Extracellular water to total body water ratio, a novel predictor of recurrence in patients with colorectal cancer.

Background: Total body water (TBW) fraction, which accounts for 60% of body weight, is an important indicator of body composition, and the extracellular water to TBW ratio (ECW/TBW) is reportedly useful in predicting clinical outcomes of patients with organ disorders. We aimed to clarify the clinical impact of preoperative ECW/TBW status on survival outcomes in cancer patients. Methods: We used a database of 320 colorectal cancer (CRC) patients who underwent potentially curative resections. Preoperative ECW/TBW was measured using a bioelectrical impedance analysis (BIA), and its correlation with patient survival outcomes, clinicopathological factors, laboratory data, and comorbidities were analyzed. Results: A high preoperative ECW/TBW was significantly associated with poorer relapse-free survival (RFS; p = 0.001) and overall survival (OS; p = 0.003). A high ECW/TBW ratio was significantly associated with older age (p < 0.001), low BMI (p = 0.009), and right-sided tumors (p = 0.03). In a multivariate analysis, a high ECW/TBW significantly predicted a higher RFS mortality (HR: 2.07, 95% CI: 1.10-3.88, p = 0.024) and OS mortality (HR: 3.23, 95% CI: 1.25-8.36, p = 0.016). Furthermore, a high ECW/TBW was significantly associated with lower hemoglobin (p < 0.001) and albumin levels (p < 0.001), but not comorbidities. Conclusions: A high preoperative ECW/TBW was a predictive factor for recurrence and poorer overall survival independent of the tumor, node, and metastasis (TNM) stage. Our data suggest that preoperative evaluation of ECW/TBW using BIA might serve as a novel tool for developing CRC treatment strategies.

Laparoscopic Observation of Adhesive Rectal Fixation after Gant-Miwa-Thiersch Procedure for Rectal Prolapse: A Case Report.

In our previous report, we have noted an increase of computed tomography (CT) attenuation values in perirectal fat tissue after Gant-Miwa-Thiersch (GMT) procedure for rectal prolapse. Based on these results, we hypothesized that the GMT procedure may have a rectal fixation effect due to inflammatory adhesions extending to the mesorectum. Herein, we report a case of laparoscopic observation of perirectal inflammation after GMT. A 79-year-old woman with a history of seizures, stroke, subarachnoid hemorrhage, and spondylosis underwent the GMT procedure under general anesthesia in the lithotomy position for rectal prolapse measuring 10 cm in length. But rectal prolapse recurred 3 weeks after surgery. Therefore, an additional Thiersch procedure was performed. However, rectal prolapse still recurred, and laparoscopic suture rectopexy was performed 17 weeks after initial surgery. During rectal mobilization, marked edema and rough membranous adhesions were observed in the retrorectal space. The average CT attenuation value obtained 13 weeks after initial surgery was found to be significantly elevated in the mesorectum compared with the subcutaneous fat, especially in the posterior side (P < 0.05). These findings suggest that the extension of inflammation to the rectal mesentery after the GMT procedure may have strengthened adhesions in the retrorectal space.

The colon inflammatory index score can predict the survival outcome after resection of colorectal cancer: a retrospective multicentre study.

PURPOSE: Many systemic inflammatory markers have been identified to be prognostic factors in various diseases, including colorectal cancer (CRC). The Colon Inflammatory Index (CII), which is based on the lactate dehydrogenase (LDH) level and the neutrophil-to-lymphocyte ratio (NLR), is reportedly a predictor of the outcome of chemotherapy in patients with metastatic CRC. This retrospective review study aimed to determine whether CII can predict the prognosis after surgical resection of CRC. METHODS: A total of 1,273 patients who underwent CRC resection were enrolled and divided into a training cohort (n = 799) and a validation cohort (n = 474). The impact of the preoperative CII score on overall survival (OS) and recurrence-free survival (RFS) was assessed. RESULTS: In the training cohort, the CII score was good in 569 patients (71.2%), intermediate in 209 (26.2%), and poor in 21 (2.6%). There were significant between-group differences in body mass index, American Society of Anaesthesiologists physical status, and preoperative tumour markers. The 5-year OS rate was significantly lower in patients with an intermediate or poor CII score (CII risk) than in those with no CII risk (73.8% vs. 84.2%; p < 0.001, log-rank test). In multivariate analysis, CII risk remained a significant independent predictor of poor OS (hazard ratio 1.75; 95% confidence interval 1.18-2.60; p = 0.006). In the validation cohort, the 5-year OS rate was significantly lower in patients with CII risk than in those with no CII risk (82.8% vs. 88.4%; p = 0.046, log-rank test). CONCLUSION: These findings indicate that the CII can predict OS after resection of CRC.

