Prostate-Specific Antigen, Digital Rectal Examination, and Transrectal Ultrasonography: Their Roles in Diagnosing Early Prostate Cancer
1993; Elsevier BV; Volume: 68; Issue: 3 Linguagem: Inglês
10.1016/s0025-6196(12)60052-4
ISSN1942-5546
AutoresMichael R. Cupp, Joseph E. Oesterling,
Tópico(s)Urologic and reproductive health conditions
ResumoIn this article, we review the current status of early detection of prostate cancer. From existing data in the medical and urologic literature, we developed an algorithm that uses the three current methods of detection: digital rectal examination (DRE), determination of the prostate-specific antigen (PSA) value, and transrectal ultrasonography (TRUS). Prostatic malignant disease is an increasing medical problem in the United States. The potential for cure is optimized by early detection and treatment of organ-confined disease. Mass screening for prostate cancer in asymptomatic men cannot be advocated until a decrease in the mortality rate is established by randomized, controlled studies; however, these data will be unavailable for at least 15 years. In the meantime, clinicians must prudently use DRE, PSA, and TRUS for early detection. Current data indicate that the PSA level is as effective as or more effective than DRE for the detection of prostate cancer. These two methods do not always detect the same malignant tumor; therefore, the combined use of DRE and PSA testing provides a more complete evaluation of the prostate gland for malignant involvement. TRUS is more costly and does not add appreciable detectability when results of both the DRE and the PSA determination are normal. Thus, TRUS is best reserved for patients who have abnormal results of DRE or increased PSA values. In this article, we review the current status of early detection of prostate cancer. From existing data in the medical and urologic literature, we developed an algorithm that uses the three current methods of detection: digital rectal examination (DRE), determination of the prostate-specific antigen (PSA) value, and transrectal ultrasonography (TRUS). Prostatic malignant disease is an increasing medical problem in the United States. The potential for cure is optimized by early detection and treatment of organ-confined disease. Mass screening for prostate cancer in asymptomatic men cannot be advocated until a decrease in the mortality rate is established by randomized, controlled studies; however, these data will be unavailable for at least 15 years. In the meantime, clinicians must prudently use DRE, PSA, and TRUS for early detection. Current data indicate that the PSA level is as effective as or more effective than DRE for the detection of prostate cancer. These two methods do not always detect the same malignant tumor; therefore, the combined use of DRE and PSA testing provides a more complete evaluation of the prostate gland for malignant involvement. TRUS is more costly and does not add appreciable detectability when results of both the DRE and the PSA determination are normal. Thus, TRUS is best reserved for patients who have abnormal results of DRE or increased PSA values. Historically, digital rectal examination (DRE) has been the only method available to evaluate the prostate gland for malignant tumors. Recently, determination of the prostate-specific antigen (PSA) value and transrectal ultrasonography (TRUS) have been added to the methods used to detect prostate cancer. The addition of these two approaches has made the detection of prostate cancer a more complex endeavor than in the past. The roles of these three tests in detecting prostate cancer are currently undefined. The development of a prudent approach for use of DRE, PSA testing, and TRUS necessitates consideration of the characteristics of prostate cancer and of these detection methods. The ultimate criterion for judging efforts to detect and treat prostate cancer will be the effect on the mortality rate for the disease. Recently, the National Cancer Institute initiated a 16-year, multicenter, randomized, controlled study to evaluate the effect of screening for early-stage prostate cancer; however, definitive data from this study will be unavailable for many years. In the interim, clinicians must use the currently available data to counsel