Evaluation of the digital rectal examination as a screening test for prostate cancer. Rotterdam section of the European Randomized Study of Screening for Prostate Cancer

BACKGROUND: The utility of digital rectal examination (DRE) as a screening test for early detection of prostate cancer has not been established. Therefore, we evaluated the usefulness of DRE as a stand-alone screening test and in conjunction with measured serum prostate-specific antigen (PSA) levels of 0-3.9 ng/mL and transrectal ultrasonography (TRUS). METHODS: Our study population consisted of 10,523 men aged 54-76 years who were randomly assigned to the screening arm of the Rotterdam, The Netherlands, section of the European Randomized Study of Screening for Prostate Cancer. The underlying prevalence of detectable prostate cancer was estimated by logistic regression analysis and used for calculating the sensitivity of DRE as a test. Pathologic characteristics of 105 radical prostatectomy specimens were used to determine the aggressiveness of the tumors diagnosed (and missed) by DRE. RESULTS: The overall detection rate for prostate cancer in this population when serum PSA measurement, DRE, and TRUS were used was 4.5%, and the detection rate with DRE alone was 2.5%. The positive predictive value of DRE ranged from 4% to 11% in men with PSA levels of 0-2.9 ng/mL and from 33% to 83% in men with PSA levels of 3.0-9.9 ng/mL or more. Most tumors detected by DRE in men with PSA levels of less than 4.0 ng/mL were small (mean volumes = 0.24-0.83 mL), and most were well differentiated (Gleason scores of 6 or less). Minimal, moderate, and advanced cancers were seen in 42%, 42%, and 16% of men, respectively, with a PSA level of 4.0 ng/mL or less. DRE alone allowed detection of 264 (55.8%) of 473 cancers; 82 (17.3%) of the 473 cancers would have remained undetected by PSA-based screening alone (i.e., no follow-up procedures for PSA values of 0-3.9 ng/mL). CONCLUSIONS: For PSA values of 0-3.9 ng/mL, the positive predictive value and sensitivity of DRE, tumor volume, and tumor grade were strongly dependent on PSA level. DRE has a poor performance in low PSA ranges.     

The efficacy of PSA density for the early detection of prostate cancer

OBJECTIVE: We studied on the efficacy of prostate specific antigen density (PSAD) for the detection of prostate cancer among patients with intermediate serum PSA levels. MATERIALS AND METHODS: Transrectal ultrasonography (TRUS) and transrectal prostate biopsy were performed in 103 patients whose PSA levels were 10 ng/ml or less despite positive digital rectal examination(DRE) or whose PSA levels were intermediate (4 to 10 ng/ml). Prostate volume was determined by TRUS and PSAD was calculated (serum PSA divided by volume of entire prostate volume). The rate of positive biopsy was compared with PSAD (more than 0.15 versus less than 0.15), DRE (positive versus negative) and patient's age (more than 61 versus 60 or less). RESULTS: The overall cancer detection rate was 43.7% in this study. There was no apparent correlation between patient's age and cancer detection rate when the patient's age was more than 61. DRE itself was not effective for the detection of prostate cancer in the patients whose PSA level was 10 ng/ml or less. Independent of DRE findings, the rate of positive biopsy was double in the patients whose PSAD was more than 0.15, compared with the patients whose PSAD was less than 0.15. CONCLUSIONS: For the early detection of prostate cancer, PSA density may be useful in the selection of patients for transrectal prostate biopsy.     

Organic dust exposures from compost handling: case presentation and respiratory exposure assessment

