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Applications in Geriatric Oncology

by Ilene Browner, M.D.

Demographics of Cancer and Aging

The Aging Population
The over-65 population is the fastest growing segment of the US population

  • Currently 1:8 people in the United States is > 65 years
  • Average life expectancy for adults > 65 years is 18.5 years
  • 18% are minorities
  • Women are the predominant gender (58% >65 years and 69% > 85 years); 40% of older women are widows
  • 30% non-institutionalized older adults live alone
  • 20% of the population in the United States will be older than 65 years by 2030.
  • The fastest growing subset of this older population is people >85 years, with an increase from 100,000 people in 1900 to an expected 7.3 million by the year 2020.
     (reference:  www.aoa.gov)

Incidence of Cancer in the Aging Population
The incidence of cancer increases with age.

  • Overall, the lifetime cancer risk is 44% in men & 38% in women.
  • Among people over the age of 65 years, there is an 11-fold increased incidence of developing cancer as compared to younger individuals. 
  • The median age at the time of a cancer diagnosis is 68 yrs
  • 56% of all cancer diagnoses & 70% of all cancer deaths occur in the over-65 population
  • In the last 30 years, the incidence of cancer has increased 26% in > 65 year-old population as compared with a 10% increase in the population < 65 years.
  • Cancer-related mortality has increased among the older population by 15%, but has decreased by 5% < 65 year-old population. 

Thus, the elderly are disproportionately affected by cancer and its associated sequelae
(Yancik.  The Cancer J. 11:437, 2005)

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Biology of Cancer and Aging

The association between cancer and aging may be attributed to age-related changes in molecular, cellular and physiologic processes.


Molecular Changes and Aging
The aging process is associated with less efficient and less active DNA repair, leading to

  • DNA adduct formation
  • Hypomethylation of DNA
  • Increased frequency of mutations, chromosomal breakage and translocations
  • Genetic instability (inactivation of suppressor genes and activation of oncogenes).

This age-altered molecular environment favors carcinogenesis.

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Cellular Changes and Aging
With aging, some cells achieve proliferative senescence, remaining biologically active without cell division. Replicative senescence has been documented in stromal fibroblasts in vitro; cells undergo a finite number of divisions and then enter a state of irreversibly arrested cell growth.  These cells are resistant to apoptosis, release tumor growth factors and enzymes, and are vulnerable to cellular dysregulation.  If cells escape from this regulated environment, they may be highly susceptible to malignant transformation.  These characteristics may provide a favorable environment for carcinogenesis and tumor growth.

Age-related alterations in growth factor (cytokines and chemokines) production and activity, metalloproteinase expression, hormonal status, inflammation, and immune cell number and function may contribute to changes in tumor biology and expression of cancers in the elderly.

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Tumorogenesis: A Simplified Model
The development of cancer is likely a multi-stage process, including Initiation, Promotion and Progression.  The aging process renders a sufficient number of cells vulnerable to carcinogenesis, and provides ample time for the multi-step process of tumorogenesis to occur. (VN Anisimov. Crit Rev Onc Heme.  45:277, 2003) 

Step 1 -Initiation:  Accumulated irreversible changes occur at the level of stem cell DNA in oncogenes, antiproliferative and apoptotic genes, and cell lines leading to cellular immortality and initiation of the multistep process.

Steps 2 & 3 -Promotion and Transformation:  Increased mitogenesis and cell division occur, promoting a “pre-malignant” phenotype.  Promotion is facilitated by the release and interaction of cytokines and chemokines, and by hormonal and metabolic changes which induce cellular senescence and primes the microenvironment and stroma for tumor progression.   Age-associated changes in levels of cytokines, chemokines and hormones, in receptor expression and in HPA-axis function may accelerate promotion and transformation phases.

Step 4 -Progression:  In this primed environment, clonal expansion and metastasis of tumor cells can occur.  The changes in gene expression and cellular proliferation in this stage may be reversible.

