• E-mail
• Print
• Comment
• Font Size
• Digg
• del.icio.us
• Discuss article

Abandoning Isolated Free PSA Screenings for More Comprehensive Cardiovascular and Cancer Screening and Education

Posted on: Sunday, 24 April 2005, 03:00 CDT

The time is ripe to abandon free PSA screenings and replace them with free comprehensive health screenings. For example, cardiovascular disease (CVD) risk screening (cholesterol, blood pressure) that could also include PSA, weight measurement, and a variety of other tests and educational assessments just make more sense in terms of the larger picture of influencing all-cause morbidity and mortality. Numerous reasons are proffered for this important change. Abandoning this myopic single-disease only approach must be embraced by numerous medical centers and health professionals before this comprehensive approach can be successfully implemented.

Recently the media was replete with stories indicating that cancer has now surpassed heart disease as the leading cause of death in Americans (Twombly, 2005). This was an interesting new finding, but it was not entirely accurate. In 2002, the latest year for which mortality data are available, cancer was responsible for 478,082 deaths and heart disease was responsible for 446,727 deaths in individuals younger than the age of 85. Therefore, cancer is now the number 1 killer for Americans younger than 85 years of age. If this age consideration was not categorized in this manner than heart disease is still the number 1 killer of Americans. In 2002, 696,947 individuals in the United States died of heart disease versus 557,271 deaths from cancer. Heart disease is the primary cause of mortality in those aged 85 and older. In fact, in this older age group, heart disease was responsible for three times more deaths (greater than 250,000) compared to cancer (approximately 80,000 deaths) in 2002. In addition, if one actually compares cardiovascular disease or CVD (heart disease and diseases of the blood vessels, including strokes) to cancer there is very little competition. CVD apparently is responsible for 38% of all deaths and is responsible for more deaths than the next five leading causes of death combined.

Death rates from all cancers combined have been slowly declining over the past decade (1.5% per year since 1993 for men and 0.8% per year for women since 1992). However, since the mid-1970s, the death rate from heart disease has been falling for a greater period of time. Therefore, even in 1999, cancer deaths outnumbered heart disease deaths in individuals younger than age 85. Even in individuals over the age of 85, heart disease deaths have declined compared to cancer. The notable improvements in mortality rates for both prominent diseases apparently were partially due to a decrease in smoking rates in the United States. For example, in women, lung cancer deaths have stabilized after increasing for several decades, and death rates from breast and colorectal cancer have decreased. In men, the death rate has also continued to fall for the three most prevalent cancers (colorectal, lung, and prostate).

Regardless, when it comes to urology it is time to set a new example or paradigm. Diseases are not necessarily in competition when it comes to patients, because there is a need to share the same goal, and that is to improve the overall health of our patients. How can this goal be achieved? One simple argument is to place the risk of disease and death in its proper perspective, and that is why the time for encouraging CVD screening and education at the same time prostate-specific antigen (PSA) screening is encouraged could have a dramatic impact on the lives of our patients.

What Is the Primary Cause of Death in Men in the U.S. and All Other Industrialized Countries?

CVD has been the number one cause of mortality in men and women every year in the United States since 1900, except for the year 1918 which was the year of the great influenza epidemic (Bonow, 2002). CVD has also been the primary cause of death in other industrialized countries, and is also the primary cause of death worldwide (Bonow, 2002; Michaud, Murray, & Bloom, 2001). Past research has shown that if all forms of primary CVD were removed, there would be a life expectancy increase of approximately 7 years. CVD has often been perceived to be a condition unique to older individuals, but individuals below the age of 65 years actually account for approximately 50% of the total diagnosed CVD annually, and account for 15% of CVD mortality. Again, this observation does not intend to belittle the impact of cancer, but just serves to place the numbers and risk in their appropriate perspective. Indeed cancer may soon become the number one cause of death around the world, but this should not change the overall goal for our patients. Ideally, decreasing the number one or number two causes of death and even further decreasing the risk of dying young from all causes should represent the best approach for our patients, regardless of the discipline that occupies our time. Therefore, encouraging our patients to understand their CVD risk (cholesterol number) as well as they seem to understand their PSA levels should be of primary importance.

