Yukihide Kanemitsu

Background: Patients with oligometastatic colorectal cancer (mCRC) remain at high risk of recurrence after curative surgery, yet the benefit of adjuvant chemotherapy remains inconclusive. This study evaluated the feasibility and efficacy of adjuvant modified (m)FOLFOXIRI (irinotecan, oxaliplatin, L-leucovorin (L-LV), 5-fluorouracil (5-FU)), as well as the utility of circulating tumour DNA (ctDNA) as a prognostic and predictive biomarker in mCRC. Methods: Between October 2020 and January 2024, patients with histologically confirmed mCRC undergoing complete metastasectomy were enrolled in this multicentre non-randomized phase II study. Eligible and consenting patients received eight cycles of mFOLFOXIRI followed by four cycles of 5-FU/L-LV; ineligible/non-consenting patients received standard of care (SOC; CAPOX (capecitabine and oxaliplatin), 5-FU, or observation). ctDNA was assessed using the tumour-informed personalized Signatera™ assay (Natera, Austin, TX, USA) at 28 days and 7 months after surgery. The primary endpoint was completion of eight cycles of mFOLFOXIRI in a target sample of 36 patients. Results: Of the 83 registered patients, 73 were enrolled (39 mFOLFOXIRI, 34 SOC). The mFOLFOXIRI completion rate was 74% (80% confidence interval 63% to 83%; P < 0.001). ctDNA positivity predicted significantly inferior recurrence-free survival across both the mFOLFOXIRI and SOC treatment groups at 28 days (hazard ratios (HR) 7.27 and 7.17, respectively) and 7 months (HR 3.96 and 4.38, respectively) after surgery. Multivariate analysis identified ctDNA positivity, RAS mutation, metachronous metastases, and mFOLFOXIRI as significant prognostic factors. mFOLFOXIRI improved recurrence-free survival compared with SOC in the overall population (HR 0.44; P = 0.012), with a trend towards benefit in ctDNA-positive but not ctDNA-negative patients. ctDNA clearance rates were 33% (mFOLFOXIRI) and 20% (SOC). Conclusions: This study indicates the feasibility of adjuvant mFOLFOXIRI in patients with mCRC, with an acceptable safety profile and potential clinical benefit among those with ctDNA positivity 28 days after surgery.

Background and Purpose: Adjuvant fluoropyrimidine (FP) as well as oxaliplatin is the key drug in stage III colorectal cancer (CRC). Reduced relative dose intensity (RDI) of oxaliplatin-based chemotherapy is associated with inferior survival, but the significance of RDI reduction during FP monotherapy is unknown.Materials and Methods: We pooled individual patient data from four JCOG randomized phase III trials of patients with pathological stage III CRC who received adjuvant FP monotherapy. RFS was the primary endpoint and OS the secondary endpoint, both measured from the end of adjuvant chemotherapy. RDI was the ratio of actual-to-planned dose. Candidate RDI cut-offs (50–90%, 5% increments) were explored separately in low-risk (pT1–3N1) and high-risk (pT4 and/or N2) groups using Cox regression models.Results: Among 2,892 patients (1,798 low-risk, 1,094 high-risk), 3-year RFS was 87.5% and 71.3%, respectively (HR 2.37; 95% CI [2.03–2.78]). In the high-risk group, RDI ≥70% was associated with better 3-year RFS than RDI <70% (72.9% vs 63.5%; HR 0.66[0.51–0.85]); no significant RFS cut-off emerged in the low-risk group. For OS, RDI ≥65% was associated with better 5-year OS than OS <65% in the high-risk group (85.6% vs 76.2%; HR 0.68; [0.49–0.94]) and the similar tendency was observed in the low risk group with a cutoff of 70% (95.6% vs 90.9%; HR 0.69 [0.47–0.99]).Conclusions: Reduced RDI of adjuvant FP monotherapy was associated with poorer RFS and OS, particularly in high-risk stage III CRC. These exploratory thresholds support maintaining adequate dose intensity, pending prospective validation.

