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Prostate Cancer

Introduction
The prostate is a walnut-sized organ that lies just below the bladder, surrounding the urethra. The function of the prostate is to enhance the motility of sperm cells by secreting a thin, alkaline fluid into the urethra.

Prostate cancer is the most common form of cancer, excluding skin cancer, in men in the United States. It is primarily diagnosed in men over 65, although it may begin much earlier. Some carcinomas of the prostate are very slow growing, while others behave aggressively. Prostate cancer often metastasizes to other tissue, including the brain, lungs, lymph nodes, and bones. Early detection is critical in order to increase the chances for survival. The cancer can be palpated upon digital rectal examination (DRE). These examinations are recommended routinely for all men over the age of 50 and high-risk men should commence at age 40.

Little is known about the causes of prostate cancer. Risk factors for prostate cancer include family history and being African-American. Insight into the history of the tumor is provided by histopathologic grading, surgical evaluation of the pelvic lymph nodes, and measurement of the primary lesion. A lesion with a size of less than 1.5mL in volume typically results in a good prognosis. Risk factors for suicide and cardiovascular disease death increase when prostate cancer is diagnosed.(1)

The majority of prostate cancers are adenocarcinomas. While most prostate cancers are found in the peripheral zone, they may occur anywhere in the prostate. Most pathologists use the Gleason grading system to assess the tumor progression. A score from 2 to 4 indicates a well-differentiated cancer; 5 to 6 correlates with a moderately differentiated cancer; and 7 to 10 indicates a poorly differentiated cancer. The poorer the differentiation of the cancer cells, the worse the prognosis. Well-differentiated tumors grow slowly, whereas poorly differentiated tumors grow rapidly and are associated with a poor prognosis.

Statistics

Cancer Research UK, 2006.

  • Worldwide, more than 670,000 men are diagnosed with prostate cancer every year, accounting for one in nine of all new cancers in males.
  • It is the second most common cancer in men after lung cancer.

Prostate Cancer Foundation, 2006.

  • One new case occurs every 2.5 minutes and a man dies from prostate cancer every 17 minutes.
  • African-American men are 65% more likely to be diagnosed with prostate cancer than Caucasian- Americans and are more than twice as likely to die from it.
  • More than 70% of all prostate cancers are diagnosed in men over the age of 65.

The National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). NIH Publication No. 06-3895, April 2006.

  • 173.8 cases per 100,000 population of men per year are diagnosed with prostate cancer.
  • Prostate cancer causes 30.3 deaths per 100,000 population of men per year.
  • 1.8 million men in the U.S. are survivors of prostate cancer.

National Vital Statistics Reports, Vol. 48, No. 11.

  • The annual number of deaths from Prostate Cancer are 32,203 (1998).
Signs and Symptoms
The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.
Early stages of prostate cancer are asymptomatic. Obstructive symptoms mimicking benign prostatic hyperplasia (BPH) occur later in the disease. Difficulty urinating, frequency, urinary retention, and diminished force of the urine stream are characteristic symptoms. If the cancer has spread, symptoms may include fatigue, nausea, weakness, back pain, swollen lymph nodes, discomfort in the perineum, hip pain, or weight loss. Blood may be present in the urine. Most prostatic cancers are detected in asymptomatic men who have an elevated PSA (Prostate Specific Antigen) level or a nodular or enlarged prostate at the time of examination.(2) Prostate cancer may also present clinically as a rectal mass.
  • Initial stages are asymptomatic
  • Difficulty urinating
  • Urinary retention
  • Diminished force of the urine stream
  • Fatigue
  • Nausea
  • Weakness
  • Back pain
  • Swollen lymph nodes
  • Discomfort in the perineum
  • Hip pain
  • Weight loss
  • Hematuria
Treatment Options
Conventional
Prostate cancer screening is utilized to detect the tumor while it is localized in the prostate and is most easily and successfully treated. Biopsy of the prostate is essential for establishing the diagnosis and is indicated when an abnormality is detected by palpation or elevated PSA. Treatment of prostate cancer is determined by the stage of the disease. If the cancer is limited to the prostate, radical prostatectomy is usually performed, with or without radiation therapy. A recent study found, however, that men who had their prostates removed after diagnosis did not survive appreciably longer than those whose cancers were monitored without intervention.(3),(4) For later stages, treatment is palliative. Because growth of the normal prostate is dependent on testicular androgens, androgen deprivation is used for treatment of advanced prostatic carcinoma. This can be achieved by four methods: surgical castration and adrenalectomy; inhibition of pituitary gonadotropin and/or ACTH production which involves estrogen therapy usually with diethylstilbestrol (DES) or treatment with luteinizing hormone-releasing hormone (LHRH) analogues such as leuprolide or buserelin; inhibition of androgen synthesis (aminoglutethimide); and inhibition of androgen binding to its receptor protein (cyproterone, flutamide, or bicalutamide). Orchiectomy may be considered, as over 90 percent of testosterone originates in the testicles. While the procedure is simple, safe, cost-effective, and produces immediate relief of symptoms, the psychological effect can be significant for many men. Chemotherapy is reserved for hormone-unresponsive disease and is used for palliation.
Nutritional Supplementation
Lycopene is a dietary component that seems to provide specific protection against prostate cancer. Results from the Health Professionals Follow-Up Study reported a lower prostate cancer risk among men who consumed larger quantities of tomatoes and related lycopene-containing food products.(5) In another study, significantly lower serum and tissue lycopene levels were observed in men with prostate cancer compared to controls.(6)

