The Effect of Body Mass Index on the Feasibility of Surgery and Prognosis of Colorectal Cancer Patients Over 80 Years Old

Objective This study aimed to evaluate the safety and feasibility of radical surgery and explore prognostic factors affecting cancer-specic survival (CSS) in colorectal cancer (CRC) patients over 80 years old. Methods From January 2010 to December 2020, a total of 372 elderly CRC patients who underwent curative resection at the National Cancer Center were enrolled and classied into a control group (BMI <24 kg/m 2 ) and an overweight group (BMI ≥ 24 kg/m 2 ). Preoperative clinical features, perioperative outcomes and postoperative pathological characteristics were collected and compared between the two groups. Results The control group and overweight group comprised 219 and 153 patients, respectively. There was no signicant difference between the two groups of patients in terms of operative time (153.0 vs 142.3 min, P=0.226), intraoperative bleeding (67.8 vs 69.3 ml, P=0.873) or other surgical outcomes or grade 3-4 postoperative complications (11.1% vs 14.6%, P=0.326). The 5-year CCS of patients in the overweight group was signicantly worse than that of the control group (63.3% vs 80.0%, P=0.046). The multivariate analysis showed that CCS was signicantly affected by BMI (HR: 2.30; 95% CI, 1.27-4.17; P=0.046) and N stage (HR: 2.97; 95% CI, 1.48-5.97; P=0.002) Conclusion The results of this study demonstrated that radical resection for CRC is safe and feasible for patients over 80 years of age. The increase in BMI does not increase the diculty of surgery or postoperative complications. BMI and N stage were independent prognostic factors for elderly CRC patients after radical resection.


Introduction
Colorectal cancer (CRC) is one of the most common causes of cancer death worldwide, and its morbidity and mortality are on the rise [1,2] . With the expansion of the population and the improvement of living standards, the ageing of the population continues to increase [3] . Therefore, in clinical practice, the proportion of older patients receiving surgical treatment for colorectal cancer is increasing. Elderly patients with CRC have unusual clinicopathological features and genetic backgrounds [4,5] . In addition, these individuals often have comorbidities such as cardiovascular and cerebrovascular diseases and diabetes and often need more rigorous and prudent standardized management during the perioperative period [6] . According to the clinical consensus and guidelines, adjuvant treatment such as chemotherapy and radiotherapy is not recommended for CRC patients older than 80 years of age regardless of TNM stage, but traditional prognostic indicators may not be suitable for elderly patients with CRC over 80 years old. Therefore, it is necessary to further investigate the perioperative safety and prognostic factors of elderly patients with CRC after curative resection.
Previous studies have only analysed the prognosis of elderly patients with CRC from a pathologicoanatomical tumour perspective [8][9][10][11][12][13][14][15] . However, due to their unique clinicopathological characteristics and lifestyle habits, some of the most common biological characteristics of elderly patients may be ignored, such as comorbidity, and body mass index (BMI), among other habits. In addition, for elderly patients over 80 years old, the proportion of deaths from non-tumour causes is relatively high, so simply calculating the overall survival rate is not su ciently rigorous. Therefore, the main purpose of the present study was to demonstrate the safety and feasibility of radical surgery for CRC in elderly patients over 80 years of age, to evaluate the prognosis of elderly CRC patients without adjuvant therapy using the tumour-speci c survival rate, and to comprehensively explore relevant prognostic factors.

Patients And Methods
From January 2010 to December 2020, all consecutive CRC patients older than 80 years of age who underwent curative resection at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, were retrospectively collected and analysed. The inclusion criteria were as follows: (1) age 80 or above; (2) pathologically con rmed colorectal adenocarcinoma; (3) no evidence of distant metastasis; and (4) no adjuvant therapy, such as radiotherapy or chemotherapy, after the operation. Patients who underwent emergency surgery or had other malignant tumours were excluded from the analysis. The study was approved by the Ethics Committee of the Cancer Hospital, Chinese Academy of Medical Sciences and was conducted in accordance with the Declaration of Helsinki and Ethical Guidelines for Clinical Research. All patients provided written informed consent.
All patients were divided into two groups according to BMI: the control group (BMI < 24 kg/m 2 ) and the overweight group (BMI ≥ 24 kg/m 2 ). Clinical characteristics, perioperative variables, pathological results and survival outcomes for all patients were obtained from the medical records, operation records, and pathology records in our hospital database. Postoperative complications were assessed using the Clavien-Dindo classi cation (CD) categories and were de ned as any condition that occurs within 30 days after surgery that affects the normal recovery process and requires conservative or surgical intervention [16] . All procedures were performed by surgeons with more than 20 years of experience in colorectal surgery. The American Joint Committee on Cancer (AJCC, eighth edition) staging system was used for tumour staging.

