Regional Lymph Nodes Status and Ratio of Metastatic to Examined Lymph Nodes Correlate with Survival in Stage IV Colorectal Cancer.

BACKGROUND: Although lymph nodes status and the ratio of metastatic to examined lymph node (LNR) are important prognostic factors in early-stage colorectal cancer (CRC), their significance in patients with metastatic disease remains unknown. The study aims to determine prognostic importance of nodal status and LNR in patients with stage IV CRC. METHODS: A cohort of 1109 eligible patients who were diagnosed with synchronous metastatic CRC in Saskatchewan during 1992-2010 and underwent primary tumor resection was evaluated. We conducted the Cox proportional multivariate analyses to determine the prognostic significance of nodal status and LNR. RESULTS: Median age was 70 years (22-98) and M:F was 1.2:1. Rectal cancer was found in 26 % of patients; 96 % had T3/T4 tumor, and 82 % had node positive disease. The median LNR was 0.36 (0-1.0). Fifty-four percent received chemotherapy. Median overall survival of patients who had LNR of <0.36 and received chemotherapy was 29.7 months (95 % CI 26.6-32.9) compared with 15.6 months (95 % CI 13.6-17.6) with LNR of ≥0.36 (P < .001). On multivariate analyses, no chemotherapy (HR 2.36 [2.0-2.79]), not having metastasectomy (HR 1.94 [1.63-2.32]), LNR ≥0.36 (HR 1.59 [1.38-1.84]). nodal status (HR 1.34 [1.14-1.59]), and T status (HR 1.23 [1.07-1.40]) were correlated with survival. Test for interaction was positive for LNR and high-grade cancer (HR 1.51 [1.10-2.10]). CONCLUSIONS: Our results suggest that nodal status and LNR are important prognostic factors independent of chemotherapy and metastasectomy in stage IV CRC patients.

Predictive Factors of the Use of Systemic Therapy in Stage IV Colorectal Cancer: Who Gets Chemotherapy?

BACKGROUND: Chemotherapy improves survival in patients with stage IV colorectal cancer (CRC). Although in a clinical trial setting, strict eligibility criteria are used for chemotherapy, little is known about the use of chemotherapy in the general population. The study aims to assess clinicopathological variables that correlate with the use of chemotherapy in patients with stage IV CRC. METHODS: A retrospective cohort study involving patients with stage IV CRC, diagnosed between 1992 and 2005, in the province of Saskatchewan was carried out. A logistic regression analysis was performed to assess the correlation of various clinicopathological factors with the use of chemotherapy. RESULTS: A total of 1,237 eligible patients were identified. Their median age was 70 years (range: 22-98) and the male:female ratio was 1.3:1. 23.8% had an ECOG performance status (PS) of ≥2 and 61.8% of the patients had a comorbid illness. 46.8% of the patients received chemotherapy. The multivariate logistic regression analysis revealed that an age of <65 years [odds ratio (OR) 3.82, 95% CI: 2.59-5.63], metastasectomy (OR 3.60, 95% CI: 1.82-7.10), normal albumin (OR 3.26, 95% CI: 2.44-4.36), no comorbid illness (OR 2.87, 95% CI: 1.34-6.16), ECOG PS of <2 (OR 2.72, 95% CI: 1.94-3.82), normal blood urea nitrogen (OR 2.24, 95% CI: 1.40-3.59), palliative radiation (OR 2.03, 95% CI: 1.38-2.99), primary tumor resection (OR 2.00, 95% CI: 1.47-2.73), and the time period (OR 1.85, 95% CI: 1.41-2.42) were significantly correlated with the use of chemotherapy. CONCLUSIONS: The use of chemotherapy appears to be increasing in stage IV CRC. Patients treated with curative intention or who underwent primary tumor resection were more likely to receive chemotherapy. Despite a known benefit of chemotherapy in elderly patients, a differential use of chemotherapy was noted in this population.

Survival impact of surgical resection of primary tumor in patients with stage IV colorectal cancer: results from a large population-based cohort study.