their patients on the use of DRE, the PSA value, and TRUS in the early detection of potentially curable prostate cancer. With the exclusion of skin cancers, prostate cancer has become the most common malignant tumor in men and is the second leading cause of death from cancer in men (after lung cancer). The American Cancer Society projected that approximately 165,000 new cases would be diagnosed and more than 35,000 associated deaths would occur in 1993.1Boring CC Squires TS Tong T Cancer statistics, 1993.CA Cancer J Clin. 1993; 43: 7-26Crossref PubMed Scopus (1223) Google Scholar Prostate cancer is generally considered a slow-growing malignant disease that becomes highly prevalent in elderly men. In comparison with other cancers, the prevalence and incidence of prostate cancer increase most rapidly with age, and epidemiologic data have shown a 40-fold increase in the prevalence of prostate cancer from age 50 to 85 years.2Carter HB Coffey DS The prostate: an increasing medical problem.Prostate. 1990; 16: 39-48Crossref PubMed Scopus (308) Google Scholar Continued improvements in life expectancy and a shift in the age distribution in favor of an older population will increase the number of patients with and dying of prostate cancer. To illustrate this increase, Carter and Coffey2Carter HB Coffey DS The prostate: an increasing medical problem.Prostate. 1990; 16: 39-48Crossref PubMed Scopus (308) Google Scholar combined the projected trends in incidence and mortality rates and the aging population of the United States and estimated a 37% increase in the number of prostate cancer-related deaths and a 90% increase in the total number of cases of prostate cancer between the early 1980s and the year 2000. In addition, numerous autopsy studies have revealed that up to 30% of men 50 years of age or older have histologic evidence of prostate cancer.3Andrews GS Latent carcinoma of the prostate.J Clin Pathol. 1949; 2: 197-208Crossref PubMed Scopus (63) Google Scholar, 4Baron E Angrist A Incidence of occult adenocarcinoma of the prostate after fifty years of age.Arch Pathol. 1941; 32: 787-793Google Scholar, 5Edwards CN Steinthorsson E Nicholson D An autopsy study of latent prostatic cancer.Cancer. 1953; 6: 531-554Crossref PubMed Scopus (76) Google Scholar, 6Franks LM Latent carcinoma of the prostate.J Pathol Bacteriol. 1954; 68: 603-616Crossref PubMed Scopus (345) Google Scholar, 7Guileyardo JM Johnson WD Welsh RA Akazaki K Correa P Prevalence of latent prostate carcinoma in two U.S. populations.J Natl Cancer Inst. 1980; 65: 311-316PubMed Google Scholar, 8Dhom G Epidemiologic aspects of latent and clinically manifest carcinoma of the prostate.J Cancer Res Clin Oncol. 1983; 106: 210-218Crossref PubMed Scopus (118) Google Scholar, 9Halpert B Sheehan EE Schmalhorst WR Scott Jr, R Carcinoma of the prostate: a survey of 5,000 autopsies.Cancer. 1963; 16: 737-742Crossref PubMed Scopus (47) Google Scholar The 1990 US census (preliminary data) showed that approximately 28,061,000 men 50 years of age or older were living in the United States in 1990. Thus, potentially 8,418,300 men had prostate cancer. This number suggests that the vast majority of cases of prostate cancer remain undetected or “latent.” The discrepancy between the prevalence of latent prostate cancer and the incidence of clinically discovered prostate cancer has contributed to apathy among some physicians relative to detection and therapy. These data, however, merely represent a “snapshot” in time and fail to consider the effect of accumulated risk. As risk accumulates, clinically evident disease will develop in approximately 23% of men with latent prostate cancer, and 30% of these men will die of prostate cancer.10Scardino PT Early detection of prostate cancer.Urol Clin North Am. 1989 Nov; 16: 635-655PubMed Google Scholar Thus, for any American man, the lifetime risk of the development of clinically evident prostate cancer is approximately 10%, and the risk of dying of prostate cancer is 3%. The current and growing magnitude of this health problem emphasizes the need for improved detection and treatment. Although hormonal and chemotherapeutic management of metastatic disease has yielded poor objective response rates, the treatment of pathologically organ-confined prostate cancer has been successful. Currently, the two most common treatments of localized prostate cancer are surgical extirpation of the prostate and radiation therapy. When the disease is pathologically confined to the prostate, surgical removal has been associated with an excellent long-term survival rate and, in comparison with radiation therapy, an advantage in the disease-free survival rate.11Lepor H Walsh PC Long-term results of radical prostatectomy in clinically localized prostate cancer: experience at the Johns Hopkins Hospital.NCI Monogr. 