Neoadjuvant CAPOX chemotherapy alone showed comparable survival to chemoradiotherapy in locally advanced rectal cancer with uninvolved mesorectal fascia.

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Journal of clinical oncology : official journal of the American Society of Clinical Oncology Published April 13, 2026 Medically reviewed April 25, 2026 Study authors: Mei Wei-Jian, Wang Xiao-Zhong, Zhang Xuan, Sun Yue-Ming, Yang Chun-Kang, Lin Jun-Zhong, Wu Zu-Guang,… PubMed ↗ DOI ↗ By Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

Key Takeaway

Consider neoadjuvant CAPOX alone for selected patients, noting comparable survival but unconfirmed non-inferiority for locoregional control.

This Phase III randomized controlled trial evaluated neoadjuvant treatment strategies for locally advanced rectal cancer within 12 cm from the anal verge with uninvolved mesorectal fascia. The study enrolled 589 patients randomized to receive either 4 cycles of CAPOX chemotherapy alone (nCT, n=300) or chemoradiotherapy with concurrent capecitabine (nCRT, n=289). Median follow-up was 48 months.

Primary and secondary outcomes assessed 3-year locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), overall survival (OS), and adverse events. The 3-year LRRFS was 97.4% in the nCRT group versus 96.3% in the nCT group (HR 1.40; 95% CI, 0.53 to 3.68). For 3-year DFS, rates were 89.2% in the nCT group versus 87.9% in the nCRT group (HR 0.88; 95% CI, 0.54 to 1.44). The 3-year OS was 95.0% in the nCT group versus 94.1% in the nCRT group (HR 0.86; 95% CI, 0.42 to 1.76).

Regarding safety, the nCT group demonstrated a lower incidence of grade 2 to 4 long-term adverse events (16.0% vs 26.3%) and proctitis (33.6% vs 41.7%) compared with the nCRT group. The study did not report serious adverse events or discontinuations.

A key limitation is that non-inferiority for LRRFS was not confirmed, largely because local recurrence rates were very low in both groups, rendering the confidence interval wide and inconclusive. While the nCT arm offered a mitigation of toxicity burden, the lack of statistical confirmation for non-inferiority in locoregional control warrants caution before adopting chemotherapy alone as a standard alternative to chemoradiotherapy for this specific population.

Study Details

Study typeRct

Sample sizen = 300

EvidenceLevel 2

Follow-up36.0 mo

PublishedApr 2026

PMID41712876

View Original Abstract ↓

PURPOSE: The neoadjuvant chemoradiotherapy (nCRT) might accentuate surgical complications and toxicity in the treatment of locally advanced rectal cancer (LARC) while neoadjuvant chemotherapy (nCT) alone shows promise as an alternative treatment. However, which patients deserve most from the nCT need further clarify. This trial aimed to assess the non-inferiority of nCT with capecitabine plus oxaliplatin (CAPOX) versus nCRT with capecitabine in LARC with uninvolved mesorectal fascia (MRF). METHODS: Patients with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to receive 4 cycles of CAPOX chemotherapy alone (nCT group) or CRT with concurrent Capecitabine (nCRT group). The primary end point is 3-year locoregional recurrence-free survival (LRRFS). Secondary end points, such as 3-year disease-free survival (DFS), 3-year overall survival (OS), and adverse events (AEs), were also reported. RESULTS: A total of 663 patients were enrolled and 589 patients received the allocated treatment (nCT, n = 300; nCRT, n = 289). LRRFS was analyzed with a median follow-up of 48 months. 3-year LRRFS was 97.4% (95% CI, 95.5 to 99.3) in the nCRT group and 96.3% (95% CI, 94.0 to 98.6) in the nCT group, resulting in a hazard ratio (HR) of 1.40 (95% CI, 0.53 to 3.68). The nCT and nCRT achieved similar 3-year DFS (89.2% 87.9%; HR, 0.88 [95% CI, 0.54 to 1.44]) and 3-year OS (95.0% 94.1%; HR, 0.86 [95% CI, 0.42 to 1.76]). The nCT group showed a lower incidence of grade 2 to 4 long-term AEs (16.0% 26.3%, = 0.002) and proctitis (33.6% 41.7%, = 0.049) compared with nCRT group. CONCLUSIONS: The non-inferiority of nCT was not confirmed with a very low incidence of local recurrence in both group. But nCT offers comparable DFS and OS while mitigating the burden of toxicity as compared to nCRT. These insights shed light on a potential paradigm shift in the treatment for LARC with uninvolved MRF.

Neoadjuvant CAPOX chemotherapy alone showed comparable survival to chemoradiotherapy in locally advanced rectal cancer with uninvolved mesorectal fascia.

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Neoadjuvant CAPOX chemotherapy alone showed comparable survival to chemoradiotherapy in locally advanced rectal cancer with uninvolved mesorectal fascia.

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