Total neoadjuvant therapy for locally advanced rectal cancer.

Abstract

662 Background: Current therapy for locally advanced rectal cancer (LARC) consists of 6 months of perioperative therapy, either with pre-operative chemo-radiotherapy (CRT) and post operative adjuvant chemotherapy (PAC) or total neoadjuvant therapy (TNT) with induction chemotherapy (ICT) followed by CRT then surgery. The aim of our study was to report on the safety, efficacy and complete response rates comparing TNT to PAC in a larger series of LARC patients (pts) at Memorial Sloan Kettering Cancer Center (MSKCC). Methods: Pts treated at MSKCC (2009-15) were analyzed based on the intended treatment schedule (TNT or PAC). 730 LARC pts were treated with CRT, of these 320 received neoadjuvant CRT and 308 received TNT. Results: In the TNT group 205 pts (73%) underwent surgery within 26 weeks of completion of treatment, of which 38 (19%) had a pCR. Of the 78 pts who did not undergo surgery within 26 weeks, 68 (87%) had a complete clinical response (cCR). In the PAC group 293 pts (92%) underwent surgery within 26 weeks and 45 (15%) had a pCR. Of the 27 pts who did not undergo surgery within 26 weeks 22 (81%) had a cCR. The median follow up was 25 mo in the TNT group and 29 mo in the PAC group. There was no statistically significant difference in the distant metastasis free survival between the treatment regimens, despite a higher number of cT4 and cN + tumors in the TNT group. Fewer distant recurrences were seen in pts who had evidence of T downstaging (P < 0.001), N downstaging (P < 0.005), the presence of a cCR (P = 0.005) or a pCR (P < 0.005). Of the pts who received all treatment at MSKCC, comparison of dose of 5-FU and oxaliplatin between the preoperative (N = 249) and postoperative regimens (N = 101) was notable for a higher average dose received of both 5FU and oxaliplatin (p < 0.005 and p < 0.001) in the ICT group. Conclusions: These data add weight to the evidence already included in the NCCN guidelines that pre-operative chemotherapy as part of TNT is a viable treatment strategy with superior compliance and delivery of systemic therapy. Given the high complete response rate, TNT may be used as part of an organ preservation treatment strategy.