Locally Recurrent Rectal Cancer in the Molecular Era: A Scoping Review of Biomarkers of Oncologic Outcome following Salvage Surgery.

Abstract

Background: Radical salvage surgery offers the only chance of cure for patients with locally recurrent rectal cancer (LRRC), yet up to 50% develop disease recurrence after surgery. Identification of those at highest risk of disease recurrence may improve selection for surgery and intensification of neoadjuvant treatment. This scoping review aimed to identify molecular determinants of oncologic outcomes following surgery for LRRC.

Materials and methods: This study was conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews. MEDLINE, Embase, CENTRAL, and Scopus databases were searched for articles published between 2005 and 2025 that reported associations between blood, tissue, or other molecular factors and postoperative oncologic outcomes (recurrence and survival) in patients undergoing treatment for LRRC.

Results: The search identified 2799 articles, of which 17 were included. Sample size varied from 21 to 213 patients. Locoregional recurrence rates after surgery ranged from 15% to 52% (various timepoints between 3 and 5 years), while 5-year overall survival ranged from 22% to 53%. Elevated carcinoembryonic antigen (CEA) was associated with shorter overall survival in 11 studies, and poorer relapse-free survival in 1 study. Elevated serum carbohydrate antigen 19-9 (CA19-9) was associated with shorter overall survival and disease-specific survival in two studies. No studies evaluating contemporary biomarkers (mutational profile, microsatellite instability, or circulating-tumour DNA) were identified.

Conclusions: Evidence evaluating molecular biomarkers in LRRC is limited and has focused on traditional serum biomarkers such as CEA and CA19-9. Contemporary colorectal cancer biomarkers including mutational profile and ctDNA are yet to be studied in this population.