What are the indications for neoadjuvant (preoperative) therapy in rectal cancer?

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Last updated: January 29, 2025View editorial policy

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From the Guidelines

Neoadjuvant therapy is indicated for patients with locally advanced rectal cancer, including those with T3 or T4 tumors, node-positive disease, or tumors with high-risk features.

Indications for Neoadjuvant Therapy

  • Locally advanced disease: Neoadjuvant therapy is recommended for patients with T3 or T4 tumors, or those with node-positive disease, as it has been shown to decrease local recurrence and improve survival 1.
  • High-risk features: Patients with tumors that have high-risk features, such as circumferential resection margin involvement, extramural depth of spread >5 mm, extramural vascular invasion (EMVI), mucinous phenotype, or poor response to chemoradiotherapy (CRT), may also benefit from neoadjuvant therapy 1.
  • Stage II or III disease: Neoadjuvant therapy is recommended for patients with stage II or III rectal cancer, as it has been shown to improve local control and reduce toxicity compared to postoperative therapy 1.

Treatment Approaches

  • Total neoadjuvant therapy (TNT): TNT, which includes neoadjuvant chemotherapy and either short-course radiation or long-course CRT, has been proposed as a way to improve adherence, decrease the occurrence of distant metastases, and ultimately improve overall survival 1.
  • Watch-and-wait nonoperative approach: For patients who achieve a clinical complete response (cCR) to neoadjuvant therapy, a watch-and-wait nonoperative approach may be considered, with careful follow-up and surveillance to monitor for disease recurrence 1.

From the Research

Indications for Neoadjuvant Therapy in Rectal Cancer

The indications for neoadjuvant therapy in rectal cancer include:

  • Locally advanced rectal cancer, where the goal is to downstage the tumor and improve local control 2, 3, 4
  • Non-metastatic unresectable tumors, where neoadjuvant therapy can help make the tumor resectable 5
  • Tumors that are at high risk of local recurrence, where neoadjuvant therapy can help reduce this risk 2, 3

Types of Neoadjuvant Therapy

Different types of neoadjuvant therapy are available, including:

  • Neoadjuvant chemoradiation, which combines chemotherapy and radiation therapy 2, 3, 4
  • Total neoadjuvant therapy, which adds chemotherapy to neoadjuvant chemoradiation 3
  • Neoadjuvant chemotherapy alone, without radiation therapy 5, 4
  • Short-course radiotherapy with delayed surgery, which is a shorter course of radiation therapy followed by a delay before surgery 4

Benefits and Risks of Neoadjuvant Therapy

Neoadjuvant therapy has several benefits, including:

  • Improved local control and reduced risk of local recurrence 2, 3
  • Downstaging of the tumor, which can make surgery more effective 2, 3
  • Potential for improved disease-free survival and overall survival 3 However, neoadjuvant therapy also has risks and toxicities, including:
  • Treatment-related toxicity and morbidity 2, 6
  • Late sequelae that can impair quality of life 6

Future Directions

Future directions in neoadjuvant therapy for rectal cancer include:

  • Optimizing current regimens and concepts of neoadjuvant therapy 4
  • Exploring new approaches, such as personalized treatments and organ preservation 4
  • Investigating the role of novel targeted therapies and immunotherapies in neoadjuvant therapy 2, 5

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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