The optimal sequencing of targeted therapies and the role of primary tumor resection (PTR) in KRAS wild-type metastatic colorectal cancer (mCRC) remain unclear. This study compared survival outcomes in patients treated with first-line cetuximab plus FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) versus bevacizumab plus FOLFIRI, followed by second-line oxaliplatin-based chemotherapy and later-line trifluridine/tipiracil or regorafenib. This retrospective cohort study used Taiwan's National Health Insurance Research Database and the Taiwan Cancer Registry. Patients diagnosed with mCRC between 2013 and 2019 were included if they received first-line cetuximab or bevacizumab plus FOLFIRI, followed by later-line trifluridine/tipiracil or regorafenib. Patients were stratified by PTR status. Primary endpoints were overall survival and survival during trifluridine/tipiracil or regorafenib treatment. Secondary endpoints included time to treatment discontinuation (TTD) and TTD during trifluridine/tipiracil or regorafenib therapy. Stabilized inverse probability of treatment weighting was used for adjustment. Among 559 patients, 278 were assigned to the non-PTR group and 281 to the PTR group. In the non-PTR group, the cetuximab cohort demonstrated significantly longer survival during trifluridine/tipiracil or regorafenib therapy (6.2 months vs. 4.9 months; hazard ratio [HR], 0.72) and longer TTD1 (the interval between initiation of first-line therapy and the start of second-line chemotherapy; 11.8 months vs. 9.5 months; HR, 0.67) than the bevacizumab cohort. Survival differences between regimens were less pronounced among patients who underwent PTR. First-line cetuximab plus FOLFIRI may confer a survival advantage over bevacizumab in patients with KRAS wild-type mCRC without PTR, including during later-line therapy with trifluridine/tipiracil or regorafenib, whereas bevacizumab appears to provide more consistent benefits in those with PTR.

The objective of this study was to evaluate the natural history of early and late rectourethral fistulas (RUFs) and to determine the long-term outcomes of a multidisciplinary management approach. A multicenter retrospective study was performed on patients with RUF who were treated by a combined colorectal and urological team. Early RUF (ERUF) was defined as occurring within 31 days after surgery, while late RUF (LRUF) was defined as occurring thereafter. Surgical procedures and the surgeons involved were recorded, in addition to clinical assessments, radiological findings, and oncological assessments. A total of 72 patients diagnosed with RUF were treated between January 1, 2010, and June 2023. Patients were divided into ERUF (n=37) and LRUF (n=35) groups. After conservative management, comparisons of success rates for graciloplasty, York-Mason, and delayed coloanal anastomosis as second and third treatments showed higher rates for graciloplasty in ERUF than in LRUF (83% vs. 40%, P=0.034; 71% vs. 33%, P=0.500; and 60% vs. 40%, P>0.999, respectively). The ERUF group demonstrated significantly higher cure rates after the second treatment (83.8% vs. 40.0%, P<0.001). At final follow-up, complete healing was significantly more frequent in ERUF than in LRUF (83.8% vs. 42.9%, P<0.005). Definitive digestive and urinary diversion rates were lower in ERUF (13.5% vs. 48.5%, P=0.001; and 13.5% vs. 25.7%, P=0.240, respectively). These findings suggest that 30% of patients required a definitive colostomy, with a significantly higher proportion observed in the LRUF group. Moreover, repeated surgical procedures in the LRUF group were frequently unsuccessful.

Current international guidelines recommend neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) for locally advanced rectal cancer (LARC). Although nCRT reduces the risk of local recurrence, it has not demonstrated a survival advantage and increases the likelihood of preoperative overtreatment. This study investigated whether upfront TME could be offered without compromising oncologic outcomes. From January 2015 to December 2020, patients with stage II/III LARC who underwent either upfront TME or nCRT followed by TME were analyzed using propensity score matching. Long-term survival outcomes were compared between the 2 groups. The primary endpoint was 5-year disease-free survival. Secondary endpoints included 5-year local recurrence-free survival, distant metastasis-free survival, and overall survival. A total of 348 patients were included, of whom 138 (39.7%) underwent upfront TME. The upfront TME group showed significantly higher 5-year disease-free survival (63.3% vs. 43.9%) and distant metastasis-free survival (88.1% vs. 70.3%). However, after excluding patients with preoperative mesorectal fascia (MRF) involvement, no significant differences were observed in long-term oncologic outcomes. Following 1:1 propensity score matching, 47 patients from each group were compared. Kaplan-Meier survival analysis revealed no significant differences in any endpoints. Cox regression analysis of the matched cohort indicated that preoperative MRF involvement, positive extramural vascular invasion, and tumor deposits were not independent prognostic factors. Upfront TME may represent a viable treatment option for selected patients with LARC, particularly those without MRF involvement, providing comparable oncologic outcomes to the standard nCRT approach.

Metastatic rectal cancer (mRC) is a highly lethal and complex disease that demands a multidisciplinary treatment approach. However, the clinical effectiveness of radiotherapy (RT) for de novo mRC remains controversial and uncertain. This retrospective cohort study examined medical records from Kaohsiung Chang Gung Memorial Hospital for patients with histologically confirmed de novo mRC diagnosed between January 2015 and December 2020. All patients received standard systemic therapy and radical surgery when feasible. The primary outcome, overall survival (OS), was assessed using the Kaplan-Meier method. Multivariable analysis was performed using a Cox regression model. Among 271 patients included in the analysis, 117 received RT and 154 did not. The median OS was significantly longer in the RT group compared with the non-RT group (27.8 months vs. 21.9 months; P=0.046). Multivariate analysis identified several independent predictors of OS: age ≥65 years (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.26-2.27; P=0.001), primary tumor resection (HR, 2.62; 95% CI, 1.90-3.61; P<0.001), M1b or M1c disease (HR, 1.97; 95% CI, 1.44-2.69; P<0.001), and receipt of RT (HR, 1.41; 95% CI, 1.02-1.94; P=0.036). RT significantly improves OS in patients with mRC, underscoring its role in treatment strategies. These findings support its inclusion in therapeutic protocols and highlight the need for larger, multicenter trials to confirm and extend these results.

