Circulating Tumor DNA to Predict Radiographic and Pathologic Response to Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer

Oncologist. 2024 Mar 4;29(3):e414-e418. doi: 10.1093/oncolo/oyad336.

Abstract

Despite advances in treatment and response assessment in locally advanced rectal cancer (LARC), it is unclear which patients should undergo nonoperative management (NOM). We performed a single-center, retrospective study to evaluate post-total neoadjuvant therapy (TNT) circulating tumor DNA (ctDNA) in predicting treatment response. We found that post-TNT ctDNA had a sensitivity of 23% and specificity of 100% for predicting residual disease upon resection, with a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 47%. For predicting poor tumor regression on MRI, ctDNA had a sensitivity of 16% and specificity of 96%, with a PPV of 75% and NPV of 60%. A commercially available ctDNA assay was insufficient to predict residual disease after TNT and should not be used alone to select patients for NOM in LARC.

Keywords: circulating tumor DNA; nonoperative management; rectal cancer; total neoadjuvant therapy.

MeSH terms

  • Chemoradiotherapy
  • Circulating Tumor DNA* / genetics
  • Humans
  • Neoadjuvant Therapy
  • Rectal Neoplasms* / diagnostic imaging
  • Rectal Neoplasms* / genetics
  • Rectal Neoplasms* / therapy
  • Retrospective Studies

Substances

  • Circulating Tumor DNA