Some Basic Facts on Prostate Cancer
(Testing and Nutrition)
Reprinted from PCRI Insights May 2001 vol. 4, no. 2

Prostate Cancer (PC) is the most common male malignancy in the Western world. In the U.S. there are approximately 180,000 new diagnoses annually. Each year, 40,000 men with established disease die from PC. This is the bad news.

The good news is that we can dramatically reduce the number of deaths from prostate cancer in three ways: 1) Prevention, 2) Earlier diagnosis, and 3) Appropriate treatment. Since you are primarily responsible for your own health (or care about the health of a loved one) it is important that you become knowledgeable in all three areas. This article is intended to give you the most current information on prevention and early diagnosis. Every man has the ability to influence both prevention and early detection. For additional information on appropriate treatments, please refer to the Papers section of the PCRI website: www.pcri.org.

The Basics of Prevention

Caloric Intake

We believe that diet should be regarded as having serious biochemical relevance to the health of the individual. We are, for the most part, what we eat (or at least what we assimilate). Western societies, especially the U.S., are consumers of excessive calories, and caloric restriction has been shown to be an important factor in augmenting the immune system and improving longevity. More specifically, scientific literature shows PC and its development is significantly linked with caloric intake (also known as energy intake).¹

Therefore, the PCRI recommends that you restrict your total caloric intake to 500 calories per meal and snacks to 100 calories per snack. (Your intake level should be adjusted for your level of activity and body mass.) If everyone were to do this, we would eliminate most cases of diabetes, hypertension, hypercholesterolemia, stroke, heart disease and a significant amount of cancer in the world today.

Types of Food

Dietary fat is significant. There are studies that show that dietary fat accelerates tumor growth rates of PC in an animal model of human PC.^2,3 Moreover, an excess of dietary fat is linked to excessive calorie consumption, since fat contains twice as many calories, gram for gram, as protein or carbohydrate. Another dietary risk factor is related to over-consumption of carbohydrates. Carbohydrate excess leads to hyperinsulinemia (excess insulin in the blood) with increased production of arachidonic acid production and its metabolites. These metabolites, Prostaglandin E-2, 5-Hete and 12-Hete Lipoxygenases, are stimulants of prostate cancer growth.^4,5 (See the July 99 Insights issue re: the eicosanoid pathways on pages 11-12.)

Therefore, the PCRI recommends that you (1) reduce or eliminate red meat, dairy fats, saturated fat, cooking oil and egg yolk (a rich source of arachidonic acid) and (2) avoid excessive carbohydrates by restricting your carbohydrate intake so that your protein to carbohydrate ratio is approximately 3:4. In addition, (3) eat five servings of fruits and vegetables each day.

This latter recommendation is surprisingly effective. In one study, men who ingested 10 or more servings of tomatoes in several forms (sauce, juice, raw or on pizza) had a 41% reduction in the incidence of PC while those who ate four to seven servings per week had a 22% reduction. The other food associated with a low prostate cancer risk was strawberries. One serving (0.5 cup/week) of strawberries was associated with a 20% decreased risk of prostate cancer.⁶

A discussion of nutrition and supplements beyond that discussed in this article may be found in the following publications:

1. Eating Your Way to Better Health, The Prostate Forum Nutrition Guide
by Charles E. “Snuffy” Myers, Jr., MD.

2. The ABC’s of Nutrition and Supplements for Prostate Cancer
by Mark A. Moyad, MPH

3. & 4. The Zone & The Anti-Aging Zone
by Barry Sears, Ph.D.

5. The Carbohydrate Addicts Healthy Heart Program
by Richard and Rachael Heller

Note: See our Books page for additional references.

If, in conjunction with dietary restrictions, we were to eliminate major factors relating to oxidative damage, such as cigarette smoking and excessive alcohol, we would eliminate 80% of disease as we know it today. In the context of caloric excess, we also have co-factors such as lack of routine exercise. However, when you are physically active, you should routinely use free-radical scavengers to prevent oxidative damage.⁷

Therefore, the PCRI recommends that you eliminate smoking, reduce alcohol consumption, and exercise properly.

