“Older adults form the majority of patients with cancer.” For more than 3 decades now, almost every article, presentation, or discussion related to cancer and aging started with this statement. As I entered the field of geriatric oncology, I thought that by simply stating this fact, everyone would be persuaded, but instead I faced a lot of “so what?” attitudes. (If you are thinking this is because of my junior status in the field, please see the commentary “Geriatric Assessment: What Are You Waiting For?” by Stuart M. Lichtman, MD, FASCO, in the July 10, 2020, issue of The ASCO Post.)
Stuart M. Lichtman, MD, FASCO
As is the case for most of us in the field, my natural reaction to the “so what?” was to discuss the particularities of older adults with cancer. Increased age is associated with various conditions, such as functional impairment, limited mobility, higher comorbidity, and polypharmacy. These geriatric syndromes have a great impact on the oncologic care of older adults with cancer, but, unfortunately, there is limited guidance regarding the management of malignancies in this patient population, as older adults have been underrepresented in clinical trials.1
Age-Related Research: Enrollment Disparity
The limited guidance in this area was shown again during the ASCO20 Virtual Scientific Program (ASCO20), with two studies uncovering new areas of age-related research enrollment disparity.2,3 An analysis of the ARCAD metastatic colorectal cancer clinical trial database demonstrated that older patients were not only underrepresented in first-line studies (just 16.4% of enrolled patients were older adults), but their odds of receiving second-line therapy decreased by 11% for each additional decade of life (P = .0117).2 The second study, a single-institution review of 6,267 patients enrolled on phase I trials, showed that just 30% were older adults and that enrollment rates decreased with older age: 870 patients were between 70 and 79 years and just 76 patients were 80 years or older.3
‘Age Is Just a Number’
The oncology field has been shifting through the years from the care of “cancer patients” to the care of “patients with cancer,” with an increasing focus on patient-centered approaches. For older adults with cancer, the geriatric assessment is an excellent tool that allows better understanding of patients and their needs beyond their diagnosis of cancer or their “numerical age.”
“The geriatric assessment is an excellent tool that allows better understanding of patients and their needs beyond their diagnosis of cancer or their ‘numerical age.’”— Rawad Elias, MD
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Data from a prospective registry of 708 older adults with gastrointestinal malignancies presented during ASCO20 showed again that age is just a number by demonstrating a comparable prevalence of geriatric deficits regardless of chronologic age.4 The study authors showed that across three age groups (60–70 vs 70–79 vs ≥ 80 years), there was no association between increased age and the prevalence of frailty (33% vs 33%, P = .97), impairment of activities of daily living (ADL) or instrumental ADL, malnutrition, cognitive impairment, falls, or anxiety.
Geriatric Data and Mortality
Another analysis based on the same registry evaluated the association of geriatric assessment deficits with mortality at 1 year.5 After adjusting for age and clinical factors, the study authors found that malnutrition and fatigue were the strongest predictors of 1-year mortality, with an estimated survival of 53% in patients with both factors and 88% for those with neither.
The impact of geriatric variables on mortality was also demonstrated in another retrospective single-center study of 304 patients.6 The study authors showed that patients who did not pass a screening cognitive or fitness test were more likely to die within 6 months compared with those without such deficits (11% vs 4%; odds ratio [OR] = 2.95, 95% confidence interval [CI] = 1.11–93.0). In addition, patients who did not pass the fitness test were more likely to have an emergency department visit within the first 6 months of care (OR = 2.40, 95% CI = 1.04–5.46).
Another analysis presented during ASCO20 showing the association of geriatric data and mortality was a prospective multicenter study that included 554 patients aged ≥ 70 years who had a geriatric assessment performed at baseline.7 A multivariate analysis showed that ADL impairment was among the predictive factors of increased risk of death within 6 months of chemotherapy initiation. Other factors included body mass index < 23 kg/m2, stage IV disease, albumin ≤ 3.5 g/dL, increased gamma-glutamyl transferase, hemoglobin < 11 g/dL, and an Eastern Cooperative Oncology Group performance status of 2. A predictive model was developed based on the multivariate analysis, with higher scores indicating an increased risk of mortality at 6 months: < 5% for a score between 0 and 2, > 15% for a score between 3 and 5, and > 25% for a score between 6 and 12.
