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ORIGINAL ARTICLE
Year : 2022  |  Volume : 18  |  Issue : 2  |  Page : 503-508

Factors contributing to the mortality of elderly patients with colorectal cancer within a year after surgery


1 Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Key Laboratory of Metabolism and Gastrointestinal Tumor, The First Affiliated Hospital of Shandong First Medical University, Key Laboratory of Laparoscopic Technology, The First Affiliated Hospital of Shandong First Medical University, Shandong Medicine and Health Key Laboratory of General Surgery, Jinan, Shandong, China
2 Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Weifang Medical College, Weifang, Shandong, China

Date of Submission28-Aug-2021
Date of Decision09-Feb-2022
Date of Acceptance07-Mar-2022
Date of Web Publication20-May-2022

Correspondence Address:
Hui Yang
Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Key Laboratory of Metabolism and Gastrointestinal Tumor, The First Affiliated Hospital of Shandong First Medical University, Key Laboratory of Laparoscopic Technology, The First Affiliated Hospital of Shandong First Medical University, Shandong Medicine and Health Key Laboratory of General Surgery, Jinan, Shandong - 250000
China
Jingbo Chen
Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Key Laboratory of Metabolism and Gastrointestinal Tumor, The First Affiliated Hospital of Shandong First Medical University, Key Laboratory of Laparoscopic Technology, The First Affiliated Hospital of Shandong First Medical University, Shandong Medicine and Health Key Laboratory of General Surgery, Jinan, Shandong - 250000
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.jcrt_1478_21

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 > Abstract 


Aims: Patients with colorectal cancer (CRC) have a lower survival rate during the first year following resection surgery. We analyzed the factors influencing this early mortality.
Methods and Material: The clinicopathological data of patients aged 70 years or older who underwent radical surgery for CRC between January 2012 and December 2018 were collected and analyzed retrospectively. A total of 242 patients (141 males and 101 females), including 93 with colon cancer and 139 with rectal cancer, were included in this study. Patients were divided into two groups according to whether they survived beyond the first year after surgery. The clinicopathological data of both groups were compared using Chi-square or Fisher's exact tests. The risk factors for mortality within 1-year after surgery were analyzed using the Cox regression model.
Results: Forty-three patients experienced at least one complication, including 34 cases with Clavien–Dindo grade I–II complications and 12 with Clavien–Dindo grade III–IV complications. Eleven patients died in the year following surgery. Patients with postoperative complications had higher mortality rates within the first year. Univariate analysis revealed that carbohydrate antigen 19-9 (CA19-9) levels, American Society of Anesthesiologists (ASA) grades, and differentiation degree influenced the 1-year overall survival (OS) and disease-free survival (DFS). Multivariate analysis confirmed that CA19-9 levels and ASA grades were independent factors affecting OS and DFS during the first year after surgery.
Conclusion: Postoperative complications were associated with the early death of elderly CRC patients. CA19-9 levels and ASA grades are independent factors influencing OS and DFS.

Keywords: Colorectal cancer, elderly patients, postoperative mortality


How to cite this article:
Shang W, Yuan W, Liu R, Yan C, Fu M, Yang H, Chen J. Factors contributing to the mortality of elderly patients with colorectal cancer within a year after surgery. J Can Res Ther 2022;18:503-8

How to cite this URL:
Shang W, Yuan W, Liu R, Yan C, Fu M, Yang H, Chen J. Factors contributing to the mortality of elderly patients with colorectal cancer within a year after surgery. J Can Res Ther [serial online] 2022 [cited 2022 Jul 7];18:503-8. Available from: https://www.cancerjournal.net/text.asp?2022/18/2/503/345527




 > Introduction Top


Colorectal cancer (CRC) is a common deadly cancer[1] affecting mostly elderly patients.[2] Elderly patients' 1-year mortality rate after radical surgery is high,[3],[4] but the prognosis of those surviving longer than a year after surgery equals that of younger patients.[3],[4],[5] Therefore, identifying the risk factors influencing elderly patients' early death after surgery is essential.

