Journal: Annual review of medicine
This article reviews how treatment of locally advanced rectal cancer has shifted from the classic trimodality approach (radiotherapy, surgery, and chemotherapy) toward more individualized, organ-preserving strategies.
Key points:
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Total neoadjuvant therapy (TNT):
The authors summarize landmark trials showing that giving all systemic therapy and radiotherapy before surgery can increase pathologic complete response rates, improve tolerance and treatment completion, and better address micrometastatic disease early.
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Nonoperative management (“watch-and-wait”):
With higher complete clinical response rates after TNT, up to roughly half of appropriately selected patients may be managed without immediate surgery, aiming to avoid permanent stomas and major functional impairment. The review outlines criteria and data that support this approach and emphasizes the need for rigorous surveillance.
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Advances in radiotherapy and chemotherapy delivery:
The article highlights evolving radiotherapy strategies (e.g., short-course vs long-course, sequencing with chemotherapy) and optimization of systemic regimens to balance disease control with toxicity and quality of life.
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Immunotherapy for mismatch repair–deficient (dMMR) tumors:
Checkpoint blockade has produced dramatic responses in selected dMMR rectal cancers, raising the possibility of curing some patients without chemoradiation or surgery. The review discusses current evidence and the need for longer follow-up and broader validation.
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Future directions:
Ongoing work includes refining patient selection for TNT and nonoperative management, integrating biomarkers (including MMR status and other molecular features), standardizing response assessment and surveillance protocols, and conducting trials focused on both survival and long-term function/quality of life.
Overall, the article frames current evidence and research as a movement from “one-size-fits-all” trimodal therapy toward biologically and response-adapted care, with organ preservation and quality of life as central goals.