1988; 7: 117-122PubMed Google Scholar, 12Lepor H Kimball AW Walsh PC Cause-specific actuarial survival analysis: a useful method for reporting survival data in men with clinically localized carcinoma of the prostate.J Urol. 1989; 141: 82-84Abstract Full Text PDF PubMed Scopus (51) Google Scholar, 13Paulson DF Randomized series of treatment with surgery versus radiation for prostate adenocarcinoma.NCI Monogr. 1988; 7: 127-131PubMed Google Scholar, 14Brendler CB Steinberg GD Marshall FF Mostwin JL Walsh PC Local recurrence and survival following nerve-sparing radical cystoprostatectomy.J Urol. 1990; 144: 1137-1141PubMed Google Scholar, 15Gibbons RP Correa Jr, RJ Brannen GE Mason JT Total prostatectomy for localized prostatic cancer.J Urol. 1984; 131: 73-76Abstract Full Text PDF PubMed Scopus (137) Google Scholar For organ-confined disease, radical prostatectomy has produced a 15-year cancer-free survival rate, comparable to that of an age-matched control population without cancer.16The management of clinically localized prostate cancer [Consensus Conference].JAMA. 1987; 258: 2727-2730Crossref PubMed Scopus (45) Google Scholar, 17Jewett HJ Bridge RW Gray Jr, GF Shelley WM The palpable nodule of prostatic cancer: results 15 years after radical excision.JAMA. 1968; 203: 403-406Crossref PubMed Scopus (139) Google Scholar Because of the currently available treatment options, detecting prostate cancer before it escapes the confines of the prostate gland is the most important prognostic factor. Although approximately 60% of patients with prostate cancer currently have clinically localized disease (clinical stage A or B) at the time of diagnosis, almost half, when undergoing bilateral pelvic lymphadenectomy or radical prostatectomy, are found not to have organ-confined disease (that is, the disease is either stage C or D1).18Chodak GW Keller P Schoenberg HW Assessment of screening for prostate cancer using the digital rectal examination.J Urol. 1989; 141: 1136-1138Abstract Full Text PDF PubMed Scopus (134) Google Scholar, 19Thompson IM Ernst JJ Gangai MP Spence CR Adenocarcinoma of the prostate: results of routine urological screening.J Urol. 1984; 132: 690-692Abstract Full Text PDF PubMed Scopus (112) Google Scholar, 20Thompson IM Rounder JB Teague JL Peek M Spence CR Impact of routine screening for adenocarcinoma of the prostate on stage distribution.J Urol. 1987; 137: 424-426Abstract Full Text PDF PubMed Scopus (65) Google Scholar Therefore, only a third of patients with prostate cancer currently have the disease detected during a potentially curable, organ-confined stage. The detection of early, organ-confined prostate cancer must be improved. To develop a rational protocol for the use of DRE, PSA testing, and TRUS in the detection of prostate cancer, we must consider the characteristics of the disease, the patient, and the detection methods. The features of prostate cancer that help determine how best to use current detection methods are tumor volume and rate of growth. When McNeal and associates21McNeal JE Bostwick DG Kindrachuk RA Redwine EA Freiha FS Stamey TA Patterns of progression in prostate cancer.Lancet. 