What Has Been the Primary Cause of Death in the Largest U.S. and Worldwide Drug Cancer Prevention Clinical Trials?

The P-1 breast cancer prevention trial that utilized tamoxifen was a landmark study because it represented the first drug ever approved by the U.S. Food and Drug Administration for the prevention of any specific cancer (Fisher et al., 1998). Individuals in this trial generally had a higher risk of being diagnosed with breast cancer, but despite this drug reducing the risk of breast cancer by 50%, few individuals and media outlets seemed to realize that CVD was the primary cause of death in the drug and placebo arms of the trial.

This was somewhat similar to the results of the Prostate Cancer Prevention Trial (PCPT), which was the first study in the history of medicine to demonstrate a reduced risk of prostate cancer in men who were randomized to a single drug - 5 mg of finasteride daily (Thompson et al., 2003). Media sources accurately reported that this drug reduced the risk of prostate cancer by 25%; however, another critical finding seemed to be bypassed because primary causes of mortality were not reported in the initial publication. Out of 1,123 deaths that occurred in the PCPT over 7 years, CVD was one of the primary causes of death and prostate cancer only accounted for less than 1% of the overall mortality.

Again, these findings do not serve to reduce the impact of breast or prostate cancer, but should emphasize to health professionals and patients that even in cancer prevention drug trials a primary cause of mortality has been CVD. Thus, any future prevention drug trial in cancer should also emphasize the potential impact of CVD in individuals attempting to reduce their cancer risk.

What Has Been the Primary Cause of Death in the Largest Diet or Dietary Supplement Trials for the Potential Prevention of Cancer?

It can be argued quite effectively that the two most promising dietary supplements from randomized trials that may reduce the risk of prostate cancer are vitamin E and selenium (Moyad, 2000). The U.S. National Cancer Institute will be allocating approximately $150 to $200 million on the 7 to 12-year Selenium and Vitamin E Chemoprevention Trial (SELECT) of over 32,000 men to determine if either agent can reduce the incidence of prostate cancer. However, the largest completed vitamin E supplement randomized trial (ATBC or Alpha-Tocopherol Beta-Carotene Study) that demonstrated a potential reduction in the risk of prostate cancer, also found that the primary cause of death was actually from ischemic heart disease, and the risk for hemorrhagic stroke was increased by 50% in the men taking just 50 mg/day of vitamin E supplements (ATBC Study Group, 2003; Heinonen et al., 1998). In addition, the only randomized trial of selenium supplements compared with placebo in the United States for high-cancer risk patients also found that the primary cause of mortality of women and men in this trial was actually from CVD (Clark et al., 1996).

Therefore, what is remarkable is that it appears that the two dietary supplement trials that provided the main impetus to conduct the SELECT study actually demonstrated that individuals have a higher risk of dying from CVD compared to cancer, but it was the cancer-only impact that has garnered the most attention. What should be as concerning is the finding that vitamin E and selenium had little to no impact on CVD. What is the goal in our aging patients? Is it to affect one disease or all-cause mortality? Is it to just shift the burden of disease to another area of medicine? SELECT will be a powerful and important study regardless of the results, but it seems that a potential missed opportunity will occur if individuals in these trials and the public are not informed or educated on the importance of CVD risk reduction as well as the potential for prostate cancer risk reduction.

Does Any Clinical Research Exist That Suggests That Some of the Mechanisms That Increase the Risk of CVD Simultaneously Increase the Risk of Prostate Cancer?

