Importance The overall incidence of colorectal cancer (CRC) has been decreasing since 1998, but there has been an apparent rise in the incidence of CRC in young adults. Objective To evaluate age-related disparities in secular trends in CRC incidence in the United States. Design A retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) CRC registry. Age at diagnosis was analyzed in 15-year intervals starting at the age of 20. SEER*Stat was used to obtain the annual cancer incidence rates, annual percent change (APC), and corresponding p-values for the secular trends. Setting Data was obtained from the National Cancer Institute’s SEER registry. Patients All patients diagnosed with colon or rectal cancer from January 1, 1975 through December 31, 2010 (N = 393,241). Main Outcome Difference in CRC incidence by age. Results Overall age-adjusted CRC incidence rate decreased by 0.92% between 1975 and 2010. There has been a steady decline in the incidence of CRC in patients age 50 years or older, but the opposite trend has been observed for young adults. For patients 20 to 34 years of age, the incidence rate of localized, regional and distant colon and rectal cancer has increased. Increasing incidence rate was also observed for rectal cancer patients aged 35 to 49. Based on current trends, in 2030 the incidence rate for colon and rectal cancer will increase by 90.0% and 124.2% for patients 20 to 34 years of age and by 27.7% and 46.0% for patients 35 to 49 years of age. Conclusion and Relevance There has been a significant increase in the incidence of CRC diagnosed in young adults, with a decline in older patients. Further studies are needed to determine the cause for these trends and identify potential preventive and early detection strategies.

BACKGROUND & AIMS Staging inadequately predicts metastatic risk in patients with colon cancer. We used a gene expression profile derived from invasive, murine colon cancer cells that were highly metastatic in an immunocompetent mouse model to identify patients with colon cancer at risk of recurrence. METHODS This phase 1, exploratory biomarker study used 55 patients with colorectal cancer from Vanderbilt Medical Center (VMC) as the training dataset and 177 patients from the Moffitt Cancer Center as the independent dataset. The metastasis-associated gene expression profile developed from the mouse model was refined with comparative functional genomics in the VMC gene expression profiles to identify a 34-gene classifier associated with high risk of metastasis and death from colon cancer. A metastasis score derived from the biologically based classifier was tested in the Moffitt dataset. RESULTS A high score was significantly associated with increased risk of metastasis and death from colon cancer across all pathologic stages and specifically in stage II and stage III patients. The metastasis score was shown to independently predict risk of cancer recurrence and death in univariate and multivariate models. For example, among stage III patients, a high score translated to increased relative risk of cancer recurrence (hazard ratio, 4.7; 95% confidence interval, 1.566–14.05). Furthermore, the metastasis score identified patients with stage III disease whose 5-year recurrence-free survival was >88% and for whom adjuvant chemotherapy did not increase survival time. CONCLUSION A gene expression profile identified from an experimental model of colon cancer metastasis predicted cancer recurrence and death, independently of conventional measures, in patients with colon cancer.

Background: Natural language processing models such as ChatGPT can generate text-based content and are poised to become a major information source in medicine and beyond. The accuracy and completeness of ChatGPT for medical queries is not known. Methods: Thirty-three physicians across 17 specialties generated 284 medical questions that they subjectively classified as easy, medium, or hard with either binary (yes/no) or descriptive answers. The physicians then graded ChatGPT-generated answers to these questions for accuracy (6-point Likert scale; range 1 – completely incorrect to 6 – completely correct) and completeness (3-point Likert scale; range 1 – incomplete to 3 - complete plus additional context). Scores were summarized with descriptive statistics and compared using Mann-Whitney U or Kruskal-Wallis testing. Results: Across all questions (n=284), median accuracy score was 5.5 (between almost completely and completely correct) with mean score of 4.8 (between mostly and almost completely correct). Median completeness score was 3 (complete and comprehensive) with mean score of 2.5. For questions rated easy, medium, and hard, median accuracy scores were 6, 5.5, and 5 (mean 5.0, 4.7, and 4.6; p=0.05). Accuracy scores for binary and descriptive questions were similar (median 6 vs. 5; mean 4.9 vs. 4.7; p=0.07). Of 36 questions with scores of 1-2, 34 were re-queried/re-graded 8-17 days later with substantial improvement (median 2 vs. 4; p<0.01). Conclusions: ChatGPT generated largely accurate information to diverse medical queries as judged by academic physician specialists although with important limitations. Further research and model development are needed to correct inaccuracies and for validation.

The majority of patients with stage IV CRC had undergone primary tumor resection but, beginning in 2001, a trend toward fewer primary tumor resections was seen. Despite the decreasing primary tumor resection rate, patient survival rates improved. However, primary tumor resection may still be overused, and current treatment practices lag behind evidence-based treatment guidelines.

Background With advances in multimodality therapy, colorectal cancer survivors are living longer. However, little is known about the quality of their long-term survival. We investigated the functional outcomes and symptoms among long-term survivors. Methods A cross-sectional study of 1,215 long-term (>5 years) colorectal cancer survivors was conducted using a validated disease-specific questionnaire. Younger-onset survivors (18–50 years) were matched 1:2 to later-onset survivors (> 50 years). Standardized mean scores were compared using one-way ANOVA. Key patient and treatment factors that impact function and symptoms were assessed by multivariate linear regression. Results 830 survivors responded at an interval of 10.8±3 years from diagnosis (68% response rate). Younger-onset survivors underwent more surgery (97.9% vs 93.6%, P<0.001) and received more chemotherapy (86.1% vs. 77.7%, P=0.004). Anxiety, body image, sexual dysfunction, embarrassment by bowel movements, micturition problems, and impotence were significant concerns. Younger-onset survivors reported worse anxiety, body image, and embarrassment with bowel movements, whereas later-onset survivors highlighted sexual dysfunction, micturition problems, and impotence. Age-at-diagnosis was a key independent determinant of long-term function and symptoms. Conclusion Long-term survivors of CRC face ongoing functional deficits and symptoms, and their survivorship experience differs by age. Age-at-diagnosis should serve as a basis for tailored, personalized survivorship care plans.