Epidemiological studies have provided valuable information on the incidence of prostate cancer and its impact on men’s lives. We now have an abundance of facts at our disposal about the economic costs of this disease in Canada. Thanks to ongoing research, we also know more about how certain factors affect the risk of developing prostate cancer, as well as about the effects of treatment on quality of life. This article summarizes findings published in a recent review article (Fradet Y, Klotz L, Trachtenberg J, Zlotta A. Can Urol Assoc J 2009; 3[3Suppl2]: S102-S108), and attempts to put these factors together to get a better view of our understanding of this disease. Questions emerge such as: How can our knowledge of risk factors and treatment side effects help reduce the toll on men’s lives and our healthcare system? What are the gaps in our knowledge?
Incidence and mortality rates
The incidence of prostate cancer in Canada has followed a course of highs and lows over the past 30 years. The rates increased steadily between 1979 and 1990, rose rapidly from 1990 to 1993, declined sharply from 1993 to 1995, and have increased moderately since 1996. The rate peaked in 1993, and again in 2001, due largely to two distinct factors: an increase in early detection with the introduction of PSA testing in 1993; and the diagnosis in 2001 of Allan Rock (then Minister of Health), which helped to raise awareness.
For 2008, the Canadian Cancer Society (CCS) estimated 24,700 new cases of prostate cancer. It is the most common non-skin cancer among Canadian men, representing 26% of all new male cancer cases. One in seven men will develop the disease, and 1 in 27 will die from it.
Luckily, mortality rates due to prostate cancer haven’t followed the same upward trend. While they rose between 1977 and 1993, with a peak in 1991 at 31.2 deaths for 100,000 men, they decreased significantly from 1993 to 1999, and have declined steadily since. CCS estimated 23.6 deaths in 100,000 men for 2008 (i.e. a 24.3% mortality decline since 1991), despite a significant increase in men’s life expectancy during the same period. Although this is great progress, likely because of earlier diagnosis and treatment, the downside is that the increased detection may include men whose prostate cancer might not actually be life-threatening.
Risk factors
Our knowledge of factors that can affect the risk of cancer developing or progressing has also increased. Some are obviously unavoidable, while others may be preventable.
- Age: The incidence of prostate cancer rises sharply in men over 50, faster than for any other major cancer. Between ages 50 and 54, 100 out of 100,000 men are diagnosed; from 60 to 64, the ratio is 500/100,000; and over 80 years, the rate is more than 700/100,000.
- Family history: Several studies have shown that men whose brothers or father had prostate cancer are at higher risk (see box, below), and they are usually diagnosed six or seven years earlier than men with no family history. Over 40% of cases diagnosed in men under age 55 may be due to heredity. Environmental factors may also be important in families with hereditary prostate cancer.
- Genetics: About 5% to 10% of prostate cancer cases, and as much as 30% to 40% of early-onset disease, may be caused by genetic mutations that are passed down. No one gene has been definitively singled out as the cause, although some genes or gene mutations have been shown to be more common in men with the disease. Men with BRCA gene mutations (most commonly associated with hereditary breast and ovarian cancer) may have an increased risk of prostate cancer.
- Race: African-American men have the highest incidence of prostate cancer, followed by Whites, Hispanics, Asian/Pacific Islanders, and American Indian/Alaskan Natives. African-American men are more likely to be diagnosed at a more advanced stage and twice as likely to die from the disease (59.4 deaths per 100,000 for blacks versus 24.6 per 100,000 for whites). Higher intake of dietary fat, poorer access to healthcare and other socioeconomic factors may all contribute to their risk, but still don’t explain the higher incidence rate.
- Diet and micronutrients: Many studies show that men who consume a high-fat diet (e.g. red meat, dairy products) have a greater risk of developing prostate cancer or of having their cancer progress. Obesity has been associated with increased risk of aggressiveness and mortality. While some micronutrients such as isoflavones (soy), green tea and lycopene (e.g. found in tomatoes) may reduce the risk, recent results from the SELECT trial have concluded that vitamin E and selenium (taken together or alone for a period of five years) do not prevent prostate cancer.
- Hormonal and sexual factors: High testosterone levels, having a vasectomy and frequent sexual activity have not been found to increase the risk of prostate cancer.
- Smoking: While smoking may not increase the actual risk of prostate cancer, it may stimulate tumour growth and thus heighten the risk of death related to the disease.
