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An Update on Prostate Cancer

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An Update on Prostate Cancer CANCER DIAGNOSIS AND MANAGEMENT ^/cME CREDIT\ MAURIE MARKMAN, MD, EDITOR An update on prostate cancer ERIC A. KLEIN, MD URING THE LAST dec- As screening for prostate cancer has become more ade both the inci- common, the issues surrounding its diagnosis and treatment dence and public have grown more complex. This review surveys recent ad- awareness of prostate Dcancer have increased dramati- vances and controversies, including definition of risk factors, the role of screening, and current treatment strategies. cally. With this growth have come a number of medical issues and i:o'J::«!IJiiHi African American heritage and age are risk factors controversies. This paper examines for prostate cancer. There appear to be familial and hereditary some of them, including: (1) the forms of prostate cancer, which are separate and distinct. relative roles of age, race, and fam- A link to vasectomy is speculative. Whether PSA should be ily history as risk factors for devel- used for screening remains controversial. The high inci- oping prostate cancer; (2) the dence of occult carcinoma associated with prostate intraepi- proper use of serum prostate-spe- thelial neoplasia dictates early re-evaluation of patients with cific antigen (PSA) assays; (3) the this finding on biopsy. Observation rather than treatment diagnosis of prostate cancer and may be a reasonable option for older patients or those with low- the meaning of prostate intraepi- grade tumors and life expectancy of less than 10 years. thelial neoplasia; (4) a new tumor The major advantage of radiation therapy over surgery is staging system that has been widely that it is less invasive, but it is associated with a higher risk of adopted; (5) the debate over the symptomatic local recurrences. Cryotherapy should be con- treatment of localized prostate sidered an investigational technique with unknown long-term cancer, including watchful waiting, results. radical prostatectomy, and radia- tion therapy; and (6) treatment INDEX TERMS: PROSTATIC NEOPLASMS options for advanced cancers. CLEVE CLIN J MED 1995; 62:325-338 CURRENT TRENDS Between 1987 and 1992, the From the Section of Urologie Oncology, the Department of Urology, The number of radical prostatecto- Cleveland Clinic Foundation. mies performed in men over age Address reprint requests to E.A.K., Department of Urology, A100, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195. 65 in the United States increased by 560%, from 7028 to 39 157.1 During the same period, the num- ber of prostate biopsies performed increased by 430%. The reasons for this expansion are many: the SEPTEMBER • OCTOBER 1995 CLEVELAND CLINIC JOURNAL OF MEDICINE 325 Downloaded from www.ccjm.org on October 1, 2021. For personal use only. All other uses require permission. PROSTATE CANCER • KLEIN development of PSA assays, transrectal ultrasonog- incidence and a higher prostate cancer death rate raphy, spring-loaded biopsy needles, widespread than Caucasians do. National data reported in 1989 screening programs, increased public awareness of suggested that the lifetime risk of developing pros- prostate cancer, and advances in surgical technique, tate cancer is 1 in 9 in African Americans and 1 in which have resulted in better functional outcomes. 11 in Caucasians.3 In one study, age-adjusted inci- Public awareness of prostate cancer has been par- dence rates rose by 2.7 and 3.1 per 100 000 yearly ticularly fueled by the deaths of several national before 1989 for Caucasians and African Ameri- celebrities. cans, respectively, and by 23.5 and 19.4 per 100 An estimated 244 000 new cases of prostate can- 000, respectively, between 1989 and 1991.4 It is cer will be diagnosed in 1995, and 40 000 men will unclear whether the incidence is actually increas- die of it.2 Prostate cancer is second only to lung ing faster in Caucasians, or whether this group cancer as a fatal malignant disease in men and is merely has better access to PSA screening and likely to continue to increase in incidence as the other tests. average age of the population increases. The higher death rate in African Americans has never been adequately explained biologically. A re- EPIDEMIOLOGY AND RISK FACTORS cent autopsy study of 152 men age 50 or younger revealed premalignant lesions and incidental carci- Despite intensive efforts during the last decade to nomas of the prostate with equal frequency in both unveil the origins of prostate cancer, the molecular races.5 Further, the cancerous foci were of similar details of its development and progression remain size and occurred as early as the third decade in both poorly understood. Long-standing epidemiologic groups. This suggests that both races are equally observations that age and race play an important prone to the early development of prostate cancer role continue to be validated by current studies. In but may have biologic differences in how the disease addition, genetic epidemiologic data have identified progresses. a