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Total Neoadjuvant Therapy vs Standard Therapy for Locally Advanced Rectal Cancer


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In a systematic review and meta-analysis reported in JAMA Network Open, Kasi et al found that total neoadjuvant therapy was associated with improved pathologic complete response rates vs standard therapy with neoadjuvant concurrent chemoradiotherapy plus adjuvant chemotherapy in patients with locally advanced rectal cancer.

As stated by the investigators, “Standard therapy for locally advanced rectal cancer includes concurrent chemoradiotherapy followed by surgery and adjuvant chemotherapy (CRT plus A). An alternative strategy known as total neoadjuvant therapy involves administration of CRT plus neoadjuvant chemotherapy before surgery with the goal of delivering uninterrupted systemic therapy to eradicate micrometastases.”

“The findings of this systematic review and meta-analysis suggest that total neoadjuvant therapy is a promising strategy in locally advanced rectal cancer, with superior rates of pathologic complete response compared with standard therapy.”
— Kasi et al

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Study Details

The meta-analysis included seven studies identified through July 2020, all from Europe or the United States, that compared total neoadjuvant therapy vs CRT plus A. The total population consisted of 2,416 unique patients, including 1,206 who received total neoadjuvant therapy.

The outcomes of interest were pathologic complete response, disease-free and overall survival, sphincter-preserving surgery, and need for ileostomy. A random-effects model based on an inverse-variance method was used for the meta-analysis.

Key Findings

Data on pathologic complete response were available from all studies. The pooled prevalence of pathologic complete response was 29.9% (range = 17.2%–38.5%) in the total neoadjuvant therapy group vs 14.9% (range = 4.2%–21.3%) in the CRT plus A group (odds ratio [OR] = 2.44, 95% confidence interval [CI] =1.99–2.98; I2 = 0%).

Data on disease-free survival were available from three studies. On pooled analysis, total neoadjuvant therapy was associated with improved disease-free survival (OR = 2.07, 95% CI =1.20–3.56; I2 = 49%). Overall survival was not consistently reported among studies.

Data on sphincter-preserving surgery were available from four studies. No significant difference was found between total neoadjuvant therapy vs CRT plus A (OR = 1.06, 95% CI = 0.73–1.54; I2 = 0%).

Data on ileostomy were available from two studies. No significant difference was found between total neoadjuvant therapy vs CRT plus A (OR= 1.05, 95% CI = 0.76–1.46; I2 = 0%).

The investigators concluded, “The findings of this systematic review and meta-analysis suggest that total neoadjuvant therapy is a promising strategy in locally advanced rectal cancer, with superior rates of pathologic complete response compared with standard therapy. However, the long-term effect on disease recurrence and overall survival needs to be explored in future studies.”

Anup Kasi, MD, MPH, of the Division of Medical Oncology, Department of Medicine, University of Kansas Medical Center, is the corresponding author for the JAMA Network Open article.

Disclosure: For full disclosures of the study authors, visit jamanetwork.com.

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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