Adjuvant chemoradiotherapy vs. radiotherapy alone in early-stage high-risk endometrial cancer: a systematic review and meta-analysis

OBJECTIVE: The benefits of adjuvant chemoradiotherapy (CRT) in patients with International Federation of Gynecology and Obstetrics (FIGO) stages I-II high-risk endometrial cancer remain controversial. We undertook a systematic review and meta-analysis to assess the efficacy of CRT over radiotherapy (RT) in patients with early-stage high-risk endometrial cancer. PATIENTS AND METHODS: We searched MEDLINE (from 1946 to May 2018), EMBASE (from 1966 to May 2018), and the Cochrane Library database for randomized controlled trials (RCTs) conducted for endometrial cancer comparing CRT to RT alone. The outcomes were overall survival (OS), failure-free survival (FFS), local recurrence rates (LRR) and the distant metastasis rate (DMR). RESULTS: Three eligible studies with 1120 participants were included in the meta-analysis. All studies were published from 1990 to 2018. The OS rates were 82.5% for the patients in the CRT group and 84.4% for patients in the RT group. The included three RCTs showed no significant difference of OS between the CRT and RT groups (odd ratio 0.98, 95% CI 0.93 to 1.02, p=0.35) with no heterogeneity (I-2=0%, p=0.47). Two studies reported 382 FFS events in 469 patients with CRT treatment (81.4%) and 376 events of the 470 patients with RT treatment (80.0%). Overall, CRT group didn't provide any benefit over RT alone (1.02, 0.95 to 1.08, p=0.62; I-2 = 0%, p=0.55) in FFS. 39 patients in CRT group (10.2%) vs. 16 patients in RT group (4.3%) were diagnosed with local recurrence. LRR was significantly more common in patients receiving adjuvant chemoradiotherapy compared with adjuvant radiotherapy (2.29, 1.31 to 3.98, p=0.004; I-2=0%, p=0.33). The distant metastasis occurred in 20 patients (5.2%) treated with CRT and 26 patients (7.0%) treated with RT. The effect of reducing DMR was equivocal between the CRT group and the RT group, with an OR of 0.74 (0.43-1.27, p=0.28; I-2=0%, p=0.87). CONCLUSIONS: This study demonstrates that adjuvant chemoradiotherapy has no advantage over radiotherapy alone for overall survival and failure-free survival in high-risk patients with FIGO stages I-II endometrial cancer. In addition, CRT is associated with a high risk of local recurrences.