Emerging evidence of immunotherapy for colorectal cancer.

Since the advent of immune checkpoint inhibitors, which modulate the interplay between the tumor cell and immune system, immunotherapy has become widely recognized as a new standard treatment for cancers including microsatellite instability-high (MSI-H) colorectal cancer. Immune checkpoint inhibitors such as pembrolizumab and nivolumab (anti-PD-1 antibodies) that act in the effector phase of T cells and ipilimumab (anti-CTLA-4 antibody) that acts mainly in the priming phase are now in clinical use. These antibodies have shown therapeutic efficacy in MSI colorectal cancer patients who have failed to respond to existing standard therapies. Pembrolizumab is also strongly recommended as first-line therapy for MSI-H metastatic colorectal cancer. Therefore, the MSI status and tumor mutation burden of the tumor should be clarified before starting treatment. Because many patients do not respond to immune checkpoint inhibitors, combination therapies with immune checkpoint inhibitors, including chemotherapy, radiotherapy, or molecularly targeted agents, are being investigated. Furthermore, treatment methods for preoperative adjuvant therapy for rectal cancer are being developed.

The impact of the advanced lung cancer inflammation index on the outcomes of patients with metastatic colorectal cancer who receive chemotherapy.

BACKGROUND: Advanced lung cancer inflammation index (ALI) is reported to be a prognosticator in various cancer patients with chemotherapy. However, the clinical impact of the ALI on treatment strategies in metastatic colorectal cancer (mCRC) patients remains unclear. METHODS: A total of 356 patients, who received first-line chemotherapy for mCRC between April 2005 and November 2019 in a single institution, were retrospectively enrolled. The association of pretreatment ALI (calculated as follows: BMI × albumin value/neutrophil-to-lymphocyte ratio) status with clinicopathological factors and patient survival outcome was analyzed, using subgroup analysis. RESULTS: The ALI-low cases were significantly associated with female sex, more synchronous metastasis, multiple metastatic sites, less primary tumor resection, less liver resection after chemotherapy, and poor overall survival (OS). A multivariate Cox proportional hazards analysis clarified that the ALI-low status was independently associated with poor OS (HR: 1.78, 95% CI 1.27-2.48, P = 0.001), in addition to right side tumor, multiple metastatic sites, and the non-performance of liver resection after chemotherapy. A subgroup analysis revealed that primary tumor resection and the resection of liver metastases after chemotherapy could not improve the prognosis of ALI-low cases in comparison with ALI-high cases, and the type of first-line chemotherapy did not significantly affect the association between the prognosis and the ALI status. CONCLUSION: ALI comprehensively evaluates the prognostic host status and is a reliable prognosticator for the mCRC patients with chemotherapy. Calculating pretreatment ALI may serve as a cost-effective and easily available tool for constructing treatment strategies.

Preoperative skeletal muscle status is associated with tumor-infiltrating lymphocytes and prognosis in patients with colorectal cancer.

Background: Sarcopenia is associated with poor prognosis in patients with colorectal cancer (CRC), but the mechanisms contributing to this association remain unclear. We hypothesized that skeletal muscle status is associated with tumor-infiltrating lymphocytes (TILs) in patients with CRC. Therefore, this study investigated the clinical effect of sarcopenia and its relationship with the local immune system in CRC patients. Methods: A total of 256 consecutive patients with CRC who underwent curative resection between 2008 and 2014 were enrolled. Sarcopenia was determined according to the skeletal muscle index (SMI), which was assessed using L3 skeletal muscle mass on axial computed tomography images, and its relationship with patient clinicopathological characteristics and survival was evaluated. Additionally, TILs (CD3+, CD8+, CD4+, and FOXP3+ T cells) were assayed by immunohistochemistry. The relationship between TILs and skeletal muscle status was evaluated. Results: Patients with a lower SMI showed significantly shorter recurrence-free and overall survival compared with those with a higher SMI. Low expression of TILs was associated with significantly shorter recurrence-free survival. SMI was significantly correlated with the number of CD3+ and CD8+ cells in the ordinal logistic regression analysis. Patients with low skeletal muscle status and low CD3+ and CD8+ cells had an unfavorable prognosis compared with patients with high skeletal muscle status and high CD3+ and CD8+ cells. Conclusion: Our data showed an association between skeletal muscle status and local immune cells, and this association may play a pivotal role in the clinical outcome of patients with CRC.

