Chemoprevention strategies in prostate cancer
- E David Crawford, MD
E David Crawford, MD
- Professor of Surgery, Urology and Radiation Oncology
- University of Colorado Denver School of Medicine
- Section Editors
- Nicholas Vogelzang, MD
Nicholas Vogelzang, MD
- Section Editor — Prostate Cancer
- Professor of Medicine
- University of Nevada School of Medicine
- US Oncology Research
- W Robert Lee, MD, MS, MEd
W Robert Lee, MD, MS, MEd
- Section Editor — Prostate Cancer
- Professor of Radiation Oncology
- Duke University Medical Center
- Jerome P Richie, MD, FACS
Jerome P Richie, MD, FACS
- Section Editor — Cancer of the Urethra, Penis, and Ureter; Urologic Surgery; Prostate Cancer
- Elliott Carr Cutler Professor of Surgery
- Harvard Medical School
Prostate cancer is the second most common cancer in men worldwide, with an estimated 1,600,000 cases and 366,000 deaths annually . In the United States there will be an estimated 161,000 cases and 26,700 deaths in 2017 .
In the United States, the incidence of prostate cancer detection dramatically rose in the early 1990s in conjunction with the increasing utilization of prostate-specific antigen (PSA) screening. After an initial peak, incidence rates fell, but they have persisted at a rate nearly twice that recorded in the pre-PSA era, suggesting that many cases are clinically indolent and would never have become clinically apparent. Despite the increase in diagnosis of early stage prostate cancer, the impact of earlier treatment on survival remains to be proven.
The implementation of the United States Preventative Services Task Force (USPSTF) guidelines assigning a recommendation level of D has reduced the number of men seeking early detection, as well as reduced the number of transrectal ultrasound (TRUS) biopsies. Some centers have reported an increase in men with more aggressive and advanced disease. (See "Screening for prostate cancer", section on 'Overdiagnosis'.)
The high incidence of prostate cancer, its associated morbidity and mortality, the complications associated with its treatment, and a partial understanding of its biologic basis have led to a focus on chemoprevention strategies. The most extensive data come from the use of 5-alpha reductase (5-AR) inhibitors; other classes of agents are also being explored.
The rationale for chemoprevention, the results with the 5-AR inhibitors, and data with other approaches are presented here. Screening for prostate cancer, an alternative approach that focuses on early detection to decrease morbidity and mortality, is discussed elsewhere. (See "Screening for prostate cancer".)
- Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Allen C, et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol 2016.
- Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67:7.
- Gaudin PB, Sesterhenn IA, Wojno KJ, et al. Incidence and clinical significance of high-grade prostatic intraepithelial neoplasia in TURP specimens. Urology 1997; 49:558.
- Sakr WA, Haas GP, Cassin BF, et al. The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients. J Urol 1993; 150:379.
- Imperato-McGinley J, Guerrero L, Gautier T, Peterson RE. Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science 1974; 186:1213.
- Kyprianou N, Isaacs JT. Activation of programmed cell death in the rat ventral prostate after castration. Endocrinology 1988; 122:552.
- Einspahr JG, Alberts DS, Gapstur SM, et al. Surrogate end-point biomarkers as measures of colon cancer risk and their use in cancer chemoprevention trials. Cancer Epidemiol Biomarkers Prev 1997; 6:37.
- Sakr WA. Prostatic intraepithelial neoplasia: A marker for high-risk groups and a potential target for chemoprevention. Eur Urol 1999; 35:474.
- Trump DL, Waldstreicher JA, Kolvenbag G, et al. Androgen antagonists: Potential role in prostate cancer prevention. Urology 2001; 57:64.
- Guess HA, Gormley GJ, Stoner E, Oesterling JE. The effect of finasteride on prostate specific antigen: review of available data. J Urol 1996; 155:3.
- Andriole GL, Marberger M, Roehrborn CG. Clinical usefulness of serum prostate specific antigen for the detection of prostate cancer is preserved in men receiving the dual 5alpha-reductase inhibitor dutasteride. J Urol 2006; 175:1657.
- Thompson IM, Goodman PJ, Tangen CM, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med 2003; 349:215.
- Thompson IM Jr, Goodman PJ, Tangen CM, et al. Long-term survival of participants in the prostate cancer prevention trial. N Engl J Med 2013; 369:603.
- Andriole GL, Humphrey PA, Serfling RJ, Grubb RL. High-grade prostate cancer in the Prostate Cancer Prevention Trial: fact or artifact? J Natl Cancer Inst 2007; 99:1355.
- Cohen YC, Liu KS, Heyden NL, et al. Detection bias due to the effect of finasteride on prostate volume: a modeling approach for analysis of the Prostate Cancer Prevention Trial. J Natl Cancer Inst 2007; 99:1366.
- Lucia MS, Epstein JI, Goodman PJ, et al. Finasteride and high-grade prostate cancer in the Prostate Cancer Prevention Trial. J Natl Cancer Inst 2007; 99:1375.
