The relationship between right-sided tumour location, tumour microenvironment, systemic inflammation, adjuvant therapy and survival in patients undergoing surgery for colon and rectal cancer

Background: There has been an increasing interest in the role of tumour location in the treatment and prognosis of patients with colorectal cancer (CRC), specifically in the adjuvant setting. Together with genomic data, this has led to the proposal that right-sided and left-sided tumours should be considered as distinct biological and clinical entities. The aim of the present study was to examine the relationship between tumour location, tumour microenvironment, systemic inflammatory response (SIR), adjuvant chemotherapy and survival in patients undergoing potentially curative surgery for stage I-III colon and rectal cancer. Methods: Clinicopathological characteristics were extracted from a prospective database. MMR and BRAF status was determined using immunohistochemistry. The tumour microenvironment was assessed using routine H& E pathological sections. SIR was assessed using modified Glasgow Prognostic Score (mGPS), neutrophil: lymphocyte ratio (NLR), neutrophil: platelet score (NPS) and lymphocyte: monocyte ratio (LMR). Results: Overall, 972 patients were included. The majority were over 65 years (68%), male (55%), TNM stage II/III (82%). In all, 40% of patients had right-sided tumours and 31% had rectal cancers. Right-sided tumour location was associated with older age (P = 0.001), deficient MMR (P = 0.005), higher T stage (P<0.001), poor tumour differentiation (P<0.001), venous invasion (P = 0.021), and high CD3(+) within cancer cell nests (P = 0.048). Right-sided location was consistently associated with a high SIR, mGPS (P<0.001) and NPS (P<0.001). There was no relationship between tumour location, adjuvant chemotherapy (P = 0.632) or cancer-specific survival (CSS; P = 0.377). In those 275 patients who received adjuvant chemotherapy, right-sided location was not associated with the MMR status (P = 0.509) but was associated with higher T stage (P = 0.001), venous invasion (P = 0.036), CD3(+) at the invasive margin (P = 0.033) and CD3(+) within cancer nests (P = 0.012). There was no relationship between tumour location, SIR or CSS in the adjuvant group. Conclusions: Right-sided tumour location was associated with an elevated tumour lymphocytic infiltrate and an elevated SIR. There was no association between tumour location and survival in the non-adjuvant or adjuvant setting in patients undergoing potentially curative surgery for stage I-III colon and rectal cancer.