Outcome of Primary Tumor in Patients With Synchronous Stage IV Colorectal Cancer Receiving Combination Chemotherapy Without Surgery As Initial Treatment

George A. Poultsides,1 Elliot L. Servais,1 Leonard B. Saltz,2

Sujata Patil,3 Nancy E. Kemeny,2 Jose G. Guillem,1 Martin Weiser,1 Larissa K.F. Temple,1 W. Douglas Wong1, Philip B.

Paty1 Departments of Surgery,1 Medicine,2 Epidemiology and Biostatistics,3

Memorial Sloan-Kettering Cancer Center, New York, NY

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.

• With recent advances in systemic chemotherapy and improvement in survival of stage IV CRC patients, the risks and benefits of a deferred surgical strategy have not been completely evaluated.

Purpose

To describe the frequency of primary tumor-related complications, which required operative or non-operative intervention, in patients who presented with synchronous stage IV CRC and who received up-front modern, triple-drug, oxaliplatin or irinotecan-based combination chemotherapy with or without bevacizumab, and no surgery as initial treatment.

MethodsInclusion Criteria:

• Patients who presented with synchronous, stage IV CRC and intact primary tumor

• January 1, 2000 and December 31, 2006 • Asymptomatic with regard to their primary tumor (no major

bleeding, perforation, impending obstruction)• No previous primary tumor–directed surgery, radiotherapy,

endoscopic stenting or ablation• Up-front, first-line chemotherapy

Bolus fluorouracil, leucovorin, and irinotecanOR

Infusional fluorouracil, leucovorin, and oxaliplatinOR

Infusional fluorouracil, leucovorin, and irinotecan With or without bevacizumab

ResultsCharacteristics of 233 patients identified:• Primary tumor location

• Right colon 37%• Left colon 29%• Rectum 34%

• Site of metastatic disease at presentation• Liver 95%• Retroperitoneal lymph nodes 39%• Lung 30%• Peritoneum 9%• Skeleton 2%• Brain

0.4%• Metastatic disease involved 1 site in 40%, 2 sites in 45%, and 3 or more sites in 14% of patients

Results

Results

• The need for emergent intervention did not correlate with overall survival when included as a time-varying covariate in a Cox regression model (p=0.81).

• The risk of emergent intervention was not associated with age (p=0.10), primary tumor anatomic location (p=0.19), number of metastatic sites (p=0.20), use of bevacizumab (p>0.99), CEA (p=0.18), albumin (p>0.99), LDH (p=0.80), or alkaline phosphatase level (p=0.33)

Conclusion• Of 233 patients with confirmed intact primary tumor who received

modern, triple-drug, combination chemotherapy for synchronous stage IV colorectal cancer at MSKCC, 93% never required surgery to palliate primary tumor-related complications.

• The overall peri-operative mortality of 0.8% for this population compares very favorably with what would have been expected, based on historical comparators, had all patients undergone initial palliative resection of the primary.

• These data strongly support the appropriateness of non-operative management as initial treatment for patients with intact primary CRC and synchronous metastases in the absence of overt obstruction or severe acute bleeding.  Such patients should not undergo resection of the primary tumor prior to initiation of chemotherapy.