Adjuvant Radiotherapy for Stage I Endometrial Cancer
Adjuvant Radiotherapy for Stage I Endometrial Cancer
Background The role of adjuvant radiotherapy in stage I endometrial cancer has changed in recent years. This updated Cochrane systematic review aimed to reexamine the efficacy and toxicity of adjuvant radiotherapy vs no treatment in stage I endometrial cancer.
Methods We searched various databases including The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and the Specialised Register of the Cochrane Gynaecological Cancer Review Group (CGCRG) for randomized controlled trials that met the predefined inclusion criteria. The primary outcome was overall survival (OS); secondary outcomes were endometrial cancer–specific survival, locoregional recurrence, distant recurrence, and toxicity. Hazard ratios (HRs) were estimated and pooled if possible; otherwise, dichotomous data were extracted. All statistical tests were two-sided.
Results Of the eight included trials, seven trials (3628 women) compared external beam radiotherapy (EBRT) and no EBRT (or vaginal brachytherapy [VBT]), and one trial (645 women) compared VBT and no additional treatment. EBRT statistically significantly reduced locoregional recurrence compared with no EBRT (or VBT alone) (HR = 0.36, 95% confidence Interval [CI] = 0.25 to 0.52; P < .001), but this did not translate into an improvement in OS (HR = 0.99, 95% CI = 0.82 to 1.20; P = .95), endometrial cancer–specific survival (HR = 0.96, 95% CI = 0.72 to 1.28; P = .80), or distant recurrence rates (risk ratio = 1.04, 95% CI = 0.80 to 1.35; P = .77). EBRT was associated with an increased risk of severe acute toxicity, severe late toxicity, and reduced quality of life scores.
Conclusions EBRT reduces the risk of locoregional recurrence but has no statistically significant impact on cancer-related deaths or OS. However, EBRT is associated with clinically and statistically significant morbidity and a reduction in quality of life.
This review is an update of a previously published review in The Cochrane Database of Systematic Reviews. Here, we examined the role of adjuvant radiotherapy after surgery for endometrial carcinoma, a disease that affects mainly postmenopausal women and is one of the most common gynecological cancers. The majority of endometrial carcinomas are diagnosed at stage I in which the cancer is confined to the body of the uterus. The initial treatment of stage I disease is usually a hysterectomy and bilateral salpingo-oophorectomy. Previously, it was advocated that a pelvic and/or para-aortic lymphadenectomy should be performed to determine the need for adjuvant therapy. However, two recent randomized trials of pelvic lymphadenectomy vs no lymphadenectomy showed no evidence of benefit for routine lymphadenectomy in patients with stage I endometrial cancer. The role of adjuvant radiotherapy in stage 1 endometrial cancer and early disease has changed over recent years. Previously, adjuvant radiotherapy had been offered to some women who had stage 1 disease based on the perceived "risks of recurrence" including histological type, grade, depth of myometrial invasion, lymphovascular invasion, and age. This practice resulted in different policies of routine adjuvant radiotherapy with external beam radiotherapy (EBRT) and/or vaginal brachytherapy (VBT) being offered at various treatment centers throughout the world. More recently, many centers stopped offering adjuvant EBRT to women who have stage I endometrial cancer.
Both pelvic EBRT and vaginal intracavitary VBT may result in acute toxicities and long-term complications, which may cause worsening of quality of life for some patients. Therefore, the decision to offer adjuvant radiotherapy must be based on true clinical benefit, which should outweigh the side effects. Our original review combined data from four randomized controlled trials of EBRT (with or without VBT) vs no EBRT and found no evidence that adjuvant EBRT improved overall survival (OS) or endometrial cancer–related survival, despite a reduction in locoregional recurrence. Since then, several larger randomized trials of adjuvant radiotherapy in early endometrial carcinoma have been reported, and subsequently, the less toxic VBT is increasingly used for local tumor control, even for high-risk endometrial cancer. However, there is still uncertainty whether this may result in more locoregional recurrences and a reduction in patient survival. Therefore, there was a need to update the Cochrane systematic review on the benefits and risks of adjuvant radiotherapy to guide the clinical management of stage I endometrial cancer.
