Assessing the Benefit of Adjuvant Chemotherapy in Rectal Cancer: An International Real-World Analysis

There is no consensus for the use of adjuvant chemotherapy (ACT) after radical resection in rectal cancer. We use real-world data from the Netherlands (NL), England and Scotland, from patients who underwent surgery without neoadjuvant chemotherapy, to explore the potential benefit of ACT.

Routine administrative healthcare data from the NL (2012-2017), England (2014-2019) and Scotland (2013-2017) were used to identify patients with a clinical or pathological T3, T4, or N+ rectal cancer; managed with radical resection ± neoadjuvant (chemo)radiotherapy. Data on patient, tumour, treatment demographics and survival were collected. Kaplan-Meier curves and Cox regression models were used to understand the association between ACT and 5-year survival. Models were estimated for the total population and different pre-defined subgroups within each cohort, unadjusted and adjusted for relevant confounding factors.

33,211 patients were included, 12,649, 18,729 and 1833 patients from NL, English and Scottish cohorts, respectively. ACT use differed with administration rates of 3.6%, 34.4% and 33.1%, respectively. The use of neo-adjuvant (chemo)radiotherapy was higher in NL (75·7%, 36.2% and 42.3%, respectively). The Hazard Ratio for death at 5 years was in favour of ACT in all three cohorts, reaching statistical significance in the English and Scottish cohorts (adjusted HR 0.66, 95% CI 0.61-0.71) and (adjusted HR 0.50, 95% CI 0.37-0.68), respectively.

Whilst this survival benefit must be interpreted with caution due to the limitations of real-world data, in the absence of high-level evidence, it offers further weight to contemporary rectal cancer literature that multimodality treatment including systemic therapy offers an OS in rectal cancer.