Key Concept: A multidisciplinary tumor board to review the specifics of each individual patient’s case provides a great opportunity to determine the ideal treatment plan and optimize outcomes.

A multidisciplinary approach to treatments of all types of cancer has long been advocated [2]. Given that many different modalities may be utilized in the treatment of Stage 4 colorectal cancer, a multidisciplinary approach is strongly recommended. The various disciplines can include surgery (including colorectal surgery, hepatobiliary surgery, thoracic surgery), medical oncology, radiation oncology, palliative care, radiology, and pathology. Through a thorough discussion of the patient’s overall condition and symptoms, the goals of care and potential curative versus palliative intent of treatment can be made. Many centers employ a tumor board conference where an individual case can be presented to representatives from each of the above specialties. A review of the patient’s history, relevant radiologic studies, pathology, and general medical condition can be made followed by discussion and input from all members of the team. This will allow for understanding of the condition of the patient, any prior treatments, as well as an explanation of goals of care. An honest discussion of the realistic expectations and prognosis of the patient can occur as well. Finally, the team can formulate a plan to include inclusion/exclusion of each therapeutic modality as well as discuss and plan for timing of each of the included treatments. This up-front communication will assure that all members of a patient’s treatment team are “on the same page.” An additional by-product of this is that the patient may further benefit from this communication by frequently precluding the need for multiple initial consults, thereby saving the patient time and energy.

Often, the questions raised at the multidisciplinary meeting revolve around timing of chemotherapy and/or radiation and the role of surgical resection. Occasionally, the oncologists and surgeons disagree as to the expectations of therapy, appropriate timing of the various therapeutic options, or when care is futile. It is not always clear which opinion is most appropriate for the patient, especially with very complex cases that cannot easily be compared to a specific trial or literature search for guidance. In cases where there are strongly held opinions that are divergent, it should be recommended to the patient to obtain a second opinion, most often from both medical oncology as well as another experienced surgeon.

Key Concept: Improvements in chemotherapeutics have allowed longer survival and an evolving role for resection following response to therapy.

In the past, many patients presenting with Stage 4 disease were started on chemotherapy (5-FU and leucovorin), and there was often felt to be a limited role for any operation. As chemotherapeutics have evolved over the last two decades (with the addition of oxaliplatin, irinotecan, cetuximab, bevacizumab, and others), patients are living longer (median survival up to 24 months or more) than ever before [3, 4], and an ever-increasing number of patients have a realistic chance of cure. As we continue to better understand the biology of colorectal cancers and the role for various adjuvant therapies, outcomes will continue to improve. A significant number of patients with initially surgically incurable disease burden are currently being treated aggressively with what has become neoadjuvant chemotherapy to the point that surgical options for cure are once again entertained. An example of this would be a patient presenting with extensive liver metastases to the point that curative resection is not feasible. After several rounds of chemotherapy, the tumor burden in the liver is reduced to the point that curative intent treatment is possible.

The Food and Drug Administration (FDA) has recently approved two new chemotherapy agents for the treatment of metastatic disease. Aflibercept (commercial name Zaltrap™, also known as VEGF Trap) is a fusion protein which binds all forms of vascular endothelial growth factor-A (VEGF-A), as well as VEGF-B, and placental growth factor (PIGF). The VELOUR study was a multinational, randomized, double-blind trial comparing FOLFIRI in combination with either Zaltrap™ or placebo. The study randomized 1,226 patients who previously had been treated with an oxaliplatin-based regimen. The addition of Zaltrap™ to the FOLFIRI regimen significantly improved both overall survival (13.5 vs. 12.1 months) and progression-free survival (6.9 vs. 4.7 months) [5].

The FDA also recently approved regorafenib (commercial name Stivarga™), an oral multi-kinase inhibitor which targets angiogenic, stromal, and oncogenic receptor tyrosine kinases. The CORRECT study enrolled 760 individuals whose disease had progressed during or within 3 months following the last administration of approved standard therapies. Median overall survival for regorafenib was 6.4 months, compared with 5.0 months for those who received placebo [6]. While modest improvements in survival with these additional agents may not significantly change practice patterns, they represent other options for patients with previously recalcitrant disease.