Molecular profiling of signet-ring-cell carcinoma (SRCC) from the stomach and colon reveals potential new therapeutic targets.

Signet ring cell carcinoma (SRCC) is rare: about 10% of gastric cancer (GC) and 1% of colorectal cancer (CRC). SRCC is associated with poor prognosis, however the underlying molecular characteristics are unknown. SRCCs were analyzed using NGS, immunohistochemistry, and in situ hybridization. Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous missense mutations, and microsatellite instability (MSI) was evaluated by NGS of known MSI loci. A total of 8500 CRC and 1100 GC were screened. Seventy-six SRCC were identified from the CRC cohort (<1%) and 98 from the GC cohort (9%). The most frequently mutated genes in CRC-SRCC were TP53 (47%), ARID1A (26%), APC (25%); in GC-SRCC were TP53 (42%), ARID1A (27%), CDH1 (11%). When compared to non-SRCC histology (N = 3522), CRC-SRCC (N = 37) more frequently had mutations in BRCA1 (11% vs 1%, P < 0.001) and less frequently mutations in APC (19% vs 78%, P < 0.001), KRAS (22% vs 51%, P = 0.001) and TP53 (47% vs 73%, P = 0.001). Among the GC cohort, SRCC (N = 54) had a higher frequency of mutations in CDH1, BAP1, and ERBB2, compared to non-SRCC (N = 540). Our data suggest that SRCCs harbor a similar molecular profile, regardless of the tumor location. Tailored therapy may become available for these patients.

Index of estimated benefit from lymph node dissection for stage I-III transverse colon cancer: an analysis of the JSCCR database.

PURPOSE: Main lymph node metastasis (LNM) dissection of transverse colon (TC) cancer is a difficult surgical procedure. Nonetheless, the main LNM ratio and the benefit of main lymph node (LN) dissection in TC cancer were unclear. This study aimed to identify high-risk patients for LNM and to evaluate the benefit of LN dissection in TC cancer. METHODS: Data for 26,552 colorectal cancer patients between 2007 and 2011 were obtained from the JSCCR database. Of these, 871 stage I-III TC cancer patients underwent surgery with radical LN dissection. These patients were evaluated using the index of estimated benefit from lymph node dissection (IEBLD), where IEBLD = (LNM ratio of each LN station) × (5-year overall survival (OS) rate of the patients with LNM) × 100. RESULTS: None of the patients with depth of invasion pT1-2 had main LNM. The presence of main LNM was associated with depth of invasion pT4, CEA-4H (carcinoembryonic antigen 4 times higher than preoperative cutoff value), or type 3, and 323 patients (37.1%) who had these factors were high-risk patients for main LNM. In these high-risk patients, the LNM ratio, 5-year OS rate of patients with LNM and IEBLD values, respectively, were 43.9%, 70.3%, and 30.5 for the pericolic LN; 20.3%, 66.0%, and 15.1 for the intermediate LN; and 9.6%, 58.5%, and 5.6 for the main LN. CONCLUSION: Main LNM is associated with depth of invasion pT4, CEA-4H, or type 3. The IEBLD for the main LN of high-risk TC cancer patients was over 5.

Activin A promotes cell proliferation, invasion and migration and predicts poor prognosis in patients with colorectal cancer.

