Japanese Journal of Clinical Oncology Advance Access published online on October 3, 2007
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hym093
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© 2007 Foundation for Promotion of Cancer Research
Histological Diagnosis of Prostate Cancer in Korean Men Aged 70–79 Years
1 Department of Urology, Seoul Veterans Hospital, Seoul
2 Department of Urology, Seoul National University College of Medicine, Seoul
3 Department of Urology, DongGuk University International Hospital, Goyang, Korea
For reprints and all correspondence: Ja Hyeon Ku, Department of Urology, Seoul National University Hospital, 28, Yongon Dong, Jongno Ku, Seoul 110-744, Korea. E-mail: randyku{at}hanmail.net
Received March 29, 2007; accepted June 8, 2007
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Abstract |
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 TOP Abstract INTRODUCTIONPATIENTS AND METHDODSRESULTSDISCUSSIONReferences |
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Background: The objective of this study was to evaluate the value of the prostate-specific antigen (PSA) in the diagnosis of prostate cancer in elderly Korean men, aged 70–79 years.
Methods: Patients with an abnormal digital rectal examination (DRE) and/or a serum PSA level greater than 2.0 ng/ml underwent a biopsy. A total of 344 men (median age 73 years) constituted the study cohort.
Results: Of 344 men, 163 (47.4%) were diagnosed with prostate cancer upon initial biopsy. The positive predictive value (PPV) for cancer was 48.4% for a PSA cutoff of 4 ng/ml, 65.3% for a cutoff of 10 ng/ml, and 87.0% for a cutoff of 20 ng/ml. When combined with an abnormal DRE, the predictive values for these PSA cutoffs increased to 79.3, 87.3 and 100%, respectively. When 10 ng/ml was chosen as a PSA cutoff level, about 50% of patients were found to have a Gleason score of 7 or higher. When 4 ng/ml was chosen as a PSA cutoff level, more than 50% of patients with an abnormal DRE were found to have a Gleason score of 7 or higher.
Conclusions: In elderly men, more than 50% of patients are found to have cancers with a Gleason score of 7 or higher when their PSA level is greater than 10 ng/ml. This threshold may be lowered to 4 ng/ml in the presence of an abnormal DRE. Our findings provide a rationale for recommending a prostate biopsy in elderly patients with an abnormal DRE and/or an elevated serum PSA level. However, at present, it is not clear whether elderly men have better outcomes when they undergo cancer screening.
Key Words: prostate-specific antigen • prostate neoplasm • prostate cancer • prostate biopsy • elderly
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INTRODUCTION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHDODSRESULTSDISCUSSIONReferences |
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Prostate cancer is predominantly a disease of elderly men. While no age has been established above which prostate-specific antigen (PSA) testing is not recommended, there is general agreement that men with a less than 10-year life expectancy are unlikely to benefit from early detection because of the long natural history of untreated, localized prostate cancer and competing causes of death. The Prostate Patient Outcomes Research Team (PPORT) reported on the national Medicare experience with prostate cancer treatment outcomes in 1993, concluding that aggressive treatment of prostate cancer in patients aged 70 years and older was generally harmful (1). The U.S. Preventive Services Task Force also suggested that men younger than 70 years old were most likely to experience any benefit from routine PSA screening (2). Thus, most of the results concerning PSA screening for prostate cancer involve cancer detection in a younger population, aged 40–70 years.
Despite the consensus that testing in the elderly has little benefit, some circumstantial information has suggested that there is a high prevalence of screening among elderly men (3–5). Screening rates for prostate cancer by serum PSA testing appear to be higher in men older than 70 years than in those 50–65 years old (6,7). Jerant et al. (8) analyzed data from the 2001 Behavioral Risk Factor Surveillance System (BRFSS) and found that PSA screening increased steadily from the age of 50 years through 75–79 years. As a result of a prolonged life expectancy, an increasing number of elderly men would be diagnosed with prostate cancer.
