Association between delayed initiation of treatment indications and survival in patients with cervical cancer: a systematic review and meta-analysis

This review evaluated the association between delayed time to initiate any treatment with survival in patients with cervical cancer. An internet-based literature search was performed in PubMed/Medline, Cochrane CENTRAL, EMBASE, Web of Science and Scopus databases. All articles published until December 2021 were included. Studies were pooled for meta-analysis in a random-effects model. Microsoft-Excel and the R programing software were employed in the analysis. Between-study heterogeneity was assessed using Q2, I2 and tau2. Results were reported as a function of 4-week delay in treatment initiation and hazard ratio using forest plots at 95% confidence interval. A p < 0.05 was considered statistically significant. Eleven studies were included in this review, comprising 50,590 patients. Overall survival was evaluated based on the pooled effect of 11 comparison groups. The subgroup on five-years follow-up following radiotherapy revealed that a 4-week delay in treatment was associated with a 1.27 times higher rate of mortality (Hazard Ratio: 1.27; 95% Confidence Interval: 1.12–1.45). However, a 4-week delay in initiation of combined chemoradiotherapy (HR: 1.31; 95%CI: 0.76–2.23) or surgery (HR: 0.96: 95% CI: 0.60–1.54) did not predict a statistically significant rate of mortality. The same length of waiting time did not predict the rate of mortality in a 3-years follow-up period (HR: 0.76; 95% CI: 0.44–1.32). A 4-week delay in radiotherapy showed a 1.72 times higher rate of disease relapse in the delayed group (HR: 1.72; 95% CI: 1.25–2.35) but not in patients for whom surgery was performed (HR: 0.89; 95% CI: 0.75–1.04). A four-week delay in initiating radiotherapy was associated with a higher rate of mortality. On the other hand, a 4-week delay in initiation of either surgery (hysterectomy) or chemoradiotherapy does not appear to be associated with overall survival, probably accounted, partially, for the waiting time paradox.

Cervical cancer; Delayed time to treatment initiation; Survival; Systematic review and meta-analysis

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