Optimal therapy for resectable rectal cancer

ABSTRACT

Alot can be gained by improving our understanding of the optimal sequence of existing therapies in rectal cancer, with the more difficult task of balancing the morbidity of recurrence with the morbidity of prescribed therapies that are particularly toxic owing to tumour location. This review aims to highlight a recent shift in treatment strategies in the opposite direction, with a focus on earlier, more intense systemic treatments with reduced local therapies. Understanding the rationale for and evidence to support this shift will help identify gaps, shape future trials, and ultimately answer the question of whether this is indeed the right path to follow with regards to maintaining local control rates and long-term outcomes for patients, and improving distal disease control and local treatment-related morbidities without compromising quality of life.

KEYWORDS:

• Locally advanced
• resectable rectal cancer

Acknowledgements

We would like to acknowledge the input of Katrin Sjoqhist, Rhana Pike, Howard Chan & Nicola Lawrence.

Financial & competing interests disclosure

Timothy Price is a member of advisory boards for AMGEN, Roche and Merck. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Multimodality treatment approaches in rectal cancer have significantly improved local recurrence rates but not translated to distal recurrence or overall survival advantages.

• The shift towards earlier, intensive systemic therapies predominantly arises from the ambition to achieve the same outcomes for all patients as for those achieving a pathological complete response (pCR).

• Multimodality treatment-related short- and long-term toxicities have been a limitation so far in further intensification of treatment.

• Evidence from studies addressing outcomes with the total neoadjuvant approach is important.

• An improved understanding of how best to establish complete clinical responses (cCR), its use as a surrogate for pCR and associated outcomes for these patients is critical.