Postoperative complications negatively affect the prognosis[6] and are more frequent in elderly CRC patients.[7] However, their impact on early postoperative death is unknown.

Here, we investigated the morbidity rate and risk factors for early death in elderly CRC patients.


 > Materials and Methods Top


Patients

This study retrospectively identified patients aged 70 years or older, who were diagnosed with primary nonmetastatic CRC and had undergone radical resection at the Department of General Surgery between January 2012 and December 2018. All patients were followed up regularly for at least 1-year after surgery or until their passing. Computed tomography or magnetic resonance imaging scans of the abdominopelvic cavity and colonoscopies and histological biopsies were conducted preoperatively for the diagnosis and clinical staging. All the resected specimens were histologically examined and the diagnosis of CRC was established. The inclusion criteria were as follows: patients ≥70 years old, histologically diagnosis of CRC, American Joint Committee on Cancer tumor node metastasis (TNM) stage (NCCN guideline) I–III, absence of distant metastasis, and availability of the complete clinical data. Patients with stage IV tumors were excluded to minimize the bias caused by metastasis. Patients who underwent a palliative operation, had a history of other malignancies, or were diagnosed with two or more malignancies were also excluded from the study. Clinicopathological data collected in the present study are listed in [Table 1]. Patients were divided into two groups according to the survival time: less than 1-year group and the exceeding 1-year group. The study was approved by the Ethics Committee in July 2021.
Table 1: Patients' characteristics

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Definitions

Clavien–Dindo classification was used to evaluate postoperative complications.[8] Grade III–IV complications were considered severe clinical complications. The primary end points were cancer recurrence or death. Overall survival (OS) was defined as the time interval between the day of the patient diagnosis and the patient death or last follow-up visit. Disease-free survival (DFS) was defined as the time interval between cancer diagnosis and tumor recurrence or death from any causes.

Statistical analysis

The data are presented as means ± standard deviations. Continuous variables are reported as medians and ranges. Continuous data were compared using the Students' t-test. Categorical variables were analyzed by the Chi-square test or Fisher's exact test. OS and DFS were visualized on a Kaplan–Meier curve and compared using the log-rank test. The risk factors for prognosis were detected by the multivariate Cox regression analysis to calculate the hazard ratio (HR) and corresponding 95% confidence interval (CI). Statistical analyses were performed using IBM SPSS Statistics for Windows, version 22.0. P < 0.05 was considered statistically significant.


 > Results Top


Patients' characteristics

A total of 242 patients, including 93 colon cancer patients and 139 rectal cancer patients, was enrolled in the study. [Table 1] shows the characteristics of each subject. The median survival time of all patients was 47.50 ± 22.65 months. The number of patients with TNM stage I, II, and III was 52 (21.5%), 76 (31.4%), and 114 (47.1%), respectively. Eleven patients (4.6%) were in the less than 1-year group was composed of 11 patients (4.6%), specifically six males and five females with an average age of 78.00 ± 4.60 years. The exceeding 1-year group was composed of 231 (95.4%) patients comprising 61 males and 51 females with an average age of 76.55 ± 5.49 years. Patients with lymph node metastasis received adjuvant chemotherapy if they requested it and their general condition allowed it. Eighty-one patients with TNM stage III tumors were willing to receive adjuvant chemotherapy and were treated with mFOLFOX6 or CAPOX regimen. In this study, one patient received neoadjuvant therapy in another hospital.

