Is there a role for specialized geriatric centers in treating geriatric cancer patients?

Journal Pre-proof Is there a role for specialized geriatric centers in treating geriatric cancer patients? Elliot G. Arsoniadis, Emily Finlayson, Fabio Potenti PII:

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European Journal of Surgical Oncology

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Please cite this article as: Arsoniadis EG, Finlayson E, Potenti F, Is there a role for specialized geriatric centers in treating geriatric cancer patients?, European Journal of Surgical Oncology (2020), doi: https:// doi.org/10.1016/j.ejso.2019.12.012. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Ltd.

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Is There A Role for Specialized Geriatric Centers In Treating Geriatric Cancer Patients? Elliot G Arsoniadis, MD1,2; Emily Finlayson, MD, MS3; Fabio Potenti, MD, MBA1 1 Department of Colorectal Surgery, Cleveland Clinic Florida, Weston, Florida, USA 2 Institute for Health Informatics, University of Minnesota, Minneapolis, Minnesota, USA 3 Department of Surgery, University of California, San Francisco, California, USA

Abstract

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As the population with colorectal cancer ages, the tailored approach required to manage

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older patients becomes all the more important for all providers and institutions treating

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colorectal cancer to adopt to improve the outcomes and well-being of this important and

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increasingly prevalent population. Joint guidelines from the American College of

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Surgeons and American Geriatric Association should be followed. Older cancer

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patients undergoing colorectal cancer surgery should be referred to centers with

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expertise in minimally invasive surgery. Likewise, older rectal cancer patients should be

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referred to centers with expertise in treating rectal cancer.

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Introduction

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The specialized needs of the geriatric cancer patient were first brought to the

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national spotlight in a 1983 symposium held jointly by the National Cancer Institute and

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National Institute on Aging. Among the conclusions reached by the symposium

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included a focus on the interdisciplinary nature of cancer care of the geriatric patient (1).

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The field of geriatric oncology was only brought to the forefront in the last decade. In

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2007 the American Society of Clinical Oncology (ASCO) published a dedicated issue of

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Journal of Clinical Oncology on the still stealth-field of geriatric oncology (2). This

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included discussion of the unique issues facing older cancer patients, as well as a call

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for renewed attention to the multidisciplinary assessment and care required for this

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population (3). In the years that followed, ASCO and other national organizations, such

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as the American College of Surgeons (ACS), would promote quality initiatives

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specifically addressing the care of geriatric cancer patients (4). As the field of geriatric

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oncology entered into the mainstream, various centers dedicated to the care of geriatric

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cancer patients would be established and even training programs for those wishing to

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care specifically for the needs of this community would be established (5). However,

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the effect of these centers on outcomes in the geriatric patient population with colorectal

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cancer has never been formally studied. Indeed, the field of geriatric oncology,

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especially related to colorectal cancer, is still in its infancy. In the era of increasing

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regionalization of care and the establishment of, among other things, accredited rectal

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cancer centers via the ACS Commission on Cancer National Accreditation Program for

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Rectal Cancer (6), we ponder the role for dedicated centers for geriatric patients with

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colorectal cancer versus a more broad approach to addressing the needs unique to this

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population.

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The Geriatric Colorectal Cancer Population There is an increasing trend of centralizing treatment for complex patient

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populations that require an organized, multidisciplinary approach to care. Within the

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United States, this has been done by the American College of Surgeons, for example, in

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the designation and verification of centers for trauma care (7) and metabolic/bariatric

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surgery (8). This has even been done for the treatment of different types of cancer (in

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the general, non-geriatric population) in accreditation programs for breast (9) and rectal

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cancer (10). Would designating accreditation of centers specializing in geriatric

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colorectal cancer treatment prove the best and most cost-effective way to deliver care to

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this complex patient population?

