Importance: Robotic surgery for rectal cancer is widely used, but data on long-term oncological outcomes are still lacking.Objective: To compare the 3-year locoregional recurrence rates of middle and low rectal cancer in patients who underwent robotic surgery vs conventional laparoscopic surgery.Design, Setting, and Participants: In this multicenter, superiority, randomized clinical trial, patients with middle or low rectal adenocarcinoma (cT1-T3, N0-N1, or ycT1-T3 Nx) and no distant metastasis were enrolled at 11 centers across 8 provinces in China from July 2016 to December 2020. Among the 1742 consecutive patients assessed for eligibility, 1240 were eligible and randomized. Follow-up continued until December 31, 2023.Interventions: Patients were randomized 1:1 to undergo robotic or conventional laparoscopic rectal cancer resection.Main Outcomes and Measures: The primary outcome was the 3-year locoregional recurrence rate. The primary analysis was performed as randomized, but excluded patients deemed ineligible after randomization. The secondary outcomes included disease-free survival; overall survival; and urinary, sexual, and defecation function.Results: Of the 1240 patients enrolled, 1171 were included in the primary analysis (586 in the robotic surgery group; mean age, 59.1 [SD, 11.0] years; and 356 were men [60.8%] vs 585 in the laparoscopic surgery group; mean age, 60.7 [SD, 9.8] years; and 354 were men [60.5%]). The median follow-up time was 43.0 months (IQR, 36.7-60.0 months). The 3-year locoregional recurrence rate was 1.6% (95% CI, 0.6%-2.6%) in the robotic group vs 4.0% (95% CI, 2.4%-5.6%) in the laparoscopic group (hazard ratio [HR], 0.45 [95% CI, 0.22-0.92], log-rank P = .03; adjusted HR, 0.39 [95% CI, 0.19-0.80]). The 3-year disease-free survival rate was higher in the robotic group (87.2%) vs the laparoscopic group (83.4%) (HR, 0.74 [95% CI, 0.56-0.98], log-rank P = .04; adjusted HR, 0.67 [95% CI, 0.50-0.89]). No significant between-group difference was observed in 3-year overall survival (94.7% in the robotic group vs 93.0% in the laparoscopic group). Patients in the robotic group also had better urinary function, male and female sexual function, and defecation function at 3 and 6 months after surgery and better urinary function and male sexual function at 12 months after surgery.Conclusions and Relevance: Compared with conventional laparoscopic surgery, robotic surgery significantly improved long-term oncological outcomes in patients with middle or low rectal cancer. With additional real-world clinical data and modern, improved training programs for surgeons, robotic surgery could be the preferred choice for patients with middle or low rectal cancer.Trial Registration: ClinicalTrials.gov Identifier: NCT02817126

An increasing number of studies have demonstrated that circular RNAs (circRNAs) can regulate gene expression through interacting with microRNAs. In this study, we analyzed the expression of antisense to CDR1as in colorectal cancer (CRC). CDR1as had a higher expression in CRC tissues compared to adjacent, normal mucosa and was positively associated with tumor size, T stage, lymph node metastasis, and poor overall survival (OS). Downregulation of CDR1as suppressed CRC cell proliferation and invasion and increased microRNA-7 (miR-7) expression. Intriguingly, ectopic expression of miR-7 in CRC cells consistently inhibited proliferation and invasion, and the miR-7 inhibitor was able to rescue the function of CDR1as knockdown. Mechanistic studies demonstrated that CDR1as silencing suppressed EGFR and IGF-1R expression, which could be partially blocked by the miR-7 inhibitor. Finally, positive correlations between CDR1as expression and EGFR and IGF-1R expression were observed in CRC samples. Thus, given the importance of CDR1as in blocking miR-7 and positively regulating EGFR and IGF-1R, dysregulated CDR1as expression may play an important role in CRC progression.