Tomatoes are the primary dietary source of lycopene and it has been reported that lycopene is one of the most effective quenchers of the singlet oxygen free radical. It is interesting to note that the highest concentrations of lycopene occur in the testes, adrenals, and prostate gland.(7) Lycopene concentration is highest in cooked tomato products. It is estimated that a minimum 4-6mg daily intake of lycopene is needed for prostate protection. Lycopene has been found to affect gene expression, thereby, indicating lycopene may reduce the risk of prostate cancer.(8)

The use of selenium as a protectant against prostate cancer is supported by results of a study designed to evaluate whether or not selenium supplementation could reduce the reoccurrence of either basal cell or squamous cell carcinoma. In this study, 974 men were randomized to receive either a daily supplement of 200mcg of selenium or a placebo. These men were treated for an average of 4.5 years and then followed for an additional 6.5 years.

Evaluation of secondary endpoints in men that initially had normal PSA levels revealed that selenium supplementation was responsible for a 63% reduction in the incidence of prostate cancer. Four men were diagnosed in the selenium-treated group, compared to 16 cases of prostate cancer in the placebo group. Additionally, compared to placebo controls, the individuals taking selenium also had significant reductions in colorectal cancer and lung cancer.(9)

In the Netherlands Cohort Study of 58,279 men aged 55- 69 years upon entry, over 1500 men exhibiting prostate cancer identifiers were found to have a decreased toenail selenium levels. Researchers concluded that this study confirmed the hypothesis that higher selenium levels might reduce prostate cancer risks.(10)

Researchers found that selenium supplementation in the SELECT trial involving over 35,000 men did not prevent prostate cancer or any other cancer.(11)

The results of a controlled study that evaluated the incidence of prostate cancer and deaths among 29133 male smokers aged 50-69 years who took vitamin E indicated that men taking 50mg of vitamin E daily had a 32 percent lower incidence of prostate cancer, and a 41 percent reduction in deaths from prostate cancer.(12) In a similar study, among current smokers and recent quitters, men who consumed at least 100 IU of supplemental vitamin E per day had a significant reduction in the risk for metastatic or fatal prostate cancer compared with nonusers of supplemental vitamin E.(13) Researchers found that vitamin E supplementation in the SELECT trial involving over 35,000 healthy men did not prevent prostate cancer or any other cancer.(14) Results were similar in another large-scale randomized trial involving 14,641 men.(15)

In order to insure the general health and well being of the prostate gland, zinc supplementation may be warranted. The prostate gland stores zinc and the concentration of zinc in the prostate gland is much higher than in other tissues in the human body.(16) Adequate zinc levels help to prevent enlargement of the prostate gland. This is because zinc influences the activity of the 5 alpha-reductase enzyme. When zinc levels are low, the activity of this enzyme is higher, causing a greater conversion of testosterone to dihydrotestosterone (DHT). On the other hand, when zinc levels are higher the activity of 5 alpha-reductase is reduced, and there is less conversion of testosterone to DHT.(17) Zinc not only prevents prostate enlargement; animal studies report it may also help to shrink a gland that is already swollen.(18) However, in a recent human study, consumption of over 100mg of supplemental zinc daily had a relative risk of advanced prostate cancer of 2.29 in comparison to nonusers and when taken for 10 years or more the relative risk increased to 2.37.(19)
Taking zinc alone isn’t enough to insure prostate health. Vitamin B6 influences zinc absorption. Apparently vitamin B6 helps to convert zinc to a form that is more absorbable by the tissues in the prostate.(20) Studies indicate that vitamin B6 is deficient in the diet of many Americans, a factor that may contribute to low zinc status and increased prostate problems. For example, data from the Second National Health and Nutrition Examination Survey (NHANES II) reported that 71% of males consumed less than the RDA for vitamin B6 on a daily basis.(21)
Herbal Supplementation