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Physiologic Changes and Aging
There is an age-related change in homeostatic and allostatic processes; physiologic and functional reserves are diminished, and are often maintained in a fragile balance.  Decreases in stem cell reserve, less efficient cellular repair mechanisms, and diminished organ tissue and function coupled with age-related comorbidities, altered catabolism of drugs, and increased exposure to reactive species, carcinogens and stressors, render older adults vulnerable to treatment-related toxicities.

Physiologic ChangeConsequence of Chemotherapy
Slow Repair of DNA DamageProlonged Toxicity

Reduced stem-cell mass and
hematopoesis

Slow recovery of blood and mucosal
cells

Reduced functional reserve of
organ systems
Risk of organ failure with additional 
tissue loss 
Reduced gastrointestinal absorptive surface, 
gastric motility, and gastric secretion
Reduced absorption
Reduced fat-free massAltered drug distribution
Greater AnemiaIncreased levels of circulating drug
Decreased liver massReduced drug metabolism
Decreased nephron massReduced drug excretion

(reference: Repetto. Supportive Oncology. 1(S2), 2003)

Age-related changes in physiology and organ function may lead to changes in the pharmacokinetics and pharmacodynamics of cancer chemotherapeutic agents, increasing the risk for drug-related morbidity in the elderly.

Pharmacokinetic shiftsPharmacodynamic shifts
  • change in fat distribution
  • change in total body water         
  • change in kidney function
  • change in hepatic function
  • increased resistance
  • increased elimination of Rx from cancer cells
  • decreased cellular catabolism of Rx
  • increased indolent behavior of tumor

Pharmacokinetics is the effect of bodily processes on the drug. PK is impacted by body composition, bioavailability and organ function. 

  • Body composition changes with age 
    • Fat distribution increases 2-fold and total body water (TBW) decreases 10-15% with age,
    • Volume of distribution (Vd) increases for lipophilic drugs and declines for hydrophilic drugs,
    • Increased age- and disease-related risk for anemia and hypoalbuminemia coupled with changes in TBW lead to alterations in drug binding, peak concentrations and half-life of chemotherapeutic agents. 
  • Bioavailability is dependent on gastrointestinal motility, splanchnic blood flow, digestive enzyme activity and mucosal integrity, all of which may be altered (reduced) with age, especially if age > 80 years
  • Age-related loss of kidney and liver organ function may impact drug dosing and tolerability due to changes in metabolism and excretion of drug. 
    • Renal function, particularly creatinine clearance (CrCl) decreases with age.  CrCl must be calculated even if serum Cr is WNL.  There may be a need to avoid or dose-reduce nephrotoxic agents e.g. platinums, capecitabine. 
    • Hepatic function declines with age, ~1% flow decrement/year after the age of 25 years.  There is also an age-related loss of liver mass and function, and a decline in P450 activity (30%) which impacts metabolism and increases the likelihood of drug-drug interactions.

 (reference:  Lichtman et al. Crit Rev Onc Hem. 46:101-114, 2003)

Pharmacodynamics is the effect of the drug in the body over time.  Age-related changes in PD may alter the activity of and increase the toxicity from chemotherapeutic agents in older cancer patients

  • Multidrug resistance:  In older patients with acute myelogenous leukemia, the over-expression of the multi-drug resistance (MDR-1) gene, which encodes for a drug efflux pump, may enhance resistance to and decrease the efficacy of chemotherapeutic agents in these patients
  • Chemotherapeutic agents often work best on vascular, hyper-oxygenated, proliferative tumors.  As a result, the indolent behavior of some tumors among older cancer patients may seem to be a favorable characteristic, but may also lead to reduced efficacy of antineoplastic therapies

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Barriers to Receiving Cancer Care

The Institute of Medicine (IOM) states that in “many cases, older patients are less likely to get effective cancer treatment than are younger patients despite evidence that the elderly can tolerate and benefit from it.”

