically visible lesion is confined to the cervix or a microscopic lesion is greater than substage IA2; substages are as follows:
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Stage IB1: Clinically visible lesion less than or equal to4 cm in greatest dimension
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Stage IB2: Clinically visible lesion greater than 4 cm in greatest dimension
Stage II: Cervical carcinoma invades beyond the uterus but not to the pelvic sidewall or to the lower third of the vagina.
Stage IIA: There is no parametrial involvement; substages are as follows:
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Stage IIA1: Clinically visible lesion less than or equal to 4 cm in greatest dimension
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Stage IIA2: Clinically visible lesion greater than 4 cm in greatest dimension
Stage IIB: There is parametrial involvement.
Stage III: Cervical carcinoma extends out to the pelvic sidewall, and/or involves the distal third of the vagina, or causes hydronephrosis or a nonfunctioning kidney.
Stage IIIA: Cervical carcinoma involves the lower third of the vagina without extension to the pelvic wall.
Stage IIIB: Cervical carcinoma extends out to the pelvic sidewall or causes hydronephrosis or a nonfunctioning kidney.
Stage IV: Tumor extends beyond the true pelvis or involves the mucosa of the bladder or rectum.
Stage IVA: Direct extension is to adjacent organs.
Stage IVB: Distant metastasis is present (including peritoneal spread; involvement of supraclavicular, mediastinal, or para-aortic lymph nodes; lung; liver; or bone).
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Radical hysterectomy specimen demonstrating the vaginal margin.
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Radical hysterectomy specimen demonstrating the parametrial margins.