Activin A is a member of the transforming growth factor­ß superfamily of cytokines and displays various pathophysiological activities, including regulation of muscle catabolism and atrophy. Activin A expression is upregulated in several human cancer types and in certain pathologies, its expression is associated with poor prognosis. In the present study, activin A expression was assessed in colorectal cancer (CRC) tissue specimens from 157 patients with primary CRC and the relationship between activin A levels and clinicopathological characteristics, including skeletal muscle mass, and prognosis, was determined. Furthermore, the effects of knockdown of endogenous or exposure to exogenous activin A on the malignant behavior of human CRC cell lines were investigated in vitro. The results indicated that activin A mRNA was significantly upregulated in CRC tumor tissues compared with normal intestinal epithelium. High activin A expression was significantly associated with shorter cancer­specific survival (P=0.047) and overall survival (P=0.014). According to a multivariate analysis, tumor activin A levels were an independent prognostic factor for overall survival (P=0.001). However, activin A mRNA levels were not associated with the skeletal muscle index. The in vitro experiments demonstrated that exposure to exogenous activin A increased the proliferation, invasion and migration of CRC cell lines, whereas knockdown of endogenous activin A had the opposite effects. In conclusion, activin A is an autocrine and paracrine regulator of CRC cell proliferation and high tumor expression of activin A is associated with poor prognosis in patients with CRC.

The advanced lung cancer inflammation index is a novel independent prognosticator in colorectal cancer patients after curative resection.

BACKGROUND: The advanced lung cancer inflammation index (ALI), which comprehensively evaluates the patient body composition and inflammation/nutritional status, is reportedly associated with the patient outcome in lung cancer. However, the clinical significance in colorectal cancer (CRC) patients after curative resection remains unclear. METHODS: A total of 813 CRC patients after curative resection between April 2005 and June 2019 in a single institution were retrospectively enrolled. The association of the preoperative ALI (calculated as follows: body mass index × albumin value/neutrophil-to-lymphocyte ratio) with clinicopathological factors, postoperative complications, and survival was analyzed. RESULTS: A low ALI was significantly associated with male gender, older age, a higher depth of tumor invasion, progressed TNM stage, and preoperative carcinoembryonic antigen (CEA) positivity. Both postoperative complications and severe complications occurred more frequently in the ALI-low group than in the ALI-high group (P < .001 and P < .001, respectively), especially postoperative complications in stage III patients (P < .001) and severe complications in stages II and III patients (P = .024 and P = .004, respectively). In addition, a low ALI was an independent predictor of a poor overall survival (hazard ratio: 2.30, 95% confidence interval: 1.52-3.50, P < .001) and relapse-free survival (hazard ratio: 1.73, 95% confidence interval: 1.22-2.44, P = .002), especially in older patients, and in patients without lymph node metastasis or severe postoperative complications. CONCLUSION: This study suggests that preoperative ALI may serve as a novel independent predictive index for severe postoperative complications and recurrence in CRC patients after curative resection.

What are the factors predictive of postoperative complications in patients with colorectal cancer undergoing stenting as a bridge to surgery?

OBJECTIVE: Using a self-expanding metal stent as a bridge to surgery (BTS) is considered a reasonable strategy for patients with acute malignant large bowel obstruction. Since postoperative complications have a negative impact on patient survival, we aim to clarify the predictors of complications in patients undergoing BTS using a self-expanding metal stent. METHODS: We conducted a retrospective review of 61 patients with colorectal cancer (CRC) who underwent stenting as a BTS at our institution. We analyzed the association of postoperative complications with clinicopathologic, surgical, and patient factors, and with the prestenting or preoperative laboratory data. RESULTS: Both postoperative complications in general and severe complications were significantly associated with a longer stenotic-section length (p = 0.007 and p = 0.003), lower preoperative hemoglobin levels (p < 0.001 and p = 0.081), and lower prestenting hemoglobin levels (p = 0.006 and p = 0.042). Multivariate logistic regression analysis showed that lower prestenting (<13.0 g/dl) and preoperative (<11.5 g/dl) hemoglobin levels were independent predictive factors for postoperative complications (odds ratio [OR]: 4.15; 95% confidence interval [CI]: 1.07-18.90; p = 0.040; and OR: 4.93; 95% CI: 1.35-20.28; p = 0.016). A stenotic-section length of 5.0 cm or greater was predictive of severe complications (OR: 25.67; 95% CI: 1.95-1185.00; p = 0.011). CONCLUSIONS: Our data suggest that lower hemoglobin levels before stenting and a longer length of the stenotic section of bowel might predict postoperative complications in patients with CRC undergoing BTS for obstruction.

Molecular differences between lymph nodes and distant metastases compared with primaries in colorectal cancer patients.

