Sidedness matters: Colon cancer outcomes in low-resource settings

Abstract

Colon cancer (CC) laterality (right vs left) is recognized as a key determinant of clinical outcomes and treatment decisions in metastatic CC. Right-sided CC (RCC) often presents in older individuals and is associated with higher rates of Kirsten rat sarcoma viral oncogene homolog and v-raf murine sarcoma viral oncogene homolog B1 mutations and deficient mismatch repair, leading to microsatellite instability-high status. Left-sided CC typically presents in younger individuals, demonstrates a more favorable prognosis, and is often Kirsten rat sarcoma viral oncogene homolog/neuroblastoma RAS viral oncogene homolog/v-raf murine sarcoma viral oncogene homolog B1 wild-type, making it more responsive to anti-epidermal growth factor receptor therapy. RCC typically responds poorly to anti-epidermal growth factor receptor agents; however, it may benefit from triplet chemotherapy (5-fluorouracil + leucovorin + oxaliplatin + irinotecan) with or without anti-angiogenic agents. Comprehensive molecular profiling remains challenging in low-resource settings due to limited access to advanced diagnostic tools. This review explores key epidemiological and molecular differences between RCC and left-sided CC. In the absence of complete genomic data, tumor sidedness can be a helpful guide for making treatment decisions. Here, we propose a practical algorithm that integrates basic immunohistochemistry to assess a tumor’s mismatch repair status and laterality, potentially facilitating therapy selection in resource-constrained environments. Recognizing laterality-specific trends in prognosis and treatment response can improve personalized care and outcomes for patients with CC in these environments, highlighting the essential role of cost-effective biomarker strategies.

Keywords: Colon cancer; Sidedness; Tailored therapy; Mismatch repair; Consensus molecular subtypes

Core Tip: Colon tumor sidedness is a practical compass for determining treatment. This review synthesizes epidemiologic, molecular, and clinical differences between right-sided colon cancer (RCC) and left-sided colon cancer (LCC). Older patients with RCC more frequently exhibit microsatellite instability-high status/deficient mismatch repair (MMR), Kirsten rat sarcoma viral oncogene homolog/v-raf murine sarcoma viral oncogene homolog B1 mutations, poorer prognosis in metastatic disease, and limited benefit from anti-epidermal growth factor receptor (EGFR). LCC is more often RAS/v-raf murine sarcoma viral oncogene homolog B1 wild-type and EGFR-responsive. We propose a low-resource plan: Prioritize MMR immunohistochemistry; consider immunotherapy for deficient MMR/microsatellite instability-high; use 5-fluorouracil + leucovorin + oxaliplatin + irinotecan ± anti-angiogenic agents for RCC and doublet ± anti-angiogenic therapy for LCC; restrict anti-EGFR to confirmed wild-type disease.