- Environmental: Exposure to some pesticides (e.g. methyl bromide) and herbicides has been linked to increased rates of prostate cancer.
Treatment, side effects and quality of life
As with other types of cancer, prostate cancer is associated with considerable anxiety, sometimes severe enough to warrant psychological therapy. Distress may heighten as the disease progresses or with more aggressive treatment, but often decreases after treatment. Patients who have problems communicating with their families and physicians are more at risk, and higher anxiety is reported in men under 65. Men treated with surgery report less depression and fatigue than those who had radiation.
The effect on health-related quality of life also varies depending on the treatment chosen. According to recent studies of men with localized prostate cancer:
- Urinary control and sexual function were better after external beam radiation therapy (EBRT) compared to surgery and brachytherapy.
- Both types of radiation (EBRT and brachytherapy) caused more bowel dysfunction.
- Obstructive and irritative symptoms were more common with brachytherapy.
- Overall symptoms and health scores were worse for men in the first year after brachytherapy compared to surgery, but improved in all years of follow-up.
Stress after diagnosis may also trigger cardiovascular (CV) events. A 2008 study found that men had a 50% higher risk of fatal CV events and a 30% increased risk of nonfatal events in the year after diagnosis, especially younger men and those without previous heart risk factors. In light of these findings, recommendations have been made that doctors try to find out which patients are at risk of high levels of anxiety and depression after diagnosis, and offer interventions and support for treatment decision-related distress and ongoing difficulties. Distress may also change PSA levels, which could influence treatment choices.
So what treatment strategy is best? A Swedish study of men (mostly unscreened) showed that radical prostatectomy was superior to no treatment in reducing prostate cancer-related mortality, especially among patients under age 65. The addition of radiotherapy to hormonal therapy for high-risk men has also shown a survival advantage, compared to hormonal therapy alone.
Despite the obvious benefits, existing treatments have side effects that can affect men’s quality of life. How do men perceive the role of these side effects? One study reported that 42% of patients defined effective treatment as one that extended survival or delayed progression, while 45% equated effectiveness with maintaining quality of life. Despite men’s concern with side effects, some studies indicate that these factors may not influence their treatment decisions. Incontinence seems to have the most impact, with impotence reported less often as a deciding factor. Patient materials on early prostate cancer may not always contain enough comprehensive information on side effects and their potential consequences on quality of life. Increasingly, it is felt that patients’ individual preference along with consideration of the possible side effects or complications of treatment should be the most important factor in determining the best strategy.
Screening
Preliminary findings from two large clinical trials (the Prostate, Lung, Colorectal and Ovarian [PLCO] Cancer Screening Trial and the European Randomized Study of Screening for Prostate Cancer [ERSPC]) were conflicting on the effectiveness of screening in reducing the number of deaths in men at average risk. While the ERSPC reported a 20% reduction in the risk of death for men who underwent PSA screening (a reduction of about seven deaths per 10,000 men screened), the researchers warned that population-based screening programs should take into account important factors such as overdiagnosis, overtreatment, quality of life, cost and cost-effectiveness.
Interestingly, biopsy might be a factor in higher mortality. Although this isn’t yet proven, one recent study showed a higher mortality rate in men who had a biopsy compared to those who didn’t. Further, the risk of death at 120 days after biopsy increases with age.
Into the future
The financial costs of prostate cancer are substantial and have increased because of PSA testing. A study in 2000 estimated the total costs in a group of almost six million Canadian men between ages 40 and 80. According to projections, about 12% of these men would develop prostate cancer over their lifetimes, and the direct medical costs of treating them would be almost $10 billion. It will be important to define which treatment is most effective in reducing the illness and mortality associated with this disease.
In addition, an effective prevention strategy would be of great value to individuals and could substantially reduce overall costs. Research is looking into the cost-effectiveness of chemoprevention in men at high risk with such agents as finasteride. A better understanding of the relationship between genetic and environmental factors would allow for new treatment strategies to decrease progression.
While it is appealing to think that early detection will lead to earlier and more effective treatments, more studies are needed to confirm this and to help clarify the role of PSA screening on prostate cancer mortality.
Dr. Yves Fradet is Professor of Surgery/Urology and Chair of the Department of Surgery at Laval University in Québec. He is Senior Vice President and Chief Scientific Officer of Diagnocure Inc, a leading developer of molecular tests for cancer detection and management.
