RISK FACTORS: Multiple sexual partners, Male partner with multiple sexual partners OR who has had a partner with cervical carcinoma, Early onset of first sexual intercourse, Current or previous HPV infections, eg, condyloma acuminatum
Medical Care: The treatment of cervical cancer varies with the stage of the disease. For early invasive cancer, surgery is the treatment of choice. In more advanced cases, radiation combined with chemotherapy is the current standard of care. In patients with disseminated disease, chemotherapy or radiation provides symptom palliation.
Stage 0: Treatment options for stage 0 cancer include loop electrosurgical excision procedure (LEEP), laser therapy, conization, and cryotherapy.
Stage IA: The treatment of choice for stage IA disease is surgeryβtotal hysterectomy, radical hysterectomy, and conization are accepted procedures. Intracavitary radiation is an option for selected patients.
Stage IB or IIA
For patients with stage IB or IIA disease, treatment options are either combined external beam radiation with brachytherapy or radical hysterectomy with bilateral pelvic lymphadenectomy.
Most retrospective studies have shown equivalent survival rates for both procedures, although such studies usually are flawed due to patient selection bias and other compounding factors. However, a recent randomized study showed identical overall and disease-free survival rates.
Quality-of-life data, particularly in the psychosexual area, is relatively scant.
Postoperative radiation to the pelvis decreases the risk of local recurrence in patients with high-risk factors (positive pelvic nodes, positive surgical margins, and residual parametrial disease).
A recent randomized trial showed that patients with parametrial involvement, positive pelvic nodes, or positive surgical margins benefit from a postoperative combination of cisplatin-containing chemotherapy and pelvic radiation.
Stage IIB-IVA
For locally advanced cervical carcinoma (stages IIB, III, and IVA), radiation therapy was the treatment of choice for many years. However, the results from large randomized clinical trials demonstrated a dramatic improvement in survival with the combined use of chemotherapy and radiation.
For treatment with radiation alone, 5-year survival rates reportedly are 65-75%, 35-50%, and 15-20% for stages IIB, III, and IVA, respectively.
Radiation therapy begins with a course of external beam radiation to reduce tumor mass to enable subsequent intracavitary application. Brachytherapy is delivered using afterloading applicators that are placed in the uterine cavity and vagina.
The results of prospective, randomized, well-conducted studies of concurrent chemoradiation changed the standard of care in this group of patients.
In the Radiation Therapy Oncology Group trial, 403 patients with bulky IB and IIB-IVA cancers were randomized to either radiotherapy to a pelvic and paraaortic field or pelvic radiation with concurrent cisplatin and fluorouracil. Rates of both disease-free survival and overall survival were significantly higher in the group that received combination treatment.
Rose and associates conducted a Gynecologic Oncology Group (GOG) trial for patients with stage IIB, III, or IVA cancer, comparing the combination of radiation with 3 different chemotherapy regimens (cisplatin alone, cisplatin/5-fluorouracil/hydroxyurea, and hydroxyurea alone). Overall survival rates were significantly higher in the 2 groups that received cisplatin-containing regimens.
In another GOG trial, patients with bulky stage IB disease were randomized to either radiation alone or a combination of weekly cisplatin and radiation. All patients had adjuvant hysterectomy. Both disease-free survival and overall survival rates were significantly higher in the combined-therapy group at 4 years of follow-up.
Based on the aforementioned study results, using cisplatin-based chemotherapy in combination with radiation for patients with locally advanced cervical cancer represents the standard of care.
Stage IVB and recurrent cancer
These patients are treated with chemotherapy. For many years, single agent cisplatin represented the standard of care. Recently, the combined use of cisplatin and topotecan was shown to significantly improve survival compared with single-agent cisplatin.
Palliative radiation is often used individually to control bleeding, pelvic pain, or urinary or partial large bowel obstructions from pelvic disease.
Total pelvic exenteration may be considered in patients with an isolated central pelvic recurrence.
Surgical Care:
Carcinoma in situ (stage 0) is treated with local ablative measures such as cryosurgery, laser ablation, and loop excision.
Hysterectomy should be reserved for patients with other gynecologic indications to justify the procedure.
After local treatment, these patients require lifelong surveillance.
Palliative radiation often is used individually to control bleeding, pelvic pain, or urinary or partial large bowel obstructions from pelvic disease.
