The standard of care for patients with an initial diagnosis of stage IV colorectal cancer (CRC) has been to resect the primary tumor before beginning systemic chemotherapy. The reason for resecting the tumor immediately after diagnosis has been: (1) to prevent tumor-related complications (e.g. obstruction) that might require emergent surgery during the subsequent treatment course; (2) emergent surgery is often associated with higher mortality; Advocates of deferring surgery believe waiting for recovery from primary surgery delays systemic chemotherapy. A recent epidemiology survey using Surveillance Epidemiology and End Results (SEER) information showed that in the 1990s, more than 2/3 of patients who presented with synchronous, stage IV CRC underwent up-front surgical resection of the primary tumors.1

Poultsides and colleagues2 conducted a prospective study to describe the incidence of primary tumor-related complications that required operative or non-operative intervention in patients who presented with stage IV CRC and who received triple-drug, oxaliplatin- or irinotecan-based combination chemotherapy with or without bevacizumab.

Results
Tumor-Directed Interventions
Of the 233 patients studied, 217 patients (93%) never required surgical intervention for primary tumor-related symptoms. Sixteen (7%) underwent emergent surgery, including eight resections and eight diversion procedures. Of the eight resections, five were performed for perforation, all at the site of the primary tumor. Two of the perforations occurred while patients were on bevacizumab treatment, which carries a 1%-2% risk of GI perforation.3 Two of the perforations were in patients who did not receive bevacizumab. The remaining three resections were performed for primary tumor obstruction. Of the 217 patients who never required emergent surgery, 47 (20% of entire cohort) eventually underwent elective curative resection of their primary tumors and metastatic disease at a median time of 6 months (range 5 to 32 months) from initiation of chemotherapy.

Discussion
Among patients with stage IV CRC and a confirmed intact primary tumor who received up-front, modern combination chemotherapy, the incidence of major complications that involved the primary tumor and required surgery was low (7%). The authors concluded that the low incidence of late, symptom-directed intervention does not justify routine use of prophylactic surgery or radiotherapy in this setting and suggest that proceeding immediately after diagnosis with prompt initiation of systemic therapy should be regarded as routine standard practice for treating patients with synchronous metastatic colorectal cancer without overt obstruction or hemorrhage.2

One limitation to this study is that all subjects received care at one institution, MSKCC. The authors noted that they chose a single-site study to assure that all complications would be captured and primary-related complications would be addressed in a timely manner. A multi-site, prospective, randomized study would provide data to offset this bias. The National Surgical Adjuvant Breast and Bowel Project (NSABP) is supporting Protocol C-10, A phase II Trial of 5-fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) Chemotherapy plus Bevacizumab for Patients with Unresectable Stage IV Colon Cancer and Synchronous Asymptomatic Primary Tumor. The primary aim of NSABP C-10 is to determine the rate of major morbidity for patients who are treated with mFOLFOX6 + bevacizumab without resection of the primary tumor. Information on NSABP C-10 can be found at http://www.nsabp.pitt.edu/C10_Information.asp

References  

1. Cook AD, Single R, McCahill LE et al. Surgical resection of primary tumors in patients who present with stage IV colorectal cancer: An analysis of Surveillance, Epidemiology, and End Results data, 1988 to 2000. Ann Surg Oncol. 2005;12:637-645. Link to abstract http://www.springerlink.com/content/h290x3302727n663/?p=eef6220f599d4826b57fb17f82c8cf3a&pi=1

2. Poultsides GA, Servais EL, Saltz LB, et al. Outcome of primary tumor in patients with synchronous stage IV colorectal cancer receiving combination chemotherapy without surgery as initial treatment. J Clin Oncol. 2009;27:3379-3384. Link to abstract http://jco.ascopubs.org/cgi/content/abstract/27/20/3379

3. Hapani S, Chu D, Shenhong W. Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysis. Lancet Oncol. 2009;10:559-568. Link to abstract http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(09)70112-3/abstract