Prioritizing Chemotherapy in Total Neoadjuvant Therapy Improves pCR Rate in Locally Advanced Rectal Cancer in...

Area of Science:

• Oncology
• Clinical Trials
• Gastrointestinal Surgery

Background:

• Neoadjuvant chemoradiotherapy (NCRT) for locally advanced rectal cancer (LARC) faces delays in resource-limited settings due to radiotherapy access.
• Total neoadjuvant therapy (TNT), initiating with chemotherapy, presents a potential alternative to overcome these limitations.

Purpose of the Study:

• To compare the efficacy and safety of TNT versus the conventional NCRT-first approach in patients with LARC.
• To evaluate pathological complete response (pCR) as the primary endpoint.

Main Methods:

• A randomized trial involving 202 LARC patients, allocated to either TNT (chemotherapy followed by NCRT, then surgery) or conventional treatment (NCRT followed by adjuvant chemotherapy and surgery).
• Primary endpoint: pCR. Secondary endpoints: treatment-related toxicity and overall survival (OS).

Main Results:

• TNT demonstrated a significantly higher pCR rate (55.4%) compared to the conventional group (42.57%, p=0.023).
• Thrombocytopenia was less frequent with TNT (5.0% vs. 12.87%, p=0.048), while dysuria was more common (15.8% vs. 5.94%, p=0.024).
• Sphincter preservation, resection margins, surgical complications, and OS did not significantly differ between groups at the time of analysis.

Conclusions:

• TNT is a feasible and well-tolerated treatment strategy for LARC, particularly beneficial in settings with radiotherapy access challenges.
• The observed improvement in pCR suggests potential oncologic benefits, but longer follow-up is needed to confirm survival outcomes.