Lymph nodes (LNs) and distant metastases can arise from independent subclones of the primary tumor. Herein, we characterized the molecular landscape and the differences between LNs, distant metastases and primary colorectal cancers (CRCs). Samples were analyzed using next generation sequencing (NGS, MiSeq on 47 genes, NextSeq on 592 genes) and immunohistochemistry. Tumor mutational burden (TMB) was calculated based on somatic nonsynonymous missense mutations, and microsatellite instability (MSI) was evaluated by NGS of known MSI loci. In total, 11,871 samples were examined, comprising primaries (N = 5862), distant (N = 5605) and LNs metastases (N = 404). The most frequently mutated genes in LNs were TP53 (72%), APC (61%), KRAS (39%), ARID1A (20%), PIK3CA (12%). LNs showed a higher mean TMB (13 mut/MB) vs distant metastases (9 mut/MB, p < 0.0001). TMB-high (≥17mut/MB) and MSI-H (8.8% and 6.9% vs 3.7%, p < 0.001 and p = 0.017, respectively) classifications were more frequent in primaries and LNs vs distant metastases (9.5% and 8.8% vs 4.2%, p < 0.001 and p = 0.001, respectively). TMB-high is significantly more common in LNs vs distant metastases and primaries (P < 0.0001), regardless MSI-H status. Overall, LNs showed significantly different rates of mutations in APC, KRAS, PI3KCA, KDM6A, and BRIP1 (p < 0.01) vs primaries, while presenting a distinct molecular profile compared to distant metastases. Our cohort of 30 paired samples confirmed the molecular heterogeneity between primaries, LNs, and distant metastases. Our data support the hypothesis that lymphatic and distant metastases harbor different mutational landscape. Our findings are hypothesis generating and need to be examined in prospective studies.

Random survival forests identify pathways with polymorphisms predictive of survival in KRAS mutant and KRAS wild-type metastatic colorectal cancer patients.

KRAS status serves as a predictive biomarker of response to treatment in metastatic colorectal cancer (mCRC). We hypothesize that complex interactions between multiple pathways contribute to prognostic differences between KRAS wild-type and KRAS mutant patients with mCRC, and aim to identify polymorphisms predictive of clinical outcomes in this subpopulation. Most pathway association studies are limited in assessing gene-gene interactions and are restricted to an individual pathway. In this study, we use a random survival forests (RSF) method for identifying predictive markers of overall survival (OS) and progression-free survival (PFS) in mCRC patients treated with FOLFIRI/bevacizumab. A total of 486 mCRC patients treated with FOLFIRI/bevacizumab from two randomized phase III trials, TRIBE and FIRE-3, were included in the current study. Two RSF approaches were used, namely variable importance and minimal depth. We discovered that Wnt/ß-catenin and tumor associated macrophage pathway SNPs are strong predictors of OS and PFS in mCRC patients treated with FOLFIRI/bevacizumab independent of KRAS status, whereas a SNP in the sex-differentiation pathway gene, DMRT1, is strongly predictive of OS and PFS in KRAS mutant mCRC patients. Our results highlight RSF as a useful method for identifying predictive SNPs in multiple pathways.

RNA-Binding Protein Polymorphisms as Novel Biomarkers to Predict Outcomes of Metastatic Colorectal Cancer: A Meta-analysis from TRIBE, FIRE-3, and MAVERICC.

RNA-binding proteins (RBPs) regulate many posttranscriptional cellular activities. Accumulating evidence suggests associations between RBPs with colonic tumorigenesis and chemosensitivity. We investigated the prognostic and predictive values of SNPs of genes encoding RBPs in metastatic colorectal cancer (mCRC), using clinical and genomic data from three randomized clinical trials of standard first-line chemotherapy for mCRC (TRIBE, FIRE-3, and MAVERICC). Genomic DNA extracted from blood samples was genotyped using an OncoArray. We tested 30 candidate SNPs of 10 major RBP-related genes with additive models. Prognostic values were estimated by meta-analysis approach. Treatment-by-SNP interactions were tested to estimate predictive values for targeted drugs and cytotoxic backbone chemotherapies. This study included 884 patients. The meta-analysis revealed prognostic values of LIN28B rs314277 [HR, 1.26; 95% confidence interval (CI), 1.06-1.49, P = 0.005, FDR-adjusted P = 0.072 for overall survival (OS)] and LIN28B rs314276 (HR, 1.25; 95% CI, 1.08-1.44, P = 0.002, FDR-adjusted P = 0.062 for OS). Although some SNPs showed potentially predictive values, these associations were not confirmed after FDR adjustment. In conclusion, the results of this study are warranting additional studies to provide the evidence that RBP-related SNPs may be associated with the prognosis of patients with mCRC treated with standard first-line chemotherapies. In addition, further studies are warranted to study the predictive value.