1986; 1: 60-63Abstract PubMed Scopus (470) Google Scholar, 22Kabalin JN McNeal JE Price HM Freiha FS Stamey TA Unsuspected adenocarcinoma of the prostate in patients undergoing cystoprostatectomy for other causes: incidence, histology and morphometric observations.J Urol. 1989; 141: 1091-1094PubMed Google Scholar studied prostate cancer from both autopsy and radical prostatectomy specimens, they compared tumor volume, local invasiveness, metastatic involvement, and histologic differentiation. They found that tumor volume correlates strongly with local invasiveness, metastatic potential, and loss of histologic differentiation. Therefore, tumor volume is a major determinant of the biologic behavior of the cancer in that the potential for prostate cancer to metastasize and dedifferentiate probably arises only in tumors that are larger than 1 to 3 ml. Thus, determination of tumor volume preoperatively has a theoretic application of stratifying patients with prostate cancer into those with clinically significant and those with clinically insignificant tumors. In the detection of prostate cancer, tumor volume also relates to the threshold volume at which a cancer becomes identifiable by current detection methods. Quantifying the volume at which DRE can detect prostate cancer is difficult. It depends on the examiner's skill and varies with the site of the tumor within the prostate. The 30% of cancers that occur in the central and transitional zones of the prostate may be more difficult to palpate than the 70% that occur in the peripheral zone.23McNeal JE Price HM Redwine EA Freiha FS Stamey TA Stage A versus stage B adenocarcinoma of the prostate: morphological comparison and biological significance.J Urol. 1988; 139: 61-65Abstract Full Text PDF PubMed Scopus (146) Google Scholar, 24McNeal JE Redwine EA Freiha FS Stamey TA Zonal distribution of prostatic adenocarcinoma: correlation with histologic pattern and direction of spread.Am J Surg Pathol. 1988; 12: 897-906Crossref PubMed Scopus (958) Google Scholar Nevertheless, Cooner and colleagues25Cooner WH Mosley BR Rutherford Jr, CL Beard JH Pond HS Terry WJ et al.Prostate cancer detection in a clinical urological practice by ultrasonography, digital rectal examination and prostate specific antigen.J Urol. 1990; 143: 1146-1154Abstract Full Text PDF PubMed Google Scholar found that the sonographically determined volumes of both palpable and nonpalpable prostate cancer were equivalent (approximately 66% were less than 3 ml). Alternatively, PSA and, more specifically, TRUS do have theoretic threshold volumes for detecting prostate cancer. Stamey and associates26Stamey TA Yang N Hay AR McNeal JE Freiha FS Redwine E Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate.N Engl J Med. 1987; 317: 909-916Crossref PubMed Scopus (2018) Google Scholar calculated that each gram of a malignant lesion of the prostate increases the serum PSA concentration by 0.3 ng/ml (Pros-Check PSA assay, Yang Laboratories, Bellevue, Washington) (0.2 ng/ml per gram for Tandem-R PSA assay, Hybritech, Incorporated, San Diego, California). Although prostate cancer, in theory, produces a constant amount of PSA per volume of tumor, Partin and associates27Partin AW Carter HB Chan DW Epstein JI Oesterling JE Rock RC et al.Prostate specific antigen in the staging of localized prostate cancer: influence of tumor differentiation, tumor volume and benign hyperplasia.J Urol. 1990; 143: 747-752Abstract Full Text PDF PubMed Scopus (530) Google Scholar found that the PSA value does not reflect tumor burden precisely because of the contribution from benign prostatic hyperplasia present in the gland and a decreasing production of PSA in higher-grade lesions. Thus, although an increase in the PSA concentration depends on a minimal tumor volume, confounding factors exist that make it less specific. With current TRUS technology, hypoechogenicity can be identified in tumors with a minimal volume of approximately 0.5 ml (approximately 7 mm in diameter). This volume sensitivity facilitates detection of prostate cancer before the loss of organ confinement and yet avoids detection of small tumors that are likely to be clinically insignificant. Unfortunately, not all cancers produce hypoechogenicity; therefore, even large tumors can be missed with TRUS.28Carter HB Hamper UM Sheth S Sanders RC Epstein JI Walsh PC Evaluation of transrectal ultrasound in the early detection of prostate cancer.J Urol. 1989; 142: 1008-1010PubMed Google Scholar Prostate cancer diagnosed with current detection methods should be considered clinically significant because of the lack of volume specificity and the high threshold volumes at which it is detectable. Rate of growth is another important disease characteristic that influences the development of a protocol for the detection of prostate cancer. In theory, cancer with a