Quality Surgical Cancer Care in Ontario

Anna Gagliardi, MSc, MLS
Program Manager
Surgical Oncology, Cancer Care Ontario,
Toronto, ON.

A. Denny DePetrillo, MD, FRCSC
Division of Gynecological Oncology,
University Health Network-Princess Margaret Hospital Site,
Toronto, ON.

A projected 134,100 new cases of cancer and 65,300 deaths from cancer will occur in Canada in 2001.¹ Forty percent of men and 35% of women will develop cancer during their lifetime and just over 25% of men and 20% of women will die of cancer. Given better and more widely used screening tests such as mammography for breast cancer and the PSA blood test for prostate cancer, more cases of cancer are being detected. Moreover, mortality from these cancers has decreased because they are being caught at an earlier, more treatable stage.

The incidence of most cancers increases with age and it is estimated that 55% of human cancer occurs in individuals 65 years of age and older. The literature on cancer treatment for the elderly is limited but it has been suggested that this demographic may be subject to underscreening, understaging, less aggressive therapy, lack of participation in clinical trials, or no treatment at all.^2,3 It has been demonstrated that older adults desire curative surgical treatment as much as younger patients, but they believe more strongly that doctors should make treatment decisions, making them more vulnerable to possible age bias.

Safety Concerns with Colon Cancer Drug

The Mayo Clinic has reported that patients taking a commonly prescribed treatment for colon cancer are dying at almost three times the rate of patients who took other medications for the same disease. The chemotherapy drug, irinotecan, has been shown to increase life expectancy by about two months for patients with advanced colorectal cancer. However, in the first two months of receiving the drug, 33 out of 1,199 patients died, among patients taking different drugs, only 10 out of 905 patients died within the same period.

The drug is manufactured by Pharmacia and marketed under the name Camptosar. Although the findings are preliminary and not statistically significant, the company has sent letters to doctors in the US advising them of the results. The finding is somewhat controversial, as this effect of the drug has not been seen previously. However, the research group at the Mayo Clinic explains that this may result from the fact that the deaths were spread out among different medical centres, and when data were pooled the effect was seen; it might not have been obvious to individual physicians. Doctors who are conducting the study will be giving the drug in lower doses and will be more aggressive about looking for warning signs of toxicity, including diarrhea, nausea, vomiting and a low white blood cell count.

The results of the study will be published in a letter in an upcoming issue of the New England Journal of Medicine.

Results of Molecular Medicine Studies Coming Fast and Furious

Oral cancer is the most common neoplasm of the head and neck and the ninth most common cancer worldwide. A simple, novel genetic test may now help with early diagnosis of this disease. The most common premalignant lesion of the oral cavity is oral leukoplakia, the presence of white patches in the mouth. Leukoplakia is recognized as an increased risk for cancer but there are no reliable clinical or histologic features that can be used to predict whether it will progress to cancer.

Researchers measured the DNA content (ploidy) of 150 patients with oral leukplakia, classified as epithelial dysplasia. What they found was that ploidy could be used to predict outcome. Patients with leukoplakia containing the normal 46 chromosomes were unlikely to progress to cancer. However, a startling 84% of patients with aneuploid lesions developed squamous cell carcinoma. The test was 97% accurate in its ability to predict that a patient would not develop cancer, and 84% accurate in its ability to predict that one would.

Unfortunately, a single molecular marker or class of markers cannot be used to predict the outcome of every case of oral leukoplakia because oral cancers develop along complex molecular pathways. Further studies are needed to support these data.

Sources

1. Sudbo J, Kildal W, Risberg B, Koppang H, Danielsen HE, Reith A. New England Journal of Medicine. 2001;344:1270-8.

Breast Cancer in the Elderly

Is there a Role for Primary and Secondary Prevention Strategies?

Ruth E Heisey, MD, CCFP, FCFP
Assistant Professor,
University of Toronto,
Family physician and Clinical Associate,
Department of Surgical Oncology,
Sunnybrook and Women's Health Science Centre, and
Princess Margaret Hospital Site,
University Health Network,
Toronto, ON.

