In theory, instrumental variable (IV) analysis, like randomized controlled trials, can adjust for measured and unmeasured confounders. IVs need to meet the following three conditions: (i) they are associated with treatment assignment; (ii) they have no direct association with the outcome and are associated with the outcome exclusively through the treatment; and (iii) they are not associated with any of the measured confounders. Studies have presented several types of IV, including preferences of the facility or physician, differential distance, and days of the week. Two types of estimation method have been introduced: two-stage least squares and two-stage residual inclusion. The assumption of monotonicity limits the generalizability of estimates of causal effects in IV analysis because the target population of IV analysis is “compliers” (those who always comply with the assigned treatment). IV analysis using two or more IVs is feasible but requires the overidentifying restriction test. Despite several limitations, IV analysis is a feasible option that may be used for causal inference in comparative effectiveness studies using retrospective observational data.
Unlike the recommendations made in many other countries, Japanese guidelines equally recommend radical hysterectomy or concurrent chemoradiotherapy for treatment of stage IIB cervical carcinoma. The main study objective was to compare the overall mortality of hysterectomy versus concurrent chemoradiotherapy as primary treatment in patients with localized or regionally extended cervical cancer.
Using Diagnosis Procedure Combination database combined with population-based cancer registry data in Osaka Prefecture, Japan, we conducted a retrospective cohort study. All adult patients who had been diagnosed with cervical cancer, registered in the population-based cancer registry from January 1, 2010 to December 31, 2015 were included. To compare overall mortality between patients who received radical hysterectomy and concurrent chemoradiotherapy as primary treatment, we performed a Cox regression analysis of the original cohort, and Kaplan-Meier analysis with stabilized inverse probability of treatment weights using propensity score.
Among 740 eligible patients, 564 patients were included in the hysterectomy group and 176 patients were included in the concurrent chemoradiotherapy group. Primary hysterectomy was not independently associated with overall mortality (adjusted HR 0.70, 95% CI 0.46–1.07) by the Cox regression analysis. The Kaplan-Meier analysis with stabilized inverse probability of treatment weights did not show a significant difference in overall mortality between the two groups (P = 0.096).
This study indicates that primary treatment type (hysterectomy versus concurrent chemoradiotherapy) was not statistically associated with overall mortality among patients diagnosed with localized or regionally extended cervical cancer.