Estimation of average causal effect using the restricted mean residual lifetime as effect measure.

Although mean residual lifetime is often of interest in biomedical studies, restricted mean residual lifetime must be considered in order to accommodate censoring. Differences in the restricted mean residual lifetime can be used as an appropriate quantity for comparing different treatment groups with respect to their survival times. In observational studies where the factor of interest is not randomized, covariate adjustment is needed to take into account imbalances in confounding factors. In this article, we develop an estimator for the average causal treatment difference using the restricted mean residual lifetime as target parameter. We account for confounding factors using the Aalen additive hazards model. Large sample property of the proposed estimator is established and simulation studies are conducted in order to assess small sample performance of the resulting estimator. The method is also applied to an observational data set of patients after an acute myocardial infarction event.

Overall survival after immunotherapy, tyrosine kinase inhibitors and surgery in treatment of metastatic renal cell cancer: outcome of 143 consecutive patients from a single centre.

OBJECTIVE: The aim of this study was to evaluate overall survival (OS) after treatment of metastatic renal cell carcinoma (mRCC) following the introduction of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors. MATERIAL AND METHODS: One-hundred and forty-three consecutive mRCC patients were given immunotherapy (n = 59), TKIs (n = 49) or sequential therapy (IMM → TKI group; n = 35). The TKI group included patients with higher age (p < 0.001), worse performance status (p = 0.005) and higher risk profile (p < 0.001) than the other two treatment groups. Number of metastases and sites and tumour histology did not differ between groups. RESULTS: First line immunotherapy gave a median OS of 16.3 months and first line TKIs 10.9 months (p = 0.003). Survival longer than 5 years was limited to immunotherapy. Sarcomatoid component, metastatic sites, papillary histology, stage, performance status and white cell blood count were related to poor OS. Using multivariate analyses to adjust for risk predictors the difference in OS disappeared. Median OS before and after introduction of TKIs was 16 months and 14 months, respectively (p = 0.189). Memorial Sloan Kettering Cancer Center (MSKCC) risk groups were related to OS (p < 0.001). Heng's prognostic criteria appeared slightly more predictive than MSKCC (p = 0.12). Metastasectomy (n = 42) may improve OS [surgery: median OS 18.8 months, 95% confidence interval (CI) 12.3-48.5; no surgery: median OS 15 months, 95% CI 10.4-16.5; p = 0.07]. CONCLUSIONS: MSKCC and Heng's prognostic algorithms were valid for prognostication and can be used for individual planning of treatment and follow-up. Surgical removal of metastases may improve OS.