Invasive procedures such as nephrostomy or diverting colostomy sometimes are performed in this group of patients to improve their quality of life.
Special effort should be made to ensure comprehensive palliative care, including adequate pain control for these patients.
The standard treatment for microinvasive disease (stage IA) is total hysterectomy.
Lymph node dissection is not required if the depth of invasion is less than 3 mm and no lymphovascular invasion is noted.
Selected patients with stage IA1 disease but no lymphovascular space invasion who desire to maintain fertility may have a therapeutic conization with close follow-up, including cytology, colposcopy, and endocervical curettage.
Patients with medical comorbidities who are not surgical candidates can be successfully treated with radiation.
Consultations:
The treatment of cervical cancer frequently requires a multidisciplinary approach involving a gynecologic oncologist, radiation oncologist, and medical oncologist.
Diet:
Proper nutrition is important for patients with cervical cancer. Every attempt should be made to encourage and provide adequate oral food intake.
Nutritional supplements such as Ensure or Boost are used when patients have had significant weight loss or cannot tolerate regular food due to nausea caused by radiation or chemotherapy.
In patients with severe anorexia, appetite stimulants such as Megace can be prescribed.
For patients who are unable to tolerate any oral intake, percutaneous endoscopic gastrostomy tubes are placed for nutritional supplementation.
In patients with extensive bowel obstruction as a result of metastatic cancer, hyperalimentation sometimes is used.
Chemotherapy should be administered in conjunction with radiation therapy to most patients with stage IB (high risk) to IVA. Cisplatin is the agent used most commonly, although 5-fluorouracil also is used frequently. For patients with metastatic disease, cisplatin remains the most active agent. Topotecan, ifosfamide, and paclitaxel also have significant activity in this setting. The combination of topotecan and cisplatin improves overall survival. However, acute toxicities are also increased.
DRUG TEATMENT :
1. CHEMOTHERAPY AGENTS :
- CISPLATIN
- 5-FLUOROURACIL
- IFOSFAMIDE
- PACLITAXEL
2. VACCINES : A human papillomavirus (HPV) vaccine is now available for prevention of HPV-associated dysplasias and neoplasias, including cervical cancer, genital warts (condyloma acuminata), and precancerous genital lesions. The immunization series should be completed in girls and young women aged 9-26 years.
- PAPILLOMAVIRUS VACCINE ( GARDASIL ) :
Quadrivalent HPV recombinant vaccine. First vaccine indicated to prevent cervical cancer, genital warts (condyloma acuminata), and precancerous genital lesions (eg, cervical adenocarcinoma in situ; cervical intraepithelial neoplasia grades 1, 2, and 3; vulvar intraepithelial neoplasia grades 2 and 3; vaginal intraepithelial neoplasia grades 2 and 3) due to HPV types 6, 11, 16, and 18. Vaccine efficacy mediated by humoral immune responses following immunization series.
PATIENT MONITORING:
. With completion of definitive therapy. each patient is evaluated with physical/pelvic examinations and Pap
smear at the following intervals:
. Every 3 months for 1-2 years
. Every 6 months until the 5th year
. Yearly thereafter
. The three most common signs of cancer recurrence are: unexplained weight loss, leg edema, and pelvic or
thigh pain
PREVENTION/AVOIDANCE:
. Stop smoking
. Avoid sexually transmitted diseases
. Regular Pap smears and pelvic exams; appropriate interval for Pap smear (reference: 1988 American College of Obstetricians and Gynecologists and American Cancer Society):
. All women who are or who have been sexually active, or who have reached age 18, should undergo an
annual Pap test and pelvic examination.
. After a woman has had three or more consecutive satisfactory annual examinations with normal findings, the Pap smear may be performed less frequently at the discretion of her physician
POSSIBLE COMPLICATIONS:
. Hemorrhage
. Pelvic infection
. Bladder dysfunction
. Genitourinary fi stula
. Ureteral obstruction with renal failure
. Bowel obstruction
. Lymphocyst
. Pulmonary embolism
. Loss of ovarian function from radiotherapy or indication for bilateral oophorectomy
EXPECTED COURSE/PROGNOSIS:
After commonly accepted surgical and radiation treatments. Five year survival after accepted surgical and radiation management of cervical malignancy