Recurrent Cervical Cancer

Recurrent cervical cancer occurs when the disease returns after initial treatment, presenting unique challenges that depend on where the cancer comes back and what treatments were used before. Understanding the available treatment options and what to expect can help patients navigate this difficult journey.

Table of contents

• What is Recurrent Cervical Cancer
• Symptoms of Recurrence
• Likelihood of Cancer Returning
• Where Cancer Can Come Back
• Treatment Options
• Outlook and Prognosis

What is Recurrent Cervical Cancer

Recurrent cervical cancer means that the cancer has come back after it has been treated.^[1] Approximately one-third of women with cervical cancer experience a recurrence during follow-up, with most relapses happening within the first 2 to 3 years after treatment.^[2] Research involving 501 women found that recurrence often occurred within approximately 20 months.^[3]

The cancer can return in the cervix itself, close to where it first started such as in the uterus or other organs in the pelvis, or it can come back in distant sites.^[1] The management of recurrent cervical cancer depends mainly on previous treatment and on the site and extent of recurrence.^[1]

Symptoms of Recurrence

While some people with recurrent cervical cancer may not experience any symptoms, others may develop warning signs that should prompt medical attention.^[3] Common symptoms include:

• Pelvic pain
• Lower back pain
• Chest pain
• Abnormal bleeding
• Vaginal discharge
• Swelling in the legs and feet

Likelihood of Cancer Returning

For some people with cervical cancer, the cancer may not return after initial treatment. However, for others, recurrence is a possibility. The likelihood of recurrence depends on several factors, such as the initial cancer stage, the type of treatment received, and the individual’s overall health.^[3]

Research shows that for people with the Federation of Gynecology and Obstetrics (FIGO) stage IB-IIA, recurrence rates are 11 to 22 percent, while for those with stage IIB-IVA, the rates are 28 to 64 percent. For people with stage III to IVB, some studies report recurrence rates as high as 70 percent.^[3]

A study found that recurrence had associations with the following risk factors: younger age, lower number of births, higher number of pregnancy losses, higher stage of the cancer, and lymph node metastasis (cancer spread to the lymph nodes).^[3]

Where Cancer Can Come Back

Cervical cancer can come back in the cervix, recur close to where it first started such as in the uterus or other organs in the pelvis, or return in distant sites.^[1] Patients with cervical cancer are at a high risk of pelvic recurrence or distant metastases within the first few years after primary treatment.^[4]

Understanding where the cancer has returned is important because it affects which treatment options are available. Cancer that comes back only in the pelvis may be treated differently than cancer that has spread to distant organs.^[1]

Treatment Options

The treatment of recurrent cervical cancer depends on many factors, including what treatment the patient had before, the location of the recurrence, and the overall condition of the patient.^[5] Your healthcare team will suggest treatments based on your needs and work with you to develop a treatment plan.^[1]

Chemoradiation

Chemoradiation, where chemotherapy is given during the same time period as radiation therapy to make the radiation therapy more effective, may be offered for recurrent cervical cancer.^[1] This is the treatment of choice for patients with pelvic failure after radical hysterectomy alone. However, the safe delivery of high doses of radiotherapy is much more difficult in this clinical setting compared with primary radiotherapy.^[1] For isolated para-aortic lymph node failure (cancer in lymph nodes near the main artery of the body), concurrent cisplatin-based chemoradiation is the treatment of choice, with satisfactory chances of a cure in asymptomatic patients.^[1]

Chemotherapy drugs such as 5-fluorouracil plus cisplatin or mitomycin, or other chemotherapy drugs may be used with radiation therapy.^[1]

Radiation Therapy

Radiation therapy may be offered for recurrent cervical cancer. Radiation therapy may be external radiation therapy, brachytherapy (internal radiation), or both.^[1] For recurrent cervical cancer, radiation therapy is often given with chemotherapy, but in some cases it may be used alone as the main treatment.^[1]

If the patient had surgery to remove the cervix and the cancer comes back only in a small area near the operation, radiation therapy may be administered. However, if the patient already received radiation therapy to the pelvis, radiation therapy cannot be administered again to the same part of the body.^[5] Radiation therapy may also be used to relieve pain, stop bleeding, or control other symptoms of advanced cervical cancer, which is called palliative therapy.^[1]

Surgery

Pelvic exenteration usually represents the only therapeutic approach with curative intent for women with central pelvic relapse who have previously received irradiation.^[1] This is an extensive surgical procedure that removes the cancer and many pelvic organs. A pelvic exenteration may be used to treat recurrent cervical cancer that comes back in the pelvis but has not spread to the side wall of the pelvis. A pelvic exenteration is only performed if cancer cannot be detected elsewhere in the body and all of the cancer can be removed by the surgery.^[5]