Follow-up
The long-term outcome of the present study was the 5-year cancer-speci c survival (CCS) rate. All patients received a follow-up survey every 2 months for the rst 2 years and every 6 months for the next 3 years. The postoperative review examinations included physical examination, biomarkers (CEA and CA-199), CT scans of the chest, abdomen, and pelvis, and colonoscopy if necessary. CCS was de ned as the time between the date of surgery and the date of death from cancer. The deadline for follow-up in this study was June 2021.

Statistical analysis
Quantitative data were analysed by the Mann-Whitney U test and are given as the mean ± standard deviation. Categorical variables were analysed by the chi-squared test and presented as frequencies and percentages. Univariate and multivariate Cox regression models were used to identify the factors predicting CSS. The Kaplan-Meier survival method was performed to analyse the 5-year CCS of the patients in different groups, and signi cant differences in CCS were compared using the log-rank test. The statistically signi cant variables (P < 0.20) in univariate analysis were subsequently tested by multivariate analysis through a Cox regression model, and the effect of each variable was assessed by the hazard ratio (HR) and 95% con dence interval (95% CI). A P value < 0.05 was considered statistically signi cant. Statistical analyses were performed using IBM SPSS Statistics software version 24.0 (IBM Corporation, Armonk, NY, USA). Table 1 summarizes the baseline characteristics of the patients. Among the 372 elderly CRC patients included in this study, 219 were in the control group, and 153 were in the overweight group. In the overweight group, the proportion of patients with ASA grade III was signi cantly lower than that in the control group (36.6% vs 48.4%, P = 0.024). There was no statistically signi cant difference between the two groups in terms of sex, age, albumin level, HGB level, habits, comorbidities, previous abdominal surgery, or tumour location (all P > 0.05).   Table 3 lists the postoperative complications of the 372 elderly CRC patients. The incidence rates of overall complications, grade 1-2 complications and grade 3-4 complications were 40.1%, 26.9% and 13.2, respectively. Among the overall complications, abdominal abscess (8.6%), anastomotic leakage (7.5%) and ileus (7.5%) were the most common. The most common grade 3-4 complication was urinary retention (2.4%), followed by pleural effusion (2.2%) and abdominal abscess (1.9%).  . 1-3).

Discussion
One of the biggest challenges in healthcare is the ageing population; in 2015, the life expectancy at birth was 82.9 years, with males expected to live to 80.5 years old and females expected to live to 85.1 years old. Elderly CRC patients are regarded as a special population with unique clinicopathological characteristics, and the increase in comorbidities typically observed in this population tend to increase the potential risk during the perioperative period. In addition, BMI has been previously reported to be associated with the incidence of postoperative complications and even the prognosis of colorectal cancer [17][18][19][20] . In the present study, to clarify the effect of BMI on the technical feasibility and oncological safety of radical surgery and the prognosis of CRC in elderly patients, we compared the short-and longterm outcomes between elderly patients in the control group and overweight group.
Along with the increase in material wealth, the incidence of obesity has increased and become a medical and social problem. It has been previously con rmed that obesity increases the di culty of CRC surgery and the incidence of postoperative complications [17,19,21] . A study involving 792 patients with low rectal cancer conducted by Zhang et al. showed that the operation time and length of postoperative hospital stay in the overweight group were signi cantly longer than those in the control group, and the increase in BMI was closely related to the incidence of postoperative complications such as pneumonia, anastomotic leakage, allergy and incisional hernia [21] . However, the results of the present study show that The safety of radical surgery for elderly patients with colorectal cancer is a concern for surgeons. Prior works have reported that the incidence of overall complications in elderly patients with CRC after radical surgery is 9.9%-25.4%, and the incidence of grade 3-5 complications is 6.5%-20.1% [22][23][24][25] . Our study showed that the incidence rates of overall complications, grade 1-2 complications and grade 3-4 complications were 40.1%, 26.9% and 13.2%, respectively, which were consistent with previous reports in the literature. In addition, this study revealed that the most common overall complication after radical resection of elderly patients with CRC is abdominal abscess (8.6%), and the most common grade 3-4 postoperative complication is urinary retention (2.4%). Therefore, in view of the above complications, more attention should be given to aseptic operation and the appropriate prolongation of antibiotic use after radical resection of CRC in elderly patients.
Obesity is clearly associated with the incidence of CRC [26] , and the relationship between obesity and colorectal cancer has been previously reported but remains controversial. Several studies believe that a high BMI is associated with a poor prognosis in patients with CRC [18,27] , while some studies believe that a high BMI is not related to prognosis [28,29] or even related to a better prognosis [30,31]  Availability of data and materials The datasets generated and/or analysed during the current study are not publicly available due to the data is con dential patient data but are available from the corresponding author on reasonable request.

Competing interests
The authors declare that they have no competing interests.

Funding
This work was supported by the Capital' s Funds for Health Improvement and Research (2016-2-4022).
The funders had no role in the design of the study, data collection, analysis, and manuscript writing.  Cancer speci c survival curve of N0 group and N1-2 group.

Figure 3
Forest plots for Cancer speci c survival of elderly CRC patients after curative resection based on multivariable COX proportional hazard model.