Clinical Calculator Based on Molecular and Clinicopathologic Characteristics Predicts Recurrence Following Resection of Stage I-III Colon Cancer

Abstract

PURPOSE Clinical calculators and nomograms have been endorsed by the American Joint Committee on Cancer (AJCC), as they provide the most individualized and accurate estimate of patient outcome. Using molecular and clinicopathologic variables, a third-generation clinical calculator was built to predict recurrence following resection of stage I-III colon cancer. METHODS Prospectively collected data from 1,095 patients who underwent colectomy between 2007 and 2014 at Memorial Sloan Kettering Cancer Center were used to develop a clinical calculator. Discrimination was measured with concordance index, and variability in individual predictions was assessed with calibration curves. The clinical calculator was externally validated with a patient cohort from Washington University's Siteman Cancer Center in St Louis. RESULTS The clinical calculator incorporated six variables: microsatellite genomic phenotype; AJCC T category; number of tumor-involved lymph nodes; presence of high-risk pathologic features such as venous, lymphatic, or perineural invasion; presence of tumor-infiltrating lymphocytes; and use of adjuvant chemotherapy. The concordance index was 0.792 (95% CI, 0.749 to 0.837) for the clinical calculator, compared with 0.708 (95% CI, 0.671 to 0.745) and 0.757 (0.715 to 0.799) for the staging schemes of the AJCC manual's 5th and 8th editions, respectively. External validation confirmed robust performance, with a concordance index of 0.738 (95% CI, 0.703 to 0.811) and calibration plots of predicted probability and observed events approaching a 45° diagonal. CONCLUSION This third-generation clinical calculator for predicting cancer recurrence following curative colectomy successfully incorporates microsatellite genomic phenotype and the presence of tumor-infiltrating lymphocytes, resulting in improved discrimination and predictive accuracy. This exemplifies an evolution of a clinical calculator to maintain relevance by incorporating emerging variables as they become validated and accepted in the oncologic community.

Lymph node status and its impact on the prognosis of left‐sided and right‐sided colon cancer: A SEER population‐based study

“…For most malignant tumors, including colon cancer, nomograms have a more accurate value than the TNM staging to predict the outcome of patients. 19 Martin et al 26 in colon cancer includes predictors of grade, N stage, T stage, colectomy, and carcinogenic antigen levels. 27 In this study, LODDS was used to assess lymph node status, and other risk factors were added to build the nomograms in LCC and RCC for predicting OS of colon cancer patients.…”

Development and Assessment of a Clinical Calculator for Estimating the Likelihood of Recurrence and Survival Among Patients With Locally Advanced Rectal Cancer Treated With Chemotherapy, Radiotherapy, and Surgery

“…29 Although our clinical calculators were developed using data from patients who received neoadjuvant chemoradiotherapy, the calculators are likely broadly applicable because they were validated using data from patients who received short-course radiotherapy with consolidation chemotherapy, a form of total neoadjuvant therapy. 29 The lower predictive accuracy (as measured by the concordance index) of the clinical calculators compared with those of colon cancer models 31,32 may be associated with tumor response to multimodality therapy and represents an opportunity for improvement, possibly with the future addition of molecular and/or radiographic variables to the model, which capture the dynamics of tumor regression. The present study designed a web interface 33 incorporating estimates from Kaplan-Meier curves for patients with complete response and risk models (depicted using nomograms) for patients with incomplete response to provide an easy-to-use method for patients and physicians to calculate the likelihood of 5-year RFS and OS.…”

Accurate population-based model for individual prediction of colon cancer recurrence

“…Knowledge about mutations, especially mismatch repair deficiency which are associated with a good prognosis at least in stage II may further improve the accuracy of nomograms [39]. This information was not available in the current material and precluded us from evaluating the predictive power of the new MSKCC nomogram [5]. Other markers, for example, circulating tumour DNA and tumour infiltrating lymphocytes, of increased recurrence risk will likely be of value in the future, though these are seldom available in populationbased cohorts.…”

“…Currently, there are several nomograms available for prediction of recurrence of colon cancer after radical surgery; the thrice updated Memorial Sloan Kettering Cancer Centre (MSKCC) nomogram [3][4][5], the ACCENT nomogram [6], a nomogram by Hoshino et al [7], and a nomogram from Special Commission on Cancer (SCOC) data [8]. The original MSKCC nomogram was based on 1320 patients who underwent surgery between 1990 and 2000 and the ACCENT nomogram is based on 15,936 stage III patients included in adjuvant treatment trials between 1989 and 2002.…”