cohort of families that appear to have a true he- Another interesting study compared PSA levels reditary form of the disease. A possible link to vasec- and pathologic stage in Caucasian and African tomies remains speculative. American patients who had equal access to screen- ing and diagnostic services within the US military Age system. In 264 patients who underwent radical pro- The incidence of prostate cancer increases with statectomy, the mean preoperative serum PSA level age, the prevalence at autopsy being 30% in men was significantly lower in Caucasians (8.9 vs 15.2 over age 50 and 70% in men in their 80s.3 A recent ng/mL), and 50% of Caucasians had organ-confined study also demonstrated that the age-adjusted inci- disease compared with only 39% of African Ameri- dence of invasive prostate cancer is rising dramati- cans.6 In another study, in men with localized pros- cally—an increase of 8% in 1989, 33% in 1990, and tate cancer, there were no differences in mean age or 72% in 1991 over 1988 figures.4 Rates, of diagnosis preoperative PSA levels between the races. How- increased for all ages beginning at age 55, with the ever, more African Americans than Caucasians had most marked increases noted in men between the locally advanced disease (68% vs 57%) and positive ages of 75 and 84- The increased incidence is un- margins (55% vs 35%), both of which impart a doubtedly due to more screening: the number of worse prognosis.7 PSA tests increased fivefold to sevenfold in the five laboratories surveyed in this study. Even so, detected Family history cases still represent only a fraction of the estimated Family history is another well-known risk factor 8 million men over age 50 who harbor cancer of the for prostate cancer. However evidence indicates prostate. This observation highlights the continued that the risk may take two forms, a familial cancer lack of understanding of the biological charac- and a less common hereditary prostate cancer. In teristics of "latent" cancers and raises important is- 1990, a large epidemiologic study demonstrated sues regarding screening and treatment. that a man's risk of developing prostate cancer is approximately twice that of the general population Racial differences if he has a first-degree relative with the disease, and African Americans have a higher age-specific is almost nine times as high when both a first and 326 CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 62 • NUMBER 5 Downloaded from www.ccjm.org on October 1, 2021. For personal use only. All other uses require permission. PROSTATE CANCER • KLEIN second degree relative are affected (Table l).8 More TABLE 1 extensive epidemiologic data have now identified a RELATIVE RISK OF DEVELOPING PROSTATE cohort of families with a hereditary form charac- CANCER ACCORDING TO FAMILY HISTORY* terized by early age at onset and autosomal domi- Relatives affected Relative risk nant inheritance. Hereditary prostate cancer should be suspected if prostate cancer occurs in One second-degree 1.7 multiple generations or in multiple family mem- One first-degree 2.0 bers, especially if the age of onset is less than 55. Two first-degree 4.9 Men in these families have an approximately 50% One first and one second-degree 8.8 risk of cancer, compared with a 13% risk in the Three or more first-degree 10.9 general population.9 Molecular genetic studies have Adapted from Steinberg et al, reference 8 suggested that the gene responsible for hereditary prostate cancer is highly penetrant and that 88% of gene carriers develop prostate cancer by the age of Role of digital rectal examination, 85. Hereditary prostate cancer is distinguished from PSA, and ultrasonography the familial form, which occurs in patients with a Those who advocate screening generally agree on positive family history but who do not exhibit early which tools to use. In a recent multicenter study, onset. However, pathologic analysis has failed to more than 6000 men underwent digital rectal ex- demonstrate substantial differences among the he- amination, PSA testing, and transrectal ultrasonog- reditary, familial, and sporadic forms.10 Further, he- raphy. The overall detection rate was highest for reditary prostate cancer does not appear to be asso- PSA testing (4-6%), followed by digital rectal ex- ciated with other cancers.11 amination (approximately 3.2%)." The positive predictive value of PSA testing was superior to that Vasectomy of digital rectal examination (31.5% vs 21%), and Several epidemiologic studies have demonstrated the combination of an elevated PSA level and ab- a higher risk of prostate cancer in men who have normal findings on rectal examination had a posi- had a vasectomy, with a relative risk of approxi- tive predictive value of 48.5%. A combination of mately 1.5, rising to approximately 1.8 by 20 years abnormal ultrasonographic findings, an elevated after vasectomy.12"14 No currently accepted biologi- PSA value, and abnormal findings on rectal exami- cal hypothesis can explain this, and the link remains nation carried a positive predictive value of 55%.
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