Several reports have revealed that patients over 70 years old with localized prostate cancer undergo disproportionately conservative therapy (9–13). Using a decision-analytic model, Schwartz et al. (14) estimated that otherwise healthy men 70 years old or older with localized prostate cancer are often subjected to watchful waiting and, as a result, potentially lose valuable years of life. Albertsen et al. (15) suggested that men whose biopsy specimens were assigned a Gleason score of 7–10 faced a high risk of death from prostate cancer when treated conservatively, even when the cancer was diagnosed as late as 74 years of age. Recent decision models have also suggested that some patient groups (e.g. healthy men older than 70 years with moderately or poorly differentiated tumors) may benefit from curative treatment (16). Although the health and life expectancy of each individual should be taken into account to avoid unnecessary screening, if many older patients with moderate- to high-grade disease benefit from potentially curative therapy, this could justify studying prostate cancer detection in the elderly.
However, to date, there is little discussion of a biopsy strategy in elderly men. In the study by Richie et al. (17), when a biopsy was performed at a PSA threshold of 4 ng/ml or after a suspicious DRE, the cancer detection rate was greater in men 80 years or older (14%) than in men aged 50–59 (3%). The positive predictive values (PPVs) for PSA were 32% (50–59 years), 30% (60–69 years), 34% (70–79%) and 38% (80+ years). Sung et al. (18) reported that prostate cancer was found in 56.8% of men age 70 years or older. The cancer detection rate was significantly higher (81.0%) in patients aged 80 years and older than those younger than 80 years. In another study, in men with gray-zone PSA (2–10 ng/ml), the overall cancer detection rate was 26.0% and prostate cancer detection was equally distributed over all PSA ranges (19).
We evaluated the cancer detection rate and the pathologic findings of biopsy in elderly Korean men aged 70–79 years. The objective of this study was to evaluate the value of PSA for prostate cancer diagnosis in this population.
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PATIENTS AND METHDODS |
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We reviewed the records of 1369 patients undergoing a transrectal ultrasonography (TRUS)-guided prostate biopsy at the Department of Urology in three hospitals. From July 2003 to June 2005, we enrolled individuals who visited our department for a variety of reasons, including prostate cancer screening and voiding symptoms, regardless of whether the visit was primary or referred. Patents with an abnormal digital rectal examination (DRE) and/or a serum PSA level greater than 2.0 ng/ml underwent a biopsy by a radiologist after patients provided written informed consent. Of these patients, some had previously undergone prostate biopsy.
All men underwent detailed clinical examinations, including determination of serum levels of total PSA quantified by immunoradiometric assay (Izotop, Hungary), DRE and TRUS. Blood samples were obtained before patients were examined by a physician. All blood was stored at –70°C for less than 1 week, and assayed for serum PSA concentration. Transaxial and sagittal scanning of the prostate was performed by a radiologist experienced in this procedure, using a 7.0 MHz transducer (Ultramake 9, ATL Inc., Washington, USA). In specimens diagnosed with prostate cancer, an additional review was performed to ascertain the Gleason score and the percentage of cancer cores (number of cores involved with cancer divided by the total number of biopsy cores).
Men were excluded from the analysis if they were younger than 70 years old or 80 years or older, had previously undergone prostate biopsy, had received a prior diagnosis of prostate cancer, had undergone prostate surgery or radiation treatment, had received 5
-reductase inhibitors, had acute urinary retention or an indwelling catheter, had gone more than 3 months between PSA measurement and biopsy or had evidence of acute urinary infection (pyuria and bacteriuria) on urinalysis. A total of 344 men aged 70–79 years (median 73) met these criteria and constituted the study cohort. The median prostate volume of the patients was 43 cm3 (range 12–170 cm3) and their serum PSA ranged from 2.2–4100 ng/ml (median 8.4 ng/ml).