Postoperative complications

Forty-three (19.2%) patients experienced postoperative complications detailed in [Table 2]. The most common complication was postoperative intestinal obstruction (16/242). In the less than 1-year group, seven cases of grade I–II complications and two cases of grade III–IV complications occurred. There were 27 cases of grade I–II complications and 10 cases of grade III–IV complications in patients surviving longer than 1 year after the operation. The incidence of severe, grade III–IV complications in the group surviving longer than 1 year after the operation was relatively low compared with that in the less than 1-year group (4.3% vs. 18.2%, respectively), but the difference was not statistically significant (P = 0.175). Overall, the complication rate was significantly higher in patients dying within 1-year after surgery (45.45%) than that in patients surviving for over a year after the operation (16.59%, P = 0.015).
Table 2: Postoperative complications developed by elderly patients with colorectal cancer after tumor resection surgery

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Risk factors for early postoperative death

The univariate Cox regression model identified that the levels of carbohydrate antigen 19-9 (CA19-9; HR = 6.106; 95% CI = 1.863–20.013; P = 0.003), American Society of Anesthesiologist (ASA) classification grades (HR = 3.471; 95% CI = 1.059–11.373; P = 0.04), and differentiation degree (HR = 4.448; 95% CI = 1.357–14.578; P = 0.014) influenced OS. Multivariate analysis confirmed that CA19-9 levels (HR = 5.683, 95% CI = 1.655–19.512; P = 0.006) and ASA grades (HR = 4.235, 95% CI = 1.263–14.196; P = 0.019) were independently associated with OS. CA19-9 levels (HR = 6.711, 95% CI = 2.046–22.017; P = 0.002), ASA grades (HR = 3.379, 95% CI = 1.031–11.071; P = 0.044), and differentiation degree (HR = 4.494, 95% CI = 1.372–14.727; P = 0.013) were also associated with DFS. The multivariate analysis revealed that CA19-9 levels (HR = 6.192, 95% CI = 1.774–21.611; P = 0.004) and ASA grades (HR = 4.252, 95% CI = 1.261–14.334; P = 0.02) were independent factors influencing DFS. The details of univariate and multivariate Cox regression analysis of the risk factors' impact on OS and DFS are presented in [Table 3] and [Table 4].
Table 3: Univariate and multivariate Cox regression analysis of the factors affecting overall survival (OS)

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Table 4: Univariate and multivariate Cox regression analyses of the risk factor for disease-free survival (DFS)

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 > Discussion Top


An increasing number of CRC patients is among the elderly.[9],[10],[11] The rate of comorbidities is higher in the elderly than in younger patients, and older patients are prone to postoperative complications and even death.[12],[13],[14] In past, the 30-day postoperative mortality after surgery has been commonly used to determine the short-term outcome of patients. However, studies have shown that the 30-day mortality rate is 4.9–6.5%, whereas the 1-year mortality rate reaches 12–23% in CRC patients.[15],[16] Because large proportions of patients die after the first postsurgery month, the 30-day mortality rate underestimates the risk of death in the first year after surgery.[3],[4] Thus, the present study focused on investigating the 1-year mortality rate and the risk factors for both OS and DFS.

Elderly patients presenting lower physiologic reserves of the heart and lungs and malnutrition are prone to postoperative complications.[7],[12] Previous studies have shown that the incidence of postoperative complications in older patients ranges from 21 to 61%.[6] We analyzed the differences in postoperative complications and survival between patients surviving less and more than 1 year after surgery. Postoperative complications have been associated with poor prognosis in elderly patients. The study of Duraes et al.[17] showed that the mortality within a year after surgery was significantly higher for elderly CRC patients with postoperative complications (53.6%) than for those without complications (9.2%). In their study, postoperative ileus was the most common complication.[18] Previous studies[19] reported that age, history of abdominal surgery, and early postoperative opioid use are independent risk factors for postoperative ileus. Electrolyte disturbances and infections can also worsen the underlying disease.[12] A meta-analysis published by Mcsorley et al. showed that the type and severity of postoperative complications affect the long-term prognosis of patients.[20] Anastomotic leakage is one of the most common and serious postoperative complications in CRC.[21] Studies have shown that the release of inflammatory mediators during acute and chronic inflammatory reactions associated with anastomotic leak leads to intraperitoneal infection. Additionally, these inflammatory biomarkers delay the mucosal healing process, enhance the invasion ability of residual tumor cells after surgery, thereby promoting local tumor recurrence and chemotherapy resistance, and reduce DFS and OS.[21],[22],[23],[24],[25] However, some studies[26] believe that there is no difference in the incidence of postoperative anastomotic leakage. The aging process diminishes physiologic functional reserves of vital organs, and most elderly patients suffer from comorbidities, such as diabetes, cardiovascular diseases, pulmonary dysfunction, and malnutrition.[7],[27],[28] Fawcett et al.[29] showed that the microcirculation in the serosal layer of the intestinal wall is important for anastomotic healing. The majority of elderly CRC patients with cardiovascular diseases also present systemic atherosclerosis, including of mesenteric vessels, which further affects the supply of blood by microcirculation at the anastomosis.[30],[31] A retrospective study by Leung et al.[32] on preoperative complications showed that chronic obstructive pulmonary disease (COPD) can predict postoperative complications. The pathogenic mechanisms involved are not clear, but patients with COPD might be prone to pneumonia, which leads to decreased blood oxygen saturation and poor tissue healing, after surgery[33] Elderly patients' comorbidities increase the length of hospital stay and the incidence of morbidity and mortality.[7] Overall, a preoperative evaluation should be fully conducted, and targeted perioperative management should be implemented in elderly patients.

