Colorectal cancer treatment commentary review

Recent advancements in molecular profiling have challenged the long-standing exclusion of right-sided RAS wild-type metastatic colorectal cancer (mCRC) from anti-EGFR therapy. The PRESSING-3 analysis of the FIRE-3 trial offers a pivotal insight by identifying a hyperselected patient subgroup free from negative predictive biomarkers who benefit from cetuximab irrespective of tumor sidedness. This commentary critiques the continued reliance on anatomical classification as a surrogate for molecular biology, arguing that sidedness, while once a useful heuristic, now oversimplifies tumor heterogeneity. We explore how PRESSING-based selection reframes eligibility from geography to genotype, providing a model for biologically accountable treatment. While acknowledging the retrospective nature and limited accessibility of current comprehensive genomic panels, we advocate for future frameworks that balance precision with practicality. Ultimately, this perspective calls for a paradigm shift: moving from anatomical exclusion to molecular inclusion, ensuring that treatment decisions reflect mechanistic fidelity rather than historical precedent. As precision oncology evolves, PRESSING offers a roadmap not only for patient selection but also for reshaping the epistemological standards of modern cancer care.