This study was designed to determine the effects of age by decade on the efficacy of digital rectal examination (DRE) and serum prostate-specific antigen (PSA) for early detection of prostate cancer in men aged fifty and over. A prospective multicenter clinical trial was conducted at six university centers. All 6,630 male volunteers underwent a serum PSA (Hybritech, Tandem) determination and DRE. Quadrant biopsies of the prostate were performed if PSA was > 4 ng/mL or DRE suspicious. A total of 1,167 biopsies were performed, and 264 cancers were detected. The cancer detection rate increased from 3 percent in men aged fifty to fifty-nine to 14 percent in men eighty years or older (p < 0.0001). PSA detected significantly more of the total cancers than DRE at all age ranges (p < 0.05). The positive predictive values (PPV) for PSA were 32 percent (50-59 years), 30 percent (60-69 years), 34 percent (70-79 years), and 38 percent (80+ years). The corresponding PPVs for DRE were 17 percent, 21 percent, 25 percent, and 38 percent. Eighteen percent of the cancers were detected solely by DRE, whereas 45 percent of cancers were detected solely by PSA. Thus, the use of both tests in combination provided the highest rate of detection in all age groups. One hundred-sixty patients underwent radical prostatectomy and pathologic staging. Cancer was organ-confined in 74 percent (25/34) of men aged fifty to fifty-nine, 76 percent (65/86) of men aged sixty to sixty-nine, and 60 percent (24/40) of men aged seventy or over (chi 2, < 70 vs. > or = 70, p < 0.05). Early detection programs yield a lower, yet still substantial, cancer detection rate in younger men, and there is a greater likelihood for detection of organ-confined disease in this age range. Younger men have the longest projected life expectancy and, therefore, the most to gain from early prostate cancer detection.     

Prostate-specific antigen in the diagnosis of organ-confined treatable prostate carcinoma

Prostate cancer is now the most common cancer and the second most common cause of death from cancer among men. Several studies have shown a frequency of autopsy-detected cancer of 40% in men over 50 years of age. In contrast, the lifetime probability of prostate cancer being diagnosed clinically is only 8%. Thus histologically documented prostate cancer only becomes clinically relevant if the tumors are > 0.5 cm3 and the life expectancy exceeds 10 years. Therapy with curative intention is only possible for organ confined disease. Because disease specific survival is about 80-90% after 10 years for conservative treatment of organ confined disease, early detection of prostate cancer is useful for patients with a life expectancy > 10 years. Organ confined prostate cancer is usually asymptomatic. The use of prostate specific antigen (PSA) combined with digital rectal examination (DRE) results in a 2-3 fold increase in prostatic carcinoma detection rate, especially of organ confined disease, by PSA. In men with a minimally elevated PSA-value of 4-10 ng/ml (Hybritech Assays), 25% will have a prostatic carcinoma regardless of the finding of the DRE, which would have reached clinical significance in the follow-up. The indication for biopsy should be established at an early date. There is no support for the common opinion that early detection programs detect clinically unimportant cancers. 95% of tumor volumes are > 0.5 cm3. Furthermore only 3-5% of subjects show prostate cancer in detection programs though 8% will develop clinical symptoms of prostate cancer during their lifetime. This difference is a reason for longitudinal programs with PSA and DRE control once a year, as proposed by the American Cancer Society and the American and Canadian Urological Association, in contrast to other health care organizations, which would wait with general screening until data from prospective randomized trials with beneficial effects of screening are available. To introduce prostate cancer therapy with curative intention for symptomatic patients as well, the cancer should be detected below a PSA level of 10 ng/ml. Insufficient specificity of PSA (2-4 patients have to undergo biopsies to detect one cancer patient) is still an unsolved problem.     

Prostate cancer screening--a physician survey in Missouri

This study investigated prostate cancer screening practices using prostate specific antigen testing (PSA), digital rectal examination (DRE), and transrectal ultrasonography (TRUS) by primary care physicians in Missouri. In 1993, a mail survey was sent to a stratified random sample of 750 physicians whose primary specialty was general practice, family practice, or internal medicine. Three separate mailings resulted in an overall adjusted response rate of 60 percent. Ninety-five percent of physicians were more inclined to use PSA compared with three years previously, with only 45 percent of physicians more inclined to use DRE. An increase in the use of PSA following a negative DRE was reported by 85 percent and a greater inclination to use TRUS following a positive PSA was reported by 90 percent Eighty-six percent agreed with the American Cancer Society (ACS) guidelines on prostate cancer screening. Using logistic regression adjusted across levels of demographic and practice factors, prevalence odds ratios were derived with results indicating that agreement with ACS guidelines and being in private practice are strong predictors of a physician's inclination to routinely screen asymptomatic patients for prostate cancer. Our findings have provided baseline information on prostate cancer screening in Missouri and suggest that primary care physicians view PSA testing as a useful procedure and appear to be using it in a manner similar to the general pattern seen across the country.     