Green tea is an evergreen shrub that has long been used in much of the world as a popular beverage and a respected medicinal agent. An early Chinese Materia Medica lists green tea as an agent to promote digestion, improve mental faculties, decrease flatulence and regulate body temperature. The results of a recent trial revealed significant reductions in serum levels of HGF, VEGF and PSA after treatment of green tea extract, with some patients demonstrating reductions in levels of greater than 30 percent. The researchers concluded that these findings suggest a potential role for green tea in the treatment or prevention of prostate cancer.(22)

Pomegranate is native to Afghanistan, Iran and Pakistan but is now cultivated throughout the world. It is categorized as an exotic fruit called superfruits. The name pomegranate comes from the Latin word, pomum (apple) and granatus (seeded). It has been used for culinary purposes as well as medicinal purposes in many coutries. Human and animal studies associated pomegranate in the prevention and slowing the progression of prostate cancer. Researchers found that pomegranate may help kill cancerous cells while leaving healthy tissues intact.(23),(24)

Diet and Lifestyle
Dietary fat: There are many studies that discuss how various factors related to diet and nutrition influence cancer. Although only a small amount of this research relates directly to the prevention or treatment of prostate cancer, the following reviews have been reported.

Most studies that have evaluated the relationship between dietary fat and prostate cancer report that diets high in total fat are associated with an increased rate of prostate cancer.(25) Even though there are some inconsistencies, there is the suggestion that diets high in saturated fat and/or animal fat increase the risk of prostate cancer.(26) Most studies on dietary meat intake, seem to report an increased risk of prostate cancer with higher meat consumption. A prospective evaluation of the relationship between meat consumption and prostate cancer used the detailed dietary data from 51,529 male participants of the Health Professionals Follow-Up Study. This study concluded that intakes of red meat and dairy products appear to be related to increased risk of metastatic prostate cancer, but increased risk did not apply to all cases of prostate cancer observed, including advanced prostate cancer.(27)