Barriers to Screening
There are several barriers to cancer screening among older adults which include but are not limited to:

  • Lack of standard guidelines for cancer screening in older adults due to limited data from clinical trials in this population.
    • Screening efficacy and effectiveness are difficult to assess.
    • Screening risks and benefits are difficult to qualify and quantify.
  • Screening may miss early, curable disease or may detect advanced yet asymptomatic disease.  The role of detecting indolent disease & the decision process that follows may lead to further (invasive) diagnostic evaluations and heightened patient anxiety without significant clinical benefit.
  • Inaccurate assessment of life expectancy and impact of co-morbidities.  Tend to underestimate life expectancy and overestimate impact of co-morbid illnesses.
    • In order to achieve a survival benefit from screening, patients should have at least a 5-year life expectancy.
    • Many cancers in the elderly are slower growing and may not contribute to morbidity and mortality (risk of lead-time bias). There is an increased likelihood of dying from other co-morbid illnesses then from a screen-detected cancer. 
  • Consideration of impact of the cancer versus the cancer-related treatment on life expectancy and quality-of-life.  Data incomplete.
  • Values and preferences of the patient, family, physician, and society erect barriers to screening.

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Barriers to Diagnosis and Treatment
As with screening, barriers to appropriate cancer care among elderly cancer patients include but are not limited to

  • Age is the primary, independent predictor of receiving no or incomplete therapy
  • Ageism may promote minimization of the complaints and medical problems of the elderly, and  de-emphasis of health promotion and disease prevention.  
  • Paternalistic assumptions persist about the elderly and their desire for and ability to tolerate therapy:  “Too dangerous”, “Not interested”.   Caregiver and physician views guide decision process; patients often not queried.
  • Reduced access to screening and care:  Age, cost, lack of a coordinating primary care physician, absent social supports and limited transportation are key determinants
  • Misconceptions regarding etiology, treatment and prognosis of cancer.  The older generation is the “Big C” generation. Inherent fear and fatalism serve as a barrier to screening, diagnosis and treatment.
  • Delay to diagnosis, related to above factors
  • Homogeneity assumption:  All older adults are not created equal.  Dramatic differences in function, health status and activity across all ages.
  • Life Expectancy is under-estimated
  • Increased number and severity of comorbid illnesses and age-related change in organ function, cognitive flexibility and physical function in this population may increase concerns re: life expectancy and ability to tolerate therapy
  • The “Unders”:  The elderly, in general, are Under-appreciated, Under-assessed, Under-enrolled, and Under-treated, resulting in
    • decreased survival due to incomplete staging, limited referrals to tertiary comprehensive cancer centers, less aggressive treatment or empiric dose reductions
    • under-enrollment of Cancer patients >65 years in clinical trials.  Only 9-15% of older adults participate in clinical trials yet >50% of all new diagnoses are made in this population.  Thus, treatment decisions are based on evidence from trials in younger patients which do not answer age-specific concerns about quality-of-life, functional outcomes, pharmacokinetics and pharmacodynamics, and treatment tolerability and benefit.

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Barriers to Cancer Therapies 
After overcoming the barriers to screening and diagnostic evaluation, decisions regarding specific treatments must be made

When discussing therapeutic options, all parties (patient, patient’s family, physicians, etc) must be included in the discussion.  Each party’s perspective must be reviewed within the context of disease- and age-related factors.  One must be conscientious of the fact that older patients may defer to family members or a physician thus, masking their own wishes.  Patient, physician and family biases may contribute to inappropriate staging and treatment decisions.

