Current therapeutic paradigms for obstructing colon cancer: room for improvement

Up to 28% of all colonic cancers will present initially as an emergency with features of obstruction. Malignant colonic obstruction confers a deleterious effect upon long-term oncological outcomes, with abbreviated disease-free survival and elevated recurrence rates.1,2 Of all potential sites of recurrence, peritoneal metastasis is particularly challenging to diagnose and treat. Traditional imaging surveillance methods have limited sensitivity for low-volume disease. In the >70% of patients with peritoneal metastasis who are not eligible for treatment with curative intent, median survival is limited to a duration of sixteen months.3 Cytoreductive surgery and HIPEC offers an opportunity for cure in a select number. However, as all cytoreductive surgeons are aware, this is a resource-intensive intervention with the potential for substantial post-operative morbidity and impairment of long-term functional outcomes.

The mainstay of management of obstructing colonic cancers remains emergency upfront resection. However, such patients are often physiologically and nutritionally compromised as a consequence of the obstruction. Emergency surgery in this context is associated with higher rates of oncologically incomplete resections (R1/R2 margin status and/or inadequate nodal yield), as well as a substantially greater burden of perioperative morbidity and mortality - up to 45% and 8% respectively - when compared to colonic resections performed on an elective basis.2,4,5 Severe perturbations of the post-operative course cause delay or omission of delivery of adjuvant systemic therapy, contributing to the impaired oncological outcomes observed in such patients.4

Given these factors, alternative approaches of managing such cases have been proposed, entailing addressing the obstruction via either stomal diversion or endoscopic stenting. This treatment paradigm facilitates deferral of definitive resection, converting an emergent procedure to an elective setting and allowing correction of nutritional deficits and optimisation of physiological status. Despite concerted efforts in some healthcare systems such as the Netherlands to effect a shift in practice towards bridge-to-surgery therapeutic strategies, upfront resection remains the dominant approach when confronted with patients with malignant colonic obstruction.5,6 In addition, there remain as yet unresolved concerns regarding the oncological safety in particular of endoscopic stenting and the potential for malignant seeding of the peritoneum in the event of overt or occult tumour perforation. No consensus has been arrived at in the literature, with a large volume of observational data and three randomised prospective trials (Stent-In-2, CReST and ESCO) reporting conflicting outcomes.7

Malignant colonic obstruction thus presents a quandary to clinicians. This state intrinsically confers heightened oncological risk prior to embarking upon any therapeutic intervention. Both upfront emergent resection and bridge-to-surgery strategies are associated with unpalatable compromises. Upfront surgery entails reduced feasibility of oncologically complete resections and the associated perioperative morbidity of emergency surgery, while stenting carries the possible risk of particularly intractable disease recurrence in the form of peritoneal metastasis. Stomal diversion therefore seems an attractive alternative, but is associated with its own not inconsiderable morbidity profile and is unappealing to patients.8

How can these paradoxes be resolved? Perhaps the answer is already known to us. Since the 1990s, neoadjuvant therapy for locally advanced rectal cancer, in varying guises, has become firmly embedded as the standard of care. While data exists supporting the use of neoadjuvant therapy for high-risk colonic carcinoma, at present this is implemented markedly less frequently, despite a favourable outcome profile when contrasted with upfront surgery.9,10 When viewed from this perspective, bridge-to-surgery treatment strategies in the setting of malignant colonic obstruction offer a dual potential advantage. The opportunity exists not only to enact optimisation of physiological derangements but also to implement systemic chemotherapy prior to definitive resection. As for rectal cancer, delivery of systemic therapy in the neoadjuvant setting for locally advanced tumours appears to be associated with improved recurrence rates and survival outcomes comparative to upfront resection, and obviates the risk of chemotherapy being delayed or omitted altogether in the event of post-operative complications.9

Thus, utilising a bridge-to-surgery strategy in conjunction with neoadjuvant chemotherapy offers a potential opportunity to ameliorate the negative prognostic impact conferred by malignant colonic obstruction, enhance the technical success rate of operative interventions and minimise the risk of future disease recurrences, including the especially challenging scenario of peritoneal metastasis. However, all such evolutions in paradigms of care must necessarily be evidence-based, and at present high-quality data to inform the validity of such an approach are wanting. There is therefore a need for large-scale prospective randomised series to be established to investigate the effectiveness of this therapeutic strategy, with the goal of advancing quality of care and outcomes in this high-risk patient cohort. Planned future trials including the Australasian DINGO (Diversion or INtestinal stenting versus upfront surGery for Obstructing colon cancer) trial and the French COnCERTO (Neoadjuvant Chemotherapy for Obstructive Colon Cancer first treated with Colostomy) trial will seek to address this deficit in the literature.