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A major hurdle is the size of the population in question. The US population, and

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the age of patients diagnosed and living with colorectal cancer, is increasing, with

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current estimates that over 50% of colorectal cancer diagnoses are in those age 70

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years or older (11). Referral of over half of the newly diagnosed colorectal cancer

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patient population to a specialized center poses clear logistical concerns. Further

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complicating the issue is the question: “what constitutes a geriatric oncology patient?” A

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simple internet search will elicit results of cancer centers with dedicated “geriatric”

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centers, whose minimum required age ranges from 65 to 80 years of age (12,13). The

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literature, however, would argue against the use of chronological age and would rather

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employ the use of a patient’s biologic/physiologic age when planning customized

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colorectal cancer care (14).

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Treatment Cost-Effectiveness Treatment of older patients with colorectal cancer is a costly endeavor. Yabroff

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et al calculated the 5-year aggregate cost of patients older than age 65 years diagnosed

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with colorectal cancer to total 3.1 billion dollars, second only to lung cancer when

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stratified by tumor site. The most costly years were the first year of life following

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diagnosis and the final year of life. Hospitalizations accounted for 60% of the costs

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during these time periods (15). Efforts at reducing these costs, both during initial

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treatment, and at the end of life, would be most cost effective.

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Geriatric patients undergoing colorectal resection are at higher risk for surgical

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complications, mortality, and functional decline (16). Geriatric patients, traditionally

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identified as age 70 years or older in most surgical literature on the topic, have higher

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rates of 30-day mortality compared to younger patients, and yet a similar rate of cancer-

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related death. The greatest threat to survival, quality of life, and cost-effectiveness of

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treatment for the geriatric patient comes in the immediate peri- and post-operative

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period (17) and the majority are cardiopulmonary complications (18). The highest value

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interventions, therefore, would be those that modify these risk factors and decrease the

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postoperative complications that drive up the cost of care of geriatric patients and

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decrease both quantity and quality of life.

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The cornerstone of care for the geriatric oncology patient is accurate fitness

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assessment prior to undergoing treatment, whether this be surgery, chemotherapy,

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radiotherapy, or a combination (19,20). Many tests of fitness and frailty exist, including

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the time-intensive Comprehensive Geriatric Assessment (CGA) (21,22) as well as the

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more readily accessible “Time Up And Go” test, the seven-item physical performance

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test, the Mini Cog, the Edmonton Frail Scale, and the Vulnerable Elderly Survey 13

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(VES 13) (23,24). Risk-stratification performed by the surgeon or oncologist as well as a

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geriatrician can then help guide decisions regarding surgery, chemotherapy, and pre-

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treatment risk-modifying interventions (14,23).

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For those individuals identified as at-risk and frail, the question then becomes, where and who should treat these patients? Should they be referred to centers devoted

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to the care of the older and at-risk patient with colorectal cancer? Rather than

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designating centers for geriatric oncology that have met certain established quality

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metrics (as it has done for breast and rectal cancer), the American College of Surgeons

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has taken a different approach to addressing the needs of the geriatric surgical patient.

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Together with the American Geriatrics Society (AGS), the ACS Coalition for Quality in

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Geriatric Surgery (CQGS) has published guidelines for the pre-, intra-, and post-

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operative care of older patients (25,26). The guidelines endorse a thorough and

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structured approach to the care of the older patient. Among the guidelines, there is a

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focus on the need to establish and document older patients’ preferences for treatment,

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including establishing a healthcare proxy. There are also more specific guidelines, such

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as minimizing preoperative fasting, goal-directed intravenous fluid administration, non-

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opioid analgesia, delirium prevention, and involvement of case managers to assist with

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care transitions to home, home with assistance, or a facility (25). These guidelines are

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not meant to be restricted to “centers of excellence” but are rather meant to be applied

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broadly to any hospital wishing to focus on ways to optimize care for older patients

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undergoing surgery. These guidelines are similar to Enhanced Recovery pathways in

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that the essential element required is the buy-in and dedication of staff at all levels of

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care. The guidelines are not strict requirements mandated for regional centers of

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geriatric surgery, but are tools that can be utilized by community hospitals – where the

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vast majority of geriatric surgery is performed. This is especially germane to the

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geriatric oncology population, as this population has been shown to be especially keen

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on receiving treatment close to home, and traveling far to a center of “geriatric

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excellence” may be in direct competition with their goals of care (27).

