Summary of findings 1. Hysterectomy (radical) with neoadjuvant chemotherapy versus chemoradiotherapy alone for women with locally advanced cervical cancer.

Hysterectomy (radical) with neoadjuvant chemotherapy versus with chemoradiotherapy alone for women with locally advanced cervical cancer
Patient or population: women with locally advanced cervical cancer Settings: outpatient Intervention: NACT + hysterectomy Comparison: CCRT
Outcomes	Relative effect (95% CI)	No. of participants (studies)	Certainty of the evidence(GRADE)	Comments
Overall survival Median follow‐up 58.5–98.4 months in the 2 trials	HR 0.94 (0.76 to 1.16)	1253 (2 RCTs)	⊕⊕⊕⊝ Moderatea	I2 = 0%
DFS Median follow‐up 58.5–98.4 months in the 2 trials	HR 1.38 (1.02 to 1.87)	633 (1 RCT)	⊕⊕⊝⊝ Lowb	—
	5‐year DFS in the NACT + surgery group was 57% vs 65.6% in the chemoradiotherapy group (P = 0.021)	620 (1 RCT)
Quality of life	—	—	—	Not reported.
SAEs and toxicity	SAEs In first trial, there were no toxic deaths reported. 198 SAEs occurred: 145 in the NACT + surgery arm vs 53 in the CCRT arm. In the second trial there were 114 grade 3 or 4 SAEs: 92 in the NACT + surgery arm vs 22 in the CCRT arm	198 (1 RCT) 114 (1 RCT)	⊕⊝⊝⊝ Very lowc	—
	Toxicity In 1 trial, NACT + surgery group, compared with the chemoradiotherapy group, there was a lower rate of rectal (5.7% with NACT + surgery vs 13.3% with chemoradiotherapy; P = 0.002), bladder (2.8% with NACT + surgery vs 7.3% with chemoradiotherapy; P = 0.017), and vaginal (19.9% with NACT + surgery vs 36.9% with chemoradiotherapy; P = 0.001) toxicity occurring or persisting 90 days after treatment completion. However, 24 months after treatment completion, there was no difference in rectal and bladder toxicities between groups, whereas vaginal toxicity continued to occur at a lower rate in the NACT + surgery group (12.0% with NACT + surgery vs 25.6% with chemoradiotherapy; P = 0.001).	114 (1 RCT)
	Treatment‐related morbidity No treatment‐related deaths in either chemoradiotherapy or NACT + surgery arm. Overall, 89% of participants in the chemoradiotherapy arm and 73% in the NACT + surgery arm had complications, with 18% in NACT + surgery arm experiencing recurrence and requiring adjuvant radiotherapy.	111 (1 RCT)
CI: confidence interval; CCRT: concurrent chemoradiotherapy; DFS: disease‐free survival; HR: hazard ratio; NACT: neoadjuvant chemotherapy; SAE: serious adverse event.
GRADE Working Group grades of evidence High certainty: further research is very unlikely to change our confidence in the estimate of effect. Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low certainty: we are very uncertain about the estimate.

^aDowngraded one level due to concerns regarding the uncertainty of risk of bias in individual trials and only two trials in meta‐analysis (although it is arguable whether the number of included participants represented relatively sparse data).
^bDowngraded two levels due to risk of bias and sparse data.
^cDowngraded three levels due to incomplete and poor reporting of important adverse events and toxicities, sparseness of data and risk of bias concerns.