Geriatric Oncology

Geriatric Oncology

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Author: Shabbir M.H. Alibhai, MD, MSc, FRCP(C)

Affiliations: Associate Professor, Dept of Medicine; Institute of Health Policy, Management, and Evaluation, University of Toronto; IMS Member

Geriatric oncology is widely used to refer to all areas of scientific inquiry related to cancer in older adults, from prevention through end of life care, spanning basic science, clinical research, and health services research.1 Two main factors have led to the emergence of geriatric oncology as an important area of research. Both relate to the compelling epidemiology. First, over 60% of all incident cancers and 71% of cancer deaths are seen in older adults (age 65+), and aging is the single greatest risk factor for malignancy across virtually all tumour sites.2,3 Second, our population is aging, especially in industrialized nations, where those age 65+ are the most rapidly growing segment of the population. In the clinical world, the median age at diagnosis for patients with lung, prostate, or colorectal cancer⎯three of the most common tumours⎯is age 70. Moreover, with increasing age comes complexity and frailty, which interact to make cancer treatment more challenging and lead to both over- and under-treatment.

So what age group does geriatric oncology actually encompass? Much of the literature uses an age cut-off of 65. Although we all recognize that age 65 is an arbitrary definition of ‘older’ adults (hearkening back to the mandatory retirement age introduced in the late 1800s), it is clear that with advancing age come many changes in the host’s ability to respond to stressors ranging from infections through surgery and chemotherapy. This is particularly true after about age 75, when the body’s reparative mechanisms and homeostatic forces become increasingly unable to cope with seemingly minor insults.4,5

I came to the field of geriatric oncology during my graduate training. I was searching for a research area for my thesis, and after two failed attempts, my supervisor introduced me to work examining quality of life in prostate cancer. Prostate cancer is an older man’s disease. My thesis examined age bias in the treatment of early-stage prostate cancer. I was able to demonstrate, using linked administrative databases in Ontario, that older men systematically received less aggressive (potentially curative) treatment than younger men, after adjusting for disease stage and remaining life expectancy.6 I have continued to do research in this area ever since, although my focus has shifted a little over the years.

Geriatric oncology research encompasses many areas. My early work was in parallel to a number of investigators in the field, who examined treatment patterns for various cancers as a function of age. Numerous studies in various countries have demonstrated that older adults receive less screening, less intensive diagnostic and staging work-ups, less intensive treatment for both early-stage and late-stage disease, and less effective pain medication for symptomatic advanced disease.7,8 Although these studies have identified many areas of possible age discrimination, important questions remain about how to reduce age discrimination while avoiding the harms of over-diagnosis and over-treatment.

My work shifted from describing age bias in prostate cancer to understanding the toxicities of treatment. I became particularly interested in understanding the impact of both disease and treatment on patient-relevant outcomes such as quality of life (QOL) and functional status. Numerous studies have shown that older adults with cancer and other serious illnesses often prioritize QOL or maintaining independence as more important goals than survival prolongation⎯illustrating the common trade-off between quantity of life and QOL.9,10 However, we also know that not all older adults have the same priorities. I continued to study prostate cancer, but began examining the toxicities of androgen deprivation therapy (ADT) in older men. ADT is one of the most widely used treatments in prostate cancer, used in almost 1 in 2 men at some point after diagnosis, particularly in advanced disease.11,12 Using large prospective cohort studies, I examined the side effects of ADT in areas of QOL, physical function, and cognitive function.13,14 In a similar way, many investigators in geriatric oncology are studying the effects of disease and various treatments on a variety of outcomes in older adults. I branched out into a second cancer site⎯acute myeloid leukemia (AML). In many ways, AML is a very different disease than prostate cancer. Although AML also primarily affects older adults, the onset is much more rapid and the prognosis is much worse⎯50% of older adults with AML are dead 6 months after diagnosis.15 The treatment of choice in AML is intensive chemotherapy (IC), but IC is incredibly toxic, resource-intensive, and less effective in older adults than younger adults for a variety of reasons.16 Not surprisingly, many older adults with AML do not receive IC, instead receiving best supportive care or investigational agents.17,18 I started out in this area comparing the QOL and functional status of older adults receiving IC vs non-IC approaches, and found similar if not superior QOL and functional status among those treated with IC.19 This illustrates the importance of critically examining common assumptions in oncology and other areas, such as the notion that older adults cannot tolerate intensive treatments for cancer and should receive more conservative treatment. While true in some settings, in many areas carefully selected older adults achieve similar benefits from treatment as younger adults, and with similar toxicities or an acceptable increased risk of some toxicities.

