One-year functional outcomes of patients aged 80 years or more undergoing colonic cancer surgery: prospective, multicentre observational study

Abstract Background Older patients are at high risk of experiencing delayed functional recovery after surgical treatment. This study aimed to identify factors that predict changes in the level of support for activities of daily living and mobility 1 year after colonic cancer surgery. Methods This was a multicentre, observational study conforming to STROBE guidelines. The prospective data included pre-and postoperative mobility and need for support in daily activities, co-morbidities, onco-geriatric screening tool (G8), clinical frailty scale (CFS), operative data, and postoperative surgical outcomes. Results A total of 167 patients aged 80 years or more with colonic cancer were recruited. After surgery, 30 per cent and 22 per cent of all patients had increased need for support and decreased motility. Multivariableanalysis with all patients demonstrated that preoperative support in daily activities outside the home (OR 3.23, 95 per cent c.i. 1.06 to 9.80, P = 0.039) was associated with an increased support at follow-up. A history of cognitive impairment (3.15, 1.06 to 9.34, P = 0.038) haemoglobin less than 120 g/l (7.48, 1.97 to 28.4, P = 0.003) and discharge to other medical facilities (4.72, 1.39 to 16.0, P = 0.013) were independently associated with declined mobility. With functionally independent patients, haemoglobin less than 120 g/l (8.31, 1.76 to 39.2, P = 0.008) and discharge to other medical facilities (4.38, 1.20 to 16.0, P = 0.026) were associated with declined mobility. Conclusion Increased need for support before surgery, cognitive impairment, preoperative anaemia, and discharge to other medical facilities predicts an increased need for support or declined mobility 1 year after colonic cancer surgery. Preoperative assessment and optimization should focus on anaemia correction, nutritional status, and mobility with detailed rehabilitation plan.


Introduction
The number of individuals aged 80 years or older is expected to double worldwide from 2020 to 2040 due increasing life expectancy 1,2 . Individuals in this age group have more than a four-fold probability of having colonic cancer than those aged 60 years 3 . Radical surgery represents the most successful treatment option for localized colonic cancer 4 ; however, older patients are at higher risk of experiencing postoperative complications and functional disability after surgical treatment 5,6 . Patients with co-morbidities, poor nutritional status, frailty, and declined functional/cognitive status are more vulnerable to adverse events, prolonged disability, and dependency 7,8 . The heterogeneity of patients in this age group can lead to different outcomes if managed surgically 9 ; however, physically and cognitively fit patients have similar surgical and functional outcomes to younger cohorts 10,11 .
In a recent study of more than 2000 patients aged more than 80 years undergoing surgery (including 649 colorectal resections), 19-26 per cent experienced a functional decline in activities of daily living within 30 days after surgery; however, the respective proportion was markedly higher (40-47 per cent) in patients with preoperative malnutrition, postoperative delirium, or major complications 12 . Loss of independence, which included the need for new walking aids and increased care needs such as a discharge to other medical facilities, was reported in 67-84 per cent of patients aged 75 years or older after discharge from the hospital after the surgical operation 13 . Prolonged and even permanent decline in functional performance has been reported in 23-69 per cent of patients 1-2 years after colorectal surgery [14][15][16] .
Maintenance of physical function and functional independence is a highly valued determinant of quality of life for aged patients; therefore, such outcomes may be prioritized over surgical outcomes and cancer survival 17 . Most patients would choose less invasive treatment options to secure their functional independence 18 . Consequently, when choosing optimal, patient-centred cancer treatment for older patients, it is essential to understand the effect of surgery on postoperative functional performance and recovery in addition to cancer prognosis 19 .
Only one study has evaluated the risk of long-term functional disability of older patients after elective colonic cancer surgery. In a study of nursing home residents, Finlayson et al. reported that half of the surviving patients had a functional decline in activities of daily living 1 year after surgery. Residents aged 80 years or older were more than 50 per cent more likely than younger residents to experience a functional decline 16 .
This study aimed to identify factors that predict increased support in activities of daily living and decreased mobility 1 year after elective surgery in patients with stage I-III colonic cancer aged 80 years and older.

