Resection vs no Resection of the Primary in Colorectal Cancer With Unresectable Metastases

Multicenter Randomized Study in Patients With Colorectal Cancer With Unresectable Metastases. Impact of Resection vs no Resection of the Primary Tumour as a Survival Factor

Main outcome: Assess the impact of cancer-related survival at 2 years in patients with unresectable metastatic colorectal cancer treated with chemotherapy alone versus surgery followed by chemotherapy. To assess overall survival. To evaluate postoperative morbidity and mortality in patients treated with resection of the primary tumor. Assess complications and meed for surgery in patients treated with systemic chemotherapy only during the course of the disease. Identify and describe the complications related to chemotherapy and toxicity in the short and medium term systemic treatment. Assessing the quality of life questionnaire QLQ-C30 and QLQ-CR29. To study prognostic survival factors.

Method: multicenter randomized clinical trail (22 hospitals). Two parallel group in which to evaluate two therapeutic strategies for colorectal cancer metastasis unresectable stage IV: chemotherapy alone versus primary tumor resection plus chemotherapy.

Subjects: patients with unresectable nonmetastatic colorectal cancer. Hypothesis:Surgical resection of the primary tumor in stage IV colorectal patients with unresectable synchronous metastases increases by 14% overall survival compared to patients receiving systemic treatment with chemotherapy without resection of the primary tumor (survival of 34% vs 20%).

Intervention: Arm B (control): chemotherapy alone, regimen according to each center. Arm A (experimental): surgery (complete tumoral resection; R0) followed by chemotherapy, regimen according to each center. Statistical Analysis: A power analysis showed that to assure a significance level of 0,05 and a beta error 0.20. 168 patients are necessary in each arm. It has been estimated a loss rate of up to 10%.

Differences between groups will be analyzed by t, U, X2, exact test and survival will be assessed according to Kaplan and Meier method. Evaluation of safety of the trial will be made in the middle of the study statistically

Inclusion Criteria:

• colorectal cancer above to 12 cm from the anal verge
• unresectable synchronous metastases
• no contraindications for chemotherapy
• absence of peritoneal carcinomatosis, central nervous system o bone metastasis.
• performance status ECOG ≤ 2 (Eastern Cooperative Oncology Group)
• uncontrolled concomitant medical conditions that may compromise to chemotherapy
• significant symptomatic cardiac disease
• not pregnancy or breastfeeding

Exclusion Criteria:

• Cases of rectal tumours below 12cm from anal verge, or locally advanced tumours invading blood vessels, nerves or bone.
• Multiple bone metastasis or central nervous system metastasis
• Other neoplastic disease in the 5 previous years, except squamous or basal cell skin carcinoma or cervical "in situ" carcinoma
• Significant heart disease (chronic congestive heart failure, symptomatic coronary disease) or myocardial infarction in the previous 6 months
• Peripheral neuropathy
• Patients who do not give informed consent