There are numerous preoperative factors that affect surgical patients. In particular, older patients undergoing surgery have age-related factors that can affect their surgical outcomes. This is particularly important in the context of colorectal cancers, which are the third most diagnosed malignancy and the fourth leading cause of cancer death worldwide [1]. The majority of colorectal cancers are still diagnosed after the age of 65 years [2]. As populations continue to age, the incidence of major colon and rectal resections for cancer in the older population are projected to increase dramatically [3]. This makes it important to understand surgical risk factors in older adults and implement timely intervention where possible. Further, three of the most important age-related preoperative factors in older surgical patients are frailty, sarcopenia, and malnutrition. Although each has been studied individually, there is little information on their associations in older surgical patients.

At present, while there are no universally agreed upon consensus criteria for defining frailty, it can be thought of as physiologic decline and an increased risk of poor health resulting from aging [4]. There are numerous definitions, which vary from clinical phenotypes with specific required criteria to operational definitions (eg, the tally of an accumulation of deficits in older patients) [5,6].

Regardless of the definition used, preoperative frailty has been shown to be associated with poor postoperative outcomes in major colorectal surgery, such as an increased number of postoperative complications, an increased length of hospital stay, higher readmission rates, and decreased long-term survival rates [7]. Frailty is also associated with an increased cost of elective surgical care [8].

Two simple-to-use frailty assessments are the Clinical Frailty Scale (CFS) and the Groningen Frailty Indicator (GFI). Each of these assessments can be rapidly performed and have been validated with multiple cohorts [9,10].

Sarcopenia is the age-related loss of muscle mass and function [11]. It is often associated with physical frailty, yet being clinically frail is not always a prerequisite for a sarcopenia diagnosis. It is also associated with malnutrition, although the two entities can occur separately [12].

Muscle function is often measured through hand grip strength, while lower extremity and torso muscle mass can be evaluated through numerous mechanisms, including computerized tomography (CT) morphometric analysis [13,14].

Sarcopenia has been associated with an increased risk of postoperative complications in patients undergoing gastrointestinal tumor resection, and it has a potential role in preoperative risk stratification if both muscle mass and function are assessed [15].

Malnutrition refers to deficiencies, imbalances, or excesses in a person’s intake of energy and nutrients [16]. In patients undergoing major abdominal surgery, malnutrition is associated with worse outcomes, including increased lengths of stay, increased in-hospital mortality rates, and higher costs of care [17]. The identification of malnutrition often relies on clinical screening tools that are reliant on various amounts of subjective recall [18]. A promising new strategy for making an objective diagnosis of dietary patterns that indicate a risk for malnutrition is urine metabolomics analysis [19]. This may play a role in assisting clinicians with identifying patients who may benefit from perioperative nutritional support.

The objective of our feasibility study is to prospectively study older patients undergoing elective colorectal cancer resection and to provide informative data for further large-scale intervention studies. This study will evaluate the risk of postoperative complications (primary outcome), length of hospital stay (secondary outcome), and mortality (secondary outcome), with the following risk factors: frailty, sarcopenia and nutritional status.

The data obtained from this study may allow for the development of novel management strategies and targeted therapies of older surgical patients who experience a combination of frailty, sarcopenia, and malnutrition.

The Older Persons Surgical Outcomes Collaboration is a collaboration of surgeons, geriatricians, and epidemiologists who collect data on surgical outcomes in older individuals through multicenter research studies [20]. This collaborative collects data across the United Kingdom (sites include Cardiff, Bristol, Bath, Glasgow, Manchester, London, and Aberdeen) from all phases of surgical care, including longitudinal follow-ups. This study will initially enroll patients at three sites—Cardiff, Bristol, and Bath. It will then be registered on the Health & Care Research Wales Clinical Portfolio in order to allow other sites to enroll their patients. Cardiff University is acting as the study sponsor.

Our study is a prospective, multicenter, UK cohort study of older (aged ≥65 years) patients with colorectal cancer undergoing surgical resection. The objectives are to determine the association between clinical outcomes and frailty, nutritional status, and sarcopenia.

The inclusion criteria include patients with a diagnosis of colorectal cancer, those who plan to undergo surgical treatment for colorectal cancer, those aged ≥65 years, those with an abdominal CT scan that was taken prior to surgery (current standard of care), and those with the ability to understand the participant information sheet and are therefore able to provide written informed consent. Patients will be excluded if their procedural treatment is not performed with curative intent (including palliative colorectal stent insertion or the treatment of locally advanced tumors not amenable to curative resection) or if they are participating in another research study.