- Lucia MS, Darke AK, Goodman PJ, et al. Pathologic characteristics of cancers detected in The Prostate Cancer Prevention Trial: implications for prostate cancer detection and chemoprevention. Cancer Prev Res (Phila) 2008; 1:167.
- Redman MW, Tangen CM, Goodman PJ, et al. Finasteride does not increase the risk of high-grade prostate cancer: a bias-adjusted modeling approach. Cancer Prev Res (Phila) 2008; 1:174.
- Pinsky P, Parnes H, Ford L. Estimating rates of true high-grade disease in the prostate cancer prevention trial. Cancer Prev Res (Phila) 2008; 1:182.
- Clark RV, Hermann DJ, Cunningham GR, et al. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. J Clin Endocrinol Metab 2004; 89:2179.
- McConnell JD, Wilson JD, George FW, et al. Finasteride, an inhibitor of 5 alpha-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia. J Clin Endocrinol Metab 1992; 74:505.
- Wurzel R, Ray P, Major-Walker KY, Shannon JB. Inhibition of type I and type II 5alpha-reductase with dutasteride (0.5 mg) significantly reduces intraprostatic dihydrotestosterone in BPH patients (abstract). J Urol 2006; 175 (4Suppl):527s.
- Iczkowski KA, Qiu J, Qian J, et al. The dual 5-alpha-reductase inhibitor dutasteride induces atrophic changes and decreases relative cancer volume in human prostate. Urology 2005; 65:76.
- Andriole GL, Bostwick DG, Brawley OW, et al. Effect of dutasteride on the risk of prostate cancer. N Engl J Med 2010; 362:1192.
- Kramer BS, Hagerty KL, Justman S, et al. Use of 5-alpha-reductase inhibitors for prostate cancer chemoprevention: American Society of Clinical Oncology/American Urological Association 2008 Clinical Practice Guideline. J Clin Oncol 2009; 27:1502.
- Kramer BS, Hagerty KL, Justman S, et al. Use of 5alpha-reductase inhibitors for prostate cancer chemoprevention: American Society of Clinical Oncology/American Urological Association 2008 Clinical Practice Guideline. J Urol 2009; 181:1642.
- Theoret MR, Ning YM, Zhang JJ, et al. The risks and benefits of 5α-reductase inhibitors for prostate-cancer prevention. N Engl J Med 2011; 365:97.
- Margel D, Urbach D, Lipscombe LL, et al. Association between metformin use and risk of prostate cancer and its grade. J Natl Cancer Inst 2013; 105:1123.
- Margel D, Urbach DR, Lipscombe LL, et al. Metformin use and all-cause and prostate cancer-specific mortality among men with diabetes. J Clin Oncol 2013; 31:3069.
- Sigounas G, Anagnostou A, Steiner M. dl-alpha-tocopherol induces apoptosis in erythroleukemia, prostate, and breast cancer cells. Nutr Cancer 1997; 28:30.
- Crispen PL, Golovine K, Markov P, et al. Inhibition of NF-kB in Prostate Cancer Cells by Vitamin E Succinate (VES) Decreases Metastatic Potential by Altering Expression of Pro-metastatic Molecules and Decreasing Cell Invasiveness and Adhesion (abstract). J Urol 2006; 175(suppl 4):261s.
- The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med 1994; 330:1029.
- 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 1998; 90:440.
- Virtamo J, Pietinen P, Huttunen JK, et al. Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. JAMA 2003; 290:476.
- Lonn E, Bosch J, Yusuf S, et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. JAMA 2005; 293:1338.
- Lippman SM, Goodman PJ, Klein EA, et al. Designing the Selenium and Vitamin E Cancer Prevention Trial (SELECT). J Natl Cancer Inst 2005; 97:94.
- Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2009; 301:39.
- Klein EA, Thompson IM Jr, Tangen CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 2011; 306:1549.
- Christen WG, Gaziano JM, Hennekens CH. Design of Physicians' Health Study II--a randomized trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials. Ann Epidemiol 2000; 10:125.
- Gaziano JM, Glynn RJ, Christen WG, et al. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA 2009; 301:52.
- Dong Y, Zhang H, Hawthorn L, et al. Delineation of the molecular basis for selenium-induced growth arrest in human prostate cancer cells by oligonucleotide array. Cancer Res 2003; 63:52.
- Sabichi AL, Lee JJ, Taylor RJ, et al. Selenium accumulation in prostate tissue during a randomized, controlled short-term trial of l-selenomethionine: a Southwest Oncology Group Study. Clin Cancer Res 2006; 12:2178.
- West DW, Slattery ML, Robison LM, et al. Adult dietary intake and prostate cancer risk in Utah: a case-control study with special emphasis on aggressive tumors. Cancer Causes Control 1991; 2:85.
