Tumor-node response heterogeneity: Exploring the “spatial biology” of neoadjuvant therapy response in rectal cancer and its clinical implications

Table 1 Representative prospective studies in spatial biology and precision oncology for colorectal cancer

Ref.	Phase	Population	Strategy	Endpoint	Status
Yao[38]	Prospective	LARC post-nCRT	ctDNA-guided adjuvant therapy decision	2-year DFS	Recruiting
University of Florida[39]	Phase II	ERC	Post-TNT ctDNA-guided watchful waiting vs surgery	Organ preservation rate	Recruiting
Mögele et al[37]	Prospective	LARC	ctDNA for prediction of pCR after nCRT	pCR prediction accuracy	Completed
Song et al[45]	Phase II	MSS ERC	Node-sparing short-course RT + CAPOX + PD-1/CTLA-4	pCR rate	Completed
Song et al[45]	Phase III	MSS LARC	Node-sparing short-course RT + CAPOX + tislelizumab vs CRT	3-year DFS	Completed
Bando et al[42]	Phase II	LARC	nCRT + nivolumab	pCR rate	Completed
Mo et al[51]	Prospective	Stage II-III CRC	ctDNA-MRD detection for recurrence risk stratification	2-year RFS	Completed
Tie et al[35] and Tie et al[36]	Phase II/III	LARC	ctDNA-guided adjuvant therapy de-escalation	Non-inferiority in RFS	Ongoing

LARC: Locally advanced rectal cancer; nCRT: Neoadjuvant chemoradiotherapy; ctDNA: Circulating tumor DNA; DFS: Disease-free survival; ERC: Early rectal cancer; TNT: Total neoadjuvant therapy; pCR: Pathological complete response; MSS: Microsatellite stable; RT: Radiotherapy; CAPOX: Capecitabine and oxaliplatin; PD-1: Programmed cell death protein 1; CTLA-4: Cytotoxic T-lymphocyte-associated protein 4; CRT: Chemoradiotherapy; CRC: Colorectal cancer; MRD: Minimal residual disease; RFS: Recurrence-free survival.