The presence of atopy does not determine the type of cellular infiltrate in nasal polyps

Prostate cancer screening with DRE, TRUS, and PSA testing was offered to 2,400 randomly selected men 55-70 years old. Among 1,782 examined, 65 (3.6%) men with prostate cancer were diagnosed. The PSA results were correlated to the diagnosis, the men's age, and the prostate volume. Least square regression analysis was used to calculate the 95% upper confidence intervals for PSA in each year of age in men without prostate cancer. The PPV was calculated for: (i) PSA > 4 ng/ml, (ii) PSAD > 0.15, (iii) PSAD > 0.20 and (iv) age-adjusted PSA reference values. A significant correlation was found between PSA and prostate volume, between PSA and age, and between the prostate volume and age. The calculated annual growth of the prostate was 1.6% and the annual increase in PSA was 2.4%. The age-adjusted upper PSA reference values for the three age categories studied (55-59, 60-64 and 65-70 years) were 5.2, 5.8, and 6.7 ng/ml, respectively. The PPVs for PSA > 4 ng/ml, PSAD > 0.15, PSAD > 0.20, and the age-adjusted PSA reference values were 17%, 14%, 22%, and 27%, respectively. Age-adjusted PSA or PSAD may increase the PPV compared to PSA > 4 ng/ml. The detection rate is, however, inadequate. A PSA cut-off at 4 ng/ml could therefore be maintained in men 55-70 years old. The median PSA values and median prostate volumes calculated for men with benign findings may serve as a reference in future studies.     

Screening for prostate cancer

In an attempt to detect prostate cancer when the tumor is still confined to the prostate, a screening program was established. We studied the efficacy of digital rectal examination (DRE) and serum prostate-specific antigen (PSA) in the early detection of prostate cancer. One thousand men aged 50-75 years underwent DRE and serum PSA determination. Transrectal ultrasound-guided biopsies were obtained in each case of a suspicious DRE. Six systematic biopsies were performed if the PSA level was > 10 ng/ml, even if DRE and transrectal ultrasonography revealed no areas suspicious of cancer. A suspicious DRE was noted in 11.5% of the subjects; 16% had elevated levels of serum PSA (> 4 ng/ml) and 3.9% had serum PSA > 10 ng/ml. Biopsies were obtained from 90 patients, of which 31 were positive for prostate cancer. The cancer detection rate was 2.2% for DRE, 2.0% for PSA > 10 ng/ml, and 3.1% for the two methods combined. Clinical staging revealed that in 29 of the 31 patients with prostate cancer, the tumor was confined to the prostate: Stage A in 9 cases and stage B in 20 cases. Only two patients had clinically advanced cancer, and 22 patients underwent radical prostatectomy. Pathological examination disclosed biologically significant tumors in 91% of the cases in terms of tumor volume and grade. Although there is little evidence that screening will result in the reduction of the disease-specific mortality rate, early detection of prostate cancer by DRE, serum PSA, and transrectal ultrasound should be encouraged.     

Retained glass foreign bodies in wounds: predictive value of wound characteristics, patient perception, and wound exploration

