by Dr. C.H. Weaver M.D. Updated 3/2022
Cervical cancer diagnosed as stage III disease is commonly detected from an abnormal Pap smear or pelvic examination or from symptoms caused by the cancer. Following a staging evaluation, a stage III cancer is said to exist if the cancer has extended beyond the cervix to the lower portion of the vagina (stage IIIA), has extended to one or both sides of the pelvis (stage IIIB), or causes a blockage of drainage from the kidneys (stage IIIB). Stage III cervical cancer is also referred to as locally advanced cancer.
The following is an overview of the treatment of stage III cervical cancer. The information is intended to help educate you about treatment options and to facilitate a shared decision-making process with your treating physician.
Stage III cervical cancer is currently best managed with a combination of radiation therapy and chemotherapy. Radiation therapy is treatment with high energy x-rays that have the ability to kill cancer cells. Radiation therapy can be administered by a machine that aims x-rays at the body (external beam radiation) or by placing small capsules of radioactive material directly into or near the cervix (internal or implant radiation). Most patients will receive both kinds of radiation therapy during their course of treatment. External beam radiation therapy for cervical cancer is administered on an outpatient basis for approximately 4 to 6 weeks.1,2
During or immediately following the external beam portion of radiation therapy, patients may also undergo an implant radiation procedure. Placing the radiation within the cervix allows a high dose of radiation to be delivered to the cancer, while reducing the radiation to the surrounding normal tissues and organs. During a procedure in the operating room, a small device is placed into the cervix and vagina and later is “loaded” with radioactive material. The radioactive material is left in place while the patient stays in the hospital for 1-3 days. This process may be performed once or twice during the course of treatment.
The addition of chemotherapy (anti-cancer drugs) has improved long-term outcomes for some patients with cervical cancer. Chemotherapy has the ability to kill cancer cells and make radiation therapy more effective at killing cancer cells. The strategy of administering chemotherapy concurrently with radiation treatment is appealing because chemotherapy and radiation therapy may act together to increase the killing of cancer cells. Chemotherapy may also destroy cells independently of radiation therapy. Clinical studies performed in patients with locally advanced cervical cancer utilizing concurrent chemotherapy and radiation therapy have improved remission rates and prolonged survival.1
Combined Chemotherapy - Radiation Therapy
Radiation therapy plus concomitant chemotherapy appears superior to radiation therapy alone. The 5-year survival rate of patients with stage IB, IIA, or IIB cervical cancer was 77% for patients treated with concurrent radiation therapy and chemotherapy, compared to only 50% for patients treated with radiation therapy alone. Concurrent chemotherapy and radiation therapy were well tolerated except for minor gastrointestinal and hematologic side effects, which were reversible. Other clinical studies have confirmed that treatment of locally advanced cervical cancer with concurrent Platinol® based chemotherapy and radiation therapy is superior to radiation therapy alone.1-3
Even with combination chemotherapy and radiation treatment, approximately 20-40% of patients with stage II cervical cancer experience recurrence of their cancer because cancer cells may have survived near the cancer despite the radiation therapy or small amounts of cancer may have spread outside the cervix and were not treated by the chemotherapy. These cancer cells cannot be detected and are referred to as micrometastases. The presence of these microscopic areas of cancer or surviving cancer cells can cause the relapses that follow treatment.
Strategies to Improve Treatment
The progress that has been made in the treatment of cervical cancer has resulted from improved development of treatments in patients with more advanced stages of cancer and participation in clinical trials. Future progress in the treatment of cervical cancer will result from continued participation in appropriate clinical trials.
The immune system is an elaborate network of cells and organs that protect the body from infection. The immune system is also part of the body’s innate disease-fighting capability to treat cancer. With cancer, part of the problem is an ineffective immune system. The immune system recognizes cancer cells as foreign and up to a point can get rid of them or keep them in check. Cancer cells are very good at finding ways to hide from, suppress, or wear out the immune system and avoid immune destruction. The immune system may not attack cancer cells because it fails to recognize them as foreign and harmful.
The goal of immunotherapy is to help the immune system recognize and eliminate cancer cells by either activating the immune system directly, or by inhibiting mechanisms of suppression of the cancer.
General types of immunotherapy include interferon, interleukin, and colony stimulating factors (cytokines), which generally activate the immune system to attack the cancer. These general immunotherapies however are not specific and their activation of the immune system can cause severe side effects by attacking normal cells along with cancer cells. Immunotherapy treatment of cancer has progressed considerably over the past 30 years and has evolved from a general to more precisely targeted immunotherapy treatment. Examples of precision immunotherapy include checkpoint inhibitors, CAR T cells, and vaccines. In an attempt to improve the chance of cure, immunotherapies are being tested alone or in combination with chemotherapy in clinical trials.
Tecentriq Immunotherapy with Chemoradiation Demonstrates Activates Immune in Cervical Cancer
The addition of the immunotherapy drug Tecentriq (atezolizumab) prior to and concurrently with chemoradiation (CRT) treatment appears safe and exhibits immune-modulating activity in women with node-positive, locally advanced cervical cancer. Overall, 36 eligible patients were treated with either 3 doses of Tecentriq (one prior to CRT, and two doses during CRT); or all 3 doses of during CRT treatment. Treatment was generally well tolerated and there was an increase in peripheral blood T-cell receptor (TCR) clonal expansion that correlated was the increased likelihood of a complete pathologic response.4
The practice of administering treatment before surgery is referred to as neoadjuvant therapy. In theory, neoadjuvant chemotherapy can decrease the size of the cancer, making it easier to remove with surgery. With the development of new chemotherapy regimens and radiation therapy, clinical trials of neoadjuvant therapy performed in patients with cervical cancer are currently ongoing.
The use of radiation prior to a simple hysterectomy is being evaluated in clinical trials for patients with larger stage IB cervical cancers. This combination of treatment appears to reduce the chance of a cancer recurrence in the area of the cancer by removing cancer cells that may have survived through the radiation therapy.
Newer Radiation Techniques:
External beam radiation therapy can be delivered more precisely to the cervix by using a special CT scan and targeting computer. This capability is known as three-dimensional conformal radiation therapy, or 3D-CRT. The use of 3D-CRT appears to reduce the chance of injury to nearby body structures, such as the bladder or rectum.
- Duenas-Gonzalez A, Zarba JJ, Alcedo JC, et al. A phase III study comparing concurrent gemcitabine (Gem) plus cisplatin (Cis) and radiation followed by adjuvant Gem plus Cis versus concurrent Cis and radiation in patients with stage IIB to IVA carcinoma of the cervix. Presented at the 2009 annual meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. Abstract CRA5507.
- Fachini AMD, Zuliani AC, Sarian LO, et al. Long-term outcomes of concomitant cisplatin plus radiotherapy versus radiotherapy alone in patients with stage IIIB squamous cervical cancer: a randomized controlled trial. Gynecol Oncol. Published online December 16, 2020. doi:10.1016/j.ygyno.2020.11.029
- Mayadev J, Zamarin D, Deng W, Lankes H, Pesci G, Park K, Banberry B, Sherry N, Ghamande S, Holman L, Mathews C, O’Cearbhaill R, Aghajanian C, Schilder R. (2022, Marh). Safety and immunogenicity of Anti PD-L1 (Atezolizumab) given as an immune primer or concurrently with extended field chemoradiotherapy for node positive locally advanced cervical cancer: an NRG Oncology trial. Paper presented at the Annual Meeting on Women’s Cancer for the Society of Gynecologic Oncology. Phoenix, AZ.