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Leave well enough alone? The role of resection in asymptomatic metastatic CRC

Posted Dec 13 2009 12:00am

The standard of care for treatment of mCRC has been surgical resection followed by adjuvant chemotherapy.  In patients presenting with symptomatic mCRC, palliative surgery is performed for bleeding, obstruction, or perforation, while in patients presenting with non-emergent symptoms and limited disease, surgery may be undertaken with a curative intent.  The role and value of surgery in patients with unresectable stage 4 colon cancer and a synchronous asymptomatic primary tumor is being currently investigated by the National Surgical Adjuvant Breast and Bowel Project in a prospective phase II study (NSABP C-10).  Current recommendations for treatment of mCRC are:

  1. Patients with evidence of significant obstruction, perforation, or uncontrolled bleeding should undergo resection of the symptomatic lesion.
  2. Patients who are unfit for surgery, or who decline surgery, should undergo endoscopic management with stents or ablation to palliate symptoms.
  3. Patients with potentially resectable metastases should undergo resections of both the primary tumor and the metastases (typically, sequentially).
    1. Chemotherapy may be administered preoperatively to assess the natural history of the underlying malignancy.
    2. If disease controlled is obtained with chemotherapy, resection of primary and secondary lesions should be considered.
  4. In patients who have diffuse, metastatic CRC with unresectable metastases, modern polychemotherapy with targeted agents will offer disease control without the mortality and morbidity of surgery directed at the primary lesion.

The hypothesis of this study is that, given the dramatic improvement in response rates with current regimens incorporating oxaliplatin and irinotecan with biologics such as bevacizumab and cetuximab, systemic chemotherapy without resection of the primary tumor is a reasonable alternative to the standard approach in these patients.  This approach takes into account the morbidity and mortality associated with colectomy in these patients compared to the potential survival benefit in an incurable disease where <10% of patients survive 5 years. 

Patients  will be treated with 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus bevacizumab. The goal is to determine if this approach leads to an increase in “major morbidity” defined as any event related to the intact primary tumor necessitating surgery or resulting in patient death. The results of this study should be very interesting and could represent a real change in thinking about how we treat primary tumors. Oncologist. 2009;14(10):963-969.

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