How We Treat Localized Rectal Cancer—An Institutional Paradigm for Total Neoadjuvant Therapy

SIMPLE SUMMARY: Treatment of locally advanced rectal cancer has been subject to pronounced changes based on the results of recent prospective trials. New paradigms have been introduced, including the shift of systemic treatment components from adjuvant to neoadjuvant setting (total neoadjuvant therapy), the omission of surgery in patients with clinical complete responses after neoadjuvant treatment (non-operative management) and the introduction of upfront immunotherapy in patients with microsatellite instability (MSI)-high/mismatch-repair-deficient (dMMR) tumors. We developed an institutional treatment algorithm which may serve as a practical tool for treating physicians without any claim to general validity. ABSTRACT: Total neoadjuvant therapy (TNT)—the neoadjuvant employment of radiotherapy (RT) or chemoradiation (CRT) as well as chemotherapy (CHT) before surgery—may lead to increased pathological complete response (pCR) rates as well as a reduction in the risk of distant metastases in locally advanced rectal cancer. Furthermore, increased response rates may allow organ-sparing strategies in a growing number of patients with low rectal cancer and upfront immunotherapy has shown very promising early results in patients with microsatellite instability (MSI)-high/mismatch-repair-deficient (dMMR) tumors. Despite the lack of a generally accepted treatment standard, we strongly believe that existing data is sufficient to adopt the concept of TNT and immunotherapy in clinical practice. The treatment algorithm presented in the following is based on our interpretation of the current data and should serve as a practical guide for treating physicians—without any claim to general validity.