This report describes associations of demographic and health-related characteristics with use of prostate cancer screening. Data are from a random-digit dial survey of Washington State residents. Analyses are restricted to men ages 40-79 years (n = 332) and examine both digital rectal examination (DRE) and blood tests for prostate-specific antigen (PSA) in the previous 2 years. Results are adjusted to be representative of the state's population. In 1996, 53.6% of men received either DRE, PSA, or both. Among those screened, 42% received DRE alone, 15% PSA alone, and 43% both PSA and DRE, and the percentages of men receiving PSA increased markedly with age (30%, ages 40-49 years; 58%, ages 50-59 years; and 77%, ages 60-79 years). After control for other demographic characteristics, the relative odds for any prostate cancer screening were 5.5 for ages 60-79 versus 40-49 years, 2.4 for 16+ versus < or = 12 years of education, and 4.0 for 2+ versus no physician visits in the previous 2 years (all P < 0.05). Characteristics generally associated with good health, including regular exercise and low fat and high fruit and vegetable intakes, were also significantly associated with prostate cancer screening. In conclusion, in 1996, approximately one-half of the men in Washington State over age 40 years had received prostate cancer screening in the previous 2 years. Few men were screened with PSA alone, and the use of PSA as part of prostate cancer screening increased markedly with age. Because PSA screening increases detection of prostate cancer, epidemiological studies of health behavior and cancer risk must carefully control for screening history to avoid detection bias.     

Chronic study on the neuronal excitability of the cochlear nuclei of the cat following electrical stimulation

OBJECTIVES: To determine: (i) the prevalence, reasons for, and demographic and psychosocial predictors of prostate cancer screening among a randomly selected sample of men; and (ii) to estimate the community expenditure involved in the screening of asymptomatic men. SUBJECTS AND METHODS: A random sample of men aged 40-79 years was selected from the State Electoral Register of New South Wales, Australia, and asked to complete a computer-assisted telephone interview. The questions determined their demographic characteristics, their subjective health rating compared with others of the same age (5-point scale), the prevalence and reasons for any screening for prostate cancer ('ever screened' and 'screened within the last 12 months'), whether they had undergone a digital rectal examination (DRE), a blood test for prostate-specific antigen (PSA) or transrectal ultrasonography (TRUS), and the prevalence of urinary symptoms. Those who had been screened were then asked to nominate the single most important factor in the decision to undergo prostate cancer screening. To estimate community expenditure, the costs for prostate cancer screening were estimated by applying Medicare schedule charges to the screening and subsequent diagnostic tests performed. Two scenarios were developed to estimate costs: the first used guidelines which do not recommend the use of routine screening for all asymptomatic men, and the second was based on guidelines where the routine use of PSA or TRUS as part of a periodic health examination is not recommended, but the use of DRE in asymptomatic men aged 50-70 years is. RESULTS: Of the 551 eligible participants, 86% completed the interview; 44% of participants reported that they had 'ever' been screened, whilst 23% had been screened in the year before the study. Among those who had been screened, the reason reported most often for screening, apart from symptoms and family history, was the doctor's recommendation after a medical assessment of their prostate cancer risk status. Screening status was predicted both by the age of the man and his symptom score. As a result, the community expenditure in New South Wales for screening among asymptomatic men was estimated to be A$6.4 million and A$5.2 million for the first and second scenarios, respectively. CONCLUSIONS: The results of this study suggest that, despite the recommendations of primary bodies that asymptomatic men not be screened for prostate cancer, screening is occurring at a high level and with significant costs to the healthcare system.     

Determination of local tumour extension in cases of carcinoma of the prostate

OBJECTIVE: Since most cases of carcinoma of the prostate (CaP) are still diagnosed at a time when the tumour has already spread beyond the prostatic capsula and therefore is incurable, recent impetus has been given to early detection with the chance of curative therapy. METHODS: This paper reviews of the literature concerning the ability of prostate-specific antigen (PSA), digital rectal examination (DRE), transrectal ultrasonography (TRUS), TRUS directed sextant biopsies, computerized tomography (CT) and magnetic resonance imaging (MRI) to determine the pathological stage of clinically organ-confined CaP. RESULTS: The combination of PSA, DRE, TRUS and TRUS directed sextant biopsies yield the best information about the pathological extent of clinically organ-confined CaP. However, while this is true for a cohort of patients, the individual patient may still suffer from locally advanced disease that was unpredictable preoperatively by applying these tests. Positive surgical margins after radical prostatectomy are a logical consequence of advanced disease and therefore will be seen as long as no better clinical staging is available to the urologist and as long as CaP does not get diagnosed earlier in the course of the disease. CONCLUSION: At the present time the determination by PSA, DRE, TRUS and TRUS directed sextant biopsies are the diagnostic procedures of choice for the clinical staging of patients with potentially organ-confined CaP, CT and MRI are unable to markedly enhance the accuracy of clinical staging in this disease.     