The past two decades have not only seen an improvement in available chemotherapeutic agents, but we have also seen an improvement in the understanding of the role of liver resection for metastatic lesions as well as the enhanced utilization of ablative techniques (e.g., radiofrequency ablation). Indications for operation have broadened, while contraindications have loosened as the operations have become safer and more common (see below—Liver Metastases).

Key Concept: Clear communication with the patient and their family is critical to discuss the goals and realistic expectations of an operation in the setting of metastatic disease.

There are two general goals of an operation: curative and palliative. More to the point, when discussing the indication for operation in patients with colorectal cancer, the goal is generally either to attempt a cure (curative) or to relieve a specific symptom (palliative). The specific indication for a patient set to undergo palliative operation will depend upon the symptom/complaint to be alleviated, such as to relieve an obstruction. It is important that during preoperative discussions and evaluation, the surgeon clearly identifies the goal of an operation with the patient and family members. A realistic discussion of prognosis is important in order for the patient to understand any proposed procedure and to have realistic expectations of the operation as well as the postoperative course.

Of the roughly 20 % of patients that present with Stage 4 disease, there is a substantial subset that has a realistic chance of being treated and cured, for example, a patient with colon cancer and unilobar liver metastases. There are multiple options for treatment of this patient in terms of order of therapy. In general, the patient will benefit from chemotherapy and surgical resection of both the primary as well as the liver for cure. Again, a strong recommendation for multidisciplinary planning is made. Traditionally, these patients underwent colon resection followed by liver resection (or occasionally synchronously) followed by systemic chemotherapy. Recently, many experts have recommended taking a “liver first” approach to these patients and perhaps proceed with systemic chemotherapy to establish an effective regimen, followed by liver resection [7]. The colon resection may also occur at the same operation, or, alternatively, they may be performed in a staged setting. We generally base that decision upon the condition of the patient, the extent and difficulty of the liver and colonic resections, and how well/easily the liver resection goes. For staged operations, some patients will benefit from further systemic chemotherapy between the procedures [8]. Alternatively, the patient could undergo the second resection prior to resumption of systemic chemotherapy. Our bias is to base recommendations for treatment on the patient’s symptoms and response to therapy. Colonic lesions that virtually “melt away” are left to further rounds of chemotherapy (Fig. 6.2), whereas significant bleeding or nearly obstructive lesions typically warrant consideration for resection followed by completion chemotherapy.

Unfortunately, some patients will present with Stage 4 disease for which cure is not realistic. Determining which symptoms can be surgically palliated is a very difficult process. A patient may have vague symptoms and be found to have metastatic disease, but determining cause and effect for a specific symptom, and thereby determining the possibility of surgical palliation, can be challenging. Bowel obstruction may be a more intuitive predicament as CT scanning can often show the site of obstruction, in the case of malignant obstruction, a mass at the transition point (Fig. 6.3). The question becomes what to do about the obstruction. Options would include surgical resection, an intraluminal colonic stent, chemotherapy, or hospice, with or without placement of a gastrostomy tube to vent the GI tract. Each of these choices depends heavily on the extent of the disease and the condition and wishes of the patient. Obviously a relatively young patient with extensive disease but otherwise good reserve is often treated very differently from an octogenarian with CHF and chronic renal failure that may have a small amount of bleeding and isolated otherwise potentially resectable metastases. In general, a malignant bowel obstruction is a very serious and ominous occurrence. Historically, surgical procedures for these patients have been fraught with complications and an in-hospital mortality of 21–28 % [9, 10].

In the case of suspected malignant bowel obstruction, each patient’s ability to undergo a major resection must be independently evaluated. Further, it is useful to determine what, if any, therapeutic options remain for the postoperative period (e.g., chemotherapy or radiation therapy). For patients with large bowel obstruction, we prefer endoscopic stenting when feasible and possible, at least initially. For patients with malignant small bowel obstruction, we generally will attempt one surgical exploration (laparoscopic when possible) for decompression via resection, internal bypass, or diversion. For a patient who is not suitable for exploration, or who is highly suspected to be inoperable based on imaging or prior attempts at relieving obstructions, a decompressive “venting” gastrostomy tube (percutaneous, endoscopic, or surgical) is often beneficial.