Top Line: The rationale of total neoadjuvant therapy (TNT) for high risk rectal cancer is to potentially reduce the risk of distant disease progression by giving chemo earlier and more consistently.

The Study: The RAPIDO trial compared the TNT versus standard approach for high risk rectal cancer. High risk meaning cT4a/4b, mesorectal fascia involvement, extramural vascular invasion, N2 disease, or lateral node involvement. The hypothesis was that TNT would reduce the overall rate of disease progression by both maintaining locoregional control and reducing distant recurrence due to increased emphasis on the systemic therapy component of treatment. RAPIDO randomized 912 patients to TNT or standard treatment with long-course neoadjuvant pre-op chemoradiation and adjuvant post-op chemotherapy as indicated. While many TNT studies simply re-sequence standard chemoradiation and chemo before surgery, here TNT consisted of initial short-course radiation followed by 6 cycles of CapeOX or 9 cycles of FOLFOX4. A total mesorectal excision (TME) was the surgical approach performed in both arms. At 3 years, the rate of disease failure was indeed significantly lower with TNT than standard therapy (23.7% vs 30.4%). And this was driven by the hypothesized decrease in distant failure (20% vs 26.8%). The pathologic complete response rate at surgery was higher with TNT (28% vs 14%), though there was a small “trend” to higher locoregional failure with TNT (8.3% vs 6%). There were no differences in any survival outcomes. Unfortunately, there’s nothing to be done about the choice for two totally different radiation approaches in each arm. eContour has a nice example of the RAPIDO approach (protocol here).

TBL: Straight from the authors’ mouths, “the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer”—including short-course neoadjuvant radiation without concurrent chemo for high-risk disease. | Bahadoer, Lancet Oncol 2021


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