Background It remains unclear whether extended lymphadenectomy provides oncological advantages in colorectal cancer. This multicentre RCT aimed to address this issue. Methods Patients with resectable primary colonic cancer were enrolled in four hospitals registered in the COLD trial, and randomized to D2 or D3 dissection in a 1 : 1 ratio. Data were analysed to assess the safety of D3 dissection. Results The study included the first 100 patients randomized in this ongoing trial. Ninety‐nine patients were included in the intention‐to‐treat (ITT) analysis (43 D2, 56 D3). Ninety‐two patients received the allocated treatment and were included in the per‐protocol (PP) analysis: 39 of 43 in the D2 group and 53 of 56 in the D3 group. There were no deaths. The 30‐day postoperative morbidity rate was 47 per cent in the D2 group and 48 per cent in the D3 group, with a risk ratio of 1·04 (95 per cent c.i. 0·68 to 1·58) (P = 0·867). There were two anastomotic leaks (5 per cent) in the D2 group and none in the D3 group. Postoperative recovery, complication and readmission rates did not differ between the groups in ITT and PP analyses. Mean lymph node yield was 26·6 and 27·8 in D2 and D3 procedures respectively. Good quality of complete mesocolic excision was more frequently noted in the D3 group (P = 0·048). Three patients in the D3 group (5 per cent) had metastases in D3 lymph nodes. D3 was never the only affected level of lymph nodes. N‐positive status was more common in the D3 group (46 per cent versus 26 per cent in D2), with a risk ratio of 1·81 (95 per cent c.i. 1·01 to 3·24) (P = 0·044). Conclusion D3 lymph node dissection is feasible and may be associated with better N staging. Registration number: NCT03009227 ( http://www.clinicaltrials.gov).

Table. Pathological Features and Molecular Profile of Early-Onset Colorectal Cancer Pathological features Molecular profile Poor differentiation Microsatellite stability Mucinous tumors More likely to exhibit LINE-1 hypomethylation and TP53 sequence variations Signet-ring morphology Less frequently harbor KRAS, BRAF V600E, and APC sequence variations Perineural/venous invasion Promoter methylation of CpG islands Abbreviations: APC, adenomatous polyposis coli; BRAF, B-Raf; KRAS, K-Ras; LINE-1, long interspersed nuclear elements; TP53, tumor protein 53.

Background The extent of lymph node dissection in colonic cancer surgery remains arguable, and evidence from RCTs regarding extended lymph node dissection outcomes is lacking. This study aimed to compare the long‐term results of D3 lymph node dissection with those of D2 dissection. Methods This is a multicentre RCT. The aim is to enrol 768 patients with primary colonic cancer assigned randomly to D2 or D3 lymph node dissection. The trial is assessing the superiority of 5‐year overall survival as the primary endpoint in patients undergoing D3 lymph node dissection versus D2 dissection. Secondary endpoints include disease‐free survival, short‐term outcomes (30‐day morbidity and mortality), quality of complete mesocolic excision and lymph node dissection, pattern of lymph node metastasis and quality of life in patients following D2 and D3 lymph node dissection. Experience of 20 D3 and 20 D2 lymph node dissections is required for surgeons to participate in the trial. For surgical accreditation four non‐edited videos of procedures will be assessed. Patients will be followed up for 5 years after last patient enrolment. Intention‐to‐treat analysis will be performed. Discussion The results of this study will demonstrate whether extended lymph node dissection is superior to standard dissection in terms of oncological outcomes, and will also assess the impact of more extensive surgery on short‐term outcomes and quality of life.

Background The molecular profile of early-onset colonic cancer is undefined. This study evaluated clinicopathological features and oncological outcomes of young patients with colonic cancer according to microsatellite status. Methods Anonymized data from an international collaboration were analysed. Criteria for inclusion were patients younger than 50 years diagnosed with stage I–III colonic cancer that was surgically resected. Clinicopathological features, microsatellite status, and disease-specific outcomes were evaluated. Results A total of 650 patients fulfilled the criteria for inclusion. Microsatellite instability (MSI) was identified in 170 (26.2 per cent), whereas 480 had microsatellite-stable (MSS) tumours (relative risk of MSI 2.5 compared with older patients). MSI was associated with a family history of colorectal cancer and lesions in the proximal colon. The proportions with pathological node-positive disease (45.9 versus 45.6 per cent; P = 1.000) and tumour budding (20.3 versus 20.5 per cent; P = 1.000) were similar in the two groups. Patients with MSI tumours were more likely to have BRAF (22.5 versus 6.9 per cent; P < 0.001) and KRAS (40.0 versus 24.2 per cent; P = 0.006) mutations, and a hereditary cancer syndrome (30.0 versus 5.0 per cent; P < 0.001; relative risk 6). Five-year disease-free survival rates in the MSI group were 95.0, 92.0, and 80.0 per cent for patients with stage I, II, and III tumours, compared with 88.0, 88.0, and 65.0 per cent in the MSS group (P = 0.753, P = 0.487, and P = 0.105 respectively). Conclusion Patients with early-onset colonic cancer have a high risk of MSI and defined genetic conditions. Those with MSI tumours have more adverse pathology (budding, KRAS/BRAF mutations, and nodal metastases) than older patients with MSI cancers.

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