Total Neoadjuvant Therapy Improves Rates of Pathological Complete Response in Rectal Cancer

Research published in JAMA Network Open found that total neoadjuvant therapy enhanced pathological complete response rates for patients with locally advanced rectal cancer.

Compared with concurrent chemoradiotherapy followed by surgery and adjuvant chemotherapy (CRT plus A), total neoadjuvant therapy for patients with locally advanced rectal cancer was associated with better pathological complete response (PCR) rates and a potential advantage for disease-free survival (DFS), according to data published in JAMA Network Open.

While the data suggest total neoadjuvant therapy is a promising strategy, the long-term effects this treatment has on disease recurrence and overall survival rates need further exploration.

“Total neoadjuvant therapy appears to be a promising treatment strategy that has been reported in several trials,” wrote the investigators who were led by Anup Kasi, MD, MPH. “Total neoadjuvant therapy enhances one’s chances of attaining a PCR, which traditionally has been shown to correspond to higher overall and disease-free survival. Our meta-analysis suggests an improved disease-free survival, although the true effect of (total neoadjuvant therapy) on overall and disease-free survival is unclear and requires further evaluation in a prospective randomized manner.”

Overall, the use of total neoadjuvant therapy was associated with an increased chance of achieving PCR (odds ratio [OR], 2.44; 95% CI, 1.99-2.98) for patients with locally advanced rectal cancer. Pooled prevalence of PCR was recorded at 29.9% (range, 17.2%-38.5%) for patients in the total neoadjuvant therapy group and 14.9% (range, 4.2%-21.3%) for those in the CRT-plus-A group.

The investigators did not find a statistically significant difference for the proportion of sphincter-preserving surgery (OR, 1.06; 95% CI, 0.73-1.54) or ileostomy (OR, 1.05; 95% CI, 0.76-1.46) between the total neoadjuvant therapy and CRT-plus-A groups.

Only 3 out of 7 total studies examined data on DFS. A pooled analysis of these results showed that patients undergoing total neoadjuvant therapy saw significantly higher odds of improved DFS (OR, 2.07; 95% CI, 1.20-3.56; I2 = 49%).

This systematic review and meta-analysis examined 2416 patients from 7 unique studies in which 1206 patients received total neoadjuvant therapy. Median age for patients receiving total neoadjuvant therapy ranged from 57 to 69 years, with 58% to 73% of patients being male.

“The pooled analysis demonstrated a significantly higher chance of achieving a PCR as well as improved disease-free survival [with total neoadjuvant therapy],” wrote the investigators. “Surgical outcomes, including rates of sphincter-preserving surgery and ileostomy, did not significantly differ among the 2 populations.”

The investigators explained that a significant limitation of the data is that none of the end points were consistently reported across the 7 unique studies analyzed. Specifically, while all 7 included PCR, only 4 studies reported the rates of sphincter-preserving surgery, 2 reported specific ileostomy requirements, and 3 reported DFS.

Moreover, there was not enough data to accurately calculate a pooled overall survival rate for patients across the 7 studies. Therefore, the investigators were limited by the data they could report in their systematic review and meta-analysis.

“Total neoadjuvant therapy theoretically offers multiple surgical advantages, such as improved odds of receiving a sphincter-sparing surgery and lower odds of requiring an ileostomy; however, neither of these outcomes was evident in our meta-analysis, suggesting that the benefit is primarily in disease control and decreased recurrence rates,” the investigators concluded.


Kasi A, Abbasi S, Handa S, et al. Total neoadjuvant therapy vs standard therapy in locally advanced rectal cancer. JAMA Network Open. 2020;3(12):e2030097. doi:10.1001/jamanetworkopen.2020.30097.