Adnan Zaidi

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.

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.

The Management of the Primary Tumor in Patients with Metastatic Colorectal Cancer

Over the past decade, the role of surgery in stage IV colorectal cancer (CRC) has evolved, yet the optimal surgical management of the primary tumor in patients with metastatic CRC that is not amenable to curative resection is unknown. A high rate of surgical resection of the primary tumor has been reported in patients with unresectable metastatic disease. Resection of the primary tumor in patients with metastatic CRC is often performed to deal with presenting primary tumor symptoms and or to prevent future primary tumor complications. Nevertheless, with access to novel agents and their efficacy in the primary tumor as well as lack of major complications related to an intact primary tumor, surgery is less commonly performed today. Although the data regarding survival advantages of resection of the primary tumor are inconsistent, overall the evidence suggests potential survival benefit of removal of the primary tumor in patients with both symptomatic and asymptomatic primary tumors even with access to more effective combination chemotherapy. However, the published literature favoring surgery mostly comprises retrospective observational studies. Consequently, the survival benefit related to surgery has been attributed to selection bias, and in the absence of randomized controlled trial no definite conclusion can be drawn. Current‐ ly, two randomized controlled trials are enrolling patients to answer this important question in the management of metastatic CRC.

Prognostic significance of regional lymph nodes status in stage IV colorectal cancer.

721 Background: Lymph node involvement is one of the most important prognostic variables in early stage CRC and an indication for adjuvant therapy. However, the prognostic significance of regional nodal metastases and the ratio of metastatic to examined lymph nodes (LNR), in stage IV CRC remain unknown. The current study aims to determine prognostic importance of nodal status and LNR in patients with stage IV CRC who undergo primary tumor resection (PTR). Methods: Retrospective cohort study involving patients with synchronous metastatic CRC diagnosed in Saskatchewan, during 1992-2010 and underwent PTR. Cox Proportional multivariate analyses were performed to determine prognostic significance of nodal status and LNR. Results: 2,294 patients were diagnosed with synchronous metastatic CRC during the study period. Of those 1257 underwent PTR, 148 patients did not have information about nodal status and were excluded. Median age of 1109 eligible patients was 70 yrs (22-98) and M:F was 1.2:1. 26% patients had r...