Cervix cancer

Introduction

In many developing countries, cancer of the cervix is the second most common cancer and cause of cancer deaths in women, in part due to limited access to cervical cancer screening and prevention programmes.

Staging

Staging of cervix cancer using the International Federation of Gynecology and Obstetrics (FIGO) system is largely defined by physical examination and limited imaging. In practice, many centres will utilize combinations of CT, MRI, and PET imaging to better de­fine the extent of the primary tumour, and nodal and distant metas­tases. The FIGO staging system is shown in Chapter 62 (Box 62.2).

Role for concurrent chemotherapy and radiation

Based on a series of five randomized trials reported in 1999, which demonstrated improved survival and acceptable toxicity, concurrent weekly cisplatin in five courses (at a dose of 40 mg/m²) and radio­therapy has become the standard of care in cervix cancer (45).

Role for radiotherapy by stage

Decisions regarding optimal treatment for early-stage disease are critically dependent on a multidisciplinary discussion between gy­naecological, radiation, and medical oncologists, with input from gy­naecological imaging and pathology. Definitive chemoradiotherapy is curative in women with cervix cancer, in part due to the combin­ation of external bean radiation with intracavitary brachytherapy, delivering a high local dose to the tumour while sparing normal tissues (46); and in part due to the increased radiosensitivity and better outcomes associated with human papillomavirus-related tu­mours, including other human papillomavirus-related sites such as oropharynx (47, 48).

Early-stage disease (stages IB2-IIA)

For women with a low risk of unrecognized local invasion or nodal metastases (IB1 without lymphovascular or deep cervical invasion), radical hysterectomy and lymph node staging is the standard of care or radical trachelectomy for those wishing to preserve fertility).

Advanced disease (stages IIB-IVA)

Bulky and advanced disease with parametrial/sidewall or nodal involvement is optimally treated with pelvic with or without para­aortic nodal chemoradiotherapy followed by brachytherapy (51). External beam pelvic radiotherapy (45-50 Gy) plus concurrent cis­platin chemotherapy, followed by intracavitary brachytherapy re­sults in progression-free and overall survival in 65-70%, depending on stage (52).

Locally advanced/metastatic cervix cancer

Patients with locally advanced or metastatic disease are assessed for suitable palliative treatment, which may include combinations of chemotherapy, radiation, or no active treatment until symptoms arise. Locally recurrent tumours may be suitable for retreatment with radiation to deal with pain and bleeding (53).

External beam radiotherapy

Treatment planning for external beam radiotherapy typically in­volves 3D imaging such as CT and MRI to define the extent of pri­mary tumour and nodes (see earlier text). The clinical target volume includes the primary cervical tumour, upper vagina, parametria, and pelvic lymph nodes including the external and internal iliac and presacral lymph nodes. In patients with involved pelvic nodes, the clinical target volume may be expanded to include common iliac nodes, and those with common iliac involvement may require treat­ment of the next echelon para-aortic lymph nodes.

Treatment techniques typically consist of four coplanar pelvic radiation fields (anterior, posterior, and right and left lateral) (Figure 68.1).

Postoperative radiotherapy

External beam chemoradiation therapy is recommended for high- risk features following modified radical hysterectomy and pelvic lymph node dissection including close or positive surgical resection margins, the presence of capillary lymphatic invasion, and positive pelvic lymph nodes. Randomized studies have shown improved out­comes, particularly with adenocarcinomas, with low rates of serious toxicity (54). External beam pelvic radiation therapy encompasses the upper vagina, parametria, central pelvic tissues, and lymph nodes, using a four- field arrangement or IMRT technique (see ‘Basic principles of radiotherapy').

Brachytherapy

Intrauterine tandem applicator with vaginal colpostats or ring using high-dose rate afterloading brachytherapy is used during or fol­lowing external radiotherapy. Increasingly, brachytherapy is being planned using MRI guidance to optimize the dose to the residual tumour while sparing normal tissue (referred to as organs at risk) such as the bladder and the rectum (Figure 68.3). Guidelines devel­oped by the GEC-ESTRO group have standardized target volume and normal organ definition (41). Typical doses are 28-30 Gy in four to five fractions (36-40 Gy low-dose rate equivalent) of high-dose rate brachytherapy in the third to fifth week of external beam radio­therapy, depending on tumour response.

Follow-up care

This involves clinic visits for assessment including pelvic exam every 3- 4 months for 2 years after completing treatment, then every 6 months to 5 years. Follow-up PET-CT or MRI pelvis is done at 3-6 months after completing treatment to confirm tumour eradica­tion. Cervical/vaginal cytology is performed at the discretion of the oncologist beginning 1 year after completing radiotherapy in order to avoid false-positive results due to radiation effects.

Vaginal dilators are recommended for 6 months after the com­pletion of brachytherapy to prevent vaginal stenosis. Some patients may require ongoing use of dilators. Hormone replacement therapy may be considered for patients who were premenopausal prior to treatment.