H Lavina A Lickley, MD, PhD, FRCSC, FACS
Professor of Surgery and Physiology,
University of Toronto,
Surgeon (special interest in Breast Disease),
Women's College Campus of Sunnybrook and Women's College Health Science Centre,
Toronto, ON.

"Old age is like everything else. To make a success of it, you've got to start young."¹ Fred Astaire

Breast cancer is the most common cause of cancer death in women over the age of 65.² Between the ages of 30 and 80 years, the annual incidence of breast cancer rises from 1:5900 to 1:290.^3,4 It has been estimated that by the year 2030, almost two-thirds of women with a diagnosis of breast cancer will be 65 years of age or older.⁵

The incidence of breast cancer among Canadian women has been rising steadily over the past decade, probably due in part to improved detection with mammographic examinations.

Hepatocellular Carcinoma in the Elderly

Morris Sherman, MB BCh, PhD, FRCP(C)
University of Toronto and,
University Health Network,
Toronto, ON.

Introduction
Although hepatocellular carcinoma (HCC) is not a common cancer in North America, it is the fifth most common cancer in the world.¹ Age standardized incidence rates vary from three per 100,000 in North American men to 80 per 100,000 in China.^1,2 HCC affects people of all ages. However, as with many cancers, the incidence of this disease increases with age, so that the peak incidence is at about age 67-70, (M Sherman, submitted) regardless of the underlying etiology. In Canada, the incidence of HCC is largely driven by three chronic liver diseases: chronic hepatitis B, chronic hepatitis C and alcoholic cirrhosis. In Toronto, hepatitis B is the single most common cause of HCC, accounting for nearly half of all cases, while elsewhere in Ontario hepatitis C and alcohol are the major causes. (M Sherman, submitted)

Prognosis
HCC causes substantial morbidity and mortality. In the absence of early detection programs, most HCC present late, with advanced incurable disease. The reported survival rates for untreated symptomatic HCC varies from 0% at four months to 1% at two years.^3-5 The prognosis for small, untreated HCC--lesions that are the target of surveillance--is not well described. However, two-year survival in excess of 50% is not unusual.

Damaged DNA and Cellular Apoptosis: The Story on Bladder Cancer in the Elderly

D'Arcy Little, MD, CCFP
Director of Medical Education,
York Community Services,
Toronto, ON

Munir A. Jamal, MD, FRCSC
Staff Urologist,
Credit Valley Hospital,
Mississauga, ON

Introduction

Epidemiology:
Cancer of the urinary bladder is essentially a disease of the elderly. The median age at diagnosis is 69 years for males and 71 years for females, and more than one-third of cases occur in patients over the age of 75 years of age.^1,2 The incidence of transitional cell carcinoma (TCC) of the bladder, the most common subtype of bladder cancer, accounting for over 90% of cases, is rising and currently ranks as the fourth highest new cancer diagnosis in men.³ However, the mortality rate of this disease has fallen over the last two decades.¹ The following review article will address the epidemiology, natural history, clinical presentation, and treatment of this disease, with an emphasis on issues pertaining to elderly patients. (See Figure 1)

Bladder cancer is unique among human neoplasms in that it has been associated with several distinct etiological factors.⁴ Risk factors related to the development of TCC, in addition to age, include tobacco smoking and occupational exposures in the dye, rubber, textile, and leather industries.

Cancer, Old Age, and the Meaning of Life

Shabbir M.H. Alibhai, MD, MSc, FRCPC
Senior Editor,
Geriatrics & Aging

Recently I saw a 72-year-old woman with metastatic uterine cancer in consultation. She was receiving palliative chemotherapy and our team felt she would benefit from short-term inpatient rehabilitation. Within a week of this consult, I saw an 81-year-old woman with an acute myocardial infarction. My team elected to start her on lipid-lowering therapy.

What do these two patients have to do with one another, and what does the latter patient have to do with this issue's theme of cancer? It is, simply put, a matter of life and death.

