Total neoadjuvant approach promising in locally advanced rectal cancer

Last Updated: 2018-04-02

By David Douglas

NEW YORK (Reuters Health) - Preoperative chemotherapy in combination with chemoradiation (total neoadjuvant therapy, or TNT) appears to have advantages over traditional approaches to treating locally advanced rectal cancer, according to new research.

TNT has been developed to optimize delivery of effective systemic therapy aimed at micrometastases, Dr. Martin R. Weiser of Memorial Sloan Kettering Cancer Center, in New York City, and colleagues note in JAMA Oncology, online March 22.

To investigate its efficacy, the team reviewed data on patients treated between 2009 and 2015. Of these, 320 received preoperative chemoradiation (chemoRT) with planned adjuvant chemotherapy. A further 308 got TNT, consisting of induction fluorouracil and oxaliplatin-based chemotherapy followed by chemoRT.

TNT was associated with improved chemotherapy dosing. For example, analysis of fluorouracil receipt showed that 95% of the TNT group received more than six cycles compared to 83% of the other group (P<0.001). There were similar findings for oxaliplatin.

Nonoperative treatment was more common in the TNT group, 24% of whom did not undergo surgery within 12 months compared to only 8% of the chemoRT group (P<0.001). Minimally invasive surgery was also more common in the TNT group (72% vs. 47%, P<0.001).

The rate of complete response (CR), including both pathologic CR in those who underwent surgery and CR for at least 12 months after treatment in those who did not, was 36% in TNT patients and 21% in the chemoRT group.

Dr. Weiser told Reuters Health email, "We were able to show that the TNT group seemed to better tolerate systemic chemotherapy and were more likely to receive their prescribed dose. We hope this leads to improved overall survival but we need to wait for the dataset to mature before this can be evaluated."

"Other benefits of TNT," he added, "are improved response and tumor downsizing. This allowed more people to be treated along the nonoperative (watch and wait) approach. Lastly, since all the treatment is given prior to the first surgery, patients who have a temporary diverting ileostomy can have it reversed generally at 6 to 12 weeks (rather than the more traditional 6 to 8 months)."

Dr. David P. Ryan of Harvard Medical School in Boston, who wrote an accompanying editorial, told Reuters Health by email that the study "is more ammunition for the argument that total neoadjuvant therapy, where all the chemotherapy and radiation is given prior to surgery for patients with locally advanced rectal cancer, is the appropriate treatment."

The study had no commercial support, and the researchers report no conflicts of interest.

SOURCE: https://bit.ly/2GPNQqX and https://bit.ly/2EgBMKc

JAMA Oncol 2018.