Predictors of Early Distant Relapse in Rectal Cancer Patients Submitted to Preoperative Chemoradiotherapy

Background: Neoadjuvant chemoradiotherapy (CRT) is a standard treatment for locally advanced rectal cancer. CRT leads to a better local control; however, this does not translate into a survival benefit. Long-term survival is mostly affected by the development of distant metastases after surgery. This study aimed to evaluate predictive clinical factors for the development of early metastatic disease after CRT. Methods: Clinical data of patients with stage II/III rectal cancer submitted to CRT between January 2000 and October 2014 were collected from prospectively maintained electronic databases of three Italian institutes. Patients were divided into two groups: those who developed metastasis within 12 months from surgical resection (Group A) and patients without or with late distant relapse (Group B). Results: Among 635 patients, 86 (13.5%) had early distant relapse within 1 year from surgery (Group A), and 549 (86.5%) did not (Group B). A higher rate of early distant relapse was associated with CEA levels above 3 ng/dL (20% vs. 10%; p <0.001), tumor lying under 5 cm from anal verge (20% vs. 9%; p <0.001), and age under 63 years (17% vs. 11%; p = 0.036). Multivariate analysis confirmed these factors to be independently correlated with a higher risk of early metastasis. Conclusions: Younger age, low tumors, and high serum CEA may be associated with unfavorable early oncological outcomes after CRT and surgery for rectal cancer. These clinical factors could be useful to select patients for more aggressive therapeutic strategies.