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Establishing goals of care, not only regarding treatment with surgical or medical

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therapy, but especially regarding end-of-life care is an important component of geriatric

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cancer care. Chastek et al showed that in the last six months of life 55% of costs were

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related to acute inpatient hospitalizations, 25% chemotherapy, and only 4% hospice

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care (28). End of life (EOL) discussion prior to this period has been shown to not only

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decrease costs by 35%, but also improved quality of life by decreasing ICU admissions

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and increasing the likelihood of death outside the hospital (29). Again, these

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discussions that have been shown to both improve the quality of care and prove cost-

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effective should not be limited to geriatric oncology centers, but should be applied

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broadly.

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Reasons for Referral: Minimally Invasive Surgery and Rectal Cancer

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In addition to following the ACS-CQGS guidelines, older patients undergoing

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colorectal cancer surgery also benefit from the use of minimally-invasive modalities.

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Stocchi and Frasson have shown that older patients undergoing laparoscopic colorectal

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resection were more likely to have preservation of their preoperative functional status

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(30) and faster discharge from the hospital (31) compared to those undergoing open

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colectomy. For older patients, laparoscopic surgery is especially beneficial in

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preventing cardiopulmonary complications and authors have advocated that it should be

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the first choice for older colorectal cancer patients undergoing colectomy (23).

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Therefore, centers with expertise in minimally invasive colorectal resection should be

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the choice for surgery for older patients with colorectal cancer.

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The case of rectal cancer in the geriatric population merits special discussion.

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Although proctectomy with total mesorectal excision remains the standard of care,

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increasingly there are patients with a complete clinical response following neoadjuvant

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chemoradiation who opt for the “Watch and Wait” approach first published by Habr-

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Gama et al (32). Older patients, especially those deemed frail, may benefit from this

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Watch-and-Wait approach. In 2015 Smith et al published their decision analysis study

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of patients undergoing radical resection versus observation and stratified by both age

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(80 years versus 60 years old) and health state (healthy versus comorbid) and showed

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that the Watch-and-Wait approach was most beneficial in the older patients (33). In a

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later cost-benefit analysis, Watch-and-Wait resulted in greater quality adjusted life years

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(QALY), although this benefit diminished as survival extended beyond two years (34).

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Older rectal cancer patients who do not have a complete clinical response

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following neoadjuvant therapy but not desiring radical surgery might also benefit from

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local excision. Although local excision following neoadjuvant therapy is approached

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with great caution and is not recommended in the general rectal cancer population, it

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may prove beneficial in older patients unfit for proctectomy either due to diminished

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physiologic reserve or due to concerns of incontinence following rectal resection and

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desiring organ preservation (35,36). Therefore, patients in whom this may prove to be a

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viable option should be treated at centers where expertise in transanal techniques,

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either using the Transanal Minimally Invasive Surgery (TAMIS) platform or Transanal

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Endoscopic Microsurgery (TEM) platform, are available.

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The Role of Chemotherapy

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The use of chemotherapy in the geriatric population, either as adjuvant therapy

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or as sole therapy for stage IV disease, should be approached similarly to surgical

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therapy, with pre-treatment screening and assessment for frailty, risk stratification, and

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management and optimization of comorbidities. In otherwise healthy older patients, 5-

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fluorouracil has proven to be both beneficial and tolerable, with overall survival rates

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similar to younger cohorts (37). Newer agents, such as oxaliplatin and irinotecan, have

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not shown benefit in older patients in large multicenter trials. The ACCENT Database

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did not show any benefit with the addition of oxaliplatin to adjuvant therapy in the more

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than 2500 patients aged 70 years or older (38). Sanoff et al found no statistically

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significant benefit in survival with the addition of oxaliplatin to 5-FU and found a

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statistically significant increase in complications with the addition of oxaliplatin (39). The

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role of biologics in treating older colorectal cancer patients is even less clear.