- Hardell L, Degerman A, Tomic R, et al. Levels of selenium in plasma and glutathione peroxidase in erythrocytes in patients with prostate cancer or benign hyperplasia. Eur J Cancer Prev 1995; 4:91.
- Kristal AR, Darke AK, Morris JS, et al. Baseline Selenium Status and Effects of Selenium and Vitamin E Supplementation on Prostate Cancer Risk. J Natl Cancer Inst 2014.
- Schwartz GG, Hulka BS. Is vitamin D deficiency a risk factor for prostate cancer? (Hypothesis). Anticancer Res 1990; 10:1307.
- Corder EH, Guess HA, Hulka BS, et al. Vitamin D and prostate cancer: a prediagnostic study with stored sera. Cancer Epidemiol Biomarkers Prev 1993; 2:467.
- Ingles SA, Coetzee GA, Ross RK, et al. Association of prostate cancer with vitamin D receptor haplotypes in African-Americans. Cancer Res 1998; 58:1620.
- Ahonen MH, Tenkanen L, Teppo L, et al. Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control 2000; 11:847.
- Ma J, Stampfer MJ, Gann PH, et al. Vitamin D receptor polymorphisms, circulating vitamin D metabolites, and risk of prostate cancer in United States physicians. Cancer Epidemiol Biomarkers Prev 1998; 7:385.
- Chan JM, Giovannucci E, Andersson SO, et al. Dairy products, calcium, phosphorous, vitamin D, and risk of prostate cancer (Sweden). Cancer Causes Control 1998; 9:559.
- Giovannucci E. Dietary influences of 1,25(OH)2 vitamin D in relation to prostate cancer: a hypothesis. Cancer Causes Control 1998; 9:567.
- Lieberman R, Bermejo C, Akaza H, et al. Progress in prostate cancer chemoprevention: modulators of promotion and progression. Urology 2001; 58:835.
- Lotan Y, Xu XC, Shalev M, et al. Differential expression of nuclear retinoid receptors in normal and malignant prostates. J Clin Oncol 2000; 18:116.
- Thaller C, Shalev M, Frolov A, et al. Fenretinide therapy in prostate cancer: effects on tissue and serum retinoid concentration. J Clin Oncol 2000; 18:3804.
- Urban D, Myers R, Manne U, et al. Evaluation of biomarker modulation by fenretinide in prostate cancer patients. Eur Urol 1999; 35:429.
- Price D, Stein B, Goluboff E, et al. Double-blind, placebo-controlled trial of toremifene for the prevention of prostate cancer in men with high-grade prostatic intrapeithelial neoplasia (abstract). J Clin Oncol 2005; 23:106s.
- Taneja SS, Morton R, Barnette G, et al. Prostate cancer diagnosis among men with isolated high-grade intraepithelial neoplasia enrolled onto a 3-year prospective phase III clinical trial of oral toremifene. J Clin Oncol 2013; 31:523.
- Narayanan BA, Narayanan NK, Pittman B, Reddy BS. Regression of mouse prostatic intraepithelial neoplasia by nonsteroidal anti-inflammatory drugs in the transgenic adenocarcinoma mouse prostate model. Clin Cancer Res 2004; 10:7727.
- Smith MR, Manola J, Kaufman DS, et al. Celecoxib versus placebo for men with prostate cancer and a rising serum prostate-specific antigen after radical prostatectomy and/or radiation therapy. J Clin Oncol 2006; 24:2723.
- Pollard M, Wolter W. Prevention of spontaneous prostate-related cancer in Lobund-Wistar rats by a soy protein isolate/isoflavone diet. Prostate 2000; 45:101.
- Bylund A, Zhang JX, Bergh A, et al. Rye bran and soy protein delay growth and increase apoptosis of human LNCaP prostate adenocarcinoma in nude mice. Prostate 2000; 42:304.
- Messina MJ, Persky V, Setchell KD, Barnes S. Soy intake and cancer risk: a review of the in vitro and in vivo data. Nutr Cancer 1994; 21:113.
- Fleshner NE, Kapusta L, Donnelly B, et al. Progression from high-grade prostatic intraepithelial neoplasia to cancer: a randomized trial of combination vitamin-E, soy, and selenium. J Clin Oncol 2011; 29:2386.
- Cuzick J, Thorat MA, Andriole G, et al. Prevention and early detection of prostate cancer. Lancet Oncol 2014; 15:e484.
- Long latency period
- Androgen dependency
- Clinical trials biomarkers
- 5-ALPHA REDUCTASE INHIBITORS
- Finasteride: Prostate Cancer Prevention Trial
- Guidelines and regulatory status
- OTHER AGENTS
- Vitamins and micronutrients
- - Vitamin E
- - Selenium
- - Vitamin D analogs
- - Retinoids
- Nonsteroidal anti-inflammatory compounds
- Dietary factors
- LIFESTYLE FACTORS
- SUMMARY AND RECOMMENDATIONS