Neoadjuvant therapy before surgical treatment.

Area of Science:

• Oncology
• Surgical Oncology
• Gastrointestinal Cancer Research

Background:

• Preoperative radiotherapy for rectal cancer reduces local recurrence but has minimal impact on overall survival.
• Total mesorectal excision (TME) surgery achieves low local recurrence rates, making metastatic disease the primary concern.
• Neoadjuvant chemotherapy (NACT) is a potential strategy to address metastatic rectal cancer.

Purpose of the Study:

• To evaluate neoadjuvant chemotherapy (NACT) as an alternative or addition to preoperative radiotherapy for rectal cancer.
• To explore novel treatment strategies beyond standard chemoradiotherapy (CRT) for improving outcomes in rectal cancer.
• To assess the efficacy and safety of integrating chemotherapy with or without radiotherapy in the preoperative setting.

Main Methods:

• Review of randomized phase III trials evaluating neoadjuvant chemotherapy and chemoradiotherapy in rectal cancer.
• Analysis of studies integrating biologically targeted agents with preoperative chemoradiotherapy (CRT).
• Exploration of alternative neoadjuvant strategies including induction NACT and consolidation chemotherapy.

Main Results:

• Addition of oxaliplatin to fluoropyrimidine-based CRT has shown limited benefits, with notable exceptions like the German CAO/ARO/AIO-04 study.
• Biologically targeted agents (cetuximab, bevacizumab) integrated into preoperative CRT have not met expectations, with some raising safety concerns.
• Alternative NACT strategies, including induction or consolidation chemotherapy, are being considered to improve treatment efficacy.

Conclusions:

• Current neoadjuvant treatment strategies for rectal cancer, including CRT with added agents, show limited improvement in pathological response and survival.
• Metastatic disease remains a significant challenge, driving the investigation of NACT as a primary or adjuvant therapy.
• Further research is needed to optimize neoadjuvant chemotherapy sequencing and combinations for improved rectal cancer outcomes.