Familial adenomatous polyposis is a hereditary condition that predisposes individuals to colorectal cancer. This study aimed to evaluate the efficacy and safety of pharmacological therapies for reducing polyp number, burden, and size in individuals with familial adenomatous polyposis. A systematic search was conducted in PubMed, Embase, Web of Science, and Cochrane. Randomized trials assessing the effects of pharmacological interventions on polyp number, polyp burden, and polyp size were included, and adverse events were also analyzed. Sixteen studies (n=985) met the inclusion criteria. The mean participant age was 38±8.3 years, with a mean follow-up of 14.6±15.8 months. Of these studies, 62.5% focused on colorectal polyps, 18.8% on rectal polyps, 18.8% on duodenal polyps, and 12.5% addressed both colorectal and duodenal polyps. Pharmacological interventions were associated with a modest but statistically significant reduction in the number of polyps (Hedges g, -0.57; 95% confidence interval [CI], -1.08 to -0.05) and in average polyp size (Hedges g, -0.26; 95% CI, -0.49 to -0.04). However, no significant reduction in overall polyp burden was observed (Hedges g, -1.07; 95% CI, -2.21 to 0.06). In subgroup analyses, nonselective cyclooxygenase inhibitors produced a large reduction in polyp burden (Hedges g, -2.72; 95% CI, -3.28 to -2.16), while metformin also demonstrated benefit in a single study (Hedges g, -1.06; 95% CI, -1.86 to -0.27). Adverse events were generally infrequent and comparable to placebo. Chemopreventive interventions may reduce polyp number, burden, and size, and they appear to have a favorable safety profile.

Fluorescence-guided surgery (FGS) has progressed from a qualitative adjunct to a quantitative, data-driven tool in colorectal surgery. Fluorescence-guided angiography for perfusion assessment shows mixed randomized results overall, with signals of benefit in low anterior resection and less-severe leaks; emerging metrics (e.g., time-to-peak, slope, time from the initial fluorescence increase to half of the maximum [T1/2MAX], time ratio [TR]) support objective decision-making. Fluorescence-guided lymphatic mapping can increase D3 yield, whereas consistent oncologic benefit remains uncertain; sentinel lymph node mapping in early colon cancer is feasible but not standard. In advanced rectal cancer, fluorescence may facilitate lateral pelvic node dissection with lower blood loss and selective clearance, though long-term outcomes require confirmation. Tumor-targeted imaging shifts FGS from anatomy to biology, aiding detection of occult disease, characterization of indeterminate lesions after therapy, and therapeutic decision-making for organ preservation. Near-infrared II (NIR-II) agents and hybrid positron emission tomography (PET)/NIR tracers promise deeper penetration and preoperative-to-intraoperative correlation but remain largely preclinical. Platform advances, automated data capture, tumor to background ratio thresholds, and artificial intelligence-assisted analytics are moving FGS toward integrated, reproducible workflows. Priorities include international standardization, prospective trials with long-term endpoints, validated tumor-targeted probes, and digital/robotic integration.

The gut microbiome is not just a bystander of colorectal carcinogenesis but is an active driver of colorectal cancer (CRC). CRC-associated microbiome contributes in the tumorigenesis through chronic inflammation, formation of toxic metabolite and genotoxins, oncogenic signal activation, immune evasion, and barrier disruption-all reinforcing a tumor microenvironment. In contrast, beneficial microbiome supports the barrier-immune-metabolic axis by maintaining mucosal integrity and balanced immune tone. Despite extensive studies of microbiome-based CRC biomarkers, microbiome-based CRC biomarkers have not been yet ready for routine clinical use due to variation across populations and lack of standardization of key steps such as sampling, analysis, cutoffs, and interpretation. Microbiome-based therapies aim to change the overall intestinal ecosystem rather than simply adding or removing single strains. At present, dietary modulation and prebiotics are considered supportive measures, while probiotics or synbiotics are in preclinical stage. Fecal microbiota transplantation (FMT) still faces important challenges in effectiveness, standardization and safety. By its role in reshaping the tumor-host immune environment, FMT is viewed as a potential option for cancer therapy after further development through well-controlled clinical trials with careful safety monitoring.

Rectal cancer, which accounts for approximately 40% of colorectal cancers, remains a major clinical concern. Recent advances in diagnostic imaging, surgical techniques, radiotherapy, and systemic treatment have steadily improved rectal cancer outcomes. Considering this, the Korean Rectal Cancer Multidisciplinary (KRCM) Committee has aimed to provide clinicians and policymakers with up-to-date, evidence-based clinical practice guidelines to support optimal decision-making, reflecting current evidence, the Korean healthcare context, and patient values and preferences. The Clinical Practice Guidelines for Rectal Cancer version 2.0 were developed through multidisciplinary collaboration with related academic societies, building upon and updating the KRCM Clinical Practice Guidelines version 1.0 (titled "Multidisciplinary guidelines for the management of rectal cancer"). These consensus guidelines of the KRCM were established based on a comprehensive literature review, evidence synthesis, with recommendation development guided by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, and consideration of applicability in real-world clinical practice under the national health insurance system. Each recommendation has been presented with its strength and level of evidence.