Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer

Key Points

  • The total neoadjuvant therapy strategy was associated with a higher rate of patients receiving planned systemic therapy.
  • Total neoadjuvant therapy was associated with a complete response rate of 36%. 

In a retrospective cohort study reported in JAMA Oncology, Cercek et al found evidence supporting the use of total neoadjuvant therapy as an effective option in locally advanced rectal cancer.

Study Details

The study involved data on 811 patients presenting with locally advanced rectal cancer (T3 or 4 or node-positive) at Memorial Sloan Kettering Cancer Center between 2009 and 2015. Of these, 320 (60% male) received neoadjuvant chemoradiation with planned adjuvant fluorouracil (5-FU)-based and oxaliplatin-based chemotherapy and 308 (59% male) received total neoadjuvant therapy consisting of induction 5-FU–based and oxaliplatin-based chemotherapy followed by chemoradiation. 

Treatment Delivery and Response

The total neoadjuvant therapy group had higher average doses received for both 5.FU and oxaliplatin (96% vs 88% and 90% vs 73%; both P < .01), as well as fewer dose reductions, higher proportions of patients receiving > 75% (93% vs 79% and 84% vs 60%) and > 90% (84% vs 55% and 61% vs 28%) of planned doses, and higher proportions receiving > 6 cycles of chemotherapy (95% vs 83% and 86% vs 63%; all P < .01). 

The rate of complete response—including both pathologic complete response in those who underwent surgery and sustained clinical complete response for ≥ 12 months posttreatment in those who did not undergo surgery—was 36% in the total neoadjuvant therapy group vs 21% in the chemoradiation plus planned adjuvant chemotherapy group.

The investigators concluded, “Our findings provide additional support for the National Comprehensive Cancer Network guidelines that categorize [total neoadjuvant therapy] as a viable treatment strategy for rectal cancer. Our data suggest that [total neoadjuvant therapy] facilitates delivery of planned systemic therapy. Long-term follow-up will determine if this finding translates into improved survival. In addition, given its high [complete response] rate, [total neoadjuvant therapy] may facilitate nonoperative treatment strategies aimed at organ preservation.”

The study was supported by a National Cancer Institute grant.

Martin R. Weiser, MD, of the Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, is the corresponding author for the JAMA Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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