Study design and population
A multicentre, prospective observational cohort study of patients aged 80 years or older with stage I-III colonic cancer was conducted in nine Finnish public hospitals. Recruitment started on 1 April 2019 and continued until 15 August 2020. Patients with metastatic disease, emergency operations, or life expectancy less than 6 months were excluded. In addition, patients who consented to the study but were treated non-operatively or found to have metastatic or benign disease at surgery were excluded from the present analysis. Our previously published articles have described the detailed study protocol, data collection, and short-term results 10,20 .
This study followed the STROBE guidelines 21 . The Ethics Committee of Tampere University Hospital (reference approval number R19028) and the institutional review boards at each study site approved the study protocol. The study was registered at http://www.clinicaltrials.gov (registration number NCT03904121) in April 2019.

Outcomes
The primary outcome measures were the changes in support for activities of daily living and mobility 1 year after surgery. Performance in activities of daily living was categorized as being able to perform activities of daily living independently, with support outside the home, with support for housework or with support for basic activities of daily living. Mobility inside and outside the home was categorized as being able to move independently without an aid, moving independently with a walking aid, or being unable to move unassisted. Based on a comparison between preoperative and 1-year postoperative function, the performance of activities of daily living was classified as 'same or with less support' or 'increased need for support', and mobility as 'same or better' or 'declined'. Patients who died during the follow-up time of 1 year were classified as those with an increased need for support or declined mobility.

Statistical analysis
Demographic data and outcomes were expressed as percentages. The median and range were calculated for age, preoperative laboratory values, and BMI. The distribution of the predictive variables in case numbers and percentages or medians with interquartile ranges according to the outcome variables of support in daily activities and mobility 1 year after surgery respectively, were calculated. When appropriate, associations between the categorical variables were tested with the Pearson chi-square test or Fisher's exact test for univariable analysis. Multivariable analyses of the factors associated with changes in performance with activities of daily living and mobility were carried out with binary logistic regression. Results are shown as odds ratios (OR) with a 95 per cent confidence interval (c.i.). All clinically (age, cognitive impairment, clinical frailty scale (CFS) 22 and mini-nutritional assessment-short form (MNA-SF) 23 ), and statistically significant variables (P < 0.05) in the univariate model were included in the multivariable model. Statistical analyses were performed with SPSS ® version 26 (IBM, Armonk, New York, USA). The analyses were performed for all patients and those patients who were independent before surgery in activities of daily living or able to move without assistance. Values are n (%).

Patients and clinical characteristics
Of the 250 eligible patients, 189 (76 per cent) patients consented to participate. Fourteen patients were treated non-operatively because of their age, withheld consent, had poor functional status, or the risks of anaesthesia. Eight patients were excluded because of metastatic or benign findings at surgery or in the pathological specimen. This left 167 patients for analysis in this study.
The median age was 84.5 (range 80-97) years, and 59 per cent were women. Before surgery, most patients lived at home (98 per cent), performed activities of daily living independently (54 per cent), were mobile without assistive devices (60 per cent), and moved unassisted outside the home (72 per cent). Table 1 shows patients' baseline characteristics.
Most of the operative procedures were performed for right-sided colonic cancer (62 per cent). An intended laparoscopic resection was performed in 112 patients (67 per cent), and 15 cases (13 per cent) were converted to open surgery due to anatomical or technical reasons. Overall, the postoperative complication rate was 40 per cent, and 13 per cent of all complications were severe. Surgical complications were reported for 23 per cent of patients. The most common surgical complications were ileus (13 per cent), anastomotic leakage (4.8 per cent), enterotomy

Preoperative status
No need for support (n = 90) 12 3 6 Need for support outside home (n = 23) The median duration of hospital stay in the operating hospital was 5 days (range 2-36 days). Ninety-one patients (54 per cent) were discharged from operating hospitals to home and the rest to other medical facilities. Within 30 days of discharge, readmission occurred in 14 patients (8.4 per cent). The overall 30-day and 1-year mortality rates were 1.8 per cent (3 of 167) and 6.6 per cent (11 of 167) respectively. The main causes of death within 1 year were cardiopulmonary (36 per cent), colonic cancer (27 per cent), and surgery-related (18 per cent) reasons.