short doubling time necessitates frequent evaluations if malignant involvement is to be detected at an early stage. Conversely, cancer with a longer doubling time, such as prostate cancer, may provide a wider window of opportunity for detection. During follow-up of 230 men with untreated prostate cancer, Stamey and Kabalin29Stamey TA Kabalin JN Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. I. Untreated patients.J Urol. 1989; 141: 1070-1075Abstract Full Text PDF PubMed Google Scholar noted that the rate of increase in serum PSA concentration in patients with clinical stage A and B cancer suggested a doubling time of at least 2 years. If patients with prostate cancer are examined annually, physicians will have several opportunities to identify the cancer at a potentially curable stage. To use DRE, PSA testing, and TRUS appropriately for the early detection of prostate cancer, clinicians must also consider predisposing factors in the development of this malignant disease. As noted previously, age is the most important factor (Fig. 1). In the United States, less than 1% of prostate cancers are detected in men younger than 50 years of age, 16% are discovered in men 50 to 64 years old, and the remaining 83% are detected in men older than 64 years of age.30National Cancer Institute Cancer Statistics Review, 1973-88. National Cancer Institute, Bethesda (MD)1991Google Scholar Because of the low incidence in men younger than 50 years of age, expending substantial resources for detection in this group is unnecessary unless other risk factors for prostate cancer exist. Men older than 50 years of age, however, are at considerably increasing risk for the development of prostate cancer. Consequently, for men 50 years of age or older, annual examination of the prostate gland for malignant tumor is strongly recommended; however, this recommendation must be balanced with the patient's state of health and life expectancy. For example, a 60-year-old man with metastatic lung cancer would be unlikely to benefit from efforts to detect prostate cancer, whereas a 70-year-old man in perfect health has a 12-year mean life expectancy and therefore may benefit from the early detection of prostate cancer. This balance of the risk of prostate cancer versus the potential benefit of early detection must be determined by the clinician for each patient before subjecting the person to a program for the detection of early prostate cancer. Although annual assessment for prostate cancer need not begin until 50 years of age in most men, detection efforts at an earlier age may be warranted in men at high risk. Recently, family history was identified as a significant risk factor for prostate cancer. In a case-control study of 691 men by Steinberg and colleagues,31Steinberg GD Carter BS Beaty TH Childs B Walsh PC Family history and the risk of prostate cancer.Prostate. 1990; 17: 337-347Crossref PubMed Scopus (543) Google Scholar prostate malignant disease was twic as likely to develop in a patient who had one first-degree relative with prostate cancer than in those with no family history of the disease. When two or three first-degree relatives were affected, the corresponding risks for development of prostate cancer were 5 and 11 times higher. Further data from Spitz and associates32Spitz MR Currier RD Fueger JJ Babaian RJ Newell GR Familial patterns of prostate cancer: a case-control analysis.J Urol. 1991; 146: 1305-1307Abstract Full Text PDF PubMed Scopus (162) Google Scholar confirmed those findings. Clearly, because of the current 10% lifetime risk for the development of prostate cancer, men with a family history of the disease should undergo detection efforts commensurate with their high-risk status. Finally, data from the Surveillance, Epidemiology, and End-Results program of the National Cancer Institute indicate that the risk of development of prostate cancer is 50% higher in black men than in white men.33Mebane C Gibbs T Horm J Current status of prostate cancer in North American black males.J Natl Med Assoc. 