Free-Radical Scavengers

Measures to prevent PC must be a routine part of the advice that general practitioners and internists give to their patients. Selenium intake and Vitamin E should be standard recommendations made to all men. This should begin at age 25 and become a life-long practice. Vitamin E has been shown to reduce the incidence of PC by 32% and death by 41%.⁸ Basic research studies have shown that vitamin E reduces growth rates of PC tumors transplanted into mice and stimulated by a high fat diet.⁹ Studies by Clark et al showed that selenium reduced the incidence of PC in men by 63%.¹⁰ A recent study published in the Journal of the National Cancer Institute determined that “statistically significant protective associations for high levels of selenium and alpha-tocopherol, (vitamin E), were observed only when gamma-tocopherol (the gamma isomer of Vitamin E) levels were high.”

Therefore, the PCRI suggests a dose of 400 IU (equivalent to 270 mg) of natural vitamin E as d-alpha tocopherol succinate with 210 mg of d-gamma tocopherol in conjunction with selenium at a dose of 200 mcg per day.

Early Detection

There is unequivocal evidence that routine testing with a simple blood test (the PSA) and evaluation of the prostate gland by an annual digital rectal examination (DRE) has significantly changed the natural history of PC. Fifteen years ago, before the common use of PSA testing, men were diagnosed due to abnormalities on DRE or due to laboratory or radiology findings indicating advanced cancer. The medical means to pick up smaller amounts of PC simply were not available. This is a common dilemma in the world of cancer medicine: how do you detect the disease at an early stage before it has spread? The PAP smear dramatically changed the course of medical history for thousands of women with cancer of the cervix. The mammogram and breast self-examination has similarly aided women in detecting breast cancer. The prostate specific antigen (PSA) is now able to detect PC in men at an earlier stage than the above screening tools discovered cervical and breast cancer in women.

PSA (Prostate Specific Antigen)

Tumor cells make many kinds of proteins. We have only a dozen or so commercial tests that measure these proteins. We call such tests biologic markers or biomarkers. The PSA blood test is one such biomarker. The PSA is the single most important biomarker in the history of cancer medicine. Since tumor growth is essentially geometric, with one cell dividing into two, two to four, four to eight and so on, a protein product of a tumor cell e.g. PSA, can reflect such geometric growth in the time it takes for PSA to double (PSA doubling time). Simply measuring the PSA each year using a reliable laboratory and graphing the results of the PSA can quickly alert the patient and physician to the possibility of malignancy.

For some bizarre reason, this incredibly inexpensive tool for alerting us has not become a routine medical practice. Yet PSA doubling can be a significant early notification that PC is present. The example below helps illustrate this concept:

A man with a PSA of 0.8 at the age of 40 in 1990 shows no real change in PSA until age 48 when the PSA has increased to 1.2., He has to be regarded with concern. If the same man has a PSA obtained six months later and it is 1.6, still well within the so-called “normal” range of up to 4.0, he must be regarded as having PC until proven otherwise. The PSA doubling time in the last six months was reduced from 14 years to 1.2 years. Between January 1990 and January 1998, his calculated PSA doubling time or PSADT was 163.78 months or close to 14 years. This is not typical of PC, which has an average PSADT of four years at diagnosis. However, between 1/98 and 7/98, his PSADT has shortened to 14.3 months. This finding should trigger additional testing and closer surveillance for such a patient. Unfortunately, this is not the case. Today’s world of medicine is still bound into absolute concepts of normal vs. abnormal.
Age	Date	PSA Reading	PSADT (PSA Doubling Time)
40	1/90	0.8	Unknown
48	1/98	1.2	Aproximately 14 years
48 1/2	7/98	1.6	Aproximately 1.2 years

Most commonly, “modern” medicine does not look at patterns or trends within the so-called normal ranges. We should take advantage of what the disease process is telling us via the biologic expressions of disease such as PSADT or PSA velocity (the rate of increase per year of PSA).