Using Geriatric Assessment Information in Clinical Practice
Of note, the use of “one-size-fits-all” predictive scores in the world of geriatric oncology has been challenging due to the heterogeneity of the older patient population, the variable behavior of malignancies, and the differences in the safety/efficacy profile of therapeutic agents. For example, a retrospective analysis presented during ASCO20 of 248 patients aged ≥ 70 from the French ELCAPA prospective cohort showed that neither the CARG (Cancer and Aging Research Group) nor the CRASH (Chemotherapy Risk Assessment Scale for High-Age Patients) validated tool was predictive of chemotherapy toxicity in this patient population.8 Therefore, as noted in the ASCO Guideline for Geriatric Oncology, the geriatric assessment is recommended as the standard assessment for older patients treated with chemotherapy.9
Despite ASCO’s recommendation, many did not know what to do with the geriatric assessment information or how to use it in daily practice. And there were still some “so what?” and “there’s no proof that it affects oncologic outcomes.” The latter statement always baffled me, not because it was not true (at the time), but because some limited their definition of outcomes improvement to the oncology aspect of care and did not see the “patient with cancer” but only the “cancer patient.”
“Patient-reported geriatric outcomes might be one of the best solutions to disseminate geriatric assessment information in daily oncology practice.”— Rawad Elias, MD
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Randomized data presented during ASCO20 showed that providing treating oncologists with a geriatric assessment summary and suggested interventions based on the detected geriatric deficits (vs geriatric assessment information alone) led to an increased number of conversations with patients about comorbidities (1.02 vs 0.52 conversation per patient, 95% CI = 0.18–0.81, P = .004), and, more commonly, these conversations were initiated by oncologists (72% vs 52%, P < .001).10 The results of this analysis suggest that the geriatric assessment allows providers to know their patients better.
This notion was replicated in another study presented during ASCO20, which was based on a prospective analysis of 100 patients with metastatic breast cancer who completed a self-administered geriatric assessment.11 Geriatric deficits were detected in 96% of patients, and interestingly, the providers were “surprised” with the results of the geriatric assessment in 33% of the cases. The geriatric assessment information led to a change in 40% of the treatment plans.
The shortage of geriatric providers in the United States hinders the propagation of the geriatric assessment beyond limited centers. However, as noted in this previous study, patient-reported geriatric outcomes might be one of the best solutions to disseminate geriatric assessment information in daily oncology practice. An analysis of the Cancer and Aging Resilience registry showed that poor self-reported health was associated with higher odds of frailty (adjusted OR = 21.8; 95% CI = 13.7–34.8) and impairments in multiple geriatric assessment domains.12 In addition, poor self-reported health was associated with decreased survival at 1 year (65% vs 84%, P < .001) and was shown to be an independent predictor of worse survival after adjusting for age, sex, race, cancer type, stage, comorbidity, and planned treatment (adjusted HR = 2.29 [1.6–3.2], P < .01).
Nassim Nicholas Taleb’s once stated: “Doctors most commonly get mixed up between absence of evidence and evidence of absence.” This statement represents well the past challenges of geriatric oncology: Some chose to ignore, for example, a patient’s history of falls or cognitive impairment because they had no proof it affects oncologic outcomes. Well, for those clenching on the “absence of evidence,” ASCO20 brought them many reasons to “geriatricize” their oncology practice.
Chemotherapy Toxicity and Geriatric Assessment
In a recent study, a geriatric intervention, based on providing treating oncologists with a geriatric assessment summary and management recommendations, led to a reduction in chemotherapy-related grade 3 to 5 toxicity by 20%.13 This was the primary outcome of a cluster randomized controlled trial that included patients aged ≥ 70 years starting a new treatment regimen for an advanced malignancy. This study randomized 41 practices and included 718 patients with a noncurable cancer who had at least a single geriatric domain impairment other than polypharmacy.
The rate of grade 3 to 5 toxicity for the overall study population within 3 months was 60.9%, dose modification was needed for 50%, and 17.7% required treatment discontinuation. Patients enrolled on the experimental arm had a higher rate of reduced-dose intensity at cycle 1 of treatment (48.7% vs 35%, adjusted relative risk [RR] = 1.37, 95% CI = 1.06–1.76, P = .016) but needed less dose modification at 3 months of treatment due to toxicity (42.1% vs 57.5%, adjusted RR = 0.85, P = .0190).
The geriatric-influenced treatment approach led to an improvement in the rate of grade 3 to 5 toxicity (50.1% vs 71%; adjusted RR = 0.74, 95% CI = 0.63–0.87, P < .01), with a significant difference seen particularly for nonhematologic adverse events (31.8% vs 51.8%; adjusted RR = 0.73, 95% CI = 0.53–0.996, P = .047) but not for hematologic toxicity (36.1% vs 43.6%; adjusted RR = 0.85; 95% CI = 0.69–1.05, P = .13). Hence, the influence of the geriatric assessment led to better treatment selection, reduced toxicity, and improved treatment delivery. Of note, the overall rate of death at 6 months was 26.5%, with no difference observed among study arms.
