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Personalized Colorectal Cancer Management in Older Adults: Summary and Recommendations

Oncology
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Introduction

A globally aging population has brought about an increasing number of older adults who require surgical intervention for a variety of ailments, including colorectal cancer.  However, given that age is often associated with an increased rate of postoperative morbidity and mortality, surgeons are faced with a growing task of assessing and mitigating frailty in older adults, as well as tailoring treatment recommendations to an individual’s goals of care[1].
Within the United States, 56% of new colorectal diagnoses occur in patients over 65 years of age[2], and many surgeons have utilized numeric age and/or perceived-frailty as relative contraindications to abdominal surgery. A 75-year-old American man without significant comorbidities has a life expectancy of roughly 18 years.  His 82-year-old counterpart, similarly without comorbidities, has a 10-year life expectancy.  However, the addition of any severe comorbidity decreases the two individuals’ life expectancies by six and two years respectively[3,4]. Therefore, it is generally accepted that patients should not be treated solely on the basis of numerical age and instead with regard to their overall functional status and goals[5].
Despite this, however, there remains uncertainty as to how to best care for and manage colorectal cancer in the elderly adult with some patients being undertreated based on age or over treated with regard to their frailty[6,7].
This review will focus on the perioperative evaluation and management of frailty in older adults undergoing investigation of colorectal cancer. We will discuss utilizing chronological versus physiological age (frailty) to estimate perioperative risk, appropriate screening for physiological age, creation of treatment plans, utilization of prehabilitation to maximize inpatient and postoperative outcomes, and the impact of geriatric consultation.

