Total neoadjuvant therapy before surgery for rectal cancer has advantages to traditional regimen

By Robyn Boyle, RPh, for MDLinx
Published April 27, 2018

Key Takeaways

A study published in JAMA Oncology states that total neoadjuvant therapy (TNT) consisting of chemotherapy with chemoradiation (chemoRT) prior to surgery for locally advanced rectal cancer (LARC) had advantages over a traditional regimen of chemoRT and postoperative adjuvant chemotherapy.

To add support to the current National Comprehensive Cancer Network (NCCN) guidelines, which categorize TNT as a viable treatment strategy for rectal cancer, Andrea Cercek, MD, from Memorial Sloan Kettering Cancer Center in New York, NY, and colleagues, compared TNT to the traditional approach in LARC patients. Tolerance to therapy, tumor response, and short-term outcomes were evaluated.

The retrospective cohort analysis used electronic records to identify patients with T3/4 or node-positive LARC treated at a colorectal surgical oncology clinic. Among 811 patients identified, 320 received chemoRT with planned adjuvant chemotherapy and 308 received TNT (induction fluorouracil- and oxaliplatin-based chemotherapy followed by chemoRT).

Following neoadjuvant therapy, surgery was performed. Patients who chose to forgo rectal resection and elected nonoperative treatment were placed under close observation. Treatment and outcome data for the two cohorts were compared.

Outcomes included pathologic complete response (pCR), defined as absence of viable tumor cells in the resection; and clinical complete response (cCR), defined as the proportion of patients who had pCR after surgery or sustained cCR for ≥12 months while under nonoperative surveillance.

Of the 628 patients overall, 59% were men and 41% were women, which was similar to the chemoRT cohort. In the TNT cohort, men and women were equally split; the mean age of the patients overall was 56.7 years.

Patients in the TNT cohort received greater percentages of the planned oxaliplatin and fluorouracil prescribed doses than those in the chemoRT with planned adjuvant chemotherapy cohort.

The complete response (CR) rate was 36% in the TNT cohort compared with 21% in the chemoRT with planned adjuvant chemotherapy cohort. This included both pCR in those who underwent surgery and sustained cCR for at least 12 months posttreatment in those who did not undergo surgery.

During the study period, staging and treatment of LARC evolved by switching from endorectal ultrasound (ERUS) to MRI for local staging, increased use of TNT, and lengthening of the interval between chemoRT and surgery.

In patients who had surgery within 12 months, median time to surgery following neoadjuvant therapy was longer in the TNT group (56 days vs 63 days, P < 0.002).

Furthermore, a higher proportion of patients in the TNT cohort did not undergo surgery within 12 months (24% vs 8%; P  <  0.001), and minimally invasive surgery was more common in the TNT cohort compared to the chemoRT with planned adjuvant chemotherapy cohort (72% vs 47%; P < 0.001).

For patients treated at the study site with complete dosing information available, a separate analysis assessed prescribed and received doses. Patients in the TNT cohort received greater percentages of the planned oxaliplatin and fluorouracil prescribed dose with fewer dose reductions than those in the chemoRT with planned adjuvant chemotherapy cohort.

The percentage of patients with sustained cCR who were treated nonoperatively beyond 12 months was 6% in the chemoRT with planned adjuvant chemotherapy group, and 22% in the TNT group.

With 24-months of follow-up, 27 of 31 patients in the TNT group and 10 of 11 patients in the chemoRT with planned adjuvant chemotherapy group had a durable cCR.

The researchers wrote that the study was limited by its retrospective design, as there are potentially important differences between the groups that may have confounded results. Furthermore, with limited follow-up, it is not known whether TNT, which optimizes dosing of systemic chemotherapy, improves disease-free survival.

“Total neoadjuvant therapy was associated with improved delivery of systemic therapy and increased response to treatment, and it provides a promising platform for nonoperative watch-and-wait protocols,” the authors concluded.

To read more about this study, click here

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