Impacts of neoadjuvant therapy on subsequent surgical difficulty, safety, and outcomes in locally advanced rectal cancer: a narrative review.

BACKGROUND AND OBJECTIVE: Locally advanced rectal cancer (LARC) is standardly treated with neoadjuvant therapy, but clinical concerns regarding its adverse impacts on subsequent surgery have led to poor guideline adherence worldwide. This review systematically synthesized literature to evaluate the effects of neoadjuvant therapy on surgical difficulty, procedural outcomes, postoperative complications, and surgery-related oncological outcomes. METHODS: A thorough search of PubMed and Web of Science was performed for literature published from January 2000 to February 2026. Clinical trials, real-world studies, meta-analyses, systematic reviews, and other review articles related to locally advanced rectal cancer, neoadjuvant therapy, and surgery were examined. KEY CONTENT AND FINDINGS: Neoadjuvant chemoradiotherapy (NACRT) was not associated with significant adverse effects on subsequent surgery compared with upfront surgery (UFS), and improved sphincter-preservation rates via tumor downstaging, especially for patients with low rectal cancer. Advances in minimally invasive surgery may further improve surgical outcomes after NACRT. Additionally, different radiotherapy modalities, prolonged intervals between radiotherapy completion and surgery, intensified chemotherapy regimens, and immunotherapy combinations did not significantly increase surgical burden or major perioperative complications, with some regimens even improving oncological outcomes. CONCLUSIONS: Neoadjuvant therapy is surgically safe for LARC without increasing perioperative risks, although the impact of radiotherapy remains somewhat controversial. The long-term oncologic outcomes and subgroup-specific effects of neoadjuvant therapy combined with surgery require further high-quality evidence.