Watch-and-Wait strategy for locally advanced rectal cancer after neoadjuvant chemoradiotherapy: a comprehensive review

The conventional treatment for locally advanced rectal cancer (LARC) primarily involves neoadjuvant chemoradiotherapy (nCRT) combined with total mesorectal excision (TME). However, surgery-related complications and long-term functional impairments can significantly compromise patients' quality of life. The watch-and-wait (W&W) strategy has emerged as a non-surgical alternative for patients achieving a clinical complete response (cCR), with advantages in organ preservation. Its safety and efficacy have been validated by multiple clinical studies. Literature retrieval was performed in PubMed (2020-2025), including reviews, RCTs/cohort studies on LARC W&W and cCR/pCR. This comprehensive review summarizes the clinical evidence, patient selection criteria, efficacy assessment methods, challenges, and future directions of the W&W strategy. Based on the latest research, when strictly selecting cCR patients (especially those with sustained cCR after neoadjuvant therapy), the 5-year disease-free survival (DFS) rate of the W&W strategy is comparable to that of the surgical group (70%-85%), with a local regrowth rate of approximately 20%-30%, which can mostly be controlled by salvage surgery. The combination of magnetic resonance imaging (MRI) and circulating tumor DNA (ctDNA) analysis significantly improves the accuracy of cCR assessment. Furthermore, integrating immunotherapy with total neoadjuvant therapy (TNT) has expanded the eligible population for the W&W strategy. This review also highlights current limitations of the W&W strategy, such as the lack of standardized assessment procedures, validated biomarkers, and long-term follow-up data. It proposes that future efforts should focus on multi-center randomized controlled trials and artificial intelligence-assisted assessment models to promote the advancement of the W&W strategy toward precision and standardization.