  • Patient’s perspective:
    • Increased pessimism: “Cancer is contagious”, “Cancer is incurable even when diagnosed at early stages,” and “Treatment for cancer is worse than the disease itself” (Beckman and Rohan. Cancer. 74:2004, 1994)
    • Less general health knowledge and literacy than younger patients
    • Less assertive in therapeutic triad and decision making
    • Emphasize desire not to be a burden
    • As likely to agree to curative treatment but quality more than quantity  of life influences decision making
    • Coping skills are more refined than younger patient
  • Caregiver’s perspective
    • Role as protector Versus caregiver Versus child or spouse
    • Limit emotional and physiologic stress on family member
    • Concern for caregiver stress
  • Physician’s Perspective
    • Limit emotional and physiologic stress on patient and family
    • Resource utilization
    • Principles of paternalism and ageism often color assessment and decision making
    • Decisions made on the basis of chronological versus physiological age
    • Lack of data impacts decision process

Surgery
Surgical management of cancer may be diagnostic, palliative or curative.  It is the first-line therapy in many cancers. 
Barrier: Surgery is frequently not offered to older cancer patients due to concerns for increased risk of surgical morbidity and mortality. However, with proper assessment of the older patient, pre-operative planning and interventions, and elective procedures, the risk is only minimally increased.

  • Surgery may be curative in early stage breast, lung, brain, GI, GU and gynecological cancers.
    • For colorectal cancer, the rate of  (1) curative surgery declines with age:  76% < 65 yrs vs. 67% >80 yrs,  (2) palliative surgery and emergent procedures increase with age: 24% vs. 33%, and 11% vs. 29% respectively (Lancet, 356:968-74, 2000
  • Surgical mortality is relatively low in non-emergent procedures:  1.5% if > 75 years versus 0.5% if < 75 years 
    • For colorectal cancer, the overall surgical mortality is 3.9% but it increases with advancing age:  0.8% if < 50 yrs versus 2.9%  if 66-80 yrs versus 6.9%  if > 80 yrs (Dimick, J Clin Res, 2003), 
    • Age-related increases in mortality may be attributable to a delay in screening and diagnosis and more emergent procedures in the setting of advanced disease. 
  • Use of alternative surgical procedures may reduce morbidity and mortality.
    • Laparoscopic options may decrease blood loss, post-operative pain, anesthesia- and narcotic-induced delirium and hospital length-of-stay, and shorten time to p.o. intake and to recovery.
  • Both co-morbidity and poor functional status at any age are predictive of increased surgical morbidity and mortality.  An ASA score > III and emergent and prolonged procedures are predictive of peri- and 30-day post-operative mortality.
    • The peri-operative period has higher morbidity and mortality in older patients due to an increased incidence of cardiovascular and infectious complications associated with the surgical procedure
      • There is an estimated 11% morbidity and 50% mortality related to cardiovascular complications
      • There is a 9-18% post-operative respiratory morbidity due to decreased ciliary movement and lung compliance in the elderly leading to increased atelectasis and infection
      • A thorough pre-operative assessment and intervention for modifiable risks can reduce peri- and post-operative risks (Ramesh et al. World J Surg Oncol. 3:17, 2005)


Radiation
Sixty percent of all cancer patients will receive radiation during the course of their treatment.
Barrier:  Application of radiation therapy is limited by a patient’s misconceptions about radiotherapy, transportation issues and frequency of therapy (daily, prolonged course). 

However,

  • Radiation is generally safe and well-tolerated with 75 – 90% of older patients completing therapy. 
  • Minimal functional impairment occurs in patients < 80 yrs.
  • New modalities of radiation, IMRT, gamma-knife, 3D conformal or brachytherapy, can reduce toxicity via organ sparing and limit the total number of required treatment sessions. 
  • Toxicity from radiation may be more pronounced when chemotherapy is given concurrently.  Sequential therapies should be considered for certain patients and for metastatic disease.
    • Radiation-induced toxicities in the elderly include:  Fatigue, mucositis (increased with combined therapy), cardiac/pulmonary symptoms (acute and delayed SOB, arrhythmias), myelosuppression (especially during pelvic and mediastinal XRT), enteritis (fibrosis and strictures), and GU symptoms (increased frequency, urgency and dysuria due to decreased tone and bladder emptying) 
    • Increased risk of hip fractures recently documented (Baxter et al. JAMA 294:2587, 2005) in elderly patients receiving pelvic radiation.  Hip fractures in the elderly are associated with an increase in morbidity and mortality 

Chemotherapy
Barrier:  Age-related changes are associated with an increased susceptibility to toxicity during chemotherapy.  However, it is difficult to tease apart age effects versus age-related (comorbid illness, disability, cognitive impairment) effects on treatment-related toxicity. 