BACKGROUND: Currently, there is very low-quality evidence available regarding benefit of surgical resection of the primary tumor (SRPT), in patients with stage IV colorectal cancer (CRC). In the absence of randomization, the reported benefit may reflect selection of younger and healthier patients with good performance status. A large population-based cohort study was undertaken to determine the survival benefit of SRPT in advanced CRC by eliminating various biases reported in the literature. METHODS: A retrospective cohort study involving patients with stage IV CRC, diagnosed between 1992 and 2005, in the province of Saskatchewan, Canada. Survival was estimated by using the Kaplan-Meier method. Survival distribution was compared by log-rank test. Cox proportional multivariate regression analysis was performed to determine survival benefit of SRPT by controlling other prognostic variables. RESULTS: A total of 1378 eligible patients were identified. Their median age was 70 years (range, 22-98 years) and male:female ratio was 1.3:1; 944 (68.5%) of them underwent SRPT. Among 1378 patients, 42.3% received chemotherapy and 19.1% received second-generation therapy. Patients who underwent SRPT and received chemotherapy had median overall survival of 18.3 months (95% confidence interval [CI] = 16.6-20 months) compared with 8.4 months (95% CI = 7.1-9.7 months) if they were treated with chemotherapy alone (P < .0001). Cox proportional analysis revealed that use of chemotherapy (hazard ratio [HR] = 0.47, 95% CI = 0.41-0.54), SRPT (HR = 0.49, 95% CI = 0.41-0.58), second-line chemotherapy (HR = 0.47, 95% CI = 0.45-0.64), and metastasectomy (HR = 0.54, 95% CI = 0.45-0.64) were correlated with superior survival. CONCLUSIONS: SRPT improves survival in patients with stage IV CRC, independent of other prognostic variables including age, performance status, comorbid illness and chemotherapy.

Primary Tumor Location and Survival in the General Population With Metastatic Colorectal Cancer.

BACKGROUND: Recent evidence from clinical trials suggests that primary tumor location in patients with metastatic colorectal cancer correlates with differential outcomes, and patients with tumors originating in the right side of the colon have inferior survival. We conducted a large population-based cohort study using individual patient data to confirm the prognostic importance of primary tumor location in the general population with metastatic colorectal cancer. METHODS: A cohort of 1947 patients who were diagnosed with metastatic colorectal cancer from 1992 to 2010 was studied. Ascending and transverse colon cancers were defined as right-sided tumors. Cox proportional multivariate analyses were done to determine prognostic significance of primary tumor location. RESULTS: The median age was 70 years (interquartile range, 60-78 years), and the male to female ratio was 1.3:1. Twenty-nine percent had World Health Organization performance status of > 1. Seven-hundred and seventy (39%) patients had right-sided tumors, and 908 (47%) received chemotherapy. The median overall survival of patients with right-sided tumors was 14 months (95% confidence interval [CI], 12.7-15.3 months) compared with 20.5 months (95% CI, 18.5-22.5 months) of patients with left-sided tumors (P < .001). On multivariate analysis, right-sided tumors (hazard ratio [HR], 1.40; 95% CI, 1.20-1.60), no metastasectomy (HR, 2.40; 95% CI, 1.90-2.90), intact primary tumor (HR, 1.60; 95% CI, 1.32-1.90), an elevated carcinoembryonic antigen level (HR, 1.54; 95% CI, 1.30-1.90), lack of combination chemotherapy (HR, 1.52; 95% CI, 1.31-1.80), stage IVb disease (HR, 1.50; 95% CI, 1.17-1.86), leukocytosis (HR, 1.44; 95% CI, 1.28-1.73), and World Health Organization performance status > 1 (HR, 1.30; 95% CI, 1.10-1.55) were correlated with inferior survival. CONCLUSIONS: Our results confirm that individuals with metastatic colorectal cancer and right-sided tumors who received chemotherapy have inferior survival independent of other known prognostic variables. Future studies are required to understand the underlying pathophysiology.

Surgical Management of the Primary Tumor in Stage IV Colorectal Cancer: A Confirmatory Retrospective Cohort Study.

