BACKGROUND: Total Neoadjuvant Therapy (TNT) is recognized as standard of care for the treatment of locally advanced rectal cancer (LAR). A potential benefit of the chemotherapy induction sequence, compared to the consolidation sequence, is the ability to measure tumor response in the early treatment phase and adjust the subsequent treatment intensity if necessary to optimize the therapeutic ratio. We examined whether complete tumor response (CR) to induction chemotherapy (IC) predicts total mesorectal excision (TME)-free survival when an organ preservation strategy is pursued.
METHODS: Our group is conducting 2 similar phase II prospective trials to evaluate the safety of an organ preservation approach for patients with LAR: A watchful waiting (WW) trial and a limited local excision (LLE) trial.
Complete responders after TNT with 6 cycles of IC (FOLFOX) followed by concurrent
chemo-radiotherapy were offered either WW or LLE. Patients with tumors within 4 cm from the anus were offered WW and LLE was offered to patients with higher tumors. Incomplete responders at the final restaging were offered TME in both trials. The radiation therapy dose ranged between 45-54 Gy, depending on the tumor location and the response to IC. In both trials, a comprehensive restaging after IC was done for all patients with a digital rectal exam, flexible endoscopy, MRI and endoscopic ultrasound.
We combined the results from these 2 trials in this abstract. Data were analyzed using descriptive statistics and the chi-squared test.
RESULTS: We included 33 patients with a mean age of 60.0 ±11.3(s.d) years, and 54.4% female (18). Nine patients presented with circumferential disease. Twenty-three tumors were staged as T3N0 while 4 as T3N1, 4 as T2N0 and 1 as T2N1. The distance of the lowest edge of the disease and anus ranged between 0-8.6 cm with a median distance of 4 cm. The craniocaudal length of the tumors ranged between 1.6-7.5 cm with a median length of 4.3 cm. Complete clinical response after IC (group A) was observed in 42% (14/33) of patients while non-complete clinical response after IC (group B) was observed in 58% (19/33) of patients. Among group A, 92.9% (13/14) patients were free from TME at last follow-up compared to 22.1% (4/18) in group B (RR=4.4, 95% CI 1.8, 10.7, p<0.001).
CONCLUSION: Our data indicate that when an organ preservation strategy is pursued, the tumor response to induction chemotherapy predicts the probability of TME-free survival early in the treatment course. This benefit of induction chemotherapy should be considered when the chemotherapy sequence or treatment escalation and de-escalation, based on tumor response, is investigated in future research designed to maximize organ preservation.

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