The long-term survival characteristics of a cohort of colorectal cancer patients and baseline variables associated with survival outcomes with or without time-varying effects

Abstract

Background Colorectal cancer is the third most common cancer in the world. In this study, we assessed the long-term survival characteristics and prognostic associations and potential time-varying effects of clinico-demographic variables and two molecular markers (microsatellite instability (MSI) and BRAF Val600Glu mutation) in a population-based patient cohort followed up to ~ 19 years. Methods The patient cohort included 738 incident cases diagnosed between 1999 and 2003. Cox models were used to analyze the association between the variables and a set of survival outcome measures (overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), metastasis-free survival (MFS), recurrence/metastasis-free survival (RMFS), and event-free survival (EFS)). Cox proportional hazard (PH) assumption was tested for all variables, and Cox models with time-varying effects were used if any departure from the PH assumption was detected. Results During the follow-up, ~ 61% patients died from any cause, ~ 26% died from colorectal cancer, and ~ 10% and ~ 20% experienced recurrences and distant metastases, respectively. Stage IV disease and post-diagnostic recurrence or metastasis were strongly linked to risk of death from colorectal cancer. If a patient had survived the first 6 years without any disease-related event (i.e., recurrence, metastasis, or death from colorectal cancer), their risks became very minimal after this time period. Distinct sets of markers were associated with different outcome measures. In some cases, the effects by variables were constant throughout the follow-up. For example, MSI-high tumor phenotype and older age at diagnosis predicted longer MFS times consistently over the follow-up. However, in some other cases, the effects of the variables varied with time. For example, adjuvant radiotherapy treatment was associated with increased risk of metastasis in patients who received this treatment after 5.5 years post-diagnosis, but not before that. Conclusions This study describes the long-term survival characteristics of a prospective cohort of colorectal cancer patients, relationships between baseline variables and a detailed set of patient outcomes over a long time, and time-varying effects of a group of variables. The results presented advance our understanding of the long-term prognostic characteristics in colorectal cancer and are expected to inspire future studies and clinical care strategies. Electronic supplementary material The online version of this article (10.1186/s12916-019-1379-5) contains supplementary material, which is available to authorized users.

Actual survival after resection of primary colorectal cancer: results from a prospective multicenter study

“…Observed cure was defined as actual 5-year survival with no recurrence [ 6 , 7 , 13 , 14 ]. At last follow-up, a patient was classified as having no evidence of disease (NED) if having survived without documented recurrence and as having died of disease (DOD) if the cause of death was listed as cancer in the national death registry.…”

Specific causes of recurrence after surgery and mortality in patients with colorectal cancer

“…demonstrated that the hazard of death in older age (>75) patients with colon cancer was 3.49 (95% confidence interval [CI], 3–4.06)[ 16 ] and the same results were found in other studies. [ 12 17 18 19 20 21 ] However, in the studies by Miyoshi et al ., Kaiser et al . and Newland, no significant results were found.…”

“…The hazard of death in rectum site of patients with CRC was 2.45 times more than that of colon site. Although some studies showed that the tumor site is related with hazard of death[ 21 22 23 ] but the finding Sharkas et al . [ 12 ] was not consistent with our results.…”

Higher ETV5 Expression Associates With Poor 5-Florouracil-Based Adjuvant Therapy Response in Colon Cancer

“…Colon cancer (CC) is the fourth most commonly diagnosed cancer (2 million cases in 2018) globally and kills nearly 1 million people annually ( Arnold et al, 2017 ) mostly due to the spread of tumor cells to other secondary organs (e.g., liver) in the later stage (stage IV) of the disease ( Yu et al, 2019 ). Therefore, successful treatment of the early-stage (stage I, II, and III) cancer is necessary in order to prevent disease progression and improve the overall survival of the patients ( Argiles et al, 2020 ).…”