Values of continuous variables are presented as a median (range) and rates are expressed as a number (%). Patients were divided into the cancer group and the no cancer group. Comparisons of data were made using the chi-square test for categorical variables and the Mann–Whitney U-test for continuous variables. To evaluate risk factors for prostate cancer, odds ratios (ORs) for prostate cancer with respect to age, PSA, prostate volume, DRE, number of cores per biopsy and core density, along with P values for trends were estimated by multivariate logistic regression analysis. Patients were stratified by age into two groups: those younger than 75 years and those 75 years or older. PSA was sorted into four categories, that is 2–3.9, 4–9.9, 10–19.9 and 20 ng/ml or greater. Prostate volume was classified as less than 40 ml, or 40 ml or greater. Number of cores per biopsy was defined as less than 12, or 12 or more. Core density loss was categorized as less than 25, or 25 or greater. Associations among these parameters and prostate cancer were described using maximum likelihood estimates of relative risk and the 95% confidence interval (CI) based on the multiple logistic regression model. A 5% level of significance was used for all statistical testing and all statistical tests were two-sided. The accuracy of PSA, alone or in conjunction with DRE findings, in predicting cancer, moderate to high-grade (Gleason score 
5) cancer, high-grade (Gleason score 8) cancer, or cancer with a Gleason score 7 was determined for these patients. Positive predictive values (PPVs) were calculated for PSA ranges and PSA cutoffs. We assessed whether serum PSA are discriminative for prostate cancer using the area under the receiver operating characteristic curve. The area under the curve is a suitable parameter to summarize the overall discriminative or diagnostic value of a model and can range from 0.5 (flipping a coin, a useless model) to 1.0 (perfect discrimination). The more the area under the receiver operating characteristic curve approached 100% (i.e. the more the receiver operating characteristic curve approached the upper left corner), the greater the predictive power. The statistical software package SPSS 10.0 (SPSS Inc., Chicago, IL, USA) was used for all statistical analyses.
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RESULTS |
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TOPAbstractINTRODUCTIONPATIENTS AND METHDODSRESULTSDISCUSSIONReferences |
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The cancer detection rate was 8% for men 40–49 years old, 19.5% for 50–59 years old, and 30.3% for 60–69 years old. The incidence of cancer with a Gleason score of 7 or higher was 5.3, 14.6 and 21.6% in those age groups, respectively (data not shown). Of 344 men 70–79 years old, 163 (47.4%) were diagnosed with prostate cancer on initial biopsy. Characteristics of the patients are reported in Table 1. There was no significant difference in age between the cancer group and the no cancer group. Patients who were diagnosed with cancer on initial biopsy had higher PSA levels (P < 0.001), lower PSA density levels (P < 0.001), smaller prostates (P < 0.001) and more abnormal DRE findings (P < 0.001) than those who were not diagnosed with cancer. There were no statistically significant differences in the number of cores per biopsy between the two groups but core density (number of cores divided by the prostate volume) was higher in the cancer groups (P < 0.001).
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To evaluate risk factors for prostate cancer, logistic regression analyses were performed. Univariate analysis indicated that PSA, prostate volume, DRE, number of cores per biopsy and core density were the possible risk factors. These variables were included in the multivariate logistic model. A PSA level of 4–9.9 had a 3-fold higher risk (OR 2.96; 95% CI 1.01–8.63; P = 0.047), a PSA level of 10–19.9 had a 7-fold higher risk (OR 6.99; 95% CI 2.26–21.68; P = 0.001) and PSA level greater than 20 ng/ml had a 40-fold higher risk (OR 40.31; 95% CI 10.41–156.09, P < 0.001) of prostate cancer than did a PSA level of 2–3.9. In the same model, the likelihood of prostate cancer was associated with all other variables (prostate volume, DRE, number of core per biopsy and core density). These results are shown in Table 2.
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The PPVs of different serum PSA ranges alone or in combination with DRE findings are listed in Table 3. In all patients, the PPV was 27.3% for a PSA of 2–3.9, 35.4% for a PSA of 4–9.9, 52.2% for a PSA of 10–10.9 and 87.0% for a PSA of 20 ng/ml or greater. The PPV for cancer with a Gleason score of 7 or higher was 18.2, 17.4, 34.4 and 77.8% in those PSA groups, respectively. In patients with an abnormal DRE, the values for these PSA ranges increased to 25.0, 67.6, 74.1 and 100%, respectively. In these patients, the PPV for cancer with a Gleason score of 7 or higher was 25.0, 35.1, 48.1 and 92.9%, respectively.