  • Must establish the goal of therapy – patient’s wishes, risks and benefits. 
  • Older patients can tolerate multi-drug regimens
    • if metastatic disease may benefit from serial single agent regimens which have equal efficacy but decreased toxicity
  • IV administration is beneficial since patients can be closely monitored and compliance to regimen is guaranteed.  It is typically covered by insurance.  However, systemic therapy may be more toxic and more disruptive to daily routine and quality of life (caregiver stress, transportation).  May consider home infusion.
  • Oral therapies may be less toxic but issues of cost and compliance as well as decreased monitoring may come into play.  Also, the role of PK and PD in patients > 80 yo is not fully understood for oral agents.
  • Must consider patient’s overall health status and comorbidites as well as drug toxicities when choosing a specific chemotherapy regimen:
    • Myelosuppression:  Hematopoiesis exists in steady state but is easily disrupted with minimal stress.  Thus, more pronounced declines in cell counts and more prolonged depression of counts are typical in older patients and often occur after the 1st cycle. 
      • Depressed counts are associated with an increased risk of infection with significant morbidity and mortality (5-30%). 
      • Administration of growth factors may decrease risk of neutropenic M & M by 50-75%.  NCCN recommends growth factors for highly myelosuppressive regimens e.g. CHOP. 
      • Anemia has been shown to decrease efficacy of treatment, alter PK, increase morbidity (fatigue, functional and cognitive decline) and may slow recovery (SJ Van Belle & V Cocquyt. Crit Rev Onc Hem. 47:1-11, 2003).  Growth factors are recommended for maintaining Hgb > 12 during therapy.
    • Gastrointestinal: Mucositis and diarrhea:  May be severe due to decreased stem cell reserve and repair.  Early attention is critical to prevent dehydration, malnutrition, and sepsis.
    • Neurotoxicity/Cardiotoxicity:  Highly vulnerable to neurotoxic (5-FU, taxanes, platinums) and cardiotoxic (anthracyclines) agents due to decreased stem cell reserve and plasticity, and associated comorbidity.

Supportive Care/End of Life Care (EOLC)

  • Should be discussed within the first several appointments
  • Should be initiated early and concurrent with any treatment plan
  • Availability of caregiver may be an obstacle to initiating EOLC
  • Older patients may be resistant to EOLC ; early education critical to acceptance

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Comprehensive Assessment of the Older Patient
“The key to safe and effective management of cancer in older patients is individualization of treatment via a synthesis of cancer- and patient-related factors” (Repetto and Balducci. Lancet Oncol. 3:289, 2002)

Patient Assessment
Patient-related assessments include an estimate of “age”, life expectancy, function and tolerance to treatment as well as a patient’s goals for treatment and life.

Age is often based on one’s “Chronological age”, a discrete ‘age in years’ cut-off.  This definition was established during the depression era and from the constraints of Medicare.  Better definitions of age should include measures of biologic and functional status. 

From a mere snapshot in time, assumptions regarding a patient’s functional and biologic status can be made, but only a direct assessment will reveal the actual nature of this status.

Oncologists often use the ECOG performance status (PS) scale or the Karnofsky scale to assess a patient’s functional level and ability to tolerate therapy.  Geriatricians use a more age-specific and global assessment of function and general health to assess patient status and potential disease and treatment outcomes.  Geriatric oncologists use a combination of performance scales and a global direct assessment, an example of which is the Comprehensive Geriatric Assessment (CGA), to evaluate older patients with cancer. Eight domains should be included in this direct assessment: Function, comorbidities, cognition, emotion, geriatric syndromes, nutrition, pharmacy, and socioeconomic status. 

