[Advances in systemic therapy-driven conversion strategies for locally advanced rectal cancer]

Locally advanced rectal cancer (LARC) remains a major therapeutic challenge in multidisciplinary oncology. The increasing emphasis on early systemic intervention has positioned total neoadjuvant therapy (TNT) as a central treatment paradigm, with the potential to improve control of occult metastatic disease and enhance tumor response before definitive local therapy. Emerging data indicate that, in selected patients, neoadjuvant strategies dominated by systemic chemotherapy-sometimes with omission or de-escalation of radiotherapy-can maintain oncologic outcomes while reducing treatment-related toxicity, supporting a more individualized approach to local treatment.Marked heterogeneity in treatment response has become evident with the incorporation of immunotherapy. Patients with mismatch repair-deficient or microsatellite instability-high (dMMR/MSI-H) LARC may achieve profound and durable responses with immune checkpoint blockade alone. In contrast, most LARC tumors are mismatch repair-proficient (pMMR/MSS) and demonstrate limited sensitivity to immunotherapy monotherapy. For this population, combination strategies incorporating immunotherapy with chemotherapy or other systemic agents have shown encouraging early efficacy in terms of tumor regression and surgical feasibility, although robust evidence for long-term survival benefit and optimal regimen selection is still lacking.Collectively, systemically driven conversion strategies enable earlier assessment of therapeutic sensitivity and provide a framework for risk-adapted, biology-informed treatment decision-making. Future efforts should focus on integrating imaging, molecular profiling, and early response assessment to refine patient selection, validate surrogate endpoints for long-term outcomes, and optimize treatment sequencing and safety in combined-modality approaches.