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Table 4 lists the PPVs for various PSA cutoffs alone or in combination with DRE findings. The PPV was 48.4% for a PSA cutoff of 4, 65.3% for a cutoff of 10 and 87.0% for a cutoff of 20 ng/ml. When 10 ng/ml was chosen as a PSA cutoff level, about 50% of patients were found to have a Gleason score of 7 or higher. In conjunction with an abnormal DRE, the values for these PSA cutoffs increased to 79.3, 87.3 and 100%, respectively. When 4 ng/ml was chosen as a PSA cutoff level, more than 50% of patients with an abnormal DRE finding were found to have a Gleason score of 7 or higher.
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In total patients, the area under the receiver operating characteristic curve of triglyceride was 69.9% (95% CI, 64.4–75.5%) for prostate cancer. Using the standard cutoff of 4 ng/ml, a sensitivity of 96.3% and a specificity of 8.3% were observed. Figure 1 presents the area under the receiver operating characteristic curves for the discriminative value of serum PSA on prostate cancer.
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DISCUSSION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHDODSRESULTSDISCUSSIONReferences |
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Generally, the detection rate of prostate cancer in Asian men is lower than that in American men (20–22). Improved specificity is important, especially in Asian men, as they generally have lower PSA levels (23,24). Since appropriate guidelines for PSA testing have not been defined in the elderly, there is disagreement over what PSA level should prompt a prostate biopsy in these men. Although the incidence of prostate cancer increases with age, Morgan et al. (25) clearly reported an age-related decline in PSA specificity. Richie et al. (17) demonstrated that, when quadrant biopsies of the prostate were performed in response to a PSA > 4 ng/ml or a suspicious DRE, the PPV for PSA was 34% in men aged 70–79 years. In Japanese men 70 years or older with gray-zone PSA (2–10 ng/ml), the overall cancer detection rate was 26.0% (19).
Knowledge of the PPVs presented in this study may be important for counseling elderly Asian men with a high PSA before they undergo biopsy. Although serious co-morbidities or prior anticoagulation may be contraindications for the procedure, the estimated major complication rate of the procedure, defined as a need for hospitalization or intravenous therapy, was only 1.9%, according to a recent series (26). Thus, elderly men with an abnormal serum PSA level or with an abnormal DRE finding should undergo biopsy since a number of those patients have clinically significant prostate cancer.
Some issues should be considered. First, in this study, patients did not undergo a repeat biopsy after a negative initial biopsy, and, thus, the study may underestimate the accuracy of PSA levels. Second, it must be recognized that our results relate to a specific group of men and that people of different ethnicities may have different experiences because serum PSA levels are race-dependent, as well as age-dependent. Third, no data regarding a family history of prostate cancer were included in the study. Fourth, in the present study, only patents with an abnormal DRE and/or serum PSA level greater than 2.0 ng/ml underwent a biopsy. Recently, Thompson et al. (27) reported the prevalence of prostate cancer among men with a serum PSA of less than 4 ng/ml and normal DRE findings. Of almost 3000 men in the group, 15% had prostate cancer, and, of these cancers, 15% were high-grade (a Gleason score of 7–9). Thus, our results may overestimate the sensitivity of the PSA test. Finally, since the predictive value of the screening tests may be different among patients presenting with symptoms as opposed to the general population, our data may not apply to population-based screening.
Overall, our findings provide a rationale for recommending prostate biopsy in elderly men aged 70–79 years with an abnormal DRE and/or an elevated serum PSA level. However, proceeding to prostate biopsy in this population may increase the risks of overdiagnosis and overtreatment since, at present, it is not clear that elderly men have better outcomes when they undergo cancer screening. In addition, definitions of what might be aggressive disease are likely not to be applicable to the individual patient. Without being able to correlate these findings to important endpoints, such as prostate cancer mortality, it will be impossible to determine what may be a clinically important cancer.
Conflict of interest statement
None declared.
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