Junyang Lu

PURPOSE: High-risk locally advanced rectal cancer (LARC) carries a substantial risk of distant recurrence, which limits disease-free survival (DFS). We compared total neoadjuvant therapy (TNT) integrating long-course radiotherapy (LCRT) with uninterrupted doublet chemotherapy (doublet-LC TNT) versus conventional neoadjuvant chemoradiotherapy (nCRT). METHODS: In this multicenter, randomized, phase III trial, patients with stage II/III LARC and at least 1 high-risk feature (cT4a-b, cN2, mesorectal fascia involvement, or cT3c-d with extramural vascular invasion) were enrolled. Patients were assigned to doublet-LC TNT (induction, concurrent, and consolidation capecitabine plus oxaliplatin with LCRT) before surgery or nCRT (capecitabine with LCRT) followed by surgery and adjuvant chemotherapy. The primary end point was DFS (ClinicalTrials.gov identifier: NCT03177382 ). RESULTS: Between June 6, 2017, and December 27, 2023, 458 patients were randomly assigned to doublet-LC TNT (n = 232) or nCRT (n = 226). At a median follow-up of 51 months, doublet-LC TNT improved 3-year DFS (74.8% v 66.0%; hazard ratio [HR], 0.674 [95% CI, 0.489 to 0.929]; P = .016). Metastasis-free survival (MFS; 77.7% v 67.6%; HR, 0.655 [95% CI, 0.469 to 0.915]) and pathologic complete response rates (pCR; 26.37% v 9.80%; P < .001) were higher with doublet-LC TNT, whereas locoregional failure remained low and comparable (6.03% v 6.19%; P = .943). Although grade ≥3 adverse events during the neoadjuvant phase were more frequent with doublet-LC TNT (27.59% v 8.56%; P < .001), severe toxicities during the entire treatment course (28.02% v 24.32%; P = .371) and major postoperative complications (3.98% v 2.94%; P = .567) were comparable. CONCLUSION: Compared with conventional nCRT, doublet-LC TNT improved DFS, MFS, and pCR rates with manageable toxicity. These findings support this intensified, doublet-based regimen as a standard option within the modern TNT paradigm. Further comparative studies are warranted to evaluate these results against other short-course radiotherapy‑based or nondoublet-concurrent TNT regimens.

Locally advanced rectal cancer (LARC) staged as mrT3 could be further subdivided into mrT3a to T3d based on depth of tumor invasion through the muscularis propria. Limited evidence exists to compare the differences across subgroups. Clinical data from patients between January 2018 and 2022 were collected. The study included patients with mrT3 LARC who received neoadjuvant chemoradiotherapy (NCRT). Based on depth of invasion through muscularis propria, patients were categorized into three groups: mrT3a (< 5 mm), mrT3b (5~10 mm), mrT3c~d group (> 10 mm). The outcomes were disease-free survival (DFS), pathological complete response (pCR), tumor recurrence and metastasis. A total of 295 patients were identified, including 65 (22.0%) in mrT3a, 155 (52.5%) in mrT3b, and 75 (25.5%) in mrT3c~d group. The tumor vertical diameter was larger in mrT3c/d group (46.3 ± 13.7 mm), compared to mrT3a (39.4 ± 14.3 mm) and mrT3b (39.8 ± 12.1 mm) groups (P < 0.001). The positive rates of mesorectal fascia (61.3% vs. 30.3% vs. 7.7%, P < 0.001) and extramural vascular invasion (62.7% vs. 40.0% vs. 27.7%, P < 0.001) were significantly higher in mrT3c/d group compared to mrT3a and mrT3b groups. The estimated pCR rates were 33.9% for mrT3a, 32.3% for mrT3b, and 21.3% for mrT3c/d group (P = 0.172). The median follow-up time was 43 (29-58) months. The metastasis and local recurrence rates were 8.8% and 2.4%. The 3y-DFS rates were 92.2% for mrT3a, 87.7% for mrT3b, and 86.2% for mrT3c/d (P = 0.549). Despite mrT3c/d patients presenting with more aggressive baseline features, standardized NCRT followed by radical surgery effectively mitigated survival disparities across mrT3 substages. These findings suggest that mrT3 subclassification may not independently predict long-term survival outcomes when patients receive optimal multimodal therapy.

Purpose To evaluate the predictive value of MRI-determined variables for pathological complete response (pCR) in locally advanced rectal cancer (LARC) patients following neoadjuvant chemoradiotherapy (NCRT). Methods Clinical data were collected from patients who received NCRT between January 2019 and 2022. Patients with rectal adenocarcinoma, cT3-4N0, or TanyN1-2 were included. pCR was defined pT0N0. Patients were divided into pCR and non-pCR group. Logistic regression analysis was performed to identify factors associated with pCR. A nomogram model was constructed to validate its predictive ability and accuracy. Results A total of 585 patients were identified, with 144 (24.6%) in the pCR group and 441 (75.4%) in the non-pCR group. Patients with mrT2-3 (OR 6.41, P < 0.001), mrN0 (OR 2.17, P < 0.001), circumferential occupation range < 1/2 cycles (OR 2.11, P < 0.001), tumor vertical diameter < 36 mm (OR 2.10, P < 0.001), negative mesorectal fascia (OR 3.21, P < 0.001), and extramural vascular invasion (OR 5.68, P < 0.001) were more likely to achieve higher pCR rates. Logistic regression analysis revealed that mrT2-3 (OR 3.50, P < 0.001), tumor vertical diameter < 36 mm (OR 2.57, P < 0.001), and negative extramural vascular invasion (OR 4.03, P < 0.001) were independent protective factors for pCR. A nomogram was developed to predict pCR, achieving a C-index of 0.778. Conclusion Patients with mrT2-3, tumor vertical diameter < 36 mm, and negative extramural vascular invasion are more likely to achieve pCR after NCRT.

PURPOSE: Complete mesocolic excision (CME) is being increasingly used for the treatment of right-sided colon cancer, although there is still no strong evidence that CME provides better long-term oncological outcomes than D2 dissection. The controversy is mainly regarding the survival benefit from extended lymph node dissection emphasized by CME. METHODS: This multicenter, open-label, randomized controlled trial (ClinicalTrials.gov identifier: NCT02619942 ) was performed across 17 hospitals in China. Patients diagnosed with stage T2-T4aNanyM0 or TanyN + M0 right-sided colon cancer were randomly assigned (1:1) to undergo either CME or D2 dissection during laparoscopic right colectomy. The primary outcome was the 3-year disease-free survival (DFS), and the main secondary outcome was the 3-year overall survival (OS). RESULTS: Between January 11, 2016, and December 26, 2019, 1,072 patients were randomly assigned (536 patients to CME and 536 patients to D2 dissection). In total, 995 patients (median age 61 years, 59% male) were included in the primary analysis (CME [n = 495] v D2 dissection [n = 500]). No significant differences were found between the groups in 3-year DFS (hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.02]; P = .06; 86.1% in the CME group v 81.9% in the D2 group) or in 3-year OS (HR, 0.70 [95% CI, 0.43 to 1.16]; P = .17; 94.7% in the CME group v 92.6% in the D2 group). CONCLUSION: This trial failed to find evidence of superior DFS outcome for CME compared with standard D2 lymph node dissection in primary surgical excision of right-sided colon cancer. Standard D2 dissection should be the routine procedure for these patients. CME should only be considered in patients with obvious mesocolic lymph node involvement.