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Kabbinavar et al showed 3-month increase in progression-free survival and a 5-month

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increase in overall survival in patients receiving bevacizumab (40). Similarly,

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Cunningham et all showed an improvement in progression free survival with the addition

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of bevacizumab to capecitabine (9.1 months versus 5.1 months), but with no

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improvement in overall survival (41). Other studies have also shown modest

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improvements in progression free survival, and an even more modest improvement in

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overall survival, with bevacizumab. These studies consistently show a significantly

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higher rate of complications, with one study showing a 40% rate of toxic events in

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patients being treated with bevacizumab (41). Among these complications, bleeding

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and thromboembolic events are the most frequent and serious consequences of the

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addition of bevacizumab (40–43). In addition to the increased complication rate with

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very modest gains in survival, there is also the question of the cost of these treatments.

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Parikh et al, in their 2017 cost-benefit analysis study, showed that addition of

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bevacizumab to traditional oxaliplatin/irinotecan chemotherapy in patients with

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metastatic colorectal cancer, while providing a minimal increase in survival, did not

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prove cost-effective (44). Although 5-FU has shown benefit as adjuvant therapy, there

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is reasonable evidence that oxaliplatin adds no benefit to older patients and serious

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discussion should be had with patients regarding the marginal benefits and significant

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risks of biologic therapies.

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The exclusion of geriatric cancer patients from most clinical trials, including new

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line chemotherapeutics/biologic therapies, is well documented (45). As the population

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of patients with colorectal cancer ages, chemotherapeutic and biologic therapies will

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need to be investigated in geriatric patients. However, it is not only in the realm of new

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treatment agents where a focus on the older colorectal cancer patient must take place.

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Indeed, further research is needed to guide not only what agents and surgeries are

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used to treat these patients, but also the manner in which colorectal cancer care is

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delivered. A start to this, at least regarding surgical care, are the guidelines and

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framework ACS and the AGA have implemented that could be utilized by any institution

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with buy-in from committed surgeons, anesthesiologists, geriatricians, and other

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affiliated specialties (25,26). These measures, and others, that various stakeholder

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organizations are endorsing will need to be subject to the scientific method and

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rigorously investigated to identify the most helpful initiatives and standards. Whether

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these measures are best implemented at specialized “geriatric centers” remains to be

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seen.

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Conclusion

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Older patients with colorectal cancer are a diverse and complex patient

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population that requires multidisciplinary management. Cornerstones of care include

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accurate fitness assessment, including early referral to a geriatrician, and goals of care

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discussion. Goals of care differ from younger colorectal cancer patients and may

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include less aggressive treatment strategies that can occur closer to home and involve

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less days in the hospital. We endorse that all institutions implement the guidelines

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proposed by ACS and AGA regarding the pre-, peri-, and post-operative care of the

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older patient, and not limit this to only “centers of excellence”. Geriatric patients

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undergoing colorectal cancer surgery should be referred to centers with expertise in

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minimally invasive techniques, as these have been shown to be especially beneficial in

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this population. Geriatric patients with rectal cancer should be referred to centers with

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expertise in treating rectal cancer (in all age groups) since this also likely shows benefit

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(46). As the population with colorectal cancer ages, the tailored approach required to

227

manage these patients becomes all the more important for all providers and institutions

228

treating colorectal cancer to adopt to improve the outcomes and well-being of this

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important and increasingly prevalent population.

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The authors all certify that we have no conflict of interest. Elliot Arsoniadis, MD Emily Finlayson, MD, MS Fabio Potenti, MD, MBA