We advise each man to begin annual PSA testing at the age of 40. For men with a family history of PC involving first-degree relatives (father, brother), testing should begin at the age of 35. Because breast cancer is genetically linked to PC, men with a family history of breast cancer should start PSA testing at age 35, along with annual digital examination of the prostate.¹²

DRE (Digital Rectal Exam)

Men can easily be tested for palpable prostate abnormalities with the DRE. The DRE done carefully and gently is an easy test that yields much information. First, it tells the physician the prostate gland volume, and important insight since the bigger the prostate, the more PSA the gland is entitled to make. A rule of thumb is that the prostate gland volume multiplied by 0.067 equals the amount of PSA produced by the benign prostate tissue. A 50-year old man with a normal prostate of 40 grams (gms) or cubic centimeters (cc) would therefore be entitled to make 2.68 ng of PSA. A PSA of 4.68 would indicate an excess of two nanograms of PSA and a need for further investigation to rule out PC.

The DRE can also aid in finding hard nodules and other evidence of disease. Palpable abnormalities of the prostate gland relate to the tumor volume or tumor burden. In other words, a DRE is an additional alarm that indicates the tumor burden of PC has increased in size sufficiently to where the tumor can now be felt. In the years before testing with PSA was routine, most prostate cancers at the time of diagnosis were palpable on DRE. Today, close to 70% of initially diagnosed PC is no longer associated with palpable disease in the U.S. This is testimony to the success of PSA screening in the earlier diagnosis of PC before the cancer has had a chance to get bulkier and manifest itself as palpable (called T2 - see staging) disease. Most men in the U.S. now have non-palpable prostate cancer or T1 disease when first diagnosed with PC. (See the April 2000 issue of Insights (pages 8-9) on the Clinical Stage.)

Additional Tools to Clarify the Diagnosis

In addition to the above simple and cost-effective tools, we now also have some relatively new laboratory enhancements that further clarify the diagnosis of PC and enable an earlier diagnosis and hence a greater chance of cure with local therapy. These enhancements include:
1 The fractionation of PSA into FREE PSA and COMPLEXED PSA
2 The use of pattern recognition using computer-generated artificial neural nets (ANN) incorporating variables such as PSA, PAP, Free PSA, CPK (creatine kinase), and patient age.

How do these fit into the medical detective work to diagnose PC early?
Medicine evolves in a step-wise fashion. Unfortunately, some of these steps turn out to be long plateaus due to the conservatism within the medical field. If we review the literature on PSA and its enhancements, we can clearly see that we are moving toward the use of all of these tools but not in a systematic fashion. The most advanced of these tools, the ANN-3, incorporates the importance of PSA testing along with free PSA percentage and the concept of pattern recognition. ANN-3 has a sensitivity of 92% in diagnosing PC. Thus, only 8% of patients who actually have PC would be missed because of false negative results with ANN-3. Therefore, this one laboratory test on an annual basis could identify early disease. Using annual ANN-3 testing, we can also calculate data on PSAV, PSADT, Free PSA % slope and detect a PSA threshold of 2.0 or greater. With the addition of an annual DRE, we should be able to diagnose well over 95% of men with PC. If we find that testing can be done every two years, it would make such testing even more cost-effective.

Patient data spreadsheets (e.g. Excel) containing the above input can be used to automatically calculate PSADT and PSAV. Given such a database, the next step would be to determine if it is necessary to proceed with systematic biopsies using newer approaches such as the 5-region biopsy or the 11-core multi-site biopsy approach.^13,14 Such an approach, using currently available methodology, could change the course of millions of lives in the U.S. alone. In the United Kingdom, where the 5-year mortality from PC is seven times greater than in the U.S., the impact of such an approach would be monumental.

Similarities in Prevention and Treatment:
The diet plan for prevention has also been shown to be effective in PC treatment.

Caloric restriction to 500 calories per meal, adjusted to the individual’s level of activity and body mass is another major step in reducing PC growth. Such studies¹⁵ have shown that a 20-40% reduction in calorie consumption:

• Increases PC cell death rate (apoptosis)
  
• Decreases angiogenesis or tumor blood vessel formation by two to three fold
  
• Decreases vascular endothelial growth factor (VEGF)
  
• Decreases circulating Insulin-like growth factor 1 (IGF-1).
  

