Hope for patients with locally advanced cervical cancer

Dr Shivona Moodley explains the standard treatment options for cervical cancer and highlights new research findings in treating advanced cervical cancer.

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Cervical cancer is the second most common cancer affecting South African women after breast cancer but is the leading cause of cancer-related death. However, this notorious disease is treatable, and can be cured if diagnosed early. 

Majority of cervical cancers are caused by an infection with human papilloma virus (HPV), a sexually transmitted virus that is usually self-limiting (resolve without treatment).

Vaccinations against HPV are available in South Africa; speak to your healthcare provider for more information on this potentially life-saving prevention strategy. 

Stages of cervical cancer

A diagnosis of cervical cancer can be extremely overwhelming and often brings immense fear and anxiety of the journey that lies ahead. The treatment of this disease is usually complex and is based on the stage of cancer. 

Early stage disease (Stage 1A – 1B2) can often be managed with some form of surgical intervention. 

Locally advanced (LA) (Stage 1B3 – 4A) tends to have a higher rate of recurrence and inferior survival compared to early stage disease. 

LA disease is defined by the presence of any of the following findings:

• Confined to the cervix with a clinically visible tumour >4 cm in greatest dimension (Stage 1B3).
• Invades beyond the uterus but not to the pelvic wall or to the lower third of vagina (Stage 2).
• Extends to the pelvic sidewall, and/or involves the lower third of vagina, and/or causes hydronephrosis or a non-functioning kidney, and/or involves pelvic and/or para-aortic lymph nodes (Stage 3).
• Invades the mucosa of the bladder or rectum or extends beyond the true pelvis (Stage 4A).

External beam radiation therapy 

External beam radiation is the use of high-energy X-rays that are produced by a treatment machine, called a linear accelerator (LINAC). 

The radiation is a localised form of therapy often targeting the disease and surrounding pelvic lymph nodes. Radiation is usually given daily Monday to Friday, over a period of five to six weeks as an outpatient. 

The radiation beam is invisible and painless. Some side effects may develop over the course of treatment including fatigue, nausea, diarrhoea, urinary tract symptoms, and a skin reaction in the treatment field. These can usually be well-managed during the course of treatment. 

Brachytherapy

High-dose rate brachytherapy is the use of internal radiation that is delivered using a radioactive source that travels through an applicator which is inserted into the vagina. 

Brachytherapy allows very localised delivery of radiation to the cervix and vagina in an effort to maximise local control by increasing the dose to the tumour while minimising toxicity to surrounding normal tissues. Studies have shown that the addition of brachytherapy resulted in higher rates of cancer-specific and overall survival.

Chemotherapy

Chemotherapy is often given to patients with locally advanced cervical cancer in addition to radiation. It acts as a radiosensitiser and enhances the efficacy of the radiation by weakening the tumour cells.

It’s often administered once weekly during the course of radiation by an intravenous infusion. 

Induction chemotherapy consists of weekly intravenous combined chemotherapy for six weeks preceding the standard weekly concurrent chemoradiation. A recent multi-centred phase 3 trial, conducted on 500 women with locally advanced cervical cancer, compared standard chemoradiation alone to induction chemotherapy followed by chemoradiation.¹ Induction chemotherapy followed by chemoradiation improved five-year survival rates from 72 to 80%. 

Immunotherapy

The addition of immunotherapy to chemoradiation has shown to have an overall survival benefit with longer follow-up and may become an option for patients with locally advanced cervical cancer in the future.² 

Sexual health after treatment

Vaginal shortening, narrowing, and dryness are significant side effects of radiation. These changes may lead to sexual dissatisfaction post-treatment due to pain or difficulty during intercourse. 

Vaginal lubricants and moisturisers can help alleviate some of these symptoms. 

The use of a vaginal dilator, which is a device that can be placed in the vagina several times a week, is often encouraged to prevent narrowing and shortening of the vagina and is an important part of post-treatment counselling. 

Women may also experience early-onset menopause due to ovarian failure with resultant symptoms of menopause including hot flushes, mood symptoms, lack of libido, and an absence of monthly periods. These symptoms can be treated with hormone replacement in pre-menopausal females.

References

1. Induction chemotherapy followed by standard chemoradiotherapy versus standard chemoradiotherapy alone in patients with locally advanced cervical cancer (GCIG INTERLACE): an international, multicentre, randomised phase 3 trial McCormack, MaryReed, Nicholas et al. The Lancet, Volume 404, Issue 10462, 1525 – 1535

2. Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial Lorusso, Domenica et al. The Lancet, Volume 404, Issue 10460, 1321 – 1332

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