I moved on to comparing QOL and functional outcomes in younger versus older patients with AML, to really understand how much worse older adults did with IC. Perhaps surprising to many in the field, in the largest study of its kind, we found remarkably similar QOL and functional impairment at the time of diagnosis (prior to treatment) among older and younger adults and, more importantly, remarkably similar QOL recovery and only slightly worse recovery in physical function domains in older adults.20 Many other investigators have performed age-stratified secondary analyses within randomized controlled trials (RCTs) to answer similar questions across different diseases and treatment regimens.

I also moved from doing observational studies to intervention-based studies in an attempt to address some of the gaps in care and negative effects of treatment in older adults. A common theme in older adults is sarcopenia (reduced muscle mass), along with loss of physiological reserve as mentioned earlier. It should come as no surprise that cancer treatments are often associated with further loss of muscle mass (with subsequent worsening QOL and functional status), and one of the most effective therapies and preventative strategies is exercise. So I started conducting clinical trials of exercise-based interventions in both AML and prostate cancer to try to reduce treatment toxicity and improve patient outcomes. Several trials have been completed, and four more are underway.21-23

Finally, many centres worldwide are moving towards geriatric assessment (GA) in all older adults with cancer prior to embarking on treatment, particularly chemotherapy. This is because aging is associated with multiple comorbidities and impairments, a number of which are subtle and not detected in traditional clinical assessments by oncologists. Geriatric clinics are used to doing comprehensive GAs and assessing multiple domains including functional status, nutritional status, cognition, comorbidity, polypharmacy, etc. Theoretically, performing GAs prior to establishing a treatment plan in older patients with cancer will identify all the issues that may impact on treatment decision-making, leading to optimized decision-making and reduction of both over- and under-treatment.24 In collaboration with Dr. Martine Puts in the Faculty of Nursing at the University of Toronto, I have become involved in multiple studies examining the value of GA in the oncology setting. First, we conducted a systematic review and meta-analysis of all the studies examining GA.25 Having identified no RCTs of GA, and recognizing that RCTs provide the highest level of evidence to support change in practice, we are currently conducting a pilot RCT of GA versus usual care in older cancer patients with either breast, gastrointestinal, or genitourinary cancer. We hope to demonstrate improvements in QOL and functional status in the group who undergoes GA accompanied by an integrated management plan to address all the issues identified during the GA.

I would be remiss if I did not mention that research in geriatric oncology is truly multi-disciplinary. I work regularly with surgical oncologists, radiation oncologists, medical oncologists, haematologic oncologists, psychologists, exercise physiologists, kinesiologists, dietitians, and biostatisticians, to name but a few.

My final message is that there is much more work to be done in this relatively young field. Many questions remain around targets ranging from telomeres to telemedicine, and I consider myself truly privileged to be able to work in this incredible area.

