Outcomes of Locally Advanced Rectal Cancer Patients Treated with Total Neoadjuvant Treatment: A Meta-Anaysis of Randomized Controlled Trials

The present meta-analysis estimates the pathological complete response, disease-free survival and overall survival probabilities of rectal cancer patients treated with Total Neoadjuvant Treatment. It provide a useful benchmark for future comparisons of the benefits of combinations of other drug families. Background & Aims: Determining outcomes using the total neoadjuvant therapy (TNT) in patients with local advanced rectal cancer is important for stratifying patients according to expected outcomes in future studies in the era of treat-ment combination. The present meta-analysis estimated the pathological complete response, disease-free survival, and overall survival probabilities of rectal cancer patients and identified predictors of outcomes. Methods: Studies reporting pathological complete response rate and time-dependent outcomes (progression or death) after total neoadjuvant treat-ment of locally advanced rectal cancer (LARC) were identified in MEDLINE through January 2022. Three independent observers extracted data on patient populations and outcomes and combined the data using a distribution-free summary sur vival cur ve. The primar y outcomes were actuarial probabilities of recurrence and survival. Results: Fourteen RCTs, including 18 TNT arms, met the inclusion cr iter ia. The pooled estimate of pathological complete response (pCR) proba-bility was 23.6%, with moderate heterogeneity between studies. The pooled estimates of actuarial disease-free survival rate were 70.6% at 3 years and 65.4% at 5 years. The pooled estimates of actuarial survival rates were 93% at 3 years and 81.6% at 5 years. In both these outcomes, heterogeneity between studies was highly significant. Conclusion: This meta-analysis showed that Total Neoadjuvant Therapy is an optimal approach for LARC patients. The results provide a useful benchmark for future comparisons of the benefits of combinations of other drug families as target therapies or immunotherapies.