Let me explain. Many readers know that I do research in prostate cancer. In my editorial in last year's cancer issue,¹ I discussed the importance of assessing the impact of treatment on both length and quality of remaining life. Whenever clinicians make treatment decisions, we explicitly or (more commonly) implicitly consider life expectancy. For both patients that I alluded to, estimating life expectancy was fundamental to the management decision.

Several randomized trials have demonstrated improvement in survival for certain malignancies, including some gynaecologic tumours, from "palliative" (i.e. non-curative) chemotherapy. The question that clinicians and patients must struggle with is whether the expected improvement in survival (for example, two to six months) is clinically important and worth the risks of treatment. Lipid-lowering therapy has been shown in numerous large, well-designed, randomized trials to prolong survival in patients with normal or elevated lipid levels after a myocardial infarction. However, most studies suggest a survival benefit is observable after 12-18 months of therapy. Conversely, lipid-lowering therapy is generally not useful if patients have a life expectancy of less than 12 months. We estimated that our 81-year-old patient would likely survive at least a year after her infarct and thus started her on a statin.

While most of this sounds straightforward, there is a potentially flawed underlying premise--namely, that physicians can accurately estimate life expectancy. How does one do this in theory? Life expectancy can be calculated by taking age-specific annual mortality risks and modifying them by factoring in risks of dying from specific illnesses from which the patient is suffering. For example, my 81-year-old woman post infarct has an average one year risk of 9.4% of dying because of her age. This number is obtained from actuarial life tables.² Depending on her cardiac status post infarct (left ventricular function, presence of heart failure, deficits on cardiac perfusion study), she might have a 20% risk of dying from her coronary artery disease. Thus her overall risk of dying would be some combination of these two risks, assuming she is otherwise well.

So how good are we at estimating life expectancy? It is interesting to note that there are very few published studies on this subject. Yet in prostate cancer, for example, clinicians are encouraged to explicitly consider life expectancy when making treatment decisions--the so-called ten-year rule.³ This rule suggests that if patients have ten or more years of life left, excluding their prostate cancer, then curative therapy is indicated, and vice versa. There may be similar rules in other areas of cancer. Beyond these guidelines, there is little published data to guide physicians when estimating remaining life.

Two studies from the field of palliative care are provocative. The more recent one, published last year,⁴ asked a group of palliative care doctors in Chicago to estimate remaining life expectancy for 504 patients newly admitted to a hospice program. Patients were followed until they died. Patients were relatively old (mean age 69) and had advanced disease (median survival 24 days). If accuracy was defined as being within 0.5 and 2.0 times the actual survival, physicians were accurate 34% of the time, optimistic 55% of the time, and pessimistic 11% of the time. Even when we consider fairly terminal patients, physicians do not perform as well as expected.

This does not mean we should forget about estimating life expectancy. Rather, it behooves us to perform more research in this area to identify better models for predicting survival. Furthermore, we must realize that disease severity and comorbid illnesses are far more powerful predictors of life expectancy than is chronological age. Until we are far better at estimating survival, guidelines like the ten-year rule in prostate cancer do little service to ourselves and our patients.

Regular readers will realize that this is the third year we are featuring the theme of cancer in Geriatrics & Aging. Much new information continues to be published about cancer screening, diagnosis, treatment, and prognosis in the elderly. In this issue, we have chosen to focus on acute myelogenous leukemia, bladder cancer, multiple myeloma, and gastro-esophageal malignancies. As always, we hope you enjoy it.

References

1. Alibhai SMH. Oncology & Aging--Bitter Truths and Misguided Paternalism. Geriatrics & Aging 2000; 3(3):3.
2. Statistics Canada. Life tables, Canada and provinces. Health Reports 1990; 2 (4(Suppl.13)):17.
3. Walsh PA, Partin AW, Epstein JI. Cancer control and quality of life following anatomical radical retropubic prostatectomy: results at 10 years. J Urol 1994; 152:1831-1836.
4. Christakis NA, Lamont EB. Extent and determinants of error in doctors' prognoses in terminally ill patients: prospective cohort study. BMJ 2000; 320:469-473.

