Treatment of Stage III Uterine Cancer
by Dr. C.H. Weaver M.D. updated 6/2022
A stage III uterine cancer extends outside the uterus, but remains confined to the pelvis. Stage IIIA cancers invade the lining of the pelvis or fallopian tubes or cancer cells can be found free in the pelvis. Stage IIIBcancer invades the vagina. Stage IIIC cancers invade the pelvic and/or para-aortic lymph nodes.
Optimal treatment of patients with stage III uterine cancer often requires more than one therapeutic approach. Thus, it is important for patients to be treated at a medical center that can offer multi-modality treatment involving gynecologic oncologists and radiation oncologists. Survival following treatment of stage III uterine cancer is influenced by the extent of spread of the cancer and the ability of the surgeon to remove all visible cancer.
Surgery
The standard treatment for stage III uterine cancer is a total abdominal hysterectomy (removal of the uterus) and bilateral salpingo-oophorectomy (removal of the fallopian tubes and ovaries) with or without removal of the pelvic and para-aortic lymph nodes. The surgeon will attempt to remove as much cancer as possible without causing major side effects. Unfortunately, some women with stage III uterine cancer cannot have all the cancer removed, especially when the cancer extends to the wall of the pelvis, other patients with stage III cancer will have microscopic cancer cells that have spread outside the uterus and therefore were not removed by surgery. These cells can cause relapses that follow treatment with surgery alone, therefore some patients may benefit from additional adjuvant treatment to decrease the risk of cancer recurrence.
To learn more about surgery, go to Surgery for Uterine Cancer.
Adjuvant Therapy
Adjuvant therapy is the delivery of cancer treatment following local treatment with surgery and may include systemic chemotherapy, hormonal therapy, immunotherapy or radiation. The decision about the need for adjuvant therapy is influenced by the extent and grade of the cancer and NGS-biomarker testing.
The optimal approach to adjuvant therapy for Stage III uterine cancer remains uncertain. Women are most often treated with radiation therapy and/or chemotherapy.1 A Phase III clinical trial (described below) reported that adjuvant chemotherapy resulted in better survival than radiation therapy among women with Stage III or IV uterine cancer, but another study found that the two treatments were similarly effective. The combination of chemotherapy and radiation therapy may be more effective than either treatment alone, but information about combined treatment remains limited.
Radiation therapy: Unlike chemotherapy, radiation therapy is considered a local treatment. Cancer cells can only be killed where the radiation is delivered to the body. If cancer exists outside the radiation field, the cancer cells are not destroyed by the radiation. Women who are candidates for adjuvant radiation therapy may be treated with external beam radiation therapy and/or vaginal brachytherapy. External beam radiation therapy (EBRT) is given via machines called linear accelerators, which produce high-energy external radiation beams that penetrate the tissues and deliver the radiation dose deep into the areas where the cancer resides. Brachytherapy treatment involves the placement of a radioactive isotope into the vagina in order to treat the “vaginal cuff” region. The vaginal cuff is the part of the vagina that was closest to the uterus; it is a common site of uterine cancer recurrence. Radiation therapy may be used alone or in combination with chemotherapy.
Chemotherapy: Chemotherapy is a systemic therapy, meaning that it can kill cancer cells throughout the body. The first Phase III clinical trial to report a benefit of adjuvant chemotherapy in women with Stage III or IV endometrial cancer was a study known as GOG 122. The study compared chemotherapy with doxorubicin and cisplatin to whole abdominal radiation. The results suggested a benefit of chemotherapy: 55% of women treated with chemotherapy were predicted to be alive at five years, compared with 42% of women treated with radiation therapy. Women treated with chemotherapy also, however, tended to experience more severe side effects: 17% of women treated with chemotherapy discontinued treatment as a result of toxicity, compared with 3% of women treated with radiation therapy.3
High-Risk Prostate Cancer: Study Highlights Role of Advanced Imaging
Advanced imaging technique called PSMA-PET more sensitive at detecting cancer spread in high-risk hormone-sensitive prostate cancer
Vepdegestrant (ARV-471): FDA Fast Track Designation in ER+/HER2- Metastatic Breast Cancer
Vepdegestrant is an investigational drug belonging to a new class of medications called PROTAC (PROteolysis TArgeting Chimera) protein degraders
The results of a clinical trial performed in 788 women with endometrial cancer at high-risk stage I or II or stage III or IV uterine cancer that did not extend beyond the abdominal cavity and had ≥2 cm residual tumor was reported in 2019 that evaluated 3 different chemotherapy treatment regimens was reported. Women were treated with either doxorubicin + plus cisplatin, Taxotere (docetaxel) + cisplatin, or paclitaxel + carboplatin and directly compared. No difference in overall survival or time to cancer progression was found suggesting all 3 regimens were feasible.
At 5 years the survival without cancer progression was 73.3% for doxorubicin + cisplatin, 79.0% for Taxotere + cisplatin, and 73.9% for paclitaxel + carboplatin; 5-year OS rates were 82.7%, 88.1%, and 86.1%, respectively.2
Chemotherapy and radiation therapy were also compared in a study conducted in Italy. In this study, overall and progression-free survival were similar in patients treated with chemotherapy and patients treated with radiation therapy.3 The reasons for the different results between this study and GOG 122 remain uncertain, but may involve differences in the patient populations studied or the specific treatment regimens used.
Some research suggests that the combination of chemotherapy and radiation therapy may increase effectiveness. A study conducted in Europe among women with high-risk Stage I, II, IIIA, or IIIC endometrial cancer reported that the combination of radiation therapy and chemotherapy resulted in better progression-free survival than radiation therapy alone.5
Taken as a whole, previous studies suggest that adjuvant radiation therapy and/or chemotherapy may benefit some women with Stage III endometrial cancer. Patients should learn about the most recent study results from their doctor.
Radiation Therapy as Primary treatment
Patients who are inoperable at diagnosis can be treated with a combination of brachytherapy and external-beam radiation therapy. For more information, go to Radiation Therapy for Uterine Cancer.
References:
- Miller DS, Fleming G, Randall ME. Chemo- and radiotherapy in adjuvant management of optimally debulked endometrial cancer. Journal of the National Comprehensive Cancer Network. 2009;7:535-541.
- JAMA Oncol. 2019 Mar 21. Epub ahead of print
- Randall ME, Filiaci VL, Muss H et al. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: A Gynecologic Oncology Group study. Journal of Clinical Oncology. 2006;24:36-44.
- Maggi R, Lissoni A, Spina F et al. Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomized trial. British Journal of Cancer. 2006;95:266-271.
- Hogberg T, Rosenberg P, Kristensen G et al. A randomized phase-III study on adjuvant treatment with radiation (RT) ± chemotherapy (CT) in early-stage high-risk endometrial cancer (NSGO-EC-9501/EORTC 55991). Presented at the 2007 annual meeting of the American Society of Clinical Oncology. Abstract 5503.