The ASA classification is now the most commonly used method for assessing anesthesia and surgical risks preoperatively. Studies have shown that there are more comorbidities in elderly patients, and high ASA grades have been linked to early postoperative mortality of patients.[34] ASA classification can be used as an indicator to predict postoperative mortality and quality of life in elderly patients with CRC.[35],[36] Kim et al.[37] showed that high ASA grades are independent risk factors for postoperative complications in elderly patients associated with early postoperative death. ASA scores and serum albumin levels are also considered as indirect indicators of a patient's physical functioning status.[38] Here, ASA grades were identified as independent risk factors for early postoperative death of elderly patients. Among the parameters influencing ASA grades, the presence of cardiovascular diseases is the most common preoperative comorbidity[30] Moreover, CRC and cardiovascular diseases share common risk factors, such as obesity and lifestyle, and many CRC patients have cardiovascular diseases[30] Patients with high ASA grades (≥ III) may suffer from perioperative myocardial infarction due to their cardiovascular disease, such as tumor hypercoagulability. They also might need long-term bed rest after the operation, leading to perioperative death and prolonging postoperative recovery time.[30],[39] Cardiovascular diseases are the most common cause of death among survivors of CRC, especially elderly patients.[31] To improve perioperative prognosis, adequate preoperative assessment is particularly important for patients with ASA grades greater than III.

In the past few decades, the TNM staging system has been widely used to predict prognosis in patients with CRC and to define adjuvant therapy after surgery.[40] It is generally believed that patients with advanced CRC, presenting lymph node or organ metastases, have higher recurrence rates, shorter survival, and shorter OS and DFS.[41] Previous studies have shown that the number of lymph nodes harvested and the positive lymph node ratio was independently associated with local relapse, treatment failure, and OS rates in rectal cancer patients.[42],[43] Also, the study of Bai et al.[44] showed that TNM stages III and IV, which are linked to increased mortality risk after tumor resection, are independent risk factors leading to poor long-term prognosis of patients. However, the present study did not identify TNM stage III (P = 0.599) as a factor influencing OS and DFS during the first postoperative year. This discrepancy might be because elderly CRC patients often die from chronic diseases and poor long-term prognosis.[44],[45] Moreover, TNM stages did not affect OS and PFS for the following potential reasons: the relatively short follow-up duration, the patients' advanced age (≥ 70 years old) as the study focused on the effects of age on OS and PFS, and the death of some patients from causes unrelated to cancer.

The present study's limitations include its retrospective design, the small sample size, and the fact that all enrolled patients came from a single center. Additionally, the period considered in this study is large, which led to differences in operative strategies and treatment regimens.

In this study, we found that postoperative complications have negative effects on the prognosis in elderly CRC patients. ASA classification and CA19-9 were found to be independent factors influencing OS and DFS. Adequate preoperative assessment and targeted treatment strategy might be essential to improve the survival of elderly CRC patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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