Response to Therapy in Acute Myeloblastic Leukemia Dependent on Genetic Make-up of Leukemic Cells

M.D. Minden, M.D., Ph.D., FRCPC
Princess Margaret Hospital
University Health Network
Toronto, ON

Introduction
Leukemias are malignancies of the blood and bone marrow and are classified as either acute or chronic malignancies of the myeloid--red blood cell, granulocyte, platelet lineage--or lymphoid--T or B lymphocyte. In this article we will focus on acute myeloblastic leukemias (AML) and recent advances in their classification and therapy.

In the United States, approximately 10,100 cases of AML are diagnosed each year and the yearly mortality rate from this disease is approximately 6,900 individuals. The incidence of AML is low in children (<1/100,000) and increases with age, such that by the time a person reaches the age of 80 the incidence is approximately 15/100,000 (Figure 1).¹ Over 60% of patients are 55 years of age or older, making this a significant problem in the aging population.

AML develops as the result of genetic changes in hematopoietic stem cells of the bone marrow.² These changes block the ability of the cell to undergo normal differentiation resulting in a blast-like morphology. In some cases, the patient may have large numbers of circulating leukemic blast cells compromising blood flow to vital organs.

Let’s Give Older Women a Chance to Beat Breast Cancer

Marilyn Schneider, Ph.D.
Executive Director,
Canadian Breast Cancer Research Initiative

Breast cancer is, in large part, a disease of aging in women. It is a disease of genes gone awry. Although a small proportion of women are born with an inherited mutant BRCA1 or BRCA2 gene that immediately puts them at very high risk for breast cancer, these inherited mutations account for only 5-10% of breast cancer cases. In most breast cancers, the woman accumulates sporadic gene mutations throughout her lifetime, and when appropriate combinations of these mutations accumulate in the woman's breast cell, she has the beginning of a breast cancer tumour.

One out of every 9.5 Canadian women is now expected to develop breast cancer sometime in her lifetime. This, however, is the lifetime risk, and this risk is known to increase with age. What is more relevant to an older woman is the probability that she will develop breast cancer over the next decade. A 60-year-old woman's probability of getting breast cancer before age 70 is 2.9% or 1 in 34; a 70-year-old woman's probability is 3.2% or 1 in 31.¹ Breast cancer is primarily a disease of older women, with only 22% of breast cancer cases occurring in women under age 50, 45% occurring in women aged 50-69, and 32% occurring in women aged 70 and over.²

On the one hand, the incidence of breast cancer has risen slowly but steadily over the past three decades, particularly for those women aged 50-69 and over the age of 70.

Radiation Therapy for the Treatment of Esophageal and Gastric Cancers in the Elderly

Jolie Ringash, MD, MSc
Department of Radiation Oncology,
Princess Margaret Hospital
University Health Network,
Toronto, ON

Background
Esophageal and gastric carcinomas are primarily diseases of older persons. Of 498 new cases of esophageal cancer in Ontario in 1997, 237 (48%) occurred in individuals aged 65 to 79, and 101 (20%) in those over the age of 80. The corresponding numbers for gastric cancer are (of a total of 1,032 cases) 492 (48%) for those aged 65 to 79, and 200 (19%) for those over 80.¹ For all age groups, gastric cancer is decreasing in incidence, with only 2, 800 cases in Canada in the year 2000. In contrast, the incidence of esophageal cancers is gradually increasing (1,350 cases in 2000).^2,3 Adenocarcinoma, primarily of the distal esophagus, has replaced squamous cell carcinoma as the most frequent histology. Tumours of the gastroesophageal junction pose a particular challenge, since management may differ depending on whether the tumour is felt to originate in esophagus or stomach.

Canadian oncologists frequently face difficult treatment decisions in the elderly. Unfortunately, since older patients are usually excluded from clinical trials, evidence for their tolerance of, and response to, therapeutic radiation is limited. Existing reports are limited to retrospective reviews and subgroup analyses, many of which originate in Japan.