Mucinous rectal adenocarcinoma and neoadjuvant therapy: Implications for surgical practice

Table 1 Evidence on the neoadjuvant response in mucinous rectal adenocarcinoma

Ref.	Design	Population	Key findings
Huang et al[3], 2021	Meta-analysis (15 studies)	> 9000 patients	MAC associated with OR 0.38 for pCR and 0.31 for tumor downstaging vs non-MAC
Zhang et al[18], 2021	Pooled analysis of 3 prospective trials	743 patients (8.5% MAC)	pCR: 7.5% in MAC vs 22.0% non-MAC; yp stage 0-I: 20.8% vs 48.7%; DFS 3-year: 58.4% vs 77.6%
McCawley et al[23], 2016	Meta-analysis	Multiple datasets	Higher CRM positivity (OR 5.02) and mortality (OR 1.53) in MAC
Yu et al[56], 2014	MRI-based prognostic study	Retrospective cohort	Poor radiologic regression; acellular mucin mimics residual tumor on MRI

Summary of key studies evaluating the pathological complete response (pCR), tumor downstaging, margin status, and imaging findings in mucinous adenocarcinoma (MAC) compared with non-MAC. Data highlighted consistent reductions in pCR and downstaging rates for MAC, higher rates of circumferential resection margin (CRM) involvement, and challenges in radiologic assessment due to acellular mucin mimicking residual tumor. DFS: Disease-free survival; MRI: Magnetic resonance imaging; OR: Odd ratio.

Table 2 Comparison of the four trials using total neoadjuvant therapy in the study arm

Study name	Primary endpoints	TNT arm	Control arm	pCR (%) study	pCR (%) control	DFS (months) study	DFS (months) control
PRODIGE23	3-year DFS	CTX/CRT/TME	CRT/TME	28	12	76	69
RAPIDO	3-year DRTF	SCRT/CTX/TME	CTX/CRT/TME	28	14	23.7	30.4
OPRA	DFS	CTX/CRT/TME	CRT/CTX/TME	NA	NA	76	76
STELLAR	DFS	SCRT/CTX/TME	CRT/TME	17.2	13.9	64.3	62.3

CRT: Long-course chemoradiotherapy; CTX: Chemotherapy; DFS: Disease-free survival; DRTF: Disease-related treatment failure; NA: Not available; pCR: Pathologic complete response; SCRT: Short-course radiotherapy; TME: Total mesorectal excision; TNT: Total neoadjuvant therapy.

Table 3 Impact of mucinous histology on surgical complexity and outcomes

Ref.	Surgical parameter	MAC	Non-MAC
Hugen et al[2], 2014; Lan et al[7], 2021	Mean tumor size (cm)	5.2-6.8	3.5-4.5
McCawley et al[23], 2016; Hugen et al[2], 2014	CRM positivity rate (%)	14-28	6-11
Hugen et al[2], 2014; Lan et al[7], 2021	Rate of T4 disease at presentation (%)	26-33	10-17
Lohsiriwat and Lohsiriwat[41], 2008; de Nes et al[39], 2021	Multivisceral resection requirement (%)	12-18	4-7
Lohsiriwat and Lohsiriwat[41], 2008	Mean operative time for extended resections (minute)	274 ± 73	157 ± 62
Lohsiriwat and Lohsiriwat[41], 2008	Median blood loss for extended resections (mL)	769 ± 549	203 ± 136
Pelvex Collaborative[40], 2019	Major complication rate (Clavien-Dindo ≥ III, %)	38%	NA
Pelvex Collaborative[40], 2019; Hendrick et al[38], 2025	R0 resection rate in extended resections (%)	~ 72	~ 88

Summary of comparative surgical parameters for mucinous adenocarcinoma (MAC) and non-MAC. Data include tumor size, frequency of T4 disease, rates of circumferential resection margin (CRM) positivity, requirement for multivisceral resection, operative time, blood loss, complication rates, and R0 (no residual disease at surgery) resection rates in extended resections. Figures are derived from comparative observational series and meta-analyses within populations with locally advanced rectal cancer. NA: Not available.

Table 4 Postoperative outcomes and recurrence patterns in mucinous rectal tumors

Ref.	Outcome	MAC	Non-MAC
Hugen et al[2], 2014; McCawley et al[23], 2016	3-year local recurrence rate (%)	14-26	4-8
Hugen et al[2], 2014; Lan et al[7], 2021	3-year disease-free survival (%)	58-64	76-82
Hugen et al[2], 2014; Lan et al[7], 2021	Common metastatic sites	Peritoneum, lung	Liver
McCawley et al[23], 2016; Hugen et al[2], 2014	Median time to recurrence (months)	13-16	18-21
Hugen et al[2], 2014	Recurrence with peritoneal carcinomatosis (%)	20-28	< 10

MAC: Mucinous adenocarcinoma.