Preliminary research on the mutation in the macrophage scavenger receptor-1 gene found that a significant early risk for prostate cancer increased the risk of CVD (Senior, 2002). Recent research continues to suggest that this interesting potential relationship may actually exist for other men with and without this \mutation. A soon to be published large prospective study included 862 patients (mean age 64 to 66 years) screened at several urologic centers in Austria and found that in group 1 (n=291), that consisted of men with a histologically documented prostate cancer, there was a statistically significant (p=0.00001) elevated cholesterol to high- density lipoprotein (HDL) ratio compared to other men without prostate cancer in this study (Sonnleithner et al., 2003). These researchers postulated that higher cholesterol levels along with lower levels of HDL could be a risk factor for prostate cancer. It is also of some notable interest that one of the largest retrospective studies of statin drug use was associated with an over 60% reduction in the risk of prostate cancer (Graaf, Beiderbeck, Egberts, Richel, & Guchelaar, 2004). Additionally, many of the lifestyle risk factors that appear to increase the risk of prostate cancer also increase the risk of CVD and can simultaneously raise cholesterol levels (Moyad & Carroll, 2004). Conversely, those lifestyle changes associated with a reduction of prostate cancer are similar to the lifestyle changes that lower the risk of CVD and reduce cholesterol levels. Therefore, why not encourage more CVD risk screening and education in men who volunteer for PSA screening? This is not a competition because everyone wins when the situation is approached in this unique manner.

What Is the Primary or Secondary Cause of Death in Men Diagnosed or Treated For Prostate Cancer?

Preliminary research of men diagnosed with prostate cancer demonstrates that the primary or at least secondary cause of death in these patients is actually CVD (Moyad, 2002; Newschaffer, Otani, McDonald, & Penberthy, 2000). This observation seems logical because of the overall impact of CVD on the general population. Thus, this should serve as another important reminder that at a prostate cancer screening or post-diagnosis or post-prostate treatment, the potential to provide comprehensive health advice and suggest CVD screening should be paramount.

Can Blood Cholesterol Levels Accurately Predict Long-Term Risk for Coronary Heart Disease, CVD, and All-Cause Mortality in Men?

Pooled or combined results of three large prospective studies with a long mean followup duration of 16 to 34 years has demonstrated a continuous, graded correlation of serum cholesterol level to the long-term risk for coronary heart disease, CVD, all- cause mortality, and a greater predicted life expectancy for younger men with lower cholesterol numbers (Stamler et al., 2000). It is of interest that men had no previous history of diabetes or myocardial infarction in these studies. These findings and numerous other investigations have resulted in the recommendation of cholesterol screening in adults 20 or more years of age at least once every 5 years (Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, 2001). CVD deaths were greater than the total deaths from cancer in all three cohorts, but there was no statistically significant relationship of baseline cholesterol levels to total cancer mortality (p>0.10) (Stamler et al., 2000). However, there was a significant relationship of cholesterol level with all-cause mortality, and prostate cancer incidence and deaths were not documented in this pooled analysis. Regardless, educating patients on the importance of CVD risk and cholesterol may have the most significant impact on our patients' risk of all-cause mortality.

Conclusion

Preliminary research from the University of Michigan and the National Prostate Cancer Coalition (NPCC) have found a high prevalence of dyslipidemia or an increased risk of general CVD in men attending free PSA screenings in several large metropolitan areas and some rural sites. Therefore, offering a lipid or other CVD risk evaluation for men and women attending general cancer screenings may identify and better educate this silent at-risk group. In fact, a cancer screening that includes a comprehensive risk assessment just makes sense when looking at the big picture of what may truly influence all-cause mortality. A review or summary of the important points that are discussed in this manuscript are provided in Table 1 (page 140).

What is the point of offering only free PSA screening without more comprehensive evaluation and education? The time is ripe to abandon free PSA screening for this more logical approach of PSA screening in combination with CVD risk assessment. Health professionals in urology have a unique opportunity to help our patients in a manner that has never before been witnessed in the post-PSA era. A universal agreement that comprehensive screening makes the most sense when attempting to improve the quality and quantity of life for our patients is the first step needed before this can be implemented at most U.S. medical centers. Yes, the time is now. Are you ready to take this first step with me?