Purpose: Tumor purity is defined as the proportion of cancer cells in the tumor tissue. The impact of tumor purity on colon cancer (CC) prognosis, genetic profile, and microenvironment has not been thoroughly accessed. Materials and methods: Clinical and transcriptomic data from three public datasets, GSE17536/17537, GSE39582, and TCGA, were retrospectively collected (n=1,248). Tumor purity of each sample was inferred by a computational method based on transcriptomic data. Survival-related analyses were performed on microarray dataset containing GSE17536/17537 and GSE39582 (n=794), whereas TCGA dataset was utilized for subsequent genomic analysis (n=454). Results: Right-sided CC patients showed a significantly lower tumor purity. Low purity CC conferred worse survival, and tumor purity was identified as an independent prognostic factor. Moreover, high tumor purity CC patients benefited more from adjuvant chemotherapy. Subsequent genomic analysis found that the mutation burden was negatively associated with tumor purity, with only APC and KRAS significantly more mutated in high purity CC. However, no somatic copy number alteration event was correlated with tumor purity. Furthermore, immune-related pathways and immunotherapy-associated markers (programmed cell death protein 1 [PD-1], programmed death-ligand 1 [PD-L1], cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Lymphocyte-activation gene 3 [LAG-3] and T-cell immunoglobulin and mucin-domain containing-3 [TIM-3]) were highly enriched in low purity samples. Notably, the relative proportion of M2 macrophages and neutrophils, which indicated worse survival in CC, was negatively associated with tumor purity. Conclusion: Tumor purity exhibited potential value for CC prognostic stratification as well as adjuvant chemotherapy benefit prediction. The relative worse survival in low purity CC may attribute to higher mutation frequency in key pathways and purity-related microenvironmental changing.

Purpose: For stage II colon cancer, the efficacy of postoperative adjuvant chemotherapy remains controversial. It is well known that tumor-associated macrophages (TAMs) are important in tumor progression. In this study, TAMs were investigated as prognostic and predictive biomarkers for the efficacy of adjuvant chemotherapy for stage II colon cancer after radical resection. Experimental Design: This study enrolled two independent cohorts of consecutive patients from one medical center with pathologic stage II colon cancer after radical resections. Macrophages were detected using IHC staining of CD68 and CD206. Infiltration densities of CD68+ TAMs, CD206+ TAMs, and ratio of CD206+ TAMs/CD68+ TAMs (CD206/CD68 ratio) were calculated as prognostic and predictive biomarkers. Results: The primary and validation cohorts consisted of 521 and 314 patients, respectively. In both cohorts, high CD206/CD68 ratio was significantly associated with poor disease-free survival (DFS) and overall survival (OS). As an independent risk factor, CD206/CD68 ratio also had significantly better prognostic efficacy than CD68+ TAM density, CD206+ TAM density, and traditional clinicopathologic high-risk factors. Moreover, adjuvant chemotherapy significantly improved DFS and OS for patients with high CD206/CD68 ratio but not for those with low CD206/CD68 ratio. The interaction analyses were also significant for DFS. In subgroup analysis, CD206/CD68 ratio was still a significant predictor for adjuvant chemotherapy for patients in traditional high-risk group of recurrence (significant interaction for DFS). Conclusions: For stage II colon cancer, CD206/CD68 ratio is a better prognostic and predictive biomarker for postoperative adjuvant chemotherapy. Together with clinicopathologic high-risk factors, it will aid in precision treatment.

The 2024 updates of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for the diagnosis and treatment of colorectal cancer emphasize standardizing cancer treatment in China, highlighting the latest advancements in evidence-based medicine, healthcare resource access, and precision medicine in oncology. These updates address disparities in epidemiological trends, clinicopathological characteristics, tumor biology, treatment approaches, and drug selection for colorectal cancer patients across diverse regions and backgrounds. Key revisions include adjustments to evidence levels for intensive treatment strategies, updates to regimens for deficient mismatch repair (dMMR)/ microsatellite instability-high (MSI-H) patients, proficient mismatch repair (pMMR)/ microsatellite stability (MSS) patients who have failed standard therapies, and rectal cancer patients with low recurrence risk. Additionally, recommendations for digital rectal examination and DNA polymerase epsilon (POLE)/ DNA polymerase delta 1 (POLD1) gene mutation testing have been strengthened. The 2024 CSCO Guidelines are based on both Chinese and international clinical research, as well as expert consensus, ensuring their relevance and applicability in clinical practice, while maintaining a commitment to scientific rigor, impartiality, and timely updates.