Personalized total neoadjuvant therapy versus chemotherapy during the ‘wait period’ versus standard chemoradiotherapy for locally advanced rectal cancer

Background This study aimed to compare current treatment response rates with personalized Total Neoadjuvant Therapy (pTNT), against extended chemotherapy in the ‘wait period’ (xCRT) and standard chemoradiotherapy (sCRT) with adjuvant chemotherapy for rectal cancer. Methods This was a multicentre retrospective cohort analysis. Consecutive patients with rectal cancer treated with pTNT over a 3.9‐year period were compared to a historical cohort of patients treated with xCRT or sCRT as part of the published WAIT Trial. pTNT patients received 8 cycles mFOLFOX6 or 6 cycles CAPOX in the neoadjuvant setting (no adjuvant treatment). Patients in the WAIT Trial received either 3 cycles 5‐FU/LV during the 10‐week wait period after chemoradiotherapy or standard chemoradiotherapy, followed by adjuvant chemotherapy. The primary endpoint was overall complete response (oCR) rate defined as the proportion of patients who achieved either complete clinical response (cCR) or pathological complete response (pCR). Results Of 284 patients diagnosed with rectal cancer during the 3.9‐year period, 107 received pTNT. Forty of these were matched with 49 patients from the WAIT Trial (25 received xCRT and 24 received sCRT). There was a significant difference in oCR between the groups (pTNT n = 21, xCRT n = 6, sCRT n = 7, P = 0.043). Of the patients that underwent surgery, pCR occurred in 13 patients with no significant difference between groups (P = 0.415). There were no significant differences in 2‐year disease‐free survival or overall survival. Conclusion Compared with sCRT and xCRT, pTNT results in a significantly higher complete response rate which may facilitate organ preservation. Clinical complete response was significantly higher in patients with locally advanced rectal cancer treated with personalised total neoadjuvant therapy than in those treated with extended chemotherapy during the 10‐week wait period after chemoradiotherapy or standard chemoradiotherapy, followed by adjuvant chemotherapy.