The CGA “currently provides the best estimate of individual functional {capacity and} reserve and life expectancy” (Balducci and Extermann. The Oncologist. 5:224, 2000).  The CGA can be used to estimate life expectancy, detect unsuspected, treatable conditions, increase diagnostic and prognostic accuracy, identify psychosocial needs, limit costs and hospitalization, improve quality of life, and maintain or improve function. 

FactorsTools for AssessmentOther Assessments
Functional Status*Activitites of Daily Living (ADL);
Instrumental Activities for Daily
Living (IADL);
Performance Status
Comorbidity**Charison Comorbidity Index
Cumulative Illness Rating
Scale - Geriatrics (CIRS-G_)
Socioeconomic Status

Living Conditions;
Caregiver presence
and competence;
Income;
Access to transportation

Nutritional StatusMini-Nutritional Assessment
(MNA)
Polypharmacy***

Number of medications;
Drug-drug interactions

Geriatric SyndromesGeriatric Depression Scale
(GDS);
Folstein Mini Mental Status
Delirium; Falls; Osteoporosis;
Neglect and abuse;
Failure to thrive

*In the functional assessment, Activities of Daily Living (ADL) are assessed.  ADLs are required for maintenance of basic, independent living and include bathing, toileting, dressing and feeding.  Deficits in ADLs are predictive of post-hospitalization and 2-year overall mortality.   Instrumental Activities of Daily Living (IADL) include shopping and cooking, house and money management, transportation and ability to take medication.   IADLs reflect one’s ability to function within society. Deficits in IADL are predictive of poor therapeutic tolerance, and often are harbingers of ADL deficits.

**Comorbidities include information about the number, types and severity of medical conditions.  Older patients are likely to have at least one comorbid illness. Three or more comorbidities may be predictive of increased disability, and decreased function and survival. 

***Polypharmacy is common among community-dwelling elders.  The average patient takes > 4 prescribed medications (not including OTC or CAM) which increase the risk for side effects and drug interactions (competition, binding, pH modification).  (Lichtman et al. Crit Rev Onc Hem. 46:101-114, 2003).

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Treatment Risk Assessment

Frailty

  • Confers an increased susceptibility to minor stressors
  • There is no consensus on the definition of frailty.  Two working definition are:
    • Balducci:  Age > 85 years, ADL dependence > 1, comorbid illnesses > 3, geriatric syndrome > 1.  Any one factor puts patient at increased risk for frailty and poorer outcomes
    • Fried:  Shrinking, weakness, fatigue, slowness, or change in activity level (Fried et al. J Gerontol Series. 56:M146, 2001). Any 3 factors define frailty status and 1-2 factors define vulnerability.  If frailty is noted, patients have an increased likelihood of hospitalization, dependence and morbidity and mortality.

Cancer is a VERY acute stressor which tests the limits of a system that may be in full homeostasis (fit) or in compensated (vulnerable or frail) homeostasis.  Cancer may alter the natural course of concurrent co-morbid conditions or these conditions may impact the efficacy and tolerability of cancer-related therapies 

The brief schematic below is one approach to the decision tree in elderly patients with a new (or recurrent) diagnosis of cancer. (Balducci. The Oncologist, 2000)  Fit patients are relatively well-defined.  Frail patients may or may not “appear” frail.  Definitions of vulnerability and frailty in elderly cancer patients are still in the process of being defined and validated.

Vulnerability-based Triage

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Treatment Outcomes Assessment
Traditional outcome measures for cancer include overall survival, disease-free survival, time-to-progression, etc.  In the older population, there may be a need to redefine treatment goals and outcome measures or more robustly include measures of QoL, therapeutic tolerability, symptom control and function.  (NCCN Practice Guidelines in Oncology: Senior Adult Oncology Version 1, 2004 can be found at http://www.nccn.org.)

Outcomes must be maximized while stressors are minimized.