1990; 82: 782-788PubMed Google Scholar Although several factors have been attributed to this difference, none has been clearly implicated. Regardless, black men have an increased risk for prostate cancer and therefore warrant more vigorous detection efforts. In summary, annual examination of the prostate for malignant tumor need not begin until 50 years of age for men who have no risk factors for prostate cancer. In black men and in men with a family history of prostate cancer, however, we recommend annual examinations beginning at age 40 years. DRE, the traditional means of evaluating the prostate gland for the presence of malignant disease, is still recommended by the American Cancer Society as an annual assessment in men 40 years of age or older.34Update January 1992: the American Cancer Society guidelines for the cancer-related checkup.CA Cancer J Clin. 1992; 42: 44-45Crossref PubMed Scopus (53) Google Scholar This detection method is subjective; it relies on a high degree of suspicion by the examiner and experience in determining the size, consistency, nodularity, and asymmetry of the prostate. Previous large-scale studies that reviewed the effects of screening for prostate cancer by using DRE concluded that it was beneficial; the 5- and 10-year survival rates were similar to those of age-matched control subjects.20Thompson IM Rounder JB Teague JL Peek M Spence CR Impact of routine screening for adenocarcinoma of the prostate on stage distribution.J Urol. 1987; 137: 424-426Abstract Full Text PDF PubMed Scopus (65) Google Scholar, 35Jenson CB Shahon DB Wangensteen OH Evaluation of annual examinations in the detection of cancer: special reference to cancer of the gastrointestinal tract, prostate, breast, and female generative tract.JAMA. 1960; 174: 1783-1788Crossref PubMed Scopus (19) Google Scholar, 36Gilbertsen VA Cancer of the prostate gland: results of early diagnosis and therapy undertaken for cure of the disease.JAMA. 1971; 215: 81-84Crossref PubMed Scopus (51) Google Scholar Additionally, men with prostate cancer diagnosed beyond the initial year of screening had clinically localized disease more frequently than did men diagnosed during initial screening. Nevertheless, the ability of DRE to detect prostate cancer in an early, organ-confined stage in asymptomatic men has been questioned. As noted previously, among men whose initial diagnosis of clinically localized prostate cancer was established by DRE, the pathologic stage of disease increased in approximately half after total prostatectomy. The remaining men with prostate cancer, however, had organ-confined disease and, therefore, were potentially curable. Other criticisms of previous studies that suggested a beneficial effect of screening by DRE include the lack of randomization and the susceptibility to lead-time bias. The sensitivity, specificity, positive predictive value, and detection rate of DRE have been estimated by various investigators (Table 1). These values, however, become difficult to interpret because an assumed prevalence rate is used in computation and an actual false-negative rate is unobtainable because normal prostates are not pathologically examined. In addition, the issue of whether DRE discovers primarily clinically significant cancers cannot be evaluated without a long-term, randomized, controlled trial. Nevertheless, the simplicity, low cost, and lack of adverse effects in combination with the ability to detect some cases of potentially curable prostate cancer ensure its continued use.Table 1Representative Sensitivity, Specificity, Positive Predictive Value, and Detection Rates of Digital Rectal Examination, Serum Prostate-Specific Antigen Value, and Transrectal Ultrasonography in the Evaluation for Prostate CancerMethod*DRE = digital rectal examination; PSA = prostate-specific antigen; TRUS = transrectal ultrasonography.Sensitivity (%)Specificity (%)Positive predictive value (%)Detection rate (%)DRE18Chodak GW Keller P Schoenberg HW Assessment of screening for prostate cancer using the digital rectal examination.J Urol. 1989; 141: 1136-1138Abstract Full Text PDF PubMed Scopus (134) Google Scholar, 37Guinan P Bush I Ray V Vieth R Rao R Bhatti R The accuracy of the rectal examination in the diagnosis of prostate carcinoma.N Engl J Med. 1980; 303: 499-503Crossref PubMed Scopus (74) Google Scholar, 38Brooman PJC Peeling WB Griffiths GJ Roberts E Evans K A comparison between digital examination and per-rectal ultrasound in the evaluation of the prostate.Br J Urol. 1981; 