Exposure of hepatic sinusoidal mononuclear cells to UW solution in situ but not ex vivo induces apoptosis

OBJECTIVES: To determine the influence of race or ethnicity on serum prostate-specific antigen (PSA) levels and PSA density (PSAD) in a population of healthy men without clinically evident prostate cancer. METHODS: This retrospective study was conducted between January 1988 and January 1993. The serum PSA levels were measured in 859 men (586 African Americans, 142 whites, and 131 Hispanics) who were participants in a prostate cancer screening program or had urinary symptoms suggestive of prostate gland pathology. All men underwent a detailed clinical examination, including digital rectal examination, serum PSA determination, and transrectal ultrasound (TRUS). None of the subjects included had clinical or TRUS evidence of prostate cancer (furthermore, 283 men were pathologically proved to be cancer-free by prostate biopsies). Serum PSA levels and PSA densities as a function of each individual's ethnic background were determined. RESULTS: The mean serum PSA level in African Americans was 2.1 ng/mL, which was significantly higher than that of whites (mean PSA of 1.53 ng/mL) and Hispanics (mean PSA of 1.83 ng/mL) (P = 0.003). Similar differences among the three groups were observed in PSA density (the mean PSAD was 0.078, 0.057, and 0.065 for African Americans, whites, and Hispanics, respectively). A separate analysis for the biopsy-negative men was performed, and the findings were consistent with the observations for the entire study group. After adjustment for age and prostate volume, the differences remained statistically significant. CONCLUSIONS: Among men without evidence of prostate cancer, African Americans have higher serum PSA levels and PSA densities than do whites or Hispanics. Race or ethnicity was an independent factor that affected serum PSA levels even after adjustment for age and prostate volume.     

The regulation of L-proline transport by insulin-like growth factor-I in human osteoblast-like SaOS-2 cells

OBJECTIVE: To examine the usefulness of clinical stage, tumour differentiation and prostate-specific antigen (PSA) level, alone and in combination, to predict regional nodal metastases in individual patients with localized prostate cancer. PATIENTS AND METHODS: The usefulness of digital rectal examination (DRE), biopsy Gleason sum and PSA, alone and in combination, to predict nodal metastases in an individual patient was examined. The study included 689 patients who had laparoscopic or open pelvic lymph node dissection for clinical stage T1-3 prostate cancer. The Kruskal-Wallis test, Mantel-Haenszel test, chi-squared test and logistic regression were used for continuous, ordinal, categorical, and multivariate analysis, respectively. RESULTS: Of the 689 patients who underwent radical prostatectomy, 52 (8%) had nodal metastases. Although clinical stage, DRE, pre-operative PSA level and biopsy Gleason sum were significantly related in the univariate analysis, only pre-operative PSA level and biopsy Gleason sum were significant predictors of lymph node status in a multivariate analysis. However, based on a receiver operating characteristic curve, a model with satisfactory sensitivity and specificity could not be obtained. CONCLUSION: Current estimations of primary prostate cancer biology using pre-operative PSA level, clinical stage and biopsy Gleason sum are not sufficiently sensitive to predict nodal metastases, and pelvic lymphadenectomy remains the definitive method of detection.     

Prevention of venous thromboembolism. Survey of in-hospital medical practice

Prostate-specific antigen (PSA) is the most important tumor marker for early detection, staging, and monitoring of men with prostatic cancer today. However, its sensitivity and specificity are not sufficient to use it as a single tool for screening for men with clinically localized prostate cancer. Recently, assays have become available that selectively detect several of the various molecular forms of PSA, especially the unbound or free PSA. Several studies have shown the clinical usefulness of percent free PSA (free PSA/total PSA) for the early detection of men with clinically localized prostate cancer. However, the use of percent free PSA for staging of prostate cancer remains controversial. Based on the case scenario presented, the value of total PSA and percent free PSA for the staging of men with clinically localized prostate cancer is reviewed.     