Postoperative functional status
After excluding the patients who had died or where data were not available, the proportion of patients living at home after surgery  Figure 2 shows postoperative changes in mobility according to different preoperative mobility levels. After 1 year, 25 per cent (24 of 95) of patients who were fully mobile before surgery had declined mobility. The 1-year mortality rates for mobile patients who were independently mobile before surgery with or without a walking aid or unable to move unassisted were 4.3 per cent, 8.9 per cent and 33 per cent respectively (P = 0.039).  Table 2 and Table S1). Among patients who were independent before surgery, those who needed more support at follow-up more often were women (42 per cent versus 20 per cent, P = 0.023), had COPD (80 per cent versus 28 per cent, P = 0.031), asthma (80 per cent versus 28 per cent, P = 0.029), and open surgery (53 per cent versus 25 per cent, P = 0.029) but had diabetes less often (9 per cent versus 39 per cent, P = 0.006) ( Table S2).

Factors associated with changes in support in activities of daily living 1 year after surgery
In multivariable logistic regression analysis, preoperative need for support in activities of daily living outside the home (P = 0.039) was independently associated with an increased need for support at follow-up. Conversely, diabetes was associated with a lower probability of increased care needs with all patients (P = 0.016) and patients who were independent before surgery (P = 0.026) ( Table 3 and Table S3).

Factors associated with changes in mobility 1 year after surgery
At 1 year after surgery, declined mobility was seen more often in patients who had preoperative haemoglobin levels less than  Table 4 and Table S4). Among patients who were fully mobile before surgery, those who experienced declined mobility, had preoperative haemoglobin levels less than 120 g/l (  Table S5).
In multivariable logistic regression analysis, a history of cognitive impairment (P = 0.035), preoperative haemoglobin level less than 120 g/l (P = 0.003), and discharge after surgery to other medical facilities (P = 0.038) were independently associated with declined mobility. Conversely, being mobile before surgery with a walking aid was associated with a diminished risk of declined mobility (P = 0.016) ( Table 3). In patients who were fully mobile before surgery, preoperative haemoglobin level less than 120 g/l (P = 0.008) and discharge to other medical facilities (P = 0.026) were significantly associated with declined mobility (Table S3).