Workup and Management

Predicting Risk: Utilizing Chronological versus Physiological Age
As Medicare eligibility in the United States starts at age 65, many research studies have utilized that time point to delineate old versus young.  However, with an aging global population, other studies have begun utilizing the ages of 70 and 75 as reference points[8-14]. Nevertheless, studies that have attempted to compare groups of patients based on chronological age have returned varied results in regards to any association between age and perioperative outcomes[15].
Additionally, age is a non-modifiable risk factor that many researchers argue should not be a sole determinant when considering treatment options.  Instead, geriatricians argue that a patients’ fitness or frailty should guide providers’ discussions regarding potential care plans[5,16].
In fact, studies have demonstrated that a variety of frailty assessment tools can reliably and consistently be utilized to predict postoperative outcomes. Of specific interest, the comprehensive geriatric assessment (CGA) addresses patients’ physical, mental, and psychosocial well-being as well as functional capabilities. A 2015 systematic review amassed six prospective studies that assessed for a relation between CGA and surgical outcomes in elective oncologic patients[17].
Ultimately, 1019 patient outcomes were analyzed and demonstrated that pre-operative dependency in the instrumental activities of daily living (IADLs), fatigue, and frailty were associated with all-cause complications.  Additionally, IADL dependency also predicted a discharge to a rehabilitation center.
Providing further support to utilize physiological age to estimate surgical risk, a Cochrane review with meta-analysis assessed the outcomes of older adults enrolled in randomized controlled trials for surgical management of hip fractures.  Ultimately, 1316 patients over the age of 64 were identified.  The meta-analysis demonstrated that utilizing the CGA pre and/or postoperatively can reduce mortality by highlighting potential areas for optimization (relative risk 0.85; 95% CI 0.68-1.05) as well as decrease the likelihood of being discharged to a facility[18].
Finally, multiple different reviews of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database have also identified frailty, not age, to be a reliable predictor of perioperative morbidity. Of 7337 patients (mean age 65.8 ± 13.6 years) undergoing elective colorectal cancer resection, frailty as assessed with an 11-point modified frailty index (m-FI) was independently associated with readmission within one month of surgery (OR 1.4; 95% CI 1.1-1.8)[19].
Additionally, another review of 295,490 patients undergoing colorectal surgery for any indication demonstrated that frailty, as assessed with a 5-point m-FI, was associated with significantly greater length of stay, likelihood of discharge to a rehabilitation facility, 30-day serious morbidity, and mortality[20].
Ambulatory Frailty Screening Tools
An ideal screening instrument will take in to consideration a patient’s functional activity, cognitive function, mobility, comorbidities, and nutritional status.  While the CGA is generally regarded as the goal-standard of assessments, it can be especially time-consuming, limiting its uptake in an ambulatory colorectal surgery practice setting[21]. The Eastern Cooperative Oncology Group Performance Status, Timed Up and Go, and the Risk Analysis Index (RAI) have been suggested as non-labor intensive instruments that can readily predict for perioperative morbidity.
A prospective study of 460 patients over the age of 70 that were undergoing oncologic surgery demonstrated that moderate/severe fatigue, IADL dependency, and an abnormal Eastern Cooperative Oncology Group Performance Status well-predicted postoperative complications.  Similarly, abnormal Eastern Cooperative Oncology Group Performance Status was associated with an extended inpatient length of stay[22].
The easy to perform Timed Up and Go (TUG) test quantifies the length of time it takes a patient to get out of a chair, walk three meters, and return to the chair and was utilized as the key measurement in a prospective multicenter study of 263 patients over the age of 69 undergoing surgical management for solid tumor. Ultimately, TUG was found to reliably predict major postoperative complications (OR 3.43; 95% CI 1.13-10.36), to be associated with a prolonged length of stay (OR 4.21; 95% CI 1.10-24.73), and to predict the need for more than three specialist consultations while inpatient (OR 5.39; 95% CI 1.85-15.77)[23].
Finally, the Risk Analysis Index (RAI) is a quick 14-question survey that assesses frailty among surgical patients and has been demonstrated to reliably predict extended length of stay, increased likelihood of intensive care unit admission, risk for discharge to a rehabilitation center, and mortality following surgeries such as colectomy[24]. Use of RAI was similarly supported through an ACS-NSQIP evaluation of 984,550 patients undergoing inpatient operations over 8-years, demonstrating that RAI is associated with increased complication rates and failure to rescue in both low- and high-risk procedures[25].
Crafting Treatment Plans
With the knowledge gained from frailty screening assessments, approaching treatment decisions for older adults with colorectal cancer should assess the individual’s goals of care with realistic outcomes. Goals of care discussions should be centered around the patient with engagement from family members, caregivers, and/or advocates as well as representatives from other involved medical specialties such as primary care and/or geriatrics[26].
Goals of care discussions should address patient values including anticipated/perceived longevity, functional status, independence, and comfort.
The surgeon should provide a realistic picture of perioperative events including morbidity, mortality, and cognitive decline.  Some patients may place extreme value on their current functional performance and cognitive status and therefore make their decisions based on the perceived ability to maintain their current functional level[27].
Of those selecting to proceed with surgical management, prehabilitation should be considered which, if available, can be facilitated by a geriatrician or primary care physician with geriatrics expertise.
Preoperative Prehabilitation
Prehabilitation is a multidisciplinary intervention meant to prevent and/or minimize functional decline related to surgery as well as to improve perioperative outcomes[28].
Classically, prehabilitation can include multiple modalities such as exercise training, nutritional therapy and supplementation, tobacco and alcohol cessation, and anxiety reduction strategies. While there are no firm recommendations regarding length of time and intensity, prehabilitation has been demonstrated to have a positive effect on patients undergoing abdominal surgery.
Specifically, a systematic review and meta-analysis of 26 heterogeneous studies compared patient outcomes divided by access to or absence of prehabilitation prior to major abdominal surgery.  Ultimately, patients who underwent prehabilitation had significantly lower rates of overall complications (OR 0.61; 95% CI 0.43-0.86), pulmonary complications (OR 0.41; 95% CI 9.25-0.67), and cardiac complications (OR 0.46; 95% CI 0.22-0.98)[29].
Notably, however, there was no uniformed definition of prehabilitation across the studies.  Further research with controlled, standardized prehabilitation programs is needed in order to continue to develop recommendations for formal prehabilitation program development.
Therefore, the duration of prehabilitation should be tailored to an individual patient’s needs, ranging from as short as 5 days to as long as 6 weeks.  Most prehabilitation models suggest a length of 4 to 6 weeks with exercise programs making the mainstay of treatment[30].
Exercise programs can be done at home, an outpatient facility, or inpatient and can involve scheduled walking, functional activities, balance exercises, and resistance/strength training.  The benefit of preoperative exercise in colorectal surgery has been demonstrated in a prospective observational study tracking 99 patients with wearable devices.  40 of these patients were deemed active based on their number of steps per day with the other 59 patients being deemed inactive.
The active patients experienced fewer overall complications (27.5% vs. 55.9%; p=0.005) and serious complications (5% vs. 20.3%; p=0.03).  Similarly, multivariate analysis demonstrated that increased preoperative activity is inversely related to postoperative complications (OR 0.38; 95% CI 0.15-0.90).  Of course, this study did not control for frailty, again demonstrating the need for studies with controlled designs[31].
Acknowledging that excess abdominal weight and/or poor nutritional status are harbingers of worse perioperative outcomes in older adults, national optimization is common in prehabilitation programs[32].
Ultimately, optimization seeks to generate sufficient protein intake in order to favor anabolic metabolism and to maintain lean body mass.  Nutritional interventions have the ability to decrease the incidence and severity of ileus, improve postoperative appetite, promote normoglycemia, and battle the perioperative inflammatory response[33].
The psychosocial domain of prehabilitation places an emphasis on patient education of the overall disease process, encouraging beneficial lifestyle modifications, and mitigating anxiety and depression. Previously, depression assessed through the Geriatric Depression Scale has been demonstrated to be an independent predictor of postoperative complications.  A prospective study of 182 patients over the age of 70 undergoing colorectal cancer surgery demonstrated that depressed adults had a higher overall complication rate than not-depressed adults (OR 3.68; 95% CI 0.96-14.08)[34].
Therefore, taught relaxation techniques, guided imagery, and problem-solving and coping strategies have been shown to bring about an improved quality of life and reduce symptoms of anxiety, depression, pain, and fatigue among patients awaiting cancer-related surgery[35].
Geriatric Consultation
In areas where geriatric consultation is an available resource, geriatricians can assist in coordinating and accomplishing the multimodal care required by a prehabilitation program.  Geriatricians have expertise in assessing and managing the geriatric syndromes of dementia, delirium, falls, and polypharmacy- all of which are known to impact perioperative outcomes. A retrospective study of older adults following cancer surgery assessed overall outcomes between patients on a standard surgical service and those on a service with geriatric co-management.
Ultimately, the adjusted probability of death within 90 days postoperatively was found to be less than half the rate of the patients managed on a standard surgical service (4.3% versus 8.9%; 95% CI 2.3-6.9, p<0.001).  While overall complication rate was similar between the two groups, the co-managed patients had a higher utilization of supportive care such as physical therapy, speech and swallow, and nutrition[36].
Similarly, in a separate study, 310 patients over the age of 69 undergoing elective colorectal surgery were assessed for frailty based on the CGA and subsequently assigned to standard care or multidisciplinary CGA-based care with geriatric guidance.  The CGA group ultimately was found to have a lower incidence of geriatric-specific complications such as delirium (11.3% vs. 29.2%; p<0.001) and other syndromes (10.3% vs. 26.2%; p<0.001)[37].