Clinical Lab Assessments
Some of the following laboratory testing can provide information necessary for diagnosis and treatment. In addition, the tests listed may also give insight to functional metabolism and functional nutrient status in the body.
Estrogen, Progesterone and Testosterone: Estradiol increases a genetic product (Bcl-2) that leads to cell proliferation and delay in apoptosis, both of which increase cancer risk. Progesterone suppresses Bcl-2 action and increases another genetic control product (p53) that slows cell proliferation and restores proper apoptosis, both of which decrease cancer risk. Testosterone (but not the DHT) stops cancer cell growth.(28) Assessment of these hormones may be useful.
This glycoprotein, exclusive to the prostate epithelium, is a smaller, more stable molecule than PAP and does not demonstrate diurnal fluctuations. PSA is used as a marker for the detection of prostate cancer.
References
  1. View Abstract:  Fang F, et al. Immediate Risk of Suicide and Cardiovascular Death After a Prostate Cancer Diagnosis: Cohort Study in the United States. J Natl Cancer Inst. Feb2010
  2. View Abstract:  Horninger W, Reissigl A, Rogatsch H, et al. Prostate cancer screening in Tyrol, Austria: experience and results. Eur Urol. 1999;35(5-6):523-38.
  3. View Abstract:  Matos-Ferreira A. New review of radical prostatectomy. Actas Urol Esp. Oct1997:817-21.
  4. View Abstract:  Fleming C, Wasson JH, Albertsen PC, Barry MJ, Wennberg JE. A decision analysis of alternative treatment strategies for clinically localized prostate cancer. JAMA. May1993;269:2650-8.
  5. View Abstract:  Clinton SK, et al. Cis-trans lycopene isomers, carotenoids, and retinol in the human prostate. Cancer Epidemiol Biomarkers Prev 1996 Oct;5(10):823-833.
  6. View Abstract:  Rao AV, et al. Serum and tissue lycopene and biomarkers of oxidation in prostate cancer patients: a case-control study. Nutr Cancer. 1999;33(2):159-64.
  7. View Abstract:  Gerster H. The potential role of lycopene for human health. J Am Coll Nutr. Apr1997;16(2):109-126.
  8. View Abstract:  Talvas J, et al. Differential effects of lycopene consumed in tomato paste and lycopene in the form of a purified extract on target genes of cancer prostatic cells. Am J Clin Nutr. Jun2010;91(6):1716-24
  9. View Abstract:  Clark LC, et al. Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br J Urol. May1998;81(5):730-4.
  10. View Abstract:  van den Brandt PA, et al. Toenail selenium levels and the subsequent risk of prostate cancer: a prospective cohort study. Cancer Epidemiol Biomarkers Prev. Sep2003;12(9):866-71
  11. View Abstract:  Lippman SM, et al. Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers. JAMA. Jan2009;301(1)
  12. View Abstract:  Heinonen, OP. Prostate cancer and supplementation with alpha tocopherol and beta-carotene: Incidence and mortality in a controlled trial. J Natl Cancer Inst. Mar1998;90(6):440-446.
  13. View Abstract:  Chan JM, et al. Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States. Cancer Epidemiol Biomarkers Prev. Oct1999;8(10):893-9.
  14. View Abstract:  Lippman SM, et al. Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers. JAMA. Jan2009;301(1)
  15. View Abstract:  Gaziano JM, et al. Vitamins E and C in the Prevention of Prostate and Total Cancer in Men. JAMA. Jan2009;301(1)
  16. View Abstract:  Pavon Maganto E. Zinc in prostatic physiopathology. I. Role of zinc in the physiology and biochemistry of the prostatic gland. Arch Esp Urol. Mar1979;32(2):143-52.
  17. View Abstract:  Leake A, et al. The effect of zinc on the 5 alpha-reduction of testosterone by the hyperplastic human prostate gland. J Steroid Biochem. Feb1984;2092:651-655.
  18. View Abstract:  Fahim MS, et al. Zinc arginine, a 5 alpha-reductase inhibitor, reduces rat ventral prostate weight and DNA without affecting testicular function. Andrologia. Nov1993;25(6):369-375.
  19. View Abstract:  Leitzmann MF, Stampfer MJ, Wu K, Colditz GA, Willett WC, Giovannucci EL. Zinc supplement use and risk of prostate cancer. J Natl Cancer Inst. Jul2003;95(13):1004-7.
  20. View Abstract:  Evans GW, Johnson EC. Effect of iron, vitamin B-6 and picolinic acid on zinc absorption in the rat. Journal of Nutrition. Jan1981;111(1):68-75.
  21. View Abstract:  Kant AK, Blcok G. Dietary vitamin B-6 intake and food sources in the US population: NHANES II, 1976-1980. Am J Clin Nutr. Oct1990;52(4):707-16.
  22. View Abstract:  McLarty J, et al. Tea Polyphenols Decrease Serum Levels of Prostate Specific Antigen, Hepatocyte Growth Factor, and Vascular Endothelial Growth Factor in Prostate Cancer Patients and Inhibit Production of Hepatocyte Growth Factor and Vascular Endothelial Growth Factor. Cancer Prev Res. Jun2009
  23. View Abstract:  Pantuck AJ, et al. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clin Cancer Res. Jul2006;12(13):4018-26
  24. View Abstract:  Albrecht M, et al. Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. J Med Food. 2004;7(3):274-83
  25. Rose DP, Connolly JM. Dietary fat, fatty acids and prostate cancer. Lipids. 1982;27:798-803.
  26. View Abstract:  Hursting SD, et al. Types of dietary fat and the incidence of cancer at 5 sites. Prev Med. 1990;19:242-253.
  27. View Abstract:  Michaud DS, Augustsson K, Rimm EB, Stampfer MJ, Willet WC, Giovannucci E. A prospective study on intake of animal products and risk of prostate cancer. Cancer Causes Control. Aug 2001;12(6):557-67.
  28. View Abstract:  Formby B, Wiley TS. Bcl-2, survivin and variant CD44 v7-v10 are downregulated and p53 is upregulated in breast cancer cells by progesterone: inhibition of cell growth and induction of apoptosis. Mol Cell Biochem. Dec1999;202(1-2): 53-61.