Prospective evaluation of prostate-specific antigen density and systematic biopsies for early detection of prostatic carcinoma

Significant controversies persist in regard to the need for systematic biopsies in patients with serum prostate-specific antigen (PSA) levels above 4 ng/mL (Hybritech assay), especially if they show no signs of prostatic cancer on digital rectal examination (DRE) or transrectal ultrasonography (TRUS). We evaluated 565 consecutive patients referred to us for prostatism, suspicious lesions on DRE, or an elevated serum PSA level. These patients do not represent a purely screened population. A detection rate of 38.4 percent was achieved by performing directed biopsies of suspicious lesions on DRE and/or TRUS, and systematic biopsies of all patients with serum PSA levels above 4 ng/mL. Among 142 patients with serum PSA between 4.1 and 10 ng/mL, but without suspicion for cancer on DRE and TRUS (DRE- TRUS-), a large number of patients (6.2) were subjected to systematic biopsies to detect one cancer. A receiver-operating characteristics curve for PSA density (PSAD) applied to this population confirmed that the best cut-off point for biopsies was a PSAD of 0.15, below which only two of twenty-three cancers would have been missed, sparing biopsies in 77 of 142 patients. A similar approach was applied to DRE- TRUS- patients with serum PSA levels above 10 ng/mL. The number of cancers in those with serum PSA between 10.1 and 14 ng/mL was too low to establish a PSAD cut-off point. In patients with serum PSA above 14 ng/mL, the best PSAD cut-off point for biopsies was 0.3, below which two of thirteen cancers would have been missed, sparing biopsies in 19 of 39 patients. We conclude that PSAD can safely reduce the number of patients subjected to systematic biopsies without significantly compromising cancer detection.     

Molecular forms of serum prostate-specific antigen. The clinical value of percent free prostate-specific antigen

The concept of measuring the proportions of various forms of PSA in serum, particularly the proportion of free to total PSA, represents a new and exciting method of detecting early curable prostate cancers and avoiding unnecessary prostate biopsies in men who have BPH only. Compared with other methods of improving diagnostic specificity, it does not require transrectal ultrasound for determination of prostate volume, as does the use of PSA density, and it does not require multiple blood sampling over a sufficiently long period, as does PSA velocity. Recent findings suggest determination of the proportion of free to total PSA, rather than that of complexed to total PSA, to be the optimal discriminator between patients with prostate cancer and those with BPH in the PSA reflex range of 2.5 or 3 ng/mL to 10 ng/mL, and to improve the clinical accuracy of the PSA test substantially. If the total PSA value is normal, percent free PSA improves the sensitivity (increases cancer detection) of the PSA test; if the total PSA value is slightly elevated, percent free PSA enhances the specificity (eliminates unnecessary negative prostate biopsies) of the PSA test. Both of these outcomes are clinically desirable in attempting to diagnose early, curable prostate cancers in a cost-effective manner among men who also have varying degrees of BPH. Figure 5 contains a diagnostic algorithm for the detection of clinically significant prostate cancers at a curable stage, employing the concept of percent free PSA. As more is learned about percent free PSA, however, it may be necessary to make modifications in how this concept is used clinically.     

Clinical significance of small (less than 0.2 cm3) hypoechoic lesions in men with normal digital rectal examinations and prostate-specific antigen levels less than 10 ng/mL

