Colorectal cancer patients who present with obstructive symptoms or substantial bleeding may require emergent surgical intervention. However, treatment decisions for most other patients are best arrived upon following discussion with a multidisciplinary team comprising diagnostic and interventional radiologists, oncologists, colorectal and hepatobiliary surgeons, gastroenterologists, radiation oncologists, and pathologists (Figure 17.1). Expertise of other individuals, such as thoracic surgeons and genetic counselors, should be called upon, as necessary. The European Colorectal Metastases Treatment Group, the American Hepato-Pancreato-Biliary Association (AHPBA), the Society of Surgical Oncology (SSO), and the Society for Surgery of Alimentary Tract (SSAT) all emphasize a multidisciplinary approach to managing cancer patients, which improves efficiency and efficacy of patient care and generally results in better outcomes.⁶, ⁷ and ⁸

Multidisciplinary management improves comprehensive preoperative evaluation (i.e., computerized tomography imaging, serology testing for carcinoembryonic antigen [CEA] levels, transrectal ultrasound for local staging of rectal cancer), and better adherence to the National Comprehensive Cancer Network guidelines. Patients initially treated in specialized centers enjoy enhanced access to multimodal therapy and more frequent oncology consultation (99% vs. 62%) with higher rates of neoadjuvant therapy implementation (76% vs. 20%) as compared to institutions that utilize a more general surgical approach to colorectal cancer.⁹ Primary surgeries for colorectal cancers performed at specialized care centers are often of higher quality than those from institutions in which cancer patients are managed by general surgeons and pathologists. For example, longitudinal data from institutions transitioning to a subspecialized cancer management model show improvement in quality assurance measures after implementation of a multidisciplinary approach. They report higher numbers of harvested lymph nodes (16 ± 1 vs. 9 ± 1), more frequent negative surgical resection margins (95% vs. 78%), and a decline in the frequency of grossly positive resection margins (15% to 2.5%) among primary colorectal cancer resection specimens.¹⁰ Pathologic evaluation of colorectal cancers also improves when performed in the multidisciplinary setting and more commonly includes ancillary testing that may be clinically important, such as evaluation for microsatellite instability (30% vs. 11%).⁹

Finally, access to specialists affords colorectal cancer patients with more surgical options, particularly when they present with, or develop, advanced disease. Only a minority of patients with liver metastases treated in specialized centers receive palliative therapy alone, and nearly two-thirds of patients with hepatic metastases deemed unresectable by nonliver surgeons are considered potentially resectable by those with expertise in hepatobiliary surgery.¹¹ Most data demonstrate the value of collaboration and centralized specialty care in affecting treatment decisions, decreasing the number of interventions, shortening delays in care, reducing the number of chemotherapy cycles, and decreasing postoperative morbidity.

Many clinical and tumor-related factors are considered when patients with stage IV colorectal cancer contemplate surgical management of extracolonic disease. Clinical features that are commonly assessed in the preoperative evaluation of these individuals include patient age, gender, Eastern Cooperative Oncology Group performance status, and American Society of Anesthesiologists physical status classification (Table 17.1). Several groups have proposed prognostic scoring systems to identify individuals unlikely to benefit from surgical management of advanced disease. Of these, seven tumor-related features have emerged as independent factors associated with poor prognosis: the presence of extrahepatic distant disease, positive surgical margins, lymph node metastases from the primary tumor, fewer than 12 months between treatment of primary tumor and detection of liver metastases, size of largest tumor deposit in the liver (>5 cm), number of metastatic deposits in liver (>1), and CEA level in excess of 200 ng/mL.²,¹²

Some molecular alterations also correlate with prognosis among colorectal cancer patients with advanced disease. Increased expression of human telomerase reverse transcriptase (hTERT), glucose transporter-1 protein (GLUT-1), p27, and thymidylate synthase (TS) promote tumor growth, and tritiated thymidine uptake, high Ki-67 immunolabeling, and TP53 mutations are adverse prognostic factors among colorectal cancer patients.¹³, ¹⁴ and ¹⁵ Alterations that affect cell signaling pathways, such as those involving COX-2, KRAS, BRAF, iNOS, HMG-CoA, RXR-??,??-catenin, and STAT3, impact response to targeted chemotherapeutic agents and, thus, affect overall prognosis. Some of these molecular markers help identify patients who may respond to specific chemotherapy regimens. For example, KRAS mutational status directly affects the efficacy of epidermal growth factor receptor (EGFR) inhibitors, such as cetuximab, as discussed in Chapter 16.¹⁶ The American Society of Clinical Oncology and National Comprehensive Cancer Network now recommend that all patients with stage IV colorectal cancer who are candidates for anti-EGFR therapy undergo KRAS mutational testing of their tumors prior to initiation of treatment.¹⁷

Patients with stage IV colorectal cancer and extraintestinal disease at multiple sites may be considered for staged resection, provided that the managing team has a reasonable expectation of achieving complete surgical resection. Potential candidates must have excellent functional status and be in good health with family support and psychosocial stability. They must be able to tolerate systemic chemotherapy and show no disease progression during chemotherapy. Metastatic deposits that are least amenable to complete eradication are approached first, as patients should not be subjected to multiple procedures and cycles of chemotherapy before undergoing the least feasible operation.

Colorectal cancer patients presenting with colorectal disease and synchronous resectable liver metastases should be considered for curative therapy via simultaneous, or staged, resections of the primary tumor and hepatic metastases with integration of neoadjuvant and adjuvant therapy (Figure 17.2). Treatment strategies and their timing are individualized according to patient needs and, thus, are best determined in a multidisciplinary setting. All patients with synchronous or metachronous distant metastases deserve consideration by physicians with expertise in the management of advanced colorectal cancer, particularly if they are initially deemed unresectable. Key elements of current management strategies are discussed below.