The association between treatment delays and patient outcomes in cervical cancer patients: a systematic review and dose–response meta-analysis

The associations of different delays in the treatment of cervical cancer (e.g., delay in initial treatment, delay in surgery, delay in concurrent chemoradiotherapy, delay in postoperative adjuvant treatment), different duration of delay and survival outcomes have not been systematically reviewed and the dose–response relationship was uncertain. To quantify the associations between different treatment delays, different delay levels and patient survival outcomes in cervical cancer patients. We conducted comprehensive searches of PubMed, Embase, the Cochrane Library, Web of Science for English literature, and CNKI, WanFang, VIP, CBM for Chinese literature, covering the period of the last 15 years. Case‒control and cohort studies reporting outcomes or prognosis from treatment delays in cervical cancer patients were included. Two researchers independently performed literature screening, data extraction, and quality evaluation. The methodological quality was assessed using the Newcastle-Ottawa Scale. The fixed or random effect model was used based on heterogeneity test. The dose–response relationship was assessed by restricted cubic spline regression model fitted with generalized least squares trend estimation. Sensitivity analysis and publication bias were also evaluated. Stata 17.0 software was used to perform analysis. A total of 18 studies were included with all assessed as high methodological quality. The results revealed that a delay in the initial treatment( P < 0.05), a delay in surgery( P < 0.05), a delay in concurrent chemoradiotherapy( P < 0.05) had negative effects on cervical cancer patients’ overall survival. The dose-response meta-analysis revealed a linear trend indicating that for each 1-week delay in the treatment, overall survival decreased by 0.9%( P < 0.001). Nonlinear trend indicated that, Compared with a delay of 1 week, the survival risks for delays of 2, 4, 6, 7.5, 9, 10.7, 14, 15, 19.3, 21.4, 30, and 32.1 weeks were 0.99(0.97–1.00), 0.96(0.93–1.00), 0.95(0.89–1.01), 0.94(0.87–1.01), 0.94(0.86–1.02), 0.94(0.86–1.04), 0.98(0.89–1.09), 1.00(0.91–1.11), 1.11(1.01–1.21), 1.17(1.07–1.29), 1.53(1.30–1.80), and 1.63(1.36–1.97), respectively. Inferior overall survival is found for cervical cancer patients with 3 types of treatment delay. Additionally, we observed a potential “J-shaped” dose-response relationship between the duration of treatment delays and the risk of overall survival, which quantifies the association between varying delay levels and survival outcomes. However, further research is required to fully explore and confirm this relationship.