Cervical cancer develops when cells on the cervix, the lower part of the uterus, grow uncontrollably. Initial treatment, often involving surgery, radiation, or chemotherapy, aims to eliminate cancerous cells and achieve remission. Remission means the signs and symptoms of cancer have disappeared. However, cancer cells may have survived the initial therapy or new malignant cells could develop later, leading to a recurrence.
Understanding Cervical Cancer Recurrence
Recurrence is the reappearance of cancer after a period where the disease was undetectable following initial treatment. This is distinct from residual disease, which is cancer detected shortly after treatment completion. Approximately one-third of individuals treated for cervical cancer experience a recurrence, with the majority occurring within the first two to three years post-treatment. The median time to recurrence is typically around 20 to 26 months after the end of therapy.
The likelihood of recurrence is influenced by the initial stage of the disease. Early-stage cancers (FIGO stage IB-IIA) have recurrence rates ranging from 11% to 22%, while advanced stages (FIGO stage III to IVB) can have rates as high as 70%. Recurrence is categorized by location: locoregional (confined to the pelvis), isolated lymph node involvement, or distant metastasis (involving sites outside the pelvis, such as the lungs or liver).
The pattern of recurrence often correlates with the initial extent of the disease. Patients without lymph node involvement at diagnosis are more likely to experience a locoregional recurrence. Conversely, the presence of positive lymph nodes during initial diagnosis is associated with a higher risk of recurrence in the lymph nodes, distant sites, or multiple areas. Understanding these patterns helps tailor surveillance and subsequent treatment strategies.
Recognizing Signs and Common Locations of Recurrence
Recognizing specific physical changes prompts medical evaluation, as early detection of recurrence can improve treatment outcomes. A common sign of locoregional recurrence is persistent pelvic pain, often accompanied by pain during sexual intercourse or abnormal vaginal bleeding. Recurrence within the pelvis can also cause symptoms related to pressure on nearby organs, such as difficult or painful urination, or rectal pain and bleeding.
Recurrence involving the lymph nodes frequently leads to lymphedema, which is swelling in the lower extremities. This occurs when cancerous cells block the lymphatic vessels, preventing fluid from draining and causing swelling in the legs and feet. A mass or hard lump may also be felt in the groin or pelvic area, indicating enlarged lymph nodes.
When the cancer has spread to distant sites, the symptoms are specific to the organ involved. Recurrence in the lungs, a frequent site of distant spread, may manifest as a persistent cough, shortness of breath, or coughing up blood. If the cancer involves the liver, symptoms may include discomfort or pain on the right side of the abdomen, loss of appetite, or jaundice (a yellowing of the skin and eyes). Recurrence in the bones often causes localized bone pain that is constant and sometimes severe enough to disrupt sleep.
Tailored Treatment Approaches for Recurrent Disease
Treatment for recurrent cervical cancer is individualized, depending on the location and extent of the disease, and prior treatments received. A primary consideration is whether the patient’s pelvis was treated with radiation therapy initially. If the recurrence is confined to the pelvis and was previously irradiated, re-irradiating the same area is typically avoided due to the risk of severe tissue damage.
In cases of central pelvic recurrence after prior radiation, surgery offers the only chance for long-term survival. The most extensive surgical option is pelvic exenteration, a salvage procedure involving the en bloc removal of pelvic organs. These organs may include the uterus, cervix, vagina, bladder, and/or rectum. This complex procedure is categorized as anterior, posterior, or total, and is only performed if no distant spread of the cancer is detected.
If the recurrence is distant or widespread, systemic therapies like chemotherapy, targeted therapy, and immunotherapy become the primary focus. Standard chemotherapy regimens often use platinum-based drugs such as cisplatin, frequently combined with paclitaxel. The addition of the targeted therapy drug bevacizumab, which blocks the formation of new blood vessels for the tumor, has been shown to improve overall survival when combined with chemotherapy.
Immunotherapy is another treatment option, particularly for tumors that express the PD-L1 protein. Immune checkpoint inhibitors, such as pembrolizumab and cemiplimab, work by blocking the PD-1 protein on immune cells, allowing the immune system to recognize and attack the cancer cells. Newer agents, like the antibody-drug conjugate tisotumab vedotin (Tivdak), deliver a potent chemotherapy payload directly to cancer cells that express the Tissue Factor protein.