Patients will be identified by the usual clinical team as part of the routine, preoperative, multidisciplinary team meeting (the cancer multidisciplinary team). After patients are identified by screening, they will be approached by the colorectal clinical nurse specialist (CNS) by phone to discuss the study. If a patient agrees to discuss the study, the CNS will send the patient a participant information sheet via postal mail to allow for time for reviews and the further consideration of participation prior to the patient attending their preoperative assessment clinic (POAC) appointment. As the POAC is a routine standard-of-care appointment for evaluating a patient’s appropriateness for undergoing anesthesia and surgery, it does not subject patients to unnecessary visits. The CNS will also inform the study team about patient interest, so that a member of the study team can attend the POAC to answer patients’ questions and obtain written informed consent.

Based on an a priori power analysis, we will estimate the true postoperative incidence of complications (estimated to be 20%) with a 95% CI of ±11%. To achieve this, 50 patients will be enrolled. Due to the nature of the study, we anticipate that all patients will be followed up.

Enrollment will occur over a 12-month period beginning in winter 2020.

Routine clinical data will be prospectively collected, including baseline demographics (age, sex, and race), height, weight, BMI, and medical comorbidities. Standard-of-care POAC laboratory results will be obtained, including full blood counts, basic metabolic panels, liver function test results, and C-reactive protein levels. Data on study specific characteristics, including urinary biomarkers for the assessment of dietary intake, radiographic muscle evaluations, and frailty assessments, will be recorded. At 90 days following surgery, the following specific outcomes will be reviewed: the length of hospital stay, readmissions to the hospital within 30 days, postoperative complications (evaluated using the Clavien-Dindo classification system), 30-day mortality, and 90-day mortality [21].

Each research site will maintain separate databases, and electronic records will be stored via standard National Health Service encryption. If hard copy data exist, they will be stored securely by each participating site’s principal investigator. All data shared with the centralized coordinating center will be deidentified and shared through a secure electronic database. All identifiable participant data will be deidentified by assigning research numbers to participants. Clinical data (including images) will be anonymized and securely stored centrally at Cardiff University for long-term storage in accordance with local guidelines (stored for 15 years). Consent forms will be stored centrally at Cardiff University.

Multiple frailty and functional assessments will be performed at the POAC to evaluate a patient’s baseline status. The following two frailty assessments will be performed: The Canadian Study of Health and Aging CFS assessment and the GFI assessment.

The CFS is a 7-point scale that is used to score patients (from 1 to 7) based on the symptom burden of comorbidities and patients’ dependence on others for activities of daily living [10]. Patients with a score of 1 to 4 will be considered as “nonfrail,” while those with CFS scores of between 5 and 7 will be considered as “frail.”

The GFI is a simple, 15-point questionnaire that can be easily completed by clinical staff [31]. These assessments will be repeated during patients’ 8-week postoperative appointments to evaluate changes in frailty over time.

In addition to frailty assessments, numerous adjunctive functional tests will be performed at the POAC appointment. Strength will be assessed by using a hand grip dynamometer with the patient’s dominant hand and averaging the best results of 3 trials [5]. Mobility will be evaluated with a 4-meter walk test (measured from a starting standing position, at a normal walking pace, and with any usual walking aids) [32]. As strength and mobility are key components of frailty and the loss of muscle function is a key component of sarcopenia, these two tests will provide adjunctive information to both our frailty assessments and measured muscle masses. These functional assessments will also be repeated at the 8-week postoperative appointment to evaluate changes over time.

Finally, as an adjunct to both frailty evaluations and urine metabolomics analyses, the Mini Nutritional Assessment–Short Form will be used at both the POAC and 8-week follow-up visits. The Mini Nutritional Assessment–Short Form is a quick screening tool that is used to identify older patients that are malnourished or at risk of malnutrition [33], which has been shown to be associated with frailty in hospitalized patients [34]. Its use in this study will allow for comparisons between this subjective malnutrition assessment and objective urine metabolomics profiles.

A baseline descriptive analysis will be carried out for all patients who consent to the study, and this will be used to summarize the extent of missing data [35].