Comorbidity Patterns in Patients Newly Diagnosed With Colorectal Cancer: Network-Based Study

Abstract

Background: Patients with colorectal cancer (CRC) often present with multiple comorbidities, and many of these can affect treatment and survival. However, previous comorbidity studies primarily focused on diseases in commonly used comorbidity indices. The comorbid status of CRC patients with respect to the entire spectrum of chronic diseases has not yet been investigated.

Objective: This study aimed to systematically analyze all chronic diagnoses and diseases co-occurring, using a network-based approach and large-scale administrative health data, and provide a complete picture of the comorbidity pattern in patients newly diagnosed with CRC from southwest China.

Methods: In this retrospective observational study, the hospital discharge records of 678 hospitals from 2015 to 2020 in Sichuan Province, China were used to identify new CRC cases in 2020 and their history of diseases. We examined all chronic diagnoses using ICD-10 (International Classification of Diseases, 10th Revision) codes at 3 digits and focused on chronic diseases with >1% prevalence in at least one subgroup (1-sided test, P<.025), which resulted in a total of 66 chronic diseases. Phenotypic comorbidity networks were constructed across all CRC patients and different subgroups by sex, age (18-59, 60-69, 70-79, and ≥80 years), area (urban and rural), and cancer site (colon and rectum), with comorbidity as a node and linkages representing significant correlations between multiple comorbidities.

Results: A total of 29,610 new CRC cases occurred in Sichuan, China in 2020. The mean patient age at diagnosis was 65.6 (SD 12.9) years, and 75.5% (22,369/29,610) had at least one comorbidity. The most prevalent comorbidities were hypertension (8581/29,610, 29.0%; 95% CI 28.5%-29.5%), hyperplasia of the prostate (3816/17,426, 21.9%; 95% CI 21.3%-22.5%), and chronic obstructive pulmonary disease (COPD; 4199/29,610, 14.2%; 95% CI 13.8%-14.6%). The prevalence of single comorbidities was different in each subgroup in most cases. Comorbidities were closely associated, with disorders of lipoprotein metabolism and hyperplasia of the prostate mediating correlations between other comorbidities. Males and females shared 58.3% (141/242) of disease pairs, whereas male-female disparities occurred primarily in diseases coexisting with COPD, cerebrovascular diseases, atherosclerosis, heart failure, or renal failure among males and with osteoporosis or gonarthrosis among females. Urban patients generally had more comorbidities with higher prevalence and more complex disease coexistence relationships, whereas rural patients were more likely to have co-existing severe diseases, such as heart failure comorbid with the sequelae of cerebrovascular disease or COPD.

Conclusions: Male-female and urban-rural disparities in the prevalence of single comorbidities and their complex coexistence relationships in new CRC cases were not due to simple coincidence. The results reflect clinical practice in CRC patients and emphasize the importance of measuring comorbidity patterns in terms of individual and coexisting diseases in order to better understand comorbidity patterns.

Keywords: colorectal cancer; comorbidity patterns; health status disparities; network analysis; prevalence; routinely collected health data.

Figure 1

Flowchart of the study participants. CRC: colorectal cancer; Z08: follow-up examination after treatment for malignant neoplasms; Z51.0: radiotherapy session; Z51.1: chemotherapy session for neoplasm; Z85: personal history of malignant neoplasm.

Figure 2

Number of comorbidities and hospitalizations for newly diagnosed colorectal cancer (CRC) patients in 2020 in Sichuan Province, China. (A) Age at diagnosis by sex. (B) Hospitalizations during the 5-year look-back period before diagnosis. (C) Frequency of patients per distinct number of comorbidities per patient among male and female patients. (D) Age-specific mean number of comorbidities by cancer site, region, and sex.

Figure 3

Clusters of comorbidities in colorectal cancer patients based on age-specific prevalence in Sichuan Province, China. (A) Optimal number of clusters using K-means clustering algorithm. (B) Age-specific prevalence of comorbidities in each cluster. Here, comorbidities with a prevalence of >20% in the ≥80 years age group were labeled with ICD-10 (International Classification of Diseases, 10th Revision) codes at 3 digits. (C) Cluster plot. Based on the principal component analysis, comorbidity prevalence in 5 dimensions (18-49, 50-59, 60-69, 70-79, and ≥80 years) was reduced to 2 dimensions (x-lab and y-lab). The ICD-10 codes are clarified in Multimedia Appendix 1.

Figure 4

Phenotypic comorbidity network (PCN) in newly diagnosed colorectal cancer (CRC) patients in Sichuan Province, China. (A) The PCN in newly diagnosed CRC patients. Nodes represent comorbidities (ICD-10 [International Classification of Diseases, 10th Revision] codes at 3 digits), such that the node size is proportional to the comorbidity prevalence in CRC patients and its color identifies the ICD-10 category. Link weights are proportional to the magnitudes of the cosine index. (B) Cumulative degree (k) distribution. The degree distribution showed an exponential decay when the degree was ≥12 (Kolmogorov-Smirnov test, P=.09). (C) The top 100 edges in the PCN. Here, the top 100 links where cosine index values were ≥0.18 are shown. (D) The degree distribution of the node and its neighbors. Here, the connected nodes (degree >0) in the PCN are shown. The ICD-10 codes are clarified in Multimedia Appendix 1.

Figure 5

Abundant connections by sex, region, and cancer site in newly diagnosed colorectal cancer patients in Sichuan Province, China. Except for those common to both subgroups (link weight difference <0.05), disease pairs were identified as abundant edges in one subgroup, including enrichment (solid lines) or only occurrence (dotted lines). For example, if the link weight difference by sex (female-male), region (rural-urban), and cancer site (rectal-colon) was ≥0.05, the disease pair was enriched in females, rural patients, and colon cancer patients, and the link was colored blue. On the other hand, if the difference was ≤−0.05, the disease pair was enriched in males, urban patients, and rectal cancer patients, and the link was colored red. The ICD-10 (International Classification of Diseases, 10th Revision) codes are clarified in Multimedia Appendix 1.