OBJECTIVES: Most men diagnosed with prostate cancer in 1998 presented with a normal digital rectal examination (DRE) and minimal elevations in serum prostate-specific antigen (PSA) (less than 10 ng/mL). Considerable attention is often given toward identifying small hypoechoic (less than 0.2 cm3) lesions at the time of transrectal ultrasound-guided prostate biopsy. We sought to determine the significance of these lesions and whether an additional biopsy of this area is clinically useful. METHODS: A prospective data base containing detailed information on 614 biopsies performed by a single urologist was examined. All patients with a hypoechoic lesion underwent sextant prostate biopsy plus a separately labeled core directed through the hypoechoic area. Eighty-one patients who fit the following criteria were assessed: PSA less than 10 ng/mL, normal DRE, and hypoechoic lesion volume less than 0.2 cm3. RESULTS: The mean age of this group was 63.5 years, and the mean PSA was 7.1 ng/mL. Of the 81 patients with small hypoechoic lesions, 20 (24.7%) were positive for cancer in at least one prostatic core. Of the 81 hypoechoic area biopsies (HABs), 14 (17.3%) were positive for cancer; 1 (1.2%) demonstrated high-grade prostatic intraepithelial neoplasia, and 66 (81 .5%) were negative. In 11 of the patients (78.6%) with positive HABs, at least one additional core was positive for cancer. In 3 of the patients (21.4%) with positive HABs, no additional cores were positive for cancer (P<0.05). CONCLUSIONS: A significant proportion of small hypoechoic lesions in patients with early T1c prostate cancer are positive for malignancy. Although the overall yield of separate hypoechoic area biopsy is low (3.7%), approximately 15% of cancers would be missed if directed HABs were not performed (P<0.05). Identification and biopsy of small hypoechoic lesions are indicated in this group of patients.     

Comparison of percent free prostate specific antigen and prostate specific antigen density as methods to enhance prostate specific antigen specificity in early prostate cancer detection in men with normal rectal examination and prostate specific antigen between 4.1 and 10 ng./ml

PURPOSE: We analyzed the behavior of prostate specific antigen (PSA) density and percent free PSA to enhance the specificity of PSA in the early diagnosis of prostate cancer in men with normal digital rectal examination and PSA serum level between 4.1 and 10 ng./ml. MATERIALS AND METHODS: PSA serum level, PSA density and percent free PSA were analyzed in 74 men with normal digital rectal examination and PSA serum level between 4.1 and 10 ng./ml. All men underwent systematic prostate biopsy, and the diagnosis was benign prostate hyperplasia in 52 and prostate cancer in 22. Furthermore, we determined the decrease in unnecessary biopsies and the cancer detection rate using 0.10 versus 0.15 as cut points for PSA density, and 20 versus 25 as cut points for percent free PSA. RESULTS: In patients with benign prostatic hyperplasia and prostate cancer, respectively, the median PSA level was 6.7 and 7.0 ng./ml. (p > 0.05), median prostate volume was 50 and 37 cc (p < 0.04), median PSA density was 0.14 and 0.19 (p < 0.007) and median percent free PSA was 18.9 and 10.1 (p < 0.005). Using PSA density cut points of 0.15 and 0.10, the decrease in negative biopsies was 53.8 and 36.5% with a sensitivity of 86.4 and 90.9%, respectively. However, using percent free PSA cut points of 20 and 25, the decrease in negative biopsies was 36.5 and 26.9% with a sensitivity of 77.3 and 95.5%, respectively. CONCLUSIONS: Although both methods could minimize unnecessary biopsies in men with normal digital rectal examination and PSA serum level between 4.1 and 10 ng./ml., the percent free PSA was more cost-effective since transrectal ultrasound was not required. In this small series of symptomatic patients a percent free PSA cut point of 25 could detect at least 95% of prostate cancers and decrease 26.9% of negative biopsies.     

A long follow-up on prostate specific antigen density and prostate biopsy

OBJECTIVE: To determine prostate specific antigen density (PSAD) in a risk population without evidence of prostatic cancer, and to assess the long-term usefulness of PSAD as a parameter for determining the need for a prostatic biopsy in patients with a normal digital rectal examination (DRE) and transrectal ultrasound (TRUS). METHODS: The records of 582 patients referred to the clinic between February, 1992 and February, 1994 were studied retrospectively. All these patients with lower urinary tract symptoms (LUTS) were evaluated based on the following parameters: digital rectal examination, serum PSA levels, prostate volume measured using transrectal ultrasound and PSAD. Prostatic biopsy was performed on 431 patients who had a serum PSA level greater than 4.0 ng/mL. A total of 299 patients (69.3%) had PSA levels between 4.0 and 10.0 ng/mL and represented the target population. The study had two parts, in the first one cancer was diagnosed just by one biopsy and in part II, the patients with negative biopsy in part I were followed for a two-year period and required 2 or 3 biopsies for diagnosis. Of the total of patients who had a negative prostate biopsy in part I of the study, 269 were followed for a period of two years with repeated prostate biopsies. RESULTS: Overall prostate cancer was detected in 22/299 (13.9%) patients, 6/105 (5.7%) with PSAD up to 0.15 and 16/194 (8.2%) with PSAD over 0.15 (p = 0.569). CONCLUSION: PSAD is a useful indicator in decreasing the number of negative biopsies in patients with benign prostatic hyperplasia. However, in a long-term follow-up the PSAD (cutoff level 0.15) was unable to predict which patients had a positive biopsy. According to our results, 5.6% of patients with prostate cancer will be missed using the PSAD criteria.     

