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

**Authors:** Peng Huang, Xiaoyue Zhao, Huanhuan Fei, Linzhu Zhang, Xiaofan Liu, Yongjun Yu, Rong Wu, Fei Fei

PMC · DOI: 10.3389/fonc.2026.1760042 · Frontiers in Oncology · 2026-02-19

## TL;DR

This paper reviews the watch-and-wait strategy for rectal cancer patients who achieve a complete response after treatment, showing it can be as effective as surgery while preserving organ function.

## Contribution

The paper provides a comprehensive review of the latest evidence and challenges in the watch-and-wait strategy for rectal cancer.

## Key findings

- The 5-year disease-free survival rate for the watch-and-wait strategy is comparable to surgery (70%-85%).
- MRI and ctDNA analysis improve the accuracy of assessing complete response in patients.
- Combining immunotherapy with total neoadjuvant therapy expands eligibility for the watch-and-wait approach.

## Abstract

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.

## Linked entities

- **Diseases:** rectal cancer (MONDO:0006519)

## Full-text entities

- **Genes:** ATM (ATM serine/threonine kinase) [NCBI Gene 472] {aka AT1, ATA, ATC, ATD, ATDC, ATE}, SPATA2 (spermatogenesis associated 2) [NCBI Gene 9825] {aka PD1, PPP1R145, tamo}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, CEACAM3 (CEA cell adhesion molecule 3) [NCBI Gene 1084] {aka CD66D, CEA, CGM1, CGM1a, W264, W282}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, AKT2 (AKT serine/threonine kinase 2) [NCBI Gene 208] {aka HIHGHH, PKBB, PKBBETA, PRKBB, RAC-BETA}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) [NCBI Gene 5290] {aka CCM4, CLAPO, CLOVE, CWS5, HMH, MCAP}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}, ATR (ATR checkpoint kinase) [NCBI Gene 545] {aka FCTCS, FRP1, MEC1, SCKL, SCKL1}, RAD50 (RAD50 double strand break repair protein) [NCBI Gene 10111] {aka NBSLD, RAD502, hRad50}, mucin [NCBI Gene 100508689]
- **Diseases:** Inflammatory (MESH:D007249), nodal disease (MESH:D004194), metastasis (MESH:D009362), telangiectasia (MESH:D013684), fibrosis (MESH:D005355), hematological and gastrointestinal reactions (MESH:D006402), CRC (MESH:D015179), DRFS (MESH:D011475), nICI (MESH:D054179), TNT (MESH:D016609), Cancer (MESH:D009369), LRFS (MESH:D009364), anastomotic leakage (MESH:D057868), rectal masses (MESH:D012002), microsatellite instability (MESH:D053842), dMMR (MESH:C536928), LARC (MESH:D012004), ulcers (MESH:D014456), LLN (MESH:D000072717), PR (MESH:D008151), pCR (MESH:D005598), CWWD (MESH:C562377), colorectal carcinogenesis (MESH:D063646), urinary, sexual, and anal sphincter dysfunction (MESH:C538254), strictures (MESH:D003251), MSI-H (MESH:D000848), necrosis (MESH:D009336), IWWD (MESH:D000082122), CR (MESH:D001766), EMVI (MESH:D009361)
- **Chemicals:** paraffin (MESH:D010232), AIO-16 (-), Camrelizumab (MESH:C000631724), formalin (MESH:D005557)
- **Species:** Homo sapiens (human, species) [taxon 9606], HF [taxon 2008765]
- **Mutations:** c.5890A>G, rs8100018, rs12569998

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## References

70 references — full list in the complete paper: https://tomesphere.com/paper/PMC12960087/full.md

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Source: https://tomesphere.com/paper/PMC12960087