Geriatric oncology: A new horizon in cancer management for older adults.

Naser AlQurini & Shabbir Alibhai

Aging and cancer

Age is the single most important risk factor for developing cancer, with more than 60% of all newly diagnosed malignant tumors and 70% of all cancer deaths occurring in persons 65 years or older. ¹ Unfortunately, simply because of age, many older adults are less likely to receive standard cancer management compared to their younger counterparts. ^2-4 Many oncologists are reluctant to offer standard treatment to their older adult patients because of increased concerns about greater risks of treatment toxicity and higher non-cancer mortality (i.e. people are more likely to die of non-cancer causes). Those concerns are based on backgrounds of more aggressive cancer biology, competing comorbidity, and decreased physiological reserve among older adults that leads to less ability to tolerate standard treatment. ¹ Among many challenges, advanced age and functional disabilities will contribute to the difficulty of caring for these complex, vulnerable patients. ⁵

Every oncologist ideally considers each patient’s physical, psychological and social factors when planning their treatment. Knowing more about their co-morbidities (especially if uncontrolled or severe, including conditions such as hypertension, diabetes, and coronary artery disease), access to health care and, most importantly, their preferences, values and beliefs will theoretically guide the treatment plan. Moreover, members of this vulnerable group are often living with either an older caregiver (elder spouse) who may also have health issues, or they are socially isolated (divorced, widowed, single). These social circumstances along with other physical and psychological issues may lead to fewer older adults being treated or considered for enrollment in clinical trials. As a result, existing medical literature features minimal data about optimal cancer management in older adults.

Age should not be the issue

Age as a number (i.e. chronological age) should not necessarily determine who should have standard cancer treatment. This is because multiple studies have shown that otherwise healthy or fit older adults derive similar benefits as younger adults from various cancer treatments including surgery, radiation, chemotherapy, and most recently immunotherapy. Instead, treatment should be decided according to functional status and physiological reserve; in other words - is this older adult fit or frail?

Frailty as a concept has emerged in multiple areas of clinical practice in the past 20 years. Frailty can be defined as a distinctive health state related to, but not synonymous with, the aging process, in which multiple body systems gradually lose their inbuilt reserve. This concept helps us to understand each cancer patient’s ability to tolerate aggressive intervention for cancer management better than solely relying on age as a number.

By identifying frail older patients with cancer, an oncologist or geriatrician can predict the risk of toxicity associated with chemotherapy by using validated tools which will help guide their management and individualized treatment plans. ⁶ Similar validated tools can also be used in pre-surgical settings to predict the risk of serious post-operative complications such as delirium, need for post-operative inpatient rehabilitation, or increased length of stay in hospital, readmission, or even death. ⁷

Screening for frailty allows oncologists, geriatricians and nurses to distinguish robust seniors from vulnerable and frail ones. Having the capability to identify robust (or fit) older adults will provide an opportunity for treatment and potentially cure by offering standard treatments like those given to their younger counterparts. In the same context, vulnerable patients will have an opportunity for assessment, management, and possibly reversal of their frailty by optimizing needed resources (e.g. exercise/rehabilitation, nutritional support), offering them single-agent (i.e. one chemotherapeutic drug rather than a multi-drug combination), single modality (i.e. chemotherapy or radiation, not combined chemoradiotherapy) with reduced doses of chemotherapy, pre-habilitation prior to major surgical procedures or offering less invasive surgery for less efficacious but more tolerable treatment, and eventually completing their cancer treatment. Identifying frail older adults who most likely will not tolerate even low-dose or single-agent chemotherapy can lead to selection of less invasive or aggressive procedures which will help direct health care resources toward more pragmatic goals such as better- tolerated treatment modalities including palliative radiation therapy for quality of life improvement and symptom management; and for the same objectives, considering referral to palliative care specialists, which will provide an opportunity for enhanced end of life planning. This subsequently will improve health care expenditures and provide wise and efficient use of resources.