References

  1. Extermann M, Aapro M, Audisio RA, et al. The SIOG 10 Priorities Initiative. International Society of Geriatric Oncology. 2011.
  2. Canadian Cancer Society’s Advisory Committee on Cancer Statistics. Canadian Cancer Statistics 2014. Toronto: Canadian Cancer Society; 2014.
  3. Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9-29.
  4. Sawhney R, Sehl M, Naeim A. Physiologic aspects of aging: impact on cancer management and decision making, part I. Cancer J. 2005;11(6):449-60.
  5. Sehl M, Sawhney R, Naeim A. Physiologic aspects of aging: impact on cancer management and decision making, part II. Cancer J. 2005;11(6):461-73.
  6. Alibhai SMH, Krahn MD, Cohen MM, et al. Is there age bias in the treatment of localized prostate carcinoma? Cancer. 2004;100(1):72-81.
  7. Ganz PA. Does (or should) chronologic age influence the choice of cancer treatment? Oncology (Huntingt). 1992;6(2 Suppl):45-9.
  8. Rose JH, O’Toole EE, Dawson NV, et al. Age differences in care practices and outcomes for hospitalized patients with cancer. J Am Geriatr Soc. 2000;48(5 Suppl):S25-32.
  9. Singer PA, Martin DK, Kelner M. Quality end-of-life care: patients’ perspectives. JAMA. 1999;281(2):163-8.
  10. Singer PA, Tasch ES, Stocking C, et al. Sex or survival: trade-offs between quality and quantity of life. J Clin Oncol. 1991;9:328-34.
  11. Meng MV, Grossfeld GD, Sadetsky N, et al. Contemporary patterns of androgen deprivation therapy use for newly diagnosed prostate cancer. Urology. 2002;60(3 Suppl 1):7-11; discussion -2.
  12. Shahinian VB, Kuo YF, Freeman JL, et al. Increasing use of gonadotropin-releasing hormone agonists for the treatment of localized prostate carcinoma. Cancer. 2005;103(8):1615-24.
  13. Alibhai SMH, Breunis H, Timilshina N, et al. Impact of androgen-deprivation therapy on physical function and quality of life in men with non-metastatic prostate cancer. J Clin Oncol. 2010;28(34):5038-45.
  14. Alibhai SMH, Breunis H, Timilshina N, et al. Impact of androgen-deprivation therapy on cognitive function in men with nonmetastatic prostate cancer. J Clin Oncol. 2010;38(34):5030-7.
  15. Ferrara F, Schiffer CA. Acute myeloid leukaemia in adults. Lancet. 2013;381(9865):484-95.
  16. Brandwein JM, Geddes M, Kassis J, et al. Treatment of older patients with acute myeloid leukemia (AML): a Canadian consensus. American journal of blood research. 2013;3(2):141-64.
  17. Alibhai SM, Leach M, Minden MD, et al. Outcomes and quality of care in acute myeloid leukemia over 40 years. Cancer. 2009;115(13):2903-11.
  18. Doria-Rose VP, Harlan LC, Stevens J, et al. Treatment of de novo acute myeloid leukemia in the United States: a report from the Patterns of Care program. Leuk Lymphoma. 2014;55(11):2549-55.
  19. Alibhai SMH, Leach M, Kermalli H, et al. The impact of acute myeloid leukemia and its treatment on quality of life and functional status in older adults. Crit Rev Oncol Hematol. 2007;64(1):19-30.
  20. Alibhai SMH, Breunis H, Timilshina N, et al. Quality of life and physical function in adults treated with intensive chemotherapy for acute myeloid leukemia improve over time independent of age. Journal of Geriatric Oncology. 2015.
  21. Alibhai SM, O’Neill S, Fisher-Schlombs K, et al. A clinical trial of supervised exercise for adult inpatients with acute myeloid leukemia (AML) undergoing induction chemotherapy. Leuk Res. 2012;36(10):1255-61.
  22. Alibhai SM, O’Neill S, Fisher-Schlombs K, et al. A pilot phase II RCT of a home-based exercise intervention for survivors of AML. Support Care Cancer. 2013.
  23. Santa Mina D, Alibhai SMH, Matthew AG, et al. A randomized trial of aerobic versus resistance exercise in prostate cancer survivors. J Aging Phys Act. 2013;21(4):455-78.
  24. Horgan AM, Knox JJ, Alibhai SMH. The comprehensive geriatric assessment in oncology: promises, pitfalls, and practicalities. Hospital Practice. 2010;38(3):128-36.
  25. Puts MT, Hardt J, Monette J, et al. Use of geriatric assessment for older adults in the oncology setting: a systematic review. J Natl Cancer Inst. 2012;104(15):1134-64.