VEGF and IGF-1 are significant growth factors for PC. Plasma levels of VEGF are increased in patients with metastatic PC.¹⁶ Therefore, nutritional counseling using new software enhancements would greatly aid in our attempts to reduce the incidence and mortality of PC. These issues and others relating to familial prostate cancer are covered in detail in Insights (vol. 2, no. 3) that can be found online at www.prostate-cancer.org.

Conclusions

The efforts of thousands of physicians and researchers throughout the U.S. have afforded us the potential to dramatically reduce the death caused by PC. But it is critical for all men to initiate action to effect these changes. Take action, not just for a week or a month, but as a life-long lifestyle change. You will receive the greatest benefits through the incorporation of a correct diet in conjunction with vitamin and mineral supplements and detailed monitoring of your yearly DRE and PSA results.

References:

1. Meyer F, Bairati I, Fradet Y, et al: Dietary energy and nutrients in relation to preclinical prostate cancer. Nutr Cancer 29:120-6, 1997.

2. duToit PJ, van Aswegen OH,du Plessis DJ: The effect of essential fatty acids on growth and urokinase-type plasminogen activator production in human prostate DU145 cells. Prostaglandins Leukot Essent Fatty Acids 55:173-7, 1996.

3. Wang Y, Corr JG, Thaler HT, et al: Decreased growth of established human prostate LNCaP tumors in nude mice fed a low-fat diet. JNCI 87:1456-62, 1995.

4. Cohen P, Peehl CM, Lamson G, et al: Insulin-like growth factors (IGFs), IGF receptors and IGF-binding proteins in primary cultures of prostate epithelial cells. J. Clin Endoctrinol Metab 73:401-407, 1991.

5. Nakao-Hayashi J, Ito H, Kanayasu T, et al: Stimulatory effects of insulin and insulin-like growth factor I on migration and tube formation by vascular endothelial cells. Atherosclerosis 92:141-149, 1992.

6. Giovannucci E, Ascherio A, Rimm EB, et al: Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst 87:1767- 1776, 1995.

7. Cooper, KH: Dr. Kenneth Cooper’s Anti-oxidant Revolution. P. Nelson Publishers, 1994.

8. Heinonen OP, Albanes D, Virtamo J, et al: Prostate cancer and supplementation with alpha-tocopherol and beta-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst 90:440-6, 1998.

9. Fleshner N, Fair WR, Huryk R, et al: Vitamin E inhibits the high-fat diet promoted growth of established human prostate LNCaP tumors in nude mice. J Urol 161:1651-4, 1999.

10. Clark LC, Combs GF Jr, Turnbull BW, et al: Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA 276:1957-63, 1996.

11. Helzlsouer KJ, Huang HY, Alberg AJ, et al: Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer. J Natl Cancer Inst 92:2018-2023, 2000.

12. Sellars, Potter JD, Rich SS, et al: Familial clustering of cancers of the breast and prostate in a population-based sample of postmenopausal women. Proc Annu Meet Am Cancer Res 35:A1724, 1994.

13. Eskew AL, Bare RL, McCullogh DL: Systematic 5 region prostate biopsy is superior to sextant method for diagnosing carcinoma of the prostate. J Urol 157:199-203, 1997.

14. Chen ME, Troncoso P, Tang K, et al: Comparison of prostate biopsy schemes by computer, simulation Urology 53:951-60, 1999.

15. Mukherjee P, Sotnikov AV, Mangian HJ, et al: Energy intake and prostate tumor growth, angiogenesis, and vascular endothelial growth factor expression. J Natl Cancer Inst 91:512-23, 1999.

16. Duque JLF, Loughlin KR, Adam RM, et al: Plasma levels of vascular endothelial growth factor are increased in patients with metastatic prostate cancer. Urology 54:523-527, 1999.
 

Prostate Cancer Research Institute (PCRI)

Material provided by PCRI is intended for educational purposes for discussion with your physician and should not be considered as medical advice. Information and opinions expressed on this website are not an endorsement by PCRI for any treatment, product or service.