Prevalence and pathological extent of prostate cancer in men with prostate specific antigen levels of 2.9 to 4.0 ng./ml

Various authors have recommended different values for the upper limit of normal for the monoclonal prostate specific antigen (PSA) assay (for example 4.0 ng./ml. or less by the manufacturer Hybritech or 2.8 ng./ml. or less by others). To our knowledge, no studies have examined the prevalence and pathological extent of prostate cancer detectable by needle biopsy in ambulatory volunteers with PSA levels in the range of 2.9 to 4.0 ng./ml. We evaluated 121 volunteers by rectal examination and transrectal ultrasonography with PSA levels in that range. We performed ultrasound-directed needle biopsy of the prostate if abnormal findings were present on either examination. The prevalence of detectable prostate cancer in this group was 7.2% (8 of 111). All 8 patients had pathologically organ confined cancer, and only 2 had suspicious findings on rectal examination but all had abnormal or suspicious ultrasound findings. We believe that the 7.2% yield from ultrasonography and biopsy in patients with a PSA level of 2.9 to 4.0 ng./ml. is too low to justify further invasive evaluation. Rather, we recommend careful followup and monitoring of these patients with serial PSA measurements and rectal examination, and advise performance of ultrasonography and biopsy if the rectal examination becomes suspicious for cancer or the PSA level increases above 4.0 ng./ml.     

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.     

The lack of predictive value of prostate specific antigen density in the detection of prostate cancer in patients with normal rectal examinations and intermediate prostate specific antigen levels

PURPOSE: The management of patients with a normal digital rectal examination and a prostate specific antigen (PSA) level of 4.0 to 10.0 ng./ml. remains controversial. To improve the specificity of cancer detection in this group, PSA density has been recommended with biopsies based on a PSA density of 0.15 or more. To evaluate PSA density as a discriminator of prostate cancer we enrolled patients in a prospective study. MATERIALS AND METHODS: A prospective evaluation was done of 44 consecutive patients with a palpably normal digital rectal examination and a serum PSA level of 4.0 to 10.0 ng./ml. enrolled during a 13-month period. All patients underwent transrectal ultrasound with sextant biopsies regardless of calculated PSA density. RESULTS: Overall, 8 of 44 men (18%) had prostate cancer. There was no significant difference in the mean PSA density between the patients with positive and negative biopsies (mean 0.12 and 0.15, respectively, p = 0.258). Also, there was no significant association between PSA or PSA density and a positive biopsy in multivariate analysis (p = 0.863). Receiver operating characteristic curves for PSA and PSA density failed to demonstrate any superior benefit for PSA density in this patient population. A PSA density of 0.15 was an unreliable indicator of cancer (sensitivity 12.5%, specificity 61.1% and positive predictive value 6.7%). CONCLUSIONS: In our study, PSA density did not discriminate between patients with positive and negative biopsies, and in fact most cancers would not have been detected if a PSA density of 0.15 or more had been used as the sole indication for biopsy. Therefore, we recommend systematic biopsies in these patients independent of calculated PSA density.     

Prevalence and predictors of a positive repeat transrectal ultrasound guided needle biopsy of the prostate

PURPOSE: We determined the prevalence of and risk factors for carcinoma in patients with 1 previously negative prostate biopsy. MATERIALS AND METHODS: Transrectal ultrasound guided prostate needle biopsies were repeated in 130 men. Risk factors analyzed included age, pathological result of initial biopsy, inter-biopsy interval, prostate specific antigen (PSA), PSA density, PSA velocity, digital rectal examination, abnormal transrectal ultrasound and family history of prostate cancer. RESULTS: A total of 39 patients (30%) had positive biopsies for cancer. Univariate analysis revealed that PSA more than 20 ng./ml. and abnormal transrectal ultrasound were more frequent in men with positive second biopsies. Using multivariate logistic regression analysis only PSA more than 20 ng./ml. was a significant risk factor (adjusted odds ratio 4.48, 95% confidence interval 1.02 to 20.1). We determined the incidence of carcinoma in patients who represent the lowest risk group as defined by PSA less than 10 ng./ml., PSA density less than 0.15 mg./ml./cm.3, PSA velocity less than 0.75, ng./ml. per year, no prostatic intraepithelial neoplasia plus negative transrectal ultrasound, digital rectal examination and family history. Of 21 patients who fit this cohort 5 (23.8%) had carcinoma on repeat biopsy. CONCLUSIONS: A significant false-negative rate for initial transrectal ultrasound guided prostate biopsies exists. Baseline risk in lowest risk patients is sufficiently high such that one cannot define a subset of patients for whom repeat biopsy is unnecessary. We recommend repeat biopsy in all patients who meet the criteria for a transrectal ultrasound guided biopsy and in whom the initial biopsy is negative.     

