[Rectal cancer: Towards personalized medicine]

Area of Science:

• Oncology
• Surgical Oncology
• Radiation Oncology

Background:

• The standard of care for locally advanced rectal cancer (LARC) has evolved to total neoadjuvant therapy (TNT), combining chemotherapy and radiotherapy before surgery.
• TNT significantly reduces distant metastases and improves disease-free survival but may lead to overtreatment and reduced quality of life in some patients.
• Patient-specific recurrence risk necessitates tailored treatment approaches, moving beyond a one-size-fits-all strategy.

Purpose of the Study:

• To evaluate the evolving landscape of neoadjuvant treatment strategies for LARC.
• To explore the potential for less aggressive, individually tailored treatment de-escalation in LARC management.
• To assess novel approaches including omission of radiotherapy or surgery and intensification or escalation of existing therapies.

Main Methods:

• Review of current standards of care and ongoing clinical trials (e.g., NORAD, PROSPECT, GRECCAR 12, OPERA, MORPHEUS).
• Analysis of treatment modifications including omission of radiotherapy, omission of surgery, chemotherapy intensification, and radiotherapy dose escalation.
• Focus on achieving pathological complete response and enabling non-operative or organ-preserving management.

Main Results:

• Total neoadjuvant therapy has demonstrably improved pathological complete response rates, reaching up to 30%.
• Trials are investigating the safety and efficacy of omitting radiotherapy in specific patient subgroups (e.g., good responders to induction chemotherapy with favorable tumor characteristics).
• Research is also exploring organ-preserving strategies through radiotherapy dose escalation and non-operative management.

Conclusions:

• While total neoadjuvant therapy followed by surgery remains the current standard for LARC, its potential for overtreatment is recognized.
• Future standards may involve less aggressive, personalized approaches with the omission of radiotherapy or surgery in carefully selected patients.
• Ongoing research aims to refine LARC treatment, balancing efficacy with improved patient quality of life and reduced treatment burden.