The use of total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC)—in which both chemoradiation and chemotherapy are administered preoperatively—is a viable treatment strategy, according to results of a single-center study by investigators from Memorial Sloan Kettering Cancer Center (MSKCC), in New York City. The findings, published in JAMA Oncology, provide further support for existing guidelines from the National Comprehensive Cancer Network.
TNT has been associated with improved delivery of planned therapy, increased downstaging, and earlier introduction of optimal systemic chemotherapy to address micrometastases.
“In addition,” reported Andrea Cercek, from MSKCC’s Department of Medicine, and colleagues, “delivery of all chemotherapy preoperatively obviates the need for postoperative therapy, reducing duration with a diverting ileostomy and alleviating the need for patients to undergo chemotherapy with a stoma.”
In the study, compared with chemoradiotherapy with planned adjuvant chemotherapy, patients receiving TNT were more likely to complete planned chemotherapy with fewer dose reductions, according to the researchers.
The retrospective study used data from 811 MSKCC patients with LARC treated between 2009 and 2015. Among these patients, 320 had received chemoradiation with planned adjuvant chemotherapy and 308 had been treated with TNT with induction fluorouracil and oxaliplatin-based chemotherapy followed by chemoradiotherapy.
Patients who underwent TNT received greater percentages of prescribed doses of planned oxaliplatin and fluorouracil than those who underwent chemoradiotherapy with planned adjuvant chemotherapy.
The complete response (CR) rate was 36% in the TNT cohort compared with 21% in the cohort that received chemoradiotherapy with adjuvant chemotherapy. CR in this study included the pathologic CR rate in patients who underwent surgery and the rate of sustained clinical response (lasting at least 12 months post treatment) in those who did not undergo surgery.
In an editorial that accompanied the article, Theodore S. Hong, MD, and David P. Ryan, MD, of Massachusetts General Hospital, emphasized that although TNT has been adopted in major academic centers, many oncologists in community settings are still not comfortable with its use.
Hong and Ryan noted that while the current study is retrospective and lacks long-term survival data, given the results, TNT may be a better choice for most patients with LARC, as far as short-term outcomes are concerned.”
“Given the lack of survival difference seen in preoperative vs postoperative therapy sequence for most solid tumor cancer trials and the emerging trend of nonoperative treatment for rectal cancer, a large definitive phase III study comparing TNT vs standard sequencing would be expensive, impractical, and likely unwelcome to most patients,” Hong and Ryan wrote.
In conclusion, Hong and Ryan said that TNT “should be considered standard of care for clearly node-positive patients with low-lying rectal tumors, given the increased compliance with chemotherapy, the improved local control, and the ability to consider nonoperative treatment. Moreover, in patients at a high risk of a margin-positive resection owing to T4 disease or an involved mesorectal fascia, TNT should be considered standard of care.”