Controversies/Limitations

There is one randomized superiority trial that evaluates the effectiveness of prehabilitation versus postoperative rehabilitation that comprises 110 frail patients with colorectal cancer.  Frailty was defined as a Fried frailty index of at least 2.
The study did not identify any difference between the two groups in terms of the 30-day Comprehensive Complications Index, 30-day overall/severe complications, length of inpatient stay, readmission rate, recovery of walking capacity, or patient-reported outcomes. However, this study also utilized a multiphase surgical pathway emphasizing minimally invasive techniques and enhanced recovery pathways.  It also integrated physical, emotional, and nutritional optimization for all patients which could confound the results of overall complications[38].
Feasibility of implementation of frailty screening and prehabilitation programs is frequently called in to question given the diversity of surgical practices throughout the United States and the globe.  There are two prospective and two randomized trials that investigate the implementation of prehabilitation programs for frail cardiac, colorectal, and orthopedic surgery patients[39-42].
Two of these studies demonstrated recruitment rates between 61% and 70%, suggesting medium feasibility.  Within all four studies, there was excellent adherence to prehabilitation prescriptions, ranging from 80% to 99%, determined by patient diaries, pedometers, and/or supervising team members. An additional barrier commonly cited to initiating and maintaining a prehabilitation program is cost.
However, given that frailty and its associated postoperative outcomes are known to increase medical expenses, programs created to specifically mitigate elements of frailty may ultimately prove cost-effective[43].

Summary

Globally, colorectal surgeons are managing a variety of conditions, including cancer, at increasing patient age.  Consistent with the goals of the American College of Surgeons Strong for Surgery initiative, colorectal surgeons must have an understanding of how to best assess for frailty and physiologic age as well as how to initiate meaningful goals of care discussions to assist in designing treatment plans.  If surgery is consistent with an individual patient’s goals of care, prehabilitation programs have been demonstrated to enhance perioperative outcomes and overall quality of life.
These programs are feasible to implement and may provide long-term cost-saving incentives by avoiding perioperative complications. If available, geriatricians should be engaged early in the diagnostic and therapeutic process. Ultimately, improving perioperative outcomes in older adults with colorectal cancer requires a multidisciplinary and multifaceted approach that is driven by the patient’s values and goals.

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