[Progress in neoadjuvant immunotherapy for locally advanced rectal cancer]

Area of Science:

• Oncology
• Immunotherapy
• Rectal Cancer Research

Background:

• Neoadjuvant chemoradiotherapy (NACRT) is standard for locally advanced rectal cancer (LARC), but pathological complete response (pCR) rates are suboptimal.
• Immunotherapy, particularly anti-PD-1 antibodies, offers new options for dMMR/MSI-H LARC, achieving high response rates and enabling watch-and-wait strategies.
• PD-1 inhibition alone has limited efficacy in pMMR/MSS LARC, necessitating combination therapies.

Purpose of the Study:

• To review the current role and future directions of immunotherapy in LARC management.
• To highlight the differential efficacy of immunotherapy based on mismatch repair (MMR) status.
• To explore novel combinatorial strategies and biomarker discovery for optimizing LARC treatment.

Main Methods:

• Review of current literature on immunotherapy in LARC.
• Analysis of clinical trial data for anti-PD-1 therapies in dMMR/MSI-H and pMMR/MSS LARC.
• Discussion of emerging research in combination therapies and biomarker development.

Main Results:

• Anti-PD-1 antibodies achieve high pCR in dMMR/MSI-H LARC, supporting non-operative management.
• Combination of immunotherapy with chemoradiotherapy shows potential for pMMR/MSS LARC, with manageable toxicity.
• Discordance between imaging and pathological response remains a challenge.

Conclusions:

• Immunotherapy is a significant advancement for specific LARC subsets (dMMR/MSI-H).
• Combinatorial approaches and biomarker discovery are crucial for improving outcomes in pMMR/MSS LARC.
• Future research should focus on optimizing ICI regimens, exploring dual immunotherapy, and leveraging AI for precision medicine in LARC.