Persistent Lymph Node Metastases After Neoadjuvant Chemoradiotherapy for Rectal Cancer

Area of Science:

• Oncology
• Surgical Oncology
• Gastrointestinal Oncology

Background:

• Patients with locally advanced rectal cancer and persistent lymph node metastases (PLNM) after neoadjuvant treatment face a high risk of metastasis.
• Optimal postsurgical management for these patients remains a challenge.

Purpose of the Study:

• To investigate the association between PLNM and pretreatment clinical factors.
• To analyze the impact of neoadjuvant treatment intensity on PLNM.
• To evaluate the long-term oncological outcomes in patients with PLNM.

Main Methods:

• Post-hoc analysis of 3 randomized clinical trials (CAO/ARO/AIO-94, -04, -12) involving 1948 patients with locally advanced rectal cancer.
• Patients received fluorouracil-based chemoradiotherapy (CRT), CRT plus oxaliplatin, or total neoadjuvant treatment (TNT).
• Associations with clinical parameters, treatment intensity, and cumulative incidences of locoregional (LR) and distant metastasis (DM) were assessed.

Main Results:

• Of 1888 analyzed patients, 522 (29%) had PLNM (ypN1: 20%, ypN2: 9%).
• Age, clinical T/N stage, grading, CEA levels, and CRT-to-surgery interval were associated with PLNM.
• TNT significantly reduced the ypN2 rate (6%) compared to CRT (11.3%).
• 5-year survival rates were 86.1% (ypN0), 74.0% (ypN1), and 43% (ypN2).
• 5-year cumulative incidences of LR/DM were 3%/20% (ypN0), 6%/40% (ypN1), and 19%/72% (ypN2).

Conclusions:

• PLNM identifies a high-risk rectal cancer phenotype associated with poor treatment outcomes.
• Consideration of more aggressive adjuvant therapy is warranted.
• Risk-adapted surveillance and early surgical intervention are crucial for CRT/chemotherapy-resistant disease.