Surgical removal of the primary tumor at the time of diagnosis was once standard practice and is still common in patients with metastatic colorectal cancer. Because cancer has already spread to other parts of the body by this stage, the purpose of this surgery is not to extend survival, but to prevent future complications, such as intestinal blockage, perforation of the bowel, and severe bleeding. However, over the past decade several new effective chemotherapy drugs for colorectal cancer have been introduced and until now there has been little data to assess whether this pre-emptive surgery is still warranted.
The research will be presented on Monday, June 1, by Philip B. Paty, MD, Memorial Sloan-Kettering Cancer Center, New York, NY, during the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO) being held from May 27 – June 2, 2009 in Orlando, Florida.
Incidence of metastatic Colorectal Cancer (mCRC)
According to GLOBOCAN 2002, a cancer incidence database produced by the International Agency for Research on Cancer (IARC) of the World Health Organization (WHO), the worldwide incidence of colorectal cancer is approximately one million cases per year. The National Cancer Institute (NCI) reports that approximately 50 percent of patients diagnosed with colorectal cancer will suffer from advanced disease that has metastasized to other parts of the body, most commonly to the liver.
Uncertain benefit
The researchers rationale is that in the absence of symptoms (bleeding, perforation, obstruction)
or resectable metastatic disease, primary tumor resection in patients who present with synchronous metastatic colorectal cancer (mCRC) is of uncertain benefit.The purpose of their 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.
“In this era of modern chemotherapy, routine surgery to remove the primary tumor in patients with unresectable metastases is no longer supported by the data,” explained Philip Paty, MD, an attending surgeon and vice chairman of clinical research at Memorial Sloan-Kettering Cancer Center (MSKCC) and the study’s senior author. “In addition to being an unnecessary procedure that carries its own risks of morbidity and mortality, surgery delays the start of chemotherapy for several weeks, and in some cases may make the patient less fit for and less tolerant of chemotherapy. Unless there is an immediate need for surgery, patients should begin chemotherapy first.”
FOLFOX, IFL and FOLFIRI
This retrospective study identified 233 consecutive patients who presented with metastatic colorectal cancer between 2000 and 2006, and were treated with chemotherapy at MSKCC, but had no serious symptoms to prompt immediate surgery. The patients received one of three triple-drug chemotherapy combinations as their initial treatment (the regimens known as FOLFOX, IFL, and FOLFIRI).
Some were also treated with the targeted therapy bevacizumab (Avastin, Roche).
Investigators determined that 217 (93%) patients never developed complications that required removal of their tumor. For the 16 patients (7%) who did eventually need surgery, the vast majority (14/16) had successful operations.
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 was 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.
Most patients with synchronous stage IV CRC who receive up-front modern combination chemotherapy never required palliative surgery for their intact primary. The 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.
Overall, the researchers concluded that the mortality attributable to surgery was very low (0.8 percent), suggesting that this approach, by avoiding unnecessary surgery, improves the overall safety of treatment.
For more information:
- American Society for Clinical Oncology (ASCO)
- Poultsides GA , Servais EL, Saltz LB, Patil S, Kemeny NE, Guillem JG, Weiser M, Temple LK, Wong W, Paty PB. Outcome of primary tumor in patients with synchronous stage IV colorectal cancer receiving combination chemotherapy without surgery as initial Treatment. CRA4030
PubMed abstracts:
- Van Cutsem E, Rivera F, Berry S, Kretzschmar A, Michael M, et al. Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol. 2009 Apr 30. [Epub ahead of print].
- Dy GK, Hobday TJ, Nelson G, Windschitl HE, O'Connell MJ, et al. Long-term survivors of metastatic colorectal cancer treated with systemic chemotherapy alone: a north central cancer treatment group review of 3811 patients, n0144. Clin Colorectal Cancer. 2009 Mar;8(2):88-93.
- Tamandl D, Gruenberger B, Herberger B, Kaczirek K, Gruenberger T. Surgery after neoadjuvant chemotherapy for colorectal liver metastases is safe and feasible in elderly patients. J Surg Oncol. 2009 Feb 20. [Epub ahead of print]
- Cao Y, Liao C, Tan A, Liu L, Mo Z, Gao F. Capecitabine plus oxaliplatin versu fluorouracil plus oxaliplatin as first line treatment for metastatic colorectal caner - meta-analysis of six randomized trials. Colorectal Dis. 2009 Feb 7. [Epub ahead of print]
Other ASCO 2009 abstracts:
- A phase III trial comparing mFOLFOX6 to mFOLFOX6 plus bevacizumab in stage II or III carcinoma of the colon: Results of NSABP Protocol C-08.
Meeting:2009 ASCO Annual Meeting Abstract No: LBA4 First Author: N. Wolmark Category: Gastrointestinal (Colorectal) Cancer - Colorectal Cancer (including liver metastases) - A quantitative multigene RT-PCR assay for prediction of recurrence in stage II colon cancer: Selection of the genes in four large studies and results of the independent, prospectively designed QUASAR validation study.
Meeting:2009 ASCO Annual Meeting Abstract No: 4000 First Author: D. KerrCategory:Gastrointestinal (Colorectal) Cancer - Colorectal Cancer (including liver metastases) - Microsatellite instability (MSI) in stage II and III colon cancer treated with 5FU-LV or 5FU-LV and irinotecan (PETACC 3-EORTC 40993-SAKK 60/00 trial).
Meeting:2009 ASCO Annual Meeting Abstract No: 4001 First Author: S. TejparCategory:Gastrointestinal (Colorectal) Cancer - Colorectal Cancer (including liver metastases)
Illustration courtesy of the American Society of Clinical Oncology.
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