Discussion
This national multicentre study analysed the impact of colonic cancer surgery on functionally independent patients aged 80 years or more than 1 year after the elective operation. This study suggests that 69 per cent of patients who were independent in daily activities before surgery maintained their  Values are n (%). *Death during hospital stay (n = 1). Missing data (n = 10).
independence well over the first year. Similarly, 76 per cent of patients who were fully mobile before surgery maintained their mobility. Decline in functional performance and mobility were associated with existing impairments, indicating that physical and cognitively independent fit patients achieve satisfactory recovery in 1 year of follow-up; however, comprehensive preoperative evaluation and optimization may be advisable even for the fittest patients to identify anaemia and malnutrition, both of which were also associated with poorer outcomes. The systemic stress reaction associated with major abdominal surgery causes a reduction in older individuals' physiological and functional capacity. Lawrence et al. reported that in patients older than 65 years undergoing general surgery, postoperative recovery with activities of daily living and with housework took up to 3 and 6 months respectively. Prolonged recovery was more often seen with patients with declined preoperative physical performance status and severe complications 24 . The postoperative reduction in physiological reserve is caused by inflammation and tissue damage with changes in metabolic function 25 . With age-related physiological changes in major organs, the impact of surgery is thus more damaging in older patients 5 , especially for those with preoperative declined functional or cognitive status, frailty, and postoperative complications 26,27 .
This study showed a 40 per cent postoperative complication rate, and 13 per cent of all complications were severe. Open surgery and postoperative complications were associated with a reduction in long-term mobility. In previous studies, severe postoperative complications have also been associated with mortality 28,29 ; however, the 6.6 per cent 1-year mortality rate for all patients was low, showing convergent development with earlier studies 10,30 . The enhanced recovery after surgery programme and minimally invasive surgery, which have been shown to benefit postoperative outcomes, were well established at the recruiting hospitals 31 . Consequently, comprehensive preoperative assessment of risks for adverse events and allowing sufficient time for patients' preoperative medical optimization is recommended. In addition, intensive mobility rehabilitation should be initiated as soon as possible.
Of the study population, 55 per cent of patients were independent before surgery without any outside support with activities of daily living, and 69 per cent of them maintained independence 1 year after surgery; however, fit women and patients needing mobility assistance outdoors might benefit from further evaluation to exclude geriatric syndromes. On the contrary, 65 per cent of patients dependent on external support outside the home had increased demand for support with activities of daily living 1 year after surgery. Those patients may already have had other co-morbidities and frailty that, before surgery, impaired functional performance. In this group, major cancer surgery might have worsened the surgical stress reaction causing significant postoperative functional decline, protracted recovery, and possible permanent disability. These findings suggest that patients dependent on support in activities of daily living might benefit from preoperative risk evaluation and structured geriatric assessment to recognize conditions such as frailty, malnutrition, and cognitive impairment 8,19 .
At 1 year, mobility had declined by 24 per cent in mobile-independent patients and by 14 per cent in patients with walking aids compared with 60 per cent in mobile-dependent patients. In addition, immobile patients had an eight-times greater risk of 1-year mortality compared with mobile patients (4 per cent versus 33 per cent). Preoperative mobility with functionally independent patients with or without walking aid was slightly decreased during the first 3 months after treatment but flattened out after that, showing recovery during the first year after major surgery. These findings emphasize that maintaining mobility even with the aid of a new mobility device is essential for satisfactory long-term mobility recovery from cancer surgery; however, a greater proportion of patients discharged to other medical facilities had a loss of independence and impaired mobility. This might be a long-term consequence from patient's preoperative status, but it may also indicate incomplete early mobilization and rehabilitation after surgery. In addition, immobilization increases the risk of sarcopenia, leading to further delay in rehabilitation 32 . To avoid adverse effects of these factors on long-term mobility, a personalized rehabilitation programme designed before surgery, including a discharge plan might be beneficial.
Patients with preoperative haemoglobin level less than 120 g/l had reduced mobility, suggesting that careful preoperative anaemia assessment and correction is essential before surgery for preservation and enhancement of postoperative mobility 33 . In addition, those with impaired nutritional status, according to MNA-SF, low BMI, and albumin values, seemed to be associated with a declined mobility, advocating nutritional supplements to optimize the nutritional status before and after surgery 34 .
Patients with impaired cognitive function and memory loss before surgery had poorer mobility and increased support for activities in daily living after surgery, in keeping with a recent study 35 . In the present study, the preoperative data showed a discrepancy between self-reported memory decline and diagnosed dementia reported earlier with the same cohort 10 . These findings emphasize that preoperative cognitive disturbances are more frequent with older individuals, and awareness of possible impairment requires cautious preoperative assessment. Consequently, the use of easily adopted cognitive tests, such as the mini-mental state examination, are recommended before surgery 36 .
Comprehensive geriatric assessment (CGA) evaluates patients' co-morbidities, polypharmacy, physical performance, cognitive impairment, functional, nutritional and emotional status, and social support 11 . CGA may be beneficial in identifying patients who are at risk of an adverse event; however, in surgical units where current resource limitations make CGA challenging, rapid screening tools for frailty, nutritional and functional prehabilitation may be advantageous 10,37 . During the study interval, some hospitals had established perioperative collaborations with geriatricians, who are increasingly participating as members at colorectal multidisciplinary teams before the commencement of cancer treatment.
The strengths of this study included a prospectively collected nationwide representative cohort. As Finland follows uniform and standardized protocols for colonic cancer surgery, the data population was homogenous and comprehensive 38 . The study equates to standard everyday surgical practice, so the outcomes are relevant with less selection bias and more relevance to real-life settings. There are some limitations to this study. The present study results were based on patient-reported questionnaires regarding the preoperative need for support with activities of daily living, mobility, and cognitive impairment, and no validated geriatric evaluation was conducted. Lack of more-detailed functional measure scales, such as the six-item activities of daily living and eight-item instrumental activities of daily living index, precluded reporting more-detailed functional changes. Almost half the patients were discharged from the surgical ward to other medical facilities instead of home, so the total duration of hospital stay and thus an excess need for supportive care and mobility decline with loss of independence was unknown. Quality of life before and after surgery was not measured.
Increased need for support in daily living before surgery, cognitive impairment, preoperative anaemia, and discharge after surgery to other medical facilities predict an increased need for support or declined mobility 1 year after colonic cancer surgery. Preoperative assessment and optimization should focus on anaemia correction, nutritional status, and mobility with a detailed rehabilitation plan.

Funding
Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital partly supported this study financially. In addition, the Cancer Foundation Finland, Mary and Georg C. Ehrnrooth Foundation, and the Finnish Cultural Foundation provided external funding by awarding a grant; however, they did not have any role in designing the study, collection, analysis, interpretation of the data, or writing the manuscript.