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.     

Microthoracoscopy: at the cutting edge of thoracic surgery

60 patients, 64 years old on average, with no evidences of prostatic cancer, but with a PSA level greater than 8.9 ng/ml, have undergone six transrectal systematic sextant biopsies. All patients had no suspicious finding on digital rectal examination. Ultrasound transrectal examinations did not show hypoechoic areas suspected of a prostatic cancer. We used an automatic biopsy gun fitted with an 18 gauge biopsy needle. Three biopsies in each lobe, at the apex, in the midline zone and at the base of the prostate, in the parasaggital plane, was performed. No complications were found during following days. Of the 60 men, with a non suspicious prostate on rectal examination, 12 had prostatic cancer. They had, on average, a PSA level of 10.8 ng/ml. The PSAD level was, on average, of 0.18 and the Gleason score was, on average, of 3.8. The patients who underwent pelvic lymphadenectomy and radical prostatectomy did not have an infiltration of the glans capsule of seminal vesicles and no lymph node metastasis were found. In our study, the digital rectal and ultrasound examination alone would have missed the 23% of prostatic cancers. Therefore, according to the literature, the PSA makes us able to discover prostatic cancer more than the clinical and instrumental evaluation alone. Furthermore the ultrasound examination presents some diagnostic limits. Particularly it is very difficult to detect small cancer arising into the hypoechoic multinodular adenoma of the transition zone. In addition 10-20% of cancers, arising into the peripheral zone, are hysoechoic with the surrounding parenchyma. For that reason, when PSA value is greater then 8.9 ng/ml without clinical or ultrasound evidence of cancer, we recommend to perform six systematic sextant biopsies. At present, the real question is to determine whether this early diagnosis is useful for patients, because there is no certainty of the therapeutic benefit in terms of quantity and quality life.     

Transition zone prostate specific antigen density: lack of use in prediction of prostatic carcinoma

PURPOSE: Among the new approaches to enhance the performance of prostate specific antigen (PSA) testing in a biopsy population is the use of the free-to-total PSA as well as the transition zone density, which is calculated by dividing the PSA by the transition zone volume. We compare these manipulations of the PSA to PSA alone in a biopsy population. MATERIALS AND METHODS: We evaluated 917 consecutive men who underwent ultrasound guided biopsy for an elevation in serum PSA or abnormality on digital rectal examination. Total PSA was measured using the Tandem-E or Tandem-R method. Prostate gland volume and transition zone were measured with ultrasound and calculated using the prolate ellipsoid formula. RESULTS: In the overall PSA range 276 men had carcinoma (30.0% of the population), while in the PSA 4.0 to 10.0 ng./ml. range 141 of 477 had cancer (29.6%). Receiver operating characteristics analysis and analysis of variance were performed. In the overall PSA series the Tandem total PSA performed as well as any PSA index to predict carcinoma. In the restricted range of total PSA 4.0 to 10.0 ng./ml. total PSA density as well as transition zone density were more predictive than PSA alone. In both PSA ranges the volume of benign glands was significantly larger than in the prostates exhibiting carcinoma. There was no statistically significant difference in outcomes of analyses between different investigators or different sites of investigation (Veterans Affairs versus university based hospitals). CONCLUSIONS: In this biopsy population transition zone PSA density did not add to the information available with total PSA and gland volume. Neither investigator nor site bias contributed to the failure of transition zone PSA density or PSA density to predict prostatic carcinoma.     

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.     

The effect of parenteral testosterone replacement on prostate specific antigen in hypogonadal men with erectile dysfunction

PURPOSE: Parenteral testosterone supplementation is a common treatment for erectile dysfunction in hypogonadal men. Despite its frequent use, the effect of testosterone on prostate specific antigen (PSA) in these patients has not been documented previously. In this study we determined the effect of parenteral testosterone replacement on PSA and PSA velocity in a group of men being treated for erectile dysfunction. MATERIALS AND METHODS: A retrospective analysis of 48 patients (mean age 65.9) was performed and 2 study groups were identified. Group 1 consisted of 27 patients with a serum PSA level before and after initiating testosterone replacement therapy, and group 2 consisted of 27 men with a minimum of 3 PSA measurements (intervals of 6 months or greater) while on testosterone replacement. Each man had erectile dysfunction, a normal digital rectal examination and a low or low-normal total serum testosterone level before initiating therapy. Testosterone replacement was discontinued if no subjective improvement in erectile function was obtained, or if prostate adenocarcinoma was suggested by digital rectal examination or PSA. RESULTS: The mean increase in PSA after initiating testosterone replacement was 0.29 ng./ml. representing a mean