Upon diagnosis of stage IV colorectal cancer, it is important to determine if the metastatic disease is potentially resectable or definitely non-resectable. If the metastatic disease is potentially resectable, then a curative resection can be considered if the primary pathology can be removed as well (Anwar et al. 2011).

In these patients, it is imperative to discuss amongst surgical, medical and radiation oncologists whether upfront surgery to remove all apparent disease or to adopt a chemotherapy +/− radiotherapy first approach before re-evaluating the suitability for surgery is preferred.

In patients with unresectable disease, chemotherapy has always been deemed the mainstay of treatment except in emergency situations (Kaufman et al. 2007). However, there remain proponents of surgical resection of the primary pathology (Bacon and Martin 1964; Lockhart-Mummery 1959; Cady et al. 1970; Cook et al. 2005). There appears to be evidence supporting a higher median survival and also reduced future complications from the primary malignancy in the group that underwent surgery for the primary pathology. But a recent Cochrane review (Cirocchi et al. 2012) has established that there is insufficient evidence to advocate surgical resection for asymptomatic patients with stage IV colorectal cancer and the surgery itself does not lead to a reduction in the risk of future complications from occurring.

In addition, surgery itself is not without its own set of perioperative complications (Clements et al. 2009). And the majority of these studies are largely retrospective in nature and lend itself to enormous amount of selection bias. It would not be surprising if the group of patients who underwent surgery for the primary pathology was generally fitter, has lower metastatic load and the primary cancer is easily resected without much morbidity.

However, if a patient with metastatic colorectal cancer presents acutely with bowel perforation, obstruction or severe bleeding, these situations may warrant urgent interventions to the primary pathology regardless of the presence or extent of metastatic disease. When the crisis is resolved, the management principles of such patients would be similar to those who present electively.

In the majority of patients with metastatic colon and rectal cancer that does not present as a surgical emergency, chemotherapy is key to prolong the overall survival in these patients. As these patients often die from systemic disease due to the massive tumour burden, the aim of treatment should be aimed towards achieving stable disease and to delay tumour progression rather than to primarily induce tumour response. Thus, significant delay in the commencement of chemotherapy could be detrimental (Michel et al. 2004; Muratore et al. 2007; Sarela et al. 2001; Scoggins et al. 1999).

Chemotherapy has not been shown to increase the incidence of complications such as bleeding, perforation or obstruction. These complications following chemotherapy are reported to only occur in less than 10 % of the patients (Nitzkorski et al. 2012). But if the patients are deemed likely to develop any crisis during chemotherapy, surgical resection or other treatment modalities to address these potential crises should be considered so as to allow uninterrupted systemic chemotherapy (Michel et al. 2004; Muratore et al. 2007; Sarela et al. 2001; Scoggins et al. 1999).

Since the 1970s, chemotherapeutic options for colon and rectal cancer are based on 5-flurouracil (5-FU) and leucovorin given as an infusion. Reports of median survival ranged between 10 and 12 months (Glimelius and Cavalli-Bjorkman 2012). Ten years on, the introduction of “doublets”, 5-FU/leucovorin plus either irinotecan (FOLFIRI) or oxaliplatin (FOLFOX) extends survival by a further 4 months. However, the FOLFIRI and FOLFOX regimes are associated with complications such as diarrhoea and neurotoxicities, respectively. But unlike the other chemotherapeutic agents, the occurrences of haematological toxicities are relatively uncommon (Fornaro et al. 2010). The onset of neurotoxicity has been the focus for many with the use of oxaliplatin-based chemotherapeutic agents. It was reported in the OPTIMOX trial that the “stop-and-go” approach to administering FOLFOX whereby high dose of FOLFOX was given before maintenance infusion of 5-FU/leucovorin was started and FOLFOX reintroduced when disease progressed reduced occurrence of such toxicities (Tournigand et al. 2006).

Since the mid-1990s, the introduction of the oral chemotherapeutic agent capecitabine (fluoropyrimidine) radically changed the treatment of colon and rectal cancer. Its presence made chemotherapy more convenient and pushed survival towards 18–20 months. Combination “doublets” of capecitabine and irinotecan (CAPIRI) or oxaliplatin (XELOX) were noted to be non-inferior to FOLFIRI and FOLFOX, except in CAPIRI where the severe gastrointestinal toxicities experienced prematurely suspended the trial (Kohne et al. 2008). The triplet form, capecitabine/irinotecan/oxaliplatin (XELOXIRI), also resulted in grade 3–4 diarrhoea. The use of 5-FU/leucovorin plus irinotecan and oxaliplatin (FOLFOXIRI) has resulted in higher radical resection of metastasis and increase in overall survival (Masi et al. 2008). FOLFOXIRI increasingly has become the choice drug in palliative chemotherapy.

The introduction of targeted chemotherapy provided an additional avenue to push survival past the 24-month mark. Tissue samples from the primary tumour and its metastatic site can be obtained via aspiration cytology or tissue block histology. Specific genetic testing (i.e. K-ras mutation) is done routinely on these tissue samples to detect if the drug can bring about specific desired response such as tumour apoptosis. Such targeted therapies seem to be breakthroughs, but we await longer-term data to demonstrate its true efficacy.