Geriatric assessment is the golden tool

The gold standard tool to assess frailty in such a population is comprehensive geriatric assessment (CGA). ⁸ In older cancer patients, it is used to determine physiologic age, guide future diagnostic and therapeutic interventions, determine any reversible deficits, and devise treatment strategies to eliminate or mitigate such deficits and to risk-stratify patients prior to potentially high-risk therapy. ⁵ However, it will be hard for oncologists to uncover and screen for all health deficits in older adults through traditional assessment in their busy clinics. In contrast, conducting comprehensive geriatric evaluation is a standard part of every geriatric specialist practice. Having a focused evaluation for senior adults diagnosed with cancer has been studied in different oncological settings and shown to carry a wide range of benefits. Consensus guidelines from the American Society of Clinical Oncology, the National Comprehensive Cancer Network, the International Society for Geriatric Oncology (SIOG), and others recommend the routine use of a geriatric assessment for the older patient with cancer, usually defined as age 65 or older. ^9-11 Among the potential benefits for CGA in cancer patients: Predicting complications and side effects from treatment, estimating survival which assist in cancer treatment decisions, detecting problems not found by routine oncological assessment, identification and treatment of new problems during follow up care, improved mental health, well-being and pain control that can be associated with a cancer diagnosis or treatment. ^13-18

A systematic review of 34 studies of geriatric assessment in older cancer patients found that multiple domains of the geriatric assessment refined the ability to predict treatment tolerability or prognosis and led to modification of cancer treatment decisions in up to one-third of patients. Most treatment modifications led to reduction in treatment intensity. As a result, geriatric assessment helped to avoid overtreatment. Importantly, geriatric assessment led to increased treatment intensity in several otherwise fit older adults, which reduces undertreatment. ¹⁹ Another systematic review of 35 studies published last fall examined the effect of a geriatric evaluation on oncologic and non-oncologic treatment decisions and outcome for older cancer patients. It confirmed the prior review’s findings that the oncologic treatment plan was altered in one-third of patients, usually to a less intensive treatment option. Non-oncologic interventions were recommended in 75% of patients, most commonly involving social, nutrition and medication-related issues. Several studies also suggested geriatric assessment led to higher cancer treatment completion. ²⁰ A few studies investigated the value of selecting chemotherapy in seniors based on their functional level rather than simply age. There was significant reduction in treatment toxicity or adverse events without compromising overall treatment efficacy. ²¹

But a golden tool comes at a price

Although guidelines recommend conducting a CGA prior to treatment, this is not always feasible. The time needed for conducting such thorough clinical assessment (typically 1-2 hours) before a treatment decision is made is not always possible. Until now, most seniors have not had this opportunity for a comprehensive assessment. Many logistic and administrative hurdles, and even patient preferences, interplay as challenges. Those challenges include, but are not limited to, lack of availability of geriatric services in many cancer centers and community settings, urgency to start cancer treatment in a timely fashion, a high volume of referrals of newly diagnosed older patients with cancer to oncology and geriatrics clinics, and multiple medical appointments needed that overwhelm older adults. Moreover, managing senior adults needs a multidisciplinary team approach, which is not always easy to coordinate and available or funded by governmental or private insurance plans. Also, time needed to implement suggestions from CGA might not always be feasible prior to commencing cancer treatment.

Future Steps

Geriatric oncology as a specialty is not available nationwide in most industrialized countries including the United States and Canada, and if available, there are simply not enough resources to meet the needs of this complex heterogeneous population. Having specialized physicians in geriatric oncology working in multidisciplinary teams focused on managing this population is a great step in the right direction, but this is not enough to address the overwhelming number of newly diagnosed patients who need to be assessed and managed through their long and difficulty treatment journey. Other models of care need to be examined.
From cancer diagnosis until treatment decision is made, older adults have multiple encounters which provide opportunities to screen for frailty. Starting with the health system’s gatekeeper level, the primary care physician (PCP), is an important step. By providing more education and training to PCPs and their teams to implement frailty screening and collaborate with oncologists to plan cancer management will expedite and facilitate management and improve communication between oncologists and PCPs in the process. ²²

By training nurse practitioners on frailty screening, conducting full geriatric assessment (with backup from geriatricians) will expand number of patients who will receive a timely CGA before a decision is made for cancer treatment. ²³

Although highly desired, there is presently no blood test or biological marker that is strongly associated with frailty. This is because many complex biological processes are implicated in aging. ²⁴ Nevertheless, the search is on. However, in the modern digital health record era, using big data at a health system level can potentially lead to developing algorithms for frailty prediction using artificial intelligence. These promising approaches may one day allow rapid identification of frailty and customized oncology decision-making.

At the individual level, steps toward educating older adults to use advanced technology and devices such as smart phones and tablets to complete frailty self-screening tools or even self-reported CGA-like tools, or use of remote monitors and wearable sensors to screen and monitor frailty markers such as mobility (e.g. step counts) and nutrition, may help to close gaps that potentially delay cancer management by helping to triage who needs a full CGA by a multidisciplinary team. ²⁵ Ultimately,such technologies need to be tested more fully but are already being used in some centers with early successes. Having more team players and/or technology involved in the geriatric oncology setting, with the notion of identifying frailty and fitness, will bring us closer to achieving the best care for this special population.

