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

AIM: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.