Abstract and Introduction
Abstract
Background The role of adjuvant radiotherapy in stage I endometrial cancer has changed in recent years. This updated Cochrane systematic review aimed to reexamine the efficacy and toxicity of adjuvant radiotherapy vs no treatment in stage I endometrial cancer.
Methods We searched various databases including The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and the Specialised Register of the Cochrane Gynaecological Cancer Review Group (CGCRG) for randomized controlled trials that met the predefined inclusion criteria. The primary outcome was overall survival (OS); secondary outcomes were endometrial cancer–specific survival, locoregional recurrence, distant recurrence, and toxicity. Hazard ratios (HRs) were estimated and pooled if possible; otherwise, dichotomous data were extracted. All statistical tests were two-sided.
Results Of the eight included trials, seven trials (3628 women) compared external beam radiotherapy (EBRT) and no EBRT (or vaginal brachytherapy [VBT]), and one trial (645 women) compared VBT and no additional treatment. EBRT statistically significantly reduced locoregional recurrence compared with no EBRT (or VBT alone) (HR = 0.36, 95% confidence Interval [CI] = 0.25 to 0.52; P < .001), but this did not translate into an improvement in OS (HR = 0.99, 95% CI = 0.82 to 1.20; P = .95), endometrial cancer–specific survival (HR = 0.96, 95% CI = 0.72 to 1.28; P = .80), or distant recurrence rates (risk ratio = 1.04, 95% CI = 0.80 to 1.35; P = .77). EBRT was associated with an increased risk of severe acute toxicity, severe late toxicity, and reduced quality of life scores.
Conclusions EBRT reduces the risk of locoregional recurrence but has no statistically significant impact on cancer-related deaths or OS. However, EBRT is associated with clinically and statistically significant morbidity and a reduction in quality of life.
Introduction
This review is an update of a previously published review in The Cochrane Database of Systematic Reviews. Here, we examined the role of adjuvant radiotherapy after surgery for endometrial carcinoma, a disease that affects mainly postmenopausal women and is one of the most common gynecological cancers. The majority of endometrial carcinomas are diagnosed at stage I in which the cancer is confined to the body of the uterus. The initial treatment of stage I disease is usually a hysterectomy and bilateral salpingo-oophorectomy. Previously, it was advocated that a pelvic and/or para-aortic lymphadenectomy should be performed to determine the need for adjuvant therapy. However, two recent randomized trials of pelvic lymphadenectomy vs no lymphadenectomy showed no evidence of benefit for routine lymphadenectomy in patients with stage I endometrial cancer. The role of adjuvant radiotherapy in stage 1 endometrial cancer and early disease has changed over recent years. Previously, adjuvant radiotherapy had been offered to some women who had stage 1 disease based on the perceived "risks of recurrence" including histological type, grade, depth of myometrial invasion, lymphovascular invasion, and age. This practice resulted in different policies of routine adjuvant radiotherapy with external beam radiotherapy (EBRT) and/or vaginal brachytherapy (VBT) being offered at various treatment centers throughout the world. More recently, many centers stopped offering adjuvant EBRT to women who have stage I endometrial cancer.
Both pelvic EBRT and vaginal intracavitary VBT may result in acute toxicities and long-term complications, which may cause worsening of quality of life for some patients. Therefore, the decision to offer adjuvant radiotherapy must be based on true clinical benefit, which should outweigh the side effects. Our original review combined data from four randomized controlled trials of EBRT (with or without VBT) vs no EBRT and found no evidence that adjuvant EBRT improved overall survival (OS) or endometrial cancer–related survival, despite a reduction in locoregional recurrence. Since then, several larger randomized trials of adjuvant radiotherapy in early endometrial carcinoma have been reported, and subsequently, the less toxic VBT is increasingly used for local tumor control, even for high-risk endometrial cancer. However, there is still uncertainty whether this may result in more locoregional recurrences and a reduction in patient survival. Therefore, there was a need to update the Cochrane systematic review on the benefits and risks of adjuvant radiotherapy to guide the clinical management of stage I endometrial cancer.
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