About the Authors

Dr. Naser AlQurini, MD, MRCGP (INT), is a clinical fellow in geriatric oncology. He is a family physician who finished his medical school at Kuwait University, and continued his residency in family medicine at the Kuwait Institute of Medical Specialties. After that, he had more training at a level of clinical fellow in the following subspecialties in Canadian universities: geriatric medicine at McMaster University, and palliative care and general practice in oncology at University of Ottawa. He finds great interest in managing and treating older adults with cancer. He is currently working in the Older Adult with Cancer Clinic (OACC) at the Princess Margaret Cancer Centre, Canada’s largest cancer centre, and affiliated with the University of Toronto.

Dr. Shabbir Alibhai, MSc, MD, FRCPC, is a Professor in the Department of Medicine, the Institute of Health Policy, Management, and Evaluation, and the Institute of Medical Sciences at the University of Toronto. He is a staff physician in the Division of General Internal Medicine and Geriatrics at the University Health Network and Sinai Health Systems, a senior scientist at the Toronto General Research Institute and the Toronto Rehabilitation Institute, and a prior Research Scientist of the Canadian Cancer Society. His research interests are in geriatric oncology, particularly in the impact of disease and treatment on quality of life and function of patients with prostate cancer, the value of geriatric assessment in older adults with cancer, and randomized trials of exercise to improve outcomes in older adults with cancer. Since 2015, he is also the medical lead for the geriatric oncology program at the Princess Margaret Cancer Centre, Canada’s largest academic cancer centre.