Time trial of dry box laparoscopic surgical training improves laparoscopic surgical skills and surgical outcomes.

INTRODUCTION: The present study assessed the utility of a dry box time trial during laparoscopic surgical training to improve laparoscopic surgical skills and surgical outcomes. METHODS: In a monthly time trial, surgeon trainees twice completed a set task that involved grasping a suture, aligning a needle with a needle holder, passing the suture, making three knots, and cutting the two tails of the suture. The mean suturing time was then analyzed. To assess the utility of this time trial, we analyzed the short-term outcomes of patients with stage I to III colon cancer who had undergone laparoscopic colectomy before and after the introduction of the time trial. RESULTS: The monthly time trial was introduced in October 2018, and 52 surgeon trainees participated in the trials examined in this study. Within 6 months of the program's introduction, the mean suturing time had significantly declined to less than 70% of the time trial, while the standard deviations had declined to less than 30%. In comparisons of the short-term outcomes of laparoscopic colon cancer surgery before (n = 49) and after (n = 46) the introduction of the time trial, the operative time tended to decline (P = .074) after the introduction of the time trial, and blood loss was significantly reduced (P = .018). The rate of postoperative complications was similar before and after the introduction. CONCLUSION: Regular time trials of laparoscopic surgical suture training using a dry box can be useful for improving laparoscopic surgical skills and surgical outcomes. Moreover, time trials can keep trainees motivated.

Total Lesion Glycolysis Ratio in Positron Emission Tomography/Computed Tomography Images During Neoadjuvant Chemotherapy Can Predict Pathological Tumor Regression Grade and Prognosis in Patients with Locally Advanced Squamous Cell Carcinoma of the Esophagus.

BACKGROUND: The usefulness of quantitating tumor lesion glycolysis (TLG) from 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) findings as a tool for determining the effect of neoadjuvant chemotherapy (NAC) in esophageal squamous cell carcinoma (ESCC) has not yet been established. METHODS: The cohort of this retrospective study comprised 46 patients who had undergone NAC and subsequent esophagectomy for locally advanced ESCC between January 2008 and December 2017. PET/CT was conducted before and after NAC to assess its therapeutic effect. Associations between changes in TLG values during NAC and clinicopathological findings, pathological tumor regression grade (TRG), and prognosis were assessed. RESULTS: Most patients received two courses of DCF (Docetaxel, Cisplatin, and Fluorouracil) as NAC. The mean TLG value of the primary tumor decreased significantly after NAC. The median follow-up period was 41 months. The Kaplan-Meier method, analyzed by log-rank test, showed that low TLG ratio (≤ 0.4) and low SUVmax ratio (≤ 0.6) were associated with favorable survival outcomes (P = 0.0073 and P = 0.032, respectively). Univariate and multivariate analysis revealed that TLG ratio and achievement of pathological cure were independent prognostic factors for overall survival. TLG ratio was also associated with pathological TRG (TRG 0-1a vs 1b-3) (P = 0.0016). CONCLUSIONS: TLG ratio before and after NAC is clinically useful in predicting both histological response and survival outcome after NAC and subsequent esophagectomy in patients with ESCC.

Precision medicine for adjuvant chemotherapy of resected colorectal cancer.

Colorectal cancer (CRC) is the most common cancer and the second leading cause of cancer death in Japan. Surgical resection is the only curative option for localized disease. However, undetectable micrometastases remaining after curative surgery may cause disease recurrence. Adjuvant chemotherapy aims to eradicate these micrometastases to improve the cure rate. Unfortunately, few reliable prognostic and predictive markers are available that identify patients at high risk for CRC during early-stage disease. However, promising biomarkers may become available in the near future. Such biomarkers provide information for stratifying a patient's risk and for selecting the optimal treatment. Here, we provide an overview of current relevant prognostic and predictive biomarkers applicable to adjuvant treatment of early-stage CRC and focus on the future of this field.