Table 1.

A Partial List of Reasons for Abandoning Isolated Free PSA Screenings for a More Comprehensive Combined Evaluation of CVD Risk and PSA

References

ATBC Study Group, The. (2003). Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: A postintervention follow-up. Journal of the American Medical Association, 290, 476- 485.

Bonow, R.O. (2002). Primary prevention of cardiovascular disease: A call to action. Circulation, 106, 3140-3141.

Clark, L.C., Combs, G.F., Jr., Turnbull, B.W., Slate, E.H., Chalker, D.K., Chow, J., et al. (1996). Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. Journal of the American Medical Association, 276, 1957-1963.

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. (2001). Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). Journal of the American Medical Association, 285, 2486-2497.

Fisher, B., Costantino, J.P., Wickerham, D.L., Redmond, C.K., Kavanah. M., Cronin, W.M., et al. (1998). Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. Journal of the National Cancer Institute, 90, 1371-1388.

Graaf, M.R., Beiderbeck, A.B., Egberts, A.C., Richel, D.J., & Guchelaar, HJ. (2004). The risk of cancer in users of statins. Journal of Clinical Oncology, 22, 2388-2394.

Heinonen, O.P., Albanes, D., Virtamo, J., Taylor, P.R., Huttunen, J.K., Hartman, A.M., et al. (1998). Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: Incidence and mortality in a controlled trial. Journal of the National Cancer Institute. 90(6), 440-446.

Michaud, C.M., Murray, C.J.L., & Bloom, B.R. (2001). Burden of disease: implications for future research. Journal of the American Medical Association. 285, 535-539.

Moyad, M.A. (2000). TAe ABCs of nutrition and supplements for prostate cancer. Ann Arbor: JW Edwards Publishing.

Moyad, M.A. (2002). Selenium and vitamin E supplements for prostate cancer: evidence or embellishment? Urology, 59(Suppl. 4A), 9-19.

Moyad, M.A., & Carroll, P.R. (2004). Lifestyle recommendations to prevent prostate cancer. Part I: Time to redirect our attention? Urologic Clinics of North America, 31(2), 289-300.

Newschaffer, C.J., Otani, K., McDonald, M.K., & Penberthy, L.T. (2000). Causes of death in elderly prostate cancer patients and in a comparison non-prostate cancer cohort. Journal of the National Cancer Institute. 92, 613-621.

Senior, K. (2002). Atherosclerosis gene increases susceptibility to prostate cancer. Lancet, 360, 928.

Sonnleithner, M., Jeschke, K., Bayer, L., et al. (2003). Dyslipoproteinernia as a risk factor in prostate cancer (abstract). Journal of Urology, 169, 76.

Stamler, J., Daviglus, M.L., Garside, D.B., Dyer, A.R., Greenland, P., & Neaton, J.D. (2000). Relationship of baseline serum cholesterol levels in 3 large cohorts of younger men to long-term coronary, cardiovascular, and allcause mortality. Journal of the American Medical Association, 284, 311-318.

Thompson, I.M., Goodmaan. P.J., Tangen, C.M., Lucia, M.S., Miller, G.J., Ford, L.G., et al. (2003). The influence of finasteride on the development of prostate cancer. New England Journal of Medicine, 349, 215- 224.

Twombly, R. (2005). Cancer surpasses heart disease as leading cause of death for all but the very elderly. Journal of the National Cancer Institute, 97(5), 330-331.

Mark A. Moyad, MD, MPH, is the Phil F. Jenkins Director of Complementary/Preventive Medicine, University of Michigan Medical Center, Department of Urology, Ann Arbor, MI.

Copyright Anthony J. Jannetti, Inc. Apr 2005

Source: Urologic Nursing

More News in this Category