Background: Effective multimodal analgesia is essential after minimally invasive colorectal surgery. This randomized trial evaluated whether adding surgeon-performed surgical rectus sheath block (SRSB) or laparoscopic bilateral dual transversus abdominis plane (BD-TAP) block to intravenous patient-controlled analgesia (IV-PCA) improved postoperative quality of recovery. Methods: This single-centre, three-arm superiority trial randomized adults undergoing minimally invasive colorectal resection (1 : 1 : 1) by stratified block allocation at a Japanese cancer centre. Patients and outcome assessors were blinded. The primary outcome was the Japanese version of the 15-item Quality of Recovery questionnaire (QoR-15) score 24 h after arrival in the postanaesthesia care unit. Missing postoperative QoR-15 item responses were handled using multiple imputation, and treatment effects were estimated using ANCOVA adjusted for the four randomization stratification factors. Each primary comparison used a Bonferroni-adjusted one-sided significance level of 0.025. Secondary outcomes included the 48-h QoR-15 score, postoperative pain scores, time to first rescue analgesia, and cumulative consumption of analgesics and antiemetics over 48 h. Results: Between July 2024 and December 2025, 320 patients were randomized (control, 110; SRSB, 107; and BD-TAP block, 103); 309 were analysed (105, 103, and 101 respectively). Compared with control, BD-TAP block resulted in a higher 24-h QoR-15 score (adjusted mean difference 10.44 (95% c.i. 3.06 to 17.83) points; one-sided P = 0.003), whereas superiority of SRSB was not demonstrated (adjusted mean difference 5.50 (95% c.i. −1.88 to 12.89) points; one-sided P = 0.072). At 48 h, the adjusted mean difference for BD-TAP block versus control was 8.01 (95% c.i. 0.18 to 15.83) points (two-sided P = 0.045), an exploratory finding unadjusted for multiplicity. The median time to first rescue analgesia was longer with SRSB (27.8 h) and BD-TAP block (25.3 h) than control (3.3 h), but cumulative 48-h fentanyl consumption and length of hospital stay did not differ significantly. No block-related complications were observed. Conclusion: BD-TAP block resulted in better 24-h recovery than IV-PCA alone. Superiority of SRSB was not demonstrated. Registration number: jRCT1031240153 (Japan Registry of Clinical Trials).

Background: Accurate pre‐treatment evaluation of lymph node metastasis (LNM) in colon cancer is important for determining an optimal treatment strategy. This diagnosis is mainly performed using the size of lymph nodes visualized on CT, although morphological diagnosis is also used. Results: Meta‐analyses of CT for diagnosis of LNM in colon cancer indicate unsatisfactory results, with pooled sensitivities of 71% and 74%, and pooled specificities of 67% and 54%. Our recent report also showed only moderate diagnostic performance, with pooled sensitivity of 66.7%, pooled specificity of 72.4%, and an AUC of the HSROC of 0.741. This is because strict positive criteria based on the size and morphology of visualized lymph nodes are difficult to establish, and currently there are limitations to determining treatment strategies based on imaging diagnosis. Diagnostic accuracy can be improved by setting individualized diagnostic criteria according to the purpose, considering underlying clinicopathological factors, and combining multiple metastasis‐related factors. New diagnostic methods such as dual‐energy CT and radiomics have also been explored. Unlike traditional diagnoses based on imaging findings, these methods quantify and evaluate parameters, and radiomics, in particular, allows detailed evaluation by quantifying high‐dimensional features that are not visible. Conclusion: Further studies are required to improve diagnostic capabilities that will enable optimal treatment strategies for LNM in colon cancer.

BACKGROUND: JCOG1107 (UMIN-CTR, number UMIN000009715) was a non-inferiority phase III trial comparing laparoscopic and open surgery for symptomatic, non-curable stage IV colon cancer. The primary analysis confirmed the non-inferiority of laparoscopic surgery in terms of progression-free survival. OBJECTIVE: To compare long-term outcomes of laparoscopic and open surgery for stage IV colon cancer. DESIGN: Multicenter, open-label, randomized, controlled phase III trial. SETTING: Forty-two Japanese institutions. PATIENTS: Participants were considered eligible if they had pathologically confirmed adenocarcinoma or adenosquamous carcinoma with a primary tumor between the cecum and rectosigmoid, presenting with stenosis and/or bleeding, and one to three non-curable factors. The required sample size was 194 to ensure 70% power, a one-sided alpha of 5%, and a non-inferiority hazard ratio margin of 1.38. INTERVENTIONS: Patients were randomized to receive either open or laparoscopic primary tumor resection, followed by modified FOLFOX6 plus bevacizumab or capecitabine plus oxaliplatin with bevacizumab. MAIN OUTCOME MEASURES: The primary endpoint was progression-free survival. RESULTS: A total of 195 patients were randomized, including 95 open and 100 laparoscopic surgeries. Postoperative chemotherapy was given to 82 and 86 patients, respectively. The median follow-up period for all randomized patients was 24.4 months. Grade ≥3 late complications occurred in one open (1.1%) and two laparoscopic (2.0%) patients. Three-year progression-free survival was 5.3% (95% confidence interval: 2.0–11.0) for open surgery and 3.0% (0.8–7.8) for laparoscopic surgery (hazard ratio: 1.028; 95% confidence interval: 0.772–1.370; p for non-inferiority = 0.02). The three-year overall survival was 31.5% (22.5–41.0) and 28.5% (20.0–37.6) (hazard ratio: 1.048; 95% confidence interval: 0.780–1.410), respectively. LIMITATIONS: Chemotherapy was administered without knowledge of microsatellite instability or RAS/BRAF mutation status. CONCLUSION: Laparoscopic surgery is non-inferior to open surgery for non-curable stage IV colon cancer and should be considered an acceptable surgical option. See Video Abstract .