  • Surgical: Assess physiologic status, application of less invasive techniques
  • Radiation: Limit combined therapy, application of newer techniques
  • Maintain marrow integrity: Prophylactic growth factors, consider sequential therapy
  • Avoid neurotoxicity: Limit use of neurotoxic agents especially in patients with known neurological deficits
  • Prevent cardiotoxicity: MUGA, liposomal agents
  • Maintain kidney function:  Always calculate CrCl, dose adjustment when needed, hydration
  • Minimize mucositis: Oral prophylaxis, early intervention
  • Control symptoms: Pain, nausea, fatigue

Pain control in older patients is a somewhat controversial topic.  There is concern for overmedication leading to delirium and sedation.  Many older patients present atypically: confusion, fatigue, depression, social withdrawal.  They do not report pain because pain is seen as a sign of weakness, may indicate disease progression and may distract the physician from caring for the disease itself.  Elderly fear addiction to narcotics, and its associated stigma.  Many older patients do not wish to complain or believe complaints will not be addressed.   However, pain must be adequately treated to avoid complications – “Start Low and go slow” using WHO pain pyramid.

Caregiver stress should be addressed. (Haley. Supportive Oncology. 1(S2), 2003)

Primary

– Physical care
– Symptom management
– Emotional support
– Fear and uncertainty
– Patient suffering

Secondary

– Schedule changes
– Support system
– Depression risk
– Illness risk
– Socioeconomic impact

                  

Stress should be minimized by involving a case Stress should be minimized by involving a case manager and clearly stating the treatment plan, increasing access to home services, facilitating transport, increasing communication among care team, patient and family, and decreasing clinic visits.

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Common Tumors in the Older Adult

Breast Cancer

  • Estimated 213,000 new cases & 41,000 deaths estimated for 2006
  • Median age at diagnosis: 64 years
  • 1:8 lifetime risk
  • 25% all new diagnoses made in the over-75 population; 50% if over-65
  • Increased hormone receptor positive status
  • UOQ mass most common
  • SI & SII most common
  • 53% over-80 patients receive substandard therapy
    (CE Holmes & HB Muss. CA Cancer J Clin. 53:227-44, 2003, Jemal et al. CA Cancer J Clin. 55:10-30, 2005)

Older women skew the lifetime risk ratio with 50% new breast cancer cases being diagnosed in women > 65 yrs.  Age confers the second highest relative risk (RR= 6.5) for breast cancer; family history confers the highest relative risk.  35% of invasive breast cancers are diagnosed in women > 70 yrs. 

The presence of hormone receptor positivity is higher among women > 65 yr:  83% < 65 yo, 87% > 65 yo and 91% > 85 yo.  There is also a reduction in proliferation markers and Her2/neu expression, thus, confirming a more favorable tumor biology.  Although early stage is common, 48% women with metastatic disease will be > 65 yo and very old women (> 85 yr) tend to present with unknown stage or metastatic disease (9%). 

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Prostate Cancer

  • Estimated 235,000 new cases & 27,000 deaths in 2006
  • Median age diagnosis 72 yr
  • Median age at death 78 yr
  • 13% lifetime risk; 1:103 (40-59 yr) versus 1:8 (60-79 yr) lifetime risk
  • If PCa (all stages), 80% > 5 yr, 61% > 10 yr and  49% > 15 yr survival
  • Elderly men more likely to die with then from their prostate cancer (1:34 men die from their PCa)
  • Cancer-related mortality increases with each decade but decreases with age > 85 years (1.1% < 55 yo VS. 28% 65-74 yo VS. 41% 75-84 yo VS 21% > 85 yo
  • Prostate cancer screening is highly controversial
    (D. Raghavan & E. Skinner. Sem Onc. 31(2):249-63 2004 and http://www.cancer.org)

Older age may correlate with worse disease-specific survival in both treated and non-treated patients. (A. Krongrad. J Urol. 156:1084, 1996)
Prostate cancer in older men may be related to alterations in androgen-estrogen balance, increased (time) exposure to carcinogens, or altered immune function (virus mediated).