“The influence of the geriatric assessment led to better treatment selection, reduced toxicity, and improved treatment delivery.”— Rawad Elias, MD
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The impact of geriatric interventions on high-grade chemotherapy toxicity was evaluated also in the GAIN study, a randomized controlled study that included patients aged 65 years and older with a diagnosis of solid tumor who planned to start a new chemotherapy regimen.14 A geriatric assessment was performed at baseline for the overall study population. Patients in the experimental arm received, in addition to the geriatric assessment, geriatric interventions based on an evaluation by a multidisciplinary team and predefined geriatric assessment triggers.
The GAIN intervention was associated with a reduction in grade 3 or 4 chemotherapy toxicity (50.5% vs 60.4%, 95% CI = 1.6–18.2, P = .02). It also resulted in improvement in both hematologic (11.3 vs 19.3%, P = .003) and nonhematologic toxicity (18.1% vs 26.2%, P = .008).
Health-Related Quality of Life and Geriatric Assessment
Integrating geriatric care into oncology treatment planning led to an improvement in health and quality-of-life outcomes in the INTEGERATE prospective study, which included 154 patients aged ≥ 70 years who were receiving systemic treatment for a solid tumor or diffuse large B-cell lymphoma.15 Patients were randomly assigned to receive geriatric assessment–triggered interventions vs routine oncologic care.
The study authors showed that geriatric care was associated with an improvement in patients’ quality of life at 12, 18, and 24 weeks based on Elderly Functional Index (ELFI) scores. Patients in the experimental arm had less of a decline in ELFI score (10% at week 12) with an earlier recovery compared with those in the routine-care arm, who had a decline of 20% at week 18 with more delayed recovery. The geriatric intervention was also associated with an improvement in hospitalization rates and successful treatment delivery, with 39% fewer emergency presentations (adjusted incidence rate ratio [IRR] = 0.61, 95% CI = 0.46–0.77, P = .007), 41% fewer unplanned hospitalizations (adjusted IRR = 0.59, 95% CI = 0.41–0.86, P < .001), 24% reduction in unplanned hospital overnight bed-days (adjusted IRR = 0.76, 95% CI = 0.68–0.85, P < .01), and an improvement in the time to first unplanned hospital admission (with a hazard ratio favoring the intervention arm of 1.81, 95% CI = 1.12–2.92, P = .015). In addition, geriatric care resulted in lower rates of treatment discontinuation due to adverse events (32.9% vs 53.2%, P = .01).
Geriatric Care and Surgical Management
Further data from ASCO20 showed that the benefit of geriatric care is not limited to medical oncology patients, but also extends to those receiving surgical management. A retrospective analysis of 1,118 patients aged ≥ 75 years showed that perioperative geriatric co-management was associated with an improvement in 30-day hospital admissions (11% vs 18%), emergency room visits (14% vs 22%), 90-day mortality (6% vs 15%), and composite adverse outcomes (20% vs 37%) compared with routine care.16
The improvement in surgical outcomes with geriatric care was confirmed in a randomized study that included 160 patients aged ≥ 65 years with a diagnosis of a gastrointestinal malignancy.17 Patients were assigned to routine care or an intervention consisting of a geriatric consultation first as an outpatient (preoperative) and then as an inpatient (postoperative).
The intention-to-treat analysis showed no impact of the geriatric intervention on any of the outcomes; however, it is important to note that, mainly due to logistical issues, 30 of the 82 patients enrolled in the experimental arm had received geriatric care both in the preoperative and postoperative settings. The per protocol analysis showed that the geriatric intervention reduced the postoperative length of stay (8.21 vs 5.9 day, P = .024) and intensive care unit use (32.4% vs 13.3%, P = .049), although it had no impact on the rate of readmission within 90 days (25% vs 16.7%, P = .362). Patients who received geriatric care had an improvement in depression symptoms and symptom burden on postoperative day 5, although there was no difference in the European Organisation for Research and Treatment of Cancer quality-of-life scores among the study arms.
“Integrating geriatrics into the daily oncology practice helps us move to the next level of care by treating the patient and not the cancer.”— Rawad Elias, MD
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Multiple data presented during ASCO20 confirmed the benefit of geriatric care. One study reiterated the need to improve the outcomes of older adults with cancer: an analysis of the Surveillance, Epidemiology, and End Results–Medicare database. This analysis included 307,944 unique patients and showed that 65% were hospitalized in the first year after diagnosis, with 31% needing two or more hospitalizations.18
Integrating geriatrics into the daily oncology practice helps us move to the next level of care by treating the patient and not the cancer. This move will impact not only individual patient outcomes, but our health-care system in general. This is the time to “geriatricize” your oncology practice. What are you waiting for?
