Current Approaches and Challenges for Monitoring Treatment Response in Colon and Rectal Cancer

Abstract

Introduction: With the advent of multidisciplinary and multimodality approaches to the management of colorectal cancer patients, there is an increasing need to define how we monitor response to novel therapies in these patients. Several factors ranging from the type of therapy used to the intrinsic biology of the tumor play a role in tumor response. All of these can aid in determining the ideal course of treatment, and may fluctuate over time, pending down-staging or progression of disease. Therefore, monitoring how disease responds to therapy requires standardization in order to ultimately optimize patient outcomes. Unfortunately, how best to do this remains a topic of debate among oncologists, pathologists, and colorectal surgeons. There may not be one single best approach. The goal of the present article is to shed some light on current approaches and challenges to monitoring treatment response for colorectal cancer.Methods: A literature search was conducted utilizing PubMed and the OVID library. Key-word combinations included colorectal cancer metastases, neoadjuvant therapy, rectal cancer, imaging modalities, CEA, down-staging, tumor response, and biomarkers. Directed searches of the embedded references from the primary articles were also performed in selected circumstances.Results: Pathologic examination of the post-treatment surgical specimen is the gold standard for monitoring response to therapy. Endoscopy is useful for evaluating local recurrence, but not in assessing tumor response outside of the limited information gained by direct examination of intra-lumenal lesions. Imaging is used to monitor tumors throughout the body for response, with CT, PET, and MRI employed in different circumstances. Overall, each has been validated in the monitoring of patients with colorectal cancer and residual tumors.Conclusion: Although there is no imaging or serum test to precisely correlate with a tumor's response to chemo- or radiation therapy, these modalities, when used in combination, can aid in allowing clinicians to adjust medical therapy, pursue operative intervention, or (in select cases) identify complete responders. Improvements are needed, however, as advances across multiple modalities could allow appropriate selection of patients for a close surveillance regimen in the absence of operative intervention.

Clinical significance and association of RUNX3 hypermethylation frequency with colorectal cancer: a meta-analysis

“…Currently, there are approximately 1.25 million patients diagnosed with CRC, and more than 600,000 patients will die from this disease every year worldwide 3. Surgical resection can be performed to remove the tumor if no lymph-node or distant metastasis is present, but the recurrence rate after surgery remains high 4,5. Therefore, investigation of the mechanism of initiation and progression and identification of prognostic markers are still needed in the treatment of CRC.…”

Targeted Confocal Laser Endomicroscopy (CLE) for the Assessment of Putative Cancer Stem Cell Markers in Colorectal cancer - A Pilot Study

“…Except colonoscopy, the current imaging techniques used for the follow-up of neoadjuvant chemotherapy effects in colon cancer are represented by CT or PET-CT, whilst the recommended methods for assessing the effects of neoadjuvant chemoradiotherapy for rectal cancer are EUS, MRI and/or PET-CT. All these techniques do have several advantages but also different boundaries, including: costs, radiations risks, limited capacity to differentiate layers of the gut wall, missing small lesions under 1 cm, false positive rate for the uninvolved lymph nodes, inter-observer variations, etc. (18).…”

“…Although an improvement of relative survival is observed in western countries, the problem of treatment failures and tumor recurrence remains a keystone. Multiple therapeutic protocols have been dedicated to CRC and several research studies have determined conventional prognostic factors, without yielding a complete cure in all cases (4).…”

Layer-resolved colorectal tissues using nonlinear microscopy

“…At present, the examination techniques in clinical application mainly include computed tomography (CT), magnetic resonance imaging (MRI), and endorectal ultrasound (ERUS). However, these techniques cannot accurately show various pathologic changes because of the lack of resolution; especially, the major flaw in the use of ERUS is its inability to distinguish tumor from fibrosis, while the accuracy of CT in evaluating colorectal cancer is limited by its ability to distinguish layers of the bowel wall [2,3]. Therefore, there is widespread interest in developing new methods for detecting colorectal diseases.…”