Early detection of recurrent prostate cancer with an ultrasensitive chemiluminescent prostate-specific antigen assay

OBJECTIVES: Treatment failure after radical prostatectomy is most commonly heralded by an increase in serum prostate-specific antigen (PSA) to detectable levels. We evaluated the clinical utility of an ultrasensitive chemiluminescent PSA assay. METHODS: We evaluated the assay in banked sera obtained from 170 men after radical prostatectomy. Controls consisted of 142 females, 29 men who had undergone cystoprostatectomy without evidence of prostate cancer, and 25 men without evidence of recurrent disease at least 5 years after prostatectomy for organ-confined disease. Lead time to diagnosis of recurrence was based on comparisons with the IMx or Tandem E assays using a cutoff of 0.1 ng/mL (100 pg/mL). RESULTS: The biologic level of detection of this assay is 8 pg/mL. Serum PSA levels were undetectable in 82.4% of females, 86.2% of the cystoprostatectomy patients, and 96% of the radical prostatectomy controls. After radical prostatectomy, PSA levels were undetectable at last check in 104 of 168 (61.9%) men. In the 24 men with prostate cancer recurrence, the enhanced sensitivity of 8 pg/mL provided a mean lead time based on conservative calculations of 12.7 to 22.5 months over conventional assays. Thirty-four of the 41 men with detectable PSA levels and no evidence of disease recurrence had PSA levels of 30 pg/mL or less. CONCLUSIONS: PSA levels are undetectable in most men who do not have recurrence of disease after radical prostatectomy. Low but detectable serum PSA levels less than or equal to 30 pg/mL can be produced by nonmalignant sources of PSA. PSA assays with enhanced sensitivity can detect recurrent prostate cancer with significant lead time over conventional assays.     

Role of PSA testing in multiphasic health screening

BACKGROUND: Although mass screening for prostate cancer does not meet the criteria for an effective screening programme, multiphasic screening which includes PSA testing is still being carried out. AIM: We decided to study and evaluate the usefulness of PSA testing in multiphasic health screening and at the same time establish age-specific ranges of normal PSA values in our local population. RESULTS: Six hundred and ninety five male patients who had their PSA levels tested during a multiphasic health screening from October 1992 to August 1995 were evaluated. Abnormal PSA levels were repeated and subjected to a DRE and TRUS biopsy if they were persistently high using age-specific PSA ranges. Our results showed 14 (4.1%) out of 695 patients who had an abnormal PSA of > 4 ng/mL. compared to 19 who had abnormal PSA levels using the age-specific PSA ranges. Of the patients who were < 40 yrs of age, no further investigations were done. Amongst those 80 years and older, none had abnormal age-specific PSA rates. No prostate cancers were picked up amongst all the patients investigated. Median age specific PSA values at the 95th percentile was calculated for each age group. A rise in the median PSA values with age was also noted. CONCLUSION: We recommend that in patients less than 40 years of age, PSA should not be carried out as the probability of prostate cancer is almost zero. Similarly, in patients who are 80 years and above and asymptomatic, such screening may not be indicated given the limited options available. Age-specific rates are a better way to reduce the negative biopsy rates in the age-groups that are amenable to curative treatment. With a local set of age-specific PSA ranges, we hope to increase the positive predictive value of PSA for prostate cancers in our local population until more specific and equally sensitive tests are made available.