Top Line: What does total neoadjuvant therapy (TNT) for rectal cancer mean?
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: [1] increasing the proportion of patients who complete systemic therapy, [2] improving pathologic complete response (pCR) rate, and [3] 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: [1] received more cycles and higher doses of planned chemo, [2] had the same pCR rate at 17-18%, and [3] 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


  1. The pCR rate was was 21% for those who only got CCRT/Xeloda prior to TME, while it was 36% for those who received TNT.

    Compare to pCR rate for the TIMING trial, where essentially the same CCRT regimen got from 0c to 6c mFOLFOX. Patients who rec'd no mFOLFOX had a pCR of 18%, while patients who rec'd 6c mFOLFOX had a pCR of 38%, nearly mirroring the MSKCC data.

    Tl;DR: TNT in rectal cancer nearly DOUBLES pCR compared to conventional CCRT alone.


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