53: 617-620Crossref PubMed Scopus (32) Google Scholar69–8984–9826–351.3–1.7PSA39Oesterling JE Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate.J Urol. 1991; 145: 907-923Abstract Full Text PDF PubMed Scopus (1173) Google Scholar, 40Catalona WJ Smith DS Ratliff TL Dodds KM Coplen DE Yuan JJJ et al.Measurement of prostate-specific antigen in serum as a screening test for prostate cancer.N Engl J Med. 1991; 324: 1156-1161Crossref PubMed Scopus (1885) Google Scholar, 41Brawer MK Chetner MP Beatie J Buchner DM Vessella RL Lange PH Screening for prostatic carcinoma with prostate specific antigen.J Urol. 1992; 147: 841-845Abstract Full Text PDF PubMed Google Scholar57–7959–6840–492.2–2.6TRUS42Lee F Littrup PJ Torp-Pedersen ST Mettlin C McHugh TA Gray JM et al.Prostate cancer: comparison of transrectal US and digital rectal examination for screening.Radiology. 1988; 168: 389-394Crossref PubMed Scopus (201) Google Scholar, 43Cooner WH Prostate-specific antigen, digital rectal examination, transrectal ultrasonic examination of the prostate in prostate cancer detection.Monogr Urol. 1991; 12: 3-13Google Scholar36–8541–7927–362.6* DRE = digital rectal examination; PSA = prostate-specific antigen; TRUS = transrectal ultrasonography. Open table in a new tab PSA, a serine protease produced only by prostatic epithelial cells, is the only known organ-specific serum marker, and its use in the follow-up of patients with prostate cancer who are undergoing treatment is well substantiated.44Oesterling JE Chan DW Epstein JI Kimball Jr, AW Bruzek DJ Rock RC et al.Prostate specific antigen in the preoperative and postoperative evaluation of localized prostatic cancer treated with radical prostatectomy.J Urol. 1988; 139: 766-772Abstract Full Text PDF PubMed Scopus (500) Google Scholar, 45Stamey TA Kabalin JN McNeal JE Johnstone IM Freiha F Redwine EA et al.Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. II. Radical prostatectomy treated patients.J Urol. 1989; 141: 1076-1083Abstract Full Text PDF PubMed Scopus (675) Google Scholar, 46Stamey TA Kabalin JN Ferrari M Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. III. Radiation treated patients.J Urol. 1989; 141: 1084-1087Abstract Full Text PDF PubMed Scopus (158) Google Scholar, 47Stamey TA Kabalin JN Ferrari M Yang N Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate. IV. Anti-androgen treated patients.J Urol. 1989; 141: 1088-1090Abstract Full Text PDF PubMed Scopus (179) Google Scholar Using the serum PSA value for detecting prostate cancer, however, has been controversial. Both normal and malignant cells produce PSA; therefore, both benign and malignant processes may increase the serum PSA level. Benign prostatic hyperplasia is the most common benign process that may increase the serum PSA concentration mildly to moderately. When several investigators compared the serum PSA levels in patients who had prostate cancer with the levels in patients who had benign prostatic hyperplasia, the difference in the serum PSA increase was statistically significant.27Partin AW Carter HB Chan DW Epstein JI Oesterling JE Rock RC et al.Prostate specific antigen in the staging of localized prostate cancer: influence of tumor differentiation, tumor volume and benign hyperplasia.J Urol. 1990; 143: 747-752Abstract Full Text PDF PubMed Scopus (530) Google Scholar, 48Lange PH Ercole CJ Lightner DJ Fraley EE Vessella R The value of serum prostate specific antigen determinations before and after radical prostatectomy.J Urol. 1989; 141: 873-879Abstract Full Text PDF PubMed Scopus (429) Google Scholar, 49Hudson MA Bahnson RR Catalona WJ Clinical use of prostate specific antigen in patients with prostate cancer.J Urol. 1989; 142: 1011-1017Abstract Full Text PDF PubMed Scopus (414) Google Scholar Unfortunately, the overlap in individual patient values is considerable. For example, in one study,39Oesterling JE Prostate specific antigen: a critical assessment of the most useful tumor marker for adenocarcinoma of the prostate.J Urol. 1991; 145: 907-923Abstract Full Text PDF PubMed Scopus (1173) Google Scholar 43% of men with prostate cancer had a normal serum PSA value, and approximately 25% of men with benign prostatic hyperplasia had a serum PSA
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