The Study: Locally advanced rectal cancer is generally treated with neoadjuvant chemoradiation (CRT), surgery, and adjuvant chemotherapy. In that order. TNT means moving adjuvant chemo to the front of the line followed by CRT and then surgery. This approach has been best described by the UK EXPERT and Spanish GCR-3 trials, which led to inclusion of TNT as a treatment option in the NCCN guidelines. People like the thought of TNT for 3 rationales:  increasing the proportion of patients who complete systemic therapy,  improving pathologic complete response (pCR) rate, and  maximizing organ preservation. The newest report retrospectively describes outcomes at MSKCC with planned TNT (n=308) or planned post-op chemo (n=320). TNT consisted of 5FU-based chemo for 4 months followed by conventional CRT and finally a total mesorectal excision. With respect to the rationales above, the patients planned for TNT:  received more cycles and higher doses of planned chemo,  had the same pCR rate at 17-18%, and  had a 3x the rate of organ preservation (8 → 24%). Importantly, over 90% of patients who didn’t have surgery after TNT were without evidence of disease at least 12 months out from treatment.
Bottom Line: With improved systemic therapy compliance and organ preservation rates, TNT is an algorithm to consider for the treatment of locally advanced rectal cancer. | Cercek, JAMA Oncol 2018