BACKGROUND: Observational studies have suggested that patients with stage IV colorectal cancer who undergo surgical resection of the primary tumor (SRPT) have better survival. Yet the results are not confirmed in the setting of a randomized controlled trial. Lack of randomization and failure to control prognostic variables such as performance status are major critiques to the findings of the observational studies. We previously have shown that SRPT, independent of chemotherapy and performance status, improves survival of stage IV CRC patients. The current study aims to validate our findings in patients with stage IV CRC who were diagnosed during the period of modern chemotherapy. METHODS: A cohort of 569 patients with stage IV CRC diagnosed during 2006-2010 in the province of Saskatchewan was evaluated. Cox regression model was used for the adjustment of prognostic variables. RESULTS: Median age was 69 years (59-95) and M: F was 1.4:1. Fifty-seven percent received chemotherapy, 91.4% received FOLFIRI or FOLFOX & 67% received a biologic agent. Median overall survival (OS) of patients who underwent SRPT and received chemotherapy was 27 months compared with 14 months of the non-resection group (p<0.0001). Median OS of patients who received all active agents and had SRPT was 39 months (95%CI: 25.1-52.9). On multivariate analysis, SRPT, hazard ratio (HR):0.44 (95%CI: 0.35-0.56), use of chemotherapy, HR: 0.33 (95%CI: 0.26-0.43), metastasectomy, HR: 0.43 (95%CI: 0.31-0.58), second line therapy, HR: 0.50 (95%CI: 0.35-0.70), and third line therapy, HR: 0.58 (95%CI: 0.41-0.83) were correlated with superior survival. CONCLUSIONS: This study confirms our findings and supports a favorable association between SRPT and survival in patients with stage IV CRC who are treated with modern therapy.

Surgical Resection of Primary Tumor in Asymptomatic or Minimally Symptomatic Patients With Stage IV Colorectal Cancer: A Canadian Province Experience.

BACKGROUND: Surgical resection of the primary tumor in patients with stage IV colorectal cancer (CRC) remains controversial. Survival benefit reported in the literature has been attributed to the selection of younger and healthier patients with good performance status. We have recently reported that resection of the primary tumor improved survival of patients with stage IV CRC. In this study we examined survival benefit of surgery in patients with asymptomatic or minimally symptomatic primary tumor. PATIENTS AND METHODS: A cohort of patients with stage IV CRC and asymptomatic or minimally symptomatic primary tumor, who were diagnosed during the period of 1992 to 2005, in the province of Saskatchewan Canada, was evaluated. The Kaplan-Meier method was used to determine survival. A multivariate Cox proportional hazard regression analysis was performed to determine prognostic importance of resection of primary tumor. A test for interaction was performed for resection of primary tumor and other important clinicopathological variables. RESULTS: A total of 834 patients with a median age of 70 years (range, 22-93) and male:female ratio of 58:42 were identified. Among them 521 (63%) patients underwent surgery and 361 (43.3%) received chemotherapy. Patients who underwent surgery and received any chemotherapy had a median overall survival of 19.7 months (95% confidence interval [CI], 16.9-22.6) compared with 8.4 months (95% CI, 6.9-10.0) if they did not have surgery (P < .0001). In multivariate analysis, 5-fluorouracil-based chemotherapy (hazard ratio [HR], 0.43; 95% CI, 0.36-0.53), surgical resection of the primary tumor (HR, 0.47; 95% CI, 0.39-0.57), metastasectomy (HR, 0.48; 95% CI, 0.38-0.62), and second-line chemotherapy (HR, 0.72; 95% CI, 0.58-0.92) were correlated with superior survival. A test for interaction between ≥ 1 metastatic sites and surgery was significant, which suggests a larger benefit of surgery in patients with stage IVA disease. CONCLUSION: Results of this large population-based cohort study suggest that resection of the primary tumor in asymptomatic or minimally symptomatic patients with stage IV CRC improved survival independent of other prognostic variables. The benefit was more pronounced in stage IVA disease.