DISCLOSURE: Dr. Elias reported no conflicts of interest.
REFERENCES
1. Soto-Perez-de-Celis E, Li D, Yuan Y, et al: Functional versus chronological age: Geriatric assessments to guide decision making in older patients with cancer. Lancet Oncol 19:e305-e316, 2018.
2. McCleary NJ, Harmsen WS, VanCutsem E, et al: Survival outcomes among older adults receiving second-line therapy for metastatic CRC: 5,289 patients from the ARCAD Clinical Trials Program. ASCO20 Virtual Scientitic Program. Abstract 7009.
3. Subbiah IM, Buzdar A, Dumbrava EEI, et al: Investigating the disparate enrollment of older adults on phase I clinical trials: Evolving participation patterns of patients 65 years and older with advanced cancer on phase I trials. ASCO20 Virtual Scientitic Program. Abstract 12044.
4. Williams GR, Obaidi MA, Weaver A, et al: Association between chronological age and geriatric assessment to identify deficits in elderly adults with cancer: Findings from the Care Registry. ASCO20 Virtual Scientitic Program. Abstract 12048.
5. Williams GR, Dai C, Obaidi MA, et al: Geriatric assessment predictors of 1-year mortality in older adults with gastrointestinal malignancies: Results from the CARE study. ASCO20 Virtual Scientitic Program. Abstract 12047.
6. Maranzano M, Neerukonda AR, Wallace JA, et al: Abbreviated geriatric assessment in new oncology patients and its association with early death. ASCO20 Virtual Scientitic Program. Abstract 12035.
7. Batlle JF, Pinto A, Basterretxea L, et al: Development and validation of an early death risk score for older patients treated with chemotherapy for cancer. ASCO20 Virtual Scientitic Program. Abstract 12030.
8. Frelaut M, Caillet P, Culine S, et al: External validation of two predictive scores of chemotherapy toxicities among older patients with solid cancer, from ELCAPA prospective cohort. ASCO20 Virtual Scientitic Program. Abstract 12050.
9. Mohile SG, Dale W, Somerfield MR, et al: Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO Guideline for Geriatric Oncology. J Clin Oncol 36:2326-2347, 2018.
10. Kleckner A, Gilmore N, Belcher E, et al: Communication about comorbidities among 527 older patients with advanced cancer and their oncologists and caregivers: A multisite cluster-randomized controlled trial. ASCO20 Virtual Scientitic Program. Abstract 12040.
11. Seedor RS, Meeker CR, Lewis B, et al: Prospective study comparing self-administered geriatric assessment to provider’s routine clinical assessment of older patients with metastatic breast cancer treated at community oncology practices. ASCO20 Virtual Scientitic Program. Abstract 12029.
12. Obaidi MA, Giri S, Mir N, et al: Use of self-rated health to identify frailty and predict mortality in older adults with cancer: Results from the CARE study. ASCO20 Virtual Scientitic Program. Abstract 12046.
13. Mohile SG, Mohamed MR, Culakova E, et al: A geriatric assessment intervention to reduce treatment toxicity in older patients with advanced cancer: A University of Rochester Cancer Center NCI community oncology research program cluster randomized clinical trial. ASCO20 Virtual Scientitic Program. Abstract 12009.
14. Li D, Sun CL, Kim H, et al: Geriatric assessment-driven intervention on chemotherapy toxicity in older adults with cancer: A randomized controlled trial. ASCO20 Virtual Scientitic Program. Abstract 12010.
15. Soo WK, King M, Pope A, et al: Integrated geriatric assessment and treatment (INTEGERATE) in older people with cancer planned for systemic anticancer therapy. ASCO20 Virtual Scientitic Program. Abstract 12011.
16. Shahrokni A, Kim SJ, Alexander K, et al: Association of geriatric comanagement with reduction in adverse surgical outcomes among patients 75 or older with cancer with prolonged hospital stay. ASCO20 Virtual Scientitic Program. Abstract 12036.
17. Qian CL, Knight HP, Ferrone CR, et al: Randomized trial of a perioperative geriatric intervention for older adults with cancer. ASCO20 Virtual Scientitic Program. Abstract 12012.
18. Halpern MT, Zhang F, Enewold L: Hospitalizations following cancer diagnosis: National values for frequency, duration, and charges. ASCO20 Virtual Scientitic Program. Abstract 12039.
Dr. Elias is a geriatric oncologist at Hartford Healthcare Cancer Institute and Assistant Professor at the University of Connecticut School of Medicine.
