Current Perspectives on the Importance of Pathological Features in Prognostication and Guidance of Adjuvant Chemotherapy in Colon Cancer

Abstract

There is not a clear consensus on which pathological features and biomarkers are important in guiding prognosis and adjuvant therapy in colon cancer. The Pathology in Colon Cancer, Prognosis and Uptake of Adjuvant Therapy (PiCC UP) Australia and New Zealand questionnaire was distributed to colorectal surgeons, medical oncologists and pathologists after institutional board approval. The aim of this study was to understand current specialist attitudes towards pathological features in the prognostication of colon cancer and adjuvant therapy in stage II disease. A 5-scale Likert score was used to assess attitudes towards 23 pathological features for prognosis and 18 features for adjuvant therapy. Data were analysed using a rating scale and graded response model in item response theory (IRT) on STATA (Stata MP, version 15; StataCorp LP). One hundred and sixty-four specialists (45 oncologists, 86 surgeons and 33 pathologists) participated. Based on IRT modelling, the most important pathological features for prognosis in colon cancer were distant metastases, lymph node metastases and liver metastases. Other features seen as important were tumour rupture, involved margin, radial margin, CRM, lymphovascular invasion and grade of differentiation. Size of tumour, location, lymph node ratio and EGFR status were considered less important. The most important features in decision making for adjuvant therapy in stage II colon cancer were tumour rupture, lymphovascular invasion and microsatellite instability. BRAF status, size of tumour, location, tumour budding and tumour infiltrating lymphocytes were factored as lesser importance. Biomarkers such as CDX2, EGFR, KRAS and BRAF status present areas for further research to improve precision oncology. This study provides the most current status on the importance of pathological features in prognostication and recommendations for adjuvant therapy in Australia and New Zealand. Results of this nationwide study may be useful to help in guiding prognosis and adjuvant treatment in colon cancer.

Evaluation of the Immunohistochemical Scoring System of CDX2 Expression as a Prognostic Biomarker in Colon Cancer

“…In the context of managing CRC, an integrated approach combines clinical, paraclinical, and histopathological parameters to effectively categorize CRC into distinct stages utilizing the TNM (Tumor Node Metastasis) classification system pioneered by the American Joint Committee on Cancer (AJCC), thereby facilitating both prognostic evaluation and the development of targeted therapeutic interventions [3,7,10,11,23]. While TNM staging remains the cornerstone in oncological patient care, its effectiveness is limited by the inability to account for genetic mutations and molecular alterations in CRC, which are crucial for accurate prognosis and therapeutic decisions [7,23].…”

“…In the context of managing CRC, an integrated approach combines clinical, paraclinical, and histopathological parameters to effectively categorize CRC into distinct stages utilizing the TNM (Tumor Node Metastasis) classification system pioneered by the American Joint Committee on Cancer (AJCC), thereby facilitating both prognostic evaluation and the development of targeted therapeutic interventions [3,7,10,11,23]. While TNM staging remains the cornerstone in oncological patient care, its effectiveness is limited by the inability to account for genetic mutations and molecular alterations in CRC, which are crucial for accurate prognosis and therapeutic decisions [7,23]. Incorporating genetic and molecular biomarker testing into CRC management has improved the TNM staging system, offering a more comprehensive understanding of disease dynamics, fostering the development of personalized therapeutic approaches, and enabling a more precise evaluation of prognosis and treatment effectiveness [7,23].…”

“…While TNM staging remains the cornerstone in oncological patient care, its effectiveness is limited by the inability to account for genetic mutations and molecular alterations in CRC, which are crucial for accurate prognosis and therapeutic decisions [7,23]. Incorporating genetic and molecular biomarker testing into CRC management has improved the TNM staging system, offering a more comprehensive understanding of disease dynamics, fostering the development of personalized therapeutic approaches, and enabling a more precise evaluation of prognosis and treatment effectiveness [7,23]. For example, insights into MMR/MSI status or mutations in the RAS (NRAS, KRAS) and BRAF genes can guide personalized therapies and enhance prognosis predictions, as highlighted below.…”

“…Currently, there is an unprecedented surge in the identification of clinically and therapeutically relevant molecular targets, with numerous novel biomarkers emerging, offering significant potential in guiding therapeutic decisions and prognostic evaluation. These include immunohistochemical analysis of CDX2 expression for prognostic stratification, tumor stroma examination for prognostic assessment, and TILs' evaluation for both prognostic and predictive purposes, alongside ongoing research exploring genetic profiling with prognostic implications in advanced CRC, and genotyping through liquid biopsy-derived circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs) [11,23,[25][26][27][28].…”

A novel approach to classification and segmentation of colon cancer imaging towards personalized medicine

“…Colorectal cancer accounts for one of the top 5 cancers with high incidence (126,240 in 2020) with a high mortality worldwide [1] [2]. Tissue biopsy remains to be the gold standard procedure for accurate diagnosis, treatment planning and prognosis prediction [3]. As an image based modality, pathology has attracted a lot of attention for development of AI algorithms and there has been a steady increase in the number of filings for FDA authorized use of AI algorithms in clinical practice [4].…”