References

1. Williams, Grant R., Amy Mackenzie, Allison Magnuson, Rebecca Olin, Andrew Chapman, Supriya Mohile, Heather Allore et al. "Comorbidity in older adults with cancer." Journal of geriatric oncology 7, no. 4 (2016): 249-257.
2. Williams, Grant R., Amy Mackenzie, Allison Magnuson, Rebecca Olin, Andrew Chapman, Supriya Mohile, Heather Allore et al. "Comorbidity in older adults with cancer." Journal of geriatric oncology 7, no. 4 (2016): 249-257.
3. Hurria, Arti, Denis Leung, Kathleen Trainor, Patrick Borgen, Larry Norton, and Clifford Hudis. "Factors influencing treatment patterns of breast cancer patients age 75 and older." Critical reviews in oncology/hematology 46, no. 2 (2003): 121-126.
4. Newcomb, Polly A., and Paul P. Carbone. "Cancer treatment and age: patient perspectives." JNCI: Journal of the National Cancer Institute 85, no. 19 (1993): 1580-1584.
5. Cohen, Harvey Jay, and Arati V. Rao. Geriatric Oncology, An Issue of Clinics in Geriatric Medicine, E-Book. Vol. 32, no. 1. Elsevier Health Sciences, 2016: Preface: xiii-xiv.
6. Hurria, Arti, Supriya Mohile, Ajeet Gajra, Heidi Klepin, Hyman Muss, Andrew Chapman, Tao Feng et al. "Validation of a prediction tool for chemotherapy toxicity in older adults with cancer." Journal of Clinical Oncology 34, no. 20 (2016): 2366.
7. Bilimoria, Karl Y., Yaoming Liu, Jennifer L. Paruch, Lynn Zhou, Thomas E. Kmiecik, Clifford Y. Ko, and Mark E. Cohen. "Development and evaluation of the universal ACS NSQIP surgical risk calculator: a decision aid and informed consent tool for patients and surgeons." Journal of the American College of Surgeons 217, no. 5 (2013): 833-842.
8. Stuck, Andreas E., Albert L. Siu, G. Darryl Wieland, L. Z. Rubenstein, and J. Adams. "Comprehensive geriatric assessment: a meta-analysis of controlled trials." The Lancet342, no. 8878 (1993): 1032-1036.
9. Wildiers, Hans, Pieter Heeren, Martine Puts, Eva Topinkova, Maryska LG Janssen-Heijnen, Martine Extermann, Claire Falandry et al. "International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer." Journal of clinical oncology 32, no. 24 (2014): 2595.
10. Mohile, Supriya G., William Dale, Mark R. Somerfield, Mara A. Schonberg, Cynthia M. Boyd, Peggy S. Burhenn, Beverly E. Canin et al. "Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: American Society of Clinical Oncology Guideline for Geriatric Oncology." Journal of clinical oncology: official journal of the American Society of Clinical Oncology 36, no. 22 (2018): 2326.
11. NCCN Clincial Practice Guidelines in Oncology, (NCCN guidelines), Older Adult Oncology, version 1.2019 ---- January 8th, 2019.
12. Kenis, C., Dominique Bron, Yves Libert, L. Decoster, K. Van Puyvelde, Pierre Scalliet, P. Cornette et al. "Relevance of a systematic geriatric screening and assessment in older patients with cancer: results of a prospective multicentric study." Annals of oncology 24, no. 5 (2013): 1306-1312.
13. Balducci, Lodovico, and Martine Extermann. "Management of cancer in the older person: a practical approach." The oncologist 5, no. 3 (2000): 224-237.
14. Repetto, Lazzaro, Lucia Fratino, Riccardo A. Audisio, Antonella Venturino, Walter Gianni, Marina Vercelli, Stefano Parodi et al. "Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: an Italian Group for Geriatric Oncology Study." Journal of clinical oncology 20, no. 2 (2002): 494-502.
15. Extermann, Martine, Julie Meyer, Margaret McGinnis, Theresa T. Crocker, Mary-Beth Corcoran, Jerry Yoder, William E. Haley, Hongbin Chen, David Boulware, and Lodovico Balducci. "A comprehensive geriatric intervention detects multiple problems in older breast cancer patients." Critical reviews in oncology/hematology 49, no. 1 (2004): 69-75.
16. Pope, D., H. Ramesh, R. Gennari, G. Corsini, M. Maffezzini, H. J. Hoekstra, D. Mobarak et al. "Pre-operative assessment of cancer in the elderly (PACE): a comprehensive assessment of underlying characteristics of elderly cancer patients prior to elective surgery." Surgical oncology 15, no. 4 (2006): 189-197.
17. Chen, Hongbin, Alan Cantor, Julie Meyer, Mary Beth Corcoran, Edward Grendys, Denise Cavanaugh, Shirley Antonek et al. "Can older cancer patients tolerate chemotherapy? A prospective pilot study." Cancer: Interdisciplinary International Journal of the American Cancer Society 97, no. 4 (2003): 1107-1114.
18. Rao, Arati V., Frank Hsieh, John R. Feussner, and Harvey Jay Cohen. "Geriatric evaluation and management units in the care of the frail elderly cancer patient." The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 60, no. 6 (2005): 798-803.
19. Puts, M. T. E., B. Santos, J. Hardt, J. Monette, V. Girre, E. G. Atenafu, E. Springall, and S. M. H. Alibhai. "An update on a systematic review of the use of geriatric assessment for older adults in oncology." Annals of Oncology 25, no. 2 (2013): 307-315.
20. Hamaker, Marije E., Marthe te Molder, Noortje Thielen, Barbara C. van Munster, Anandi H. Schiphorst, and Lieke H. van Huis. "The effect of a geriatric evaluation on treatment decisions and outcome for older cancer patients–A systematic review." Journal of geriatric oncology 9, no. 5 (2018): 430-440.
21. Corre, Romain, Laurent Greillier, Hervé Le Caër, Clarisse Audigier-Valette, Nathalie Baize, Henri Bérard, Lionel Falchero et al. "Use of a comprehensive geriatric assessment for the management of elderly patients with advanced non-small-cell lung cancer: the phase III randomized ESOGIA-GFPC-GECP 08-02 study." J Clin Oncol 34, no. 13 (2016): 1476-83.
22. Puts, Martine TE, Fay J. Strohschein, M. Elisabeth Del Giudice, Rana Jin, Allison Loucks, Ana Patricia Ayala, and Shabbir HM Alibhai. "Role of the geriatrician, primary care practitioner, nurses, and collaboration with oncologists during cancer treatment delivery for older adults: A narrative review of the literature." Journal of geriatric oncology 9, no. 4 (2018): 398-404.
23. Decoster, Lore, K. Van Puyvelde, S. Mohile, U. Wedding, U. Basso, G. Colloca, S. Rostoft et al. "Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations." Annals of Oncology 26, no. 2 (2014): 288-300.
24. Mitnitski, Arnold, Joanna Collerton, Carmen Martin-Ruiz, Carol Jagger, Thomas von Zglinicki, Kenneth Rockwood, and Thomas BL Kirkwood. "Age-related frailty and its association with biological markers of ageing." BMC medicine 13, no. 1 (2015): 161.
25. Frederique Retornaz. Frailty in older adult cancer patients, J Gerontol: Vol. 63A, No. 5, 518–522.