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Lung Cancer

  • Estimated 174,000 new cases & 162,000 deaths in 2006
  • 1:13 (male) & 1:18 (female) lifetime risk
  • Median age at diagnosis:  71 years
  • ~70% cases occur in the over-65 population
  • 30% all cancer deaths due to lung cancer
  • Leading cause of cancer mortality for > 65 years & of all-cause mortality for 65-74 year olds
  • High rate of surgical morbidity & mortality
  • Present at advanced stages
  • Therapy is often palliative
  • 15% 5-year survival (all stages):  60% patients die within 1 year of their diagnosis and 75% with 2 years
    (http://www.cancer.org and Jemal et al. CA Cancer J Clin, 55:10-30, 2005)

Age > 65 years imparts a 15-fold increased incidence of lung cancer & 16.5-fold increased lung cancer-mortality when compared to < 65 years. (LAG Ries. SEER data. http://seer.cancer.gov/csr/1975_2000

Unfortunately, age is the primary determinant for withholding therapy.  According to A. Hurria and M. Kris, CA Cancer J Clin, 53:325-41, 2003, patients > 65 years receive less treatment than younger patients (12% vs. 29%). 

Surgery: There is a 65% decrease in likelihood of undergoing surgery for loco-regional control with each decade of life after 65.  Yet, surgery for SI or SII can be curative and studies have shown that older patients can tolerate lobectomy with similar complication and survival rates as younger patients.  Surgical risk must be assessed with regard to age-related changes in cardio-pulmonary function and for comorbidities.  In patients > 65 years, older age, anemia & disease stage are prognostic for survival peri- & post-surgical resection.  Consider VATS if peripheral lesion; this procedure preserves intercostal muscles, reduces pain and decreases LOS in hospital.

Radiation:  May be curative for early stage disease in non-surgical candidates but survival rates are lower than rates for surgery alone.  Radiation is relatively well tolerated, with age being a risk factor for greater weight loss (which in the elderly is predictive of poor outcome).  Excellent modality for palliation.  Concurrent chemoradiation is relatively well tolerated, but increased risk of acute toxicity vs. sequential therapy. 

Chemotherapy: Patients > 65 years are less likely to receive chemotherapy for metastatic disease (5%) vs. younger patients (19%).  Single agent therapy improves QoL and survival.

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Colon Cancer

  • Estimated 107,000 new cases & 55,000 deaths in 2006
  • Lifetime risk 1:17 (6%)
  • Probability increases with age (0.06% probability if < 40 years and 4% probability if > 70 years). 
  • 65% newly diagnosed cases are in patients > 65 years
  • Median age at diagnosis is 71 years
  • Proximal & right-sided lesions are more common
  • Late presentation associated with more advanced disease at diagnosis, and higher rates of bowel perforation, bowel obstruction and anemia
  • 5-year relative survival is 90% for early stage disease and < 10% for metastatic disease
    (Balducci. Cancer Control. 8S2, 2001; www.cancer.org)

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Non-Hodgkins Lymphoma

  • Estimated 59,000 new cases and 19,000 deaths in 2006
  • 5th most common cancer in the elderly
  • 1:46 lifetime risk
  • Peak incidence in patients > 75 yo
  • Median age at diagnosis:  66 years and at death: 74 years
  • 5-year survival rate 60%
  • Age > 60 years is a poor prognostic factor (IPI and FLIPI)
  • Typically presents as painless, enlarged lymph nodes
  • 30% older patients are incompletely staged and 23% are inadequately treated based on age alone
  • If fully staged and treated, no difference in complete remission rates between older and younger patients
  • Myelotoxicity is the primary dose- and treatment-limiting toxicity

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Summary

  • Avoid the “Unders”
  • De-emphasize the “Overs”
  • Remember: Chronological age and physiologic age may be different 
  • Treat the patient, not his age or disease
  • Individualization of treatment leads to more effective management of disease and overall improved outcomes
  • CGA is a diagnostic tool, allowing for early intervention & prevention
  • Older patients can tolerate standard-dose cancer therapies
  • Vulnerable & frail patients benefit from disease- & function-specific interventions
  • We still have a lot to learn….

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