Abstract: Five studies met the inclusion criteria. Three included studies compared extended-field RT versus pelvic RT, one included study compared extended-field RT with pelvic CRT, and one study compared extended-field CRT versus pelvic CRT. Extended-field radiotherapy versus pelvic radiotherapy alone Compared to pelvic RT, extended-field RT probably reduces the risk of death (hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.48 to 0.94; 1 study; 337 participants; moderate-certainty evidence) and para-aortic lymph node recurrence (risk ratio (RR) 0.36, 95% CI 0.18 to 0.70; 2 studies; 477 participants; moderate-certainty evidence), although there may or may not have been improvement in the risk of disease progression (HR 0.92, 95% CI 0.69 to 1.22; 1 study; 337 participants; moderate-certainty evidence) and severe adverse events (RR 1.05, 95% CI 0.79 to 1.41; 2 studies; 776 participants; moderate-certainty evidence). Extended-field radiotherapy versus pelvic chemoradiotherapy In a comparison of extended-field RT versus pelvic CRT, women given pelvic CRT probably had a lower risk of death (HR 0.50, 95% CI 0.39 to 0.64; 1 study; 389 participants; moderate-certainty evidence) and disease progression (HR 0.52, 95% CI 0.37 to 0.72; 1 study; 389 participants; moderate-certainty evidence). Participants given extended-field RT may or may not have had a lower risk of para-aortic lymph node recurrence (HR 0.44, 95% CI 0.20 to 0.99; 1 study; 389 participants; low-certainty evidence) and acute severe adverse events (RR 0.05, 95% CI 0.02 to 0.11; 1 study; 388 participants; moderate-certainty evidence). There were no clear differences in terms of late severe adverse events among the comparison groups (RR 1.06, 95% CI 0.69 to 1.62; 1 study; 386 participants; moderate-certainty evidence). Extended-field chemoradiotherapy versus pelvic chemoradiotherapy Very low-certainty evidence obtained from one small study (74 participants) showed that, compared to pelvic CRT, extended-field CRT may or may not have reduced risk of death (HR 0.37, 95% CI 0.14 to 0.96) and disease progression (HR 0.25, 95% CI 0.07 to 0.87). There were no clear differences between the groups in the risks of para-aortic lymph node recurrence (RR 0.19, 95% CI 0.02 to 1.54; very low-certainty evidence) and severe adverse events (acute: RR 0.95, 95% CI 0.20 to 4.39; late: RR 0.95, 95% CI 0.06 to 14.59; very low-certainty evidence). Moderate-certainty evidence shows that, compared with pelvic RT alone, extended-field RT probably improves overall survival and reduces risk of para-aortic lymph node recurrence. However, pelvic RT alone would now be considered substandard treatment, so this result cannot be extrapolated to modern standards of care. Low- to moderate-certainty evidence suggests that pelvic CRT may increase overall and progression-free survival compared to extended-field RT, although there may or may not be a higher rate of para-aortic recurrence and acute adverse events. Extended-field CRT versus pelvic CRT may improve overall or progression-free survival, but these findings should be interpreted with caution due to very low-certainty evidence. High-quality RCTs, comparing modern treatment techniques in CRT, are needed to more fully inform treatment for locally advanced cervical cancer without obvious para-aortic node involvement.

Plain-language summary: We searched databases from their inception to August 2018 and found five studies that met the inclusion criteria. Three studies compared extended-field RT versus pelvic RT. None of these three studies compared against the current gold-standard of pelvic CRT. One study compared extended-field RT versus pelvic CRT and one study compared extended-field CRT versus pelvic CRT. Compared with pelvic RT alone, women given extended-field RT may have been less likely to die and probably were less likely to have a cervical cancer come back (recurrence) in the para-aortic lymph nodes. However, extended-field RT may have made little or no difference to how often their cancer recurred elsewhere and how often they experience severe side effects. Pelvic CRT is the modern standard of treatment for locally advanced cervical cancer. In a comparison of extended-field RT alone versus pelvic CRT, women given pelvic CRT were probably less likely to die or have recurrence of their cancer. Women given extended-field RT alone may have been less likely to experience a recurrence within the para-aortic lymph nodes and have had adverse events during or shortly after treatment. There were no clear differences regarding the late adverse events between the two groups. Women given extended-field CRT may or may not have been less likely to die or have cancer progression than those women pelvic CRT. There were no clear differences in the chances of experiencing a cancer recurrence in the para-aortic lymph nodes and severe side effects between the groups. The evidence for outcomes in the comparison of extended-field RT alone versus pelvic RT alone were of moderate certainty. In the comparison of extended-field RT versus pelvic CRT, the evidence regarding the survival and side effects were of moderate certainty. The evidence for para-aortic recurrence was of low certainty. The evidence for all outcomes in a comparison of extended-field CRT versus pelvic CRT were of very-low certainty because of concerns regarding the high risk of bias and results coming from a single trial of very few women. We are moderately certain that, compared with pelvic RT alone, extended-field RT probably improves overall survival and reduces risk of para-aortic lymph node recurrence. However, pelvic RT alone would now not be considered the standard of care in women well enough to receive CRT, so these results should be reviewed with caution and cannot be extrapolated to modern treatment techniques. Low- to moderate-certainty evidence supports the use of pelvic CRT rather than extended-field RT alone, as it appears to reduce the risk of death and cancer progression. The likelihood of experiencing unwanted side effects during treatment was higher among women receiving pelvic CRT than extended-field RT. Evidence comparing extended-field CRT to pelvic CRT was very low certainty regarding outcomes and it may or may not improve survival.