In recent series, the 5-year overall survival after pelvic exenteration ranged from 21 to 61 percent, and operative mortality ranged from 1 to 10 percent.^[1] Free surgical margins (no cancer cells at the edge of removed tissue), negative lymph nodes, small tumor size, and long disease-free interval were associated with a more favorable prognosis.^[1] Currently, pelvic reconstructive procedures such as continent urinary conduit, low colorectal anastomosis, and vaginal reconstruction with myocutaneous flaps are strongly recommended after exenteration.^[1]

A radical hysterectomy may be offered for a small recurrence in the cervix or uterus if previous treatment did not include radiation therapy to the pelvis.^[1]

Chemotherapy

Chemotherapy is administered with palliative intent to women with distant or loco-regional recurrences not amenable by surgery or radiotherapy.^[1] It may be offered for recurrent cervical cancer to relieve pain or control the symptoms of advanced cervical cancer.^[1]

Cisplatin is the most widely used drug, with a response rate of 17 to 38 percent and a median overall survival of 6.1 to 7.1 months.^[1] Cisplatin-based combination chemotherapy achieves higher response rates (22 to 68 percent) when compared with single-agent cisplatin, but median overall survival is usually less than one year.^[1]

Chemotherapy drugs used to treat recurrent cervical cancer, used alone or in combination, include:^[1]

• Cisplatin
• Carboplatin
• Paclitaxel
• Topotecan
• Gemcitabine
• 5-fluorouracil
• Ifosfamide
• Docetaxel
• Irinotecan
• Mitomycin
• Vinorelbine
• Epirubicin
• Doxorubicin

Common chemotherapy drug combinations include cisplatin and ifosfamide, cisplatin and paclitaxel, cisplatin and gemcitabine, cisplatin and topotecan, and paclitaxel and topotecan.^[1]

In a recent Gynecologic Oncology Group trial, the combination of topotecan plus cisplatin obtained a significantly longer overall survival than single-agent cisplatin in patients with metastatic or recurrent or persistent cervical cancer. A subsequent study showed a trend in terms of longer overall survival and better quality of life for the doublet cisplatin plus paclitaxel versus the doublets cisplatin plus topotecan, cisplatin plus vinorelbine, and cisplatin plus gemcitabine.^[1]

Targeted Therapy

Targeted therapy uses drugs that target specific proteins or genes involved in cancer growth. The most common targeted therapy drug used to treat cervical cancer is bevacizumab (Avastin). It is usually given in combination with chemotherapy.^[1]

Immunotherapy

Immunotherapy helps to strengthen or restore the immune system’s ability to fight cancer. You may be offered immunotherapy for recurrent cervical cancer.^[1] If chemotherapy was used to treat metastatic cervical cancer but it didn’t respond or the cancer comes back, then you may be offered cemiplimab (Libtayo).^[1]

Pembrolizumab (Keytruda) may also be offered for recurrent cervical cancer in combination with chemotherapy. It is sometimes given with the targeted therapy drug bevacizumab. Pembrolizumab is only used for cervical cancer tumors that have the PD-L1 checkpoint protein.^[1]

Molecularly targeted therapy may represent a novel therapeutic tool, but its use alone or in combination with chemotherapy is still investigational.^[1]

Outlook and Prognosis

The curability of cervical cancer depends on various factors, including the stage and extent of recurrence. Doctors typically use the term “remission” instead of “cure” when discussing cancer treatment because cancer can return even after successful treatment.^[3]

A doctor may consider a person “cured” if they remain in complete remission, meaning there is no evidence of cancer, for 5 years or more after treatment. However, the criteria for considering someone cured can vary depending on the case and the cancer stage.^[3] Localized treatments such as surgery or radiation therapy may be successful for cancer confined to a small area. However, if cancer has spread to distant organs or lymph nodes, treatment may focus on managing symptoms and improving quality of life rather than attempting to cure the cancer.^[3]

When cervical cancer returns, it can be more challenging to treat and has a poor outlook, with an estimated overall survival of 13 to 17 months.^[3] Whether treatment for recurrent cervical cancer will work can depend on various factors, such as the length of time between the original diagnosis and when the cervical cancer recurred, a person’s age, a person’s overall health, the treatment, and how well a person can tolerate the treatment.^[3]

For pelvic exenteration, approximately one-third of patients with recurrent cancer will survive free of cancer after treatment.^[5] Free surgical margins, negative lymph nodes, small tumor size, and long disease-free interval were associated with a more favorable prognosis.^[1]