CRA4030 Background: In the absence of symptoms (bleeding, perforation, obstruction) or resectable metastatic disease, primary tumor resection in patients who present with synchronous metastatic colorectal cancer (CRC) is of uncertain benefit. The purpose of this study was to describe the frequency of intervention necessary to palliate the intact primary tumor in patients who present with synchronous stage IV CRC and receive up-front modern combination chemotherapy without prophylactic surgery. Methods: Using a prospective institutional database, we identified 233 consecutive patients from 2000 through 2006 with synchronous metastatic CRC and an unresected primary tumor who received oxaliplatin- or irinotecan-based, triple-drug chemotherapy (FOLFOX, IFL, or FOLFIRI) with or without bevacizumab as their initial treatment. The incidence of subsequent use of surgery, radiotherapy, and/or endoluminal stenting to manage primary tumor complications was recorded. Results: Of 233 patients, 217 (93%) never required surgical palliation of their primary tumor. Sixteen patients (7%) required emergent surgery for primary tumor obstruction or perforation, 10 patients (4%) required nonoperative intervention (stent or radiotherapy), whereas 213 (89%) never required any direct symptomatic management for their intact primary. Of those, 47 (20%) ultimately underwent elective colon resection at the time of metastasectomy and 8 (3%) during laparotomy for hepatic artery infusion pump placement. Neither use of bevacizumab, location of the primary tumor in the rectum, or metastatic disease burden were associated with increased intervention rate. In addition, when included as a time-varying covariate in a Cox regression model, the need for emergent intervention did not correlate with overall survival. Conclusions: Most patients with synchronous stage IV CRC who receive up-front modern combination chemotherapy never require palliative surgery for their intact primary. These data support the use of chemotherapy, without routine prophylactic resection, as the appropriate standard practice for patients with neither obstructed nor hemorrhaging primary colorectal tumors in the setting of metastatic disease. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Bristol-Myers Squibb, Genentech, ImClone, Pfizer, Roche sanofi-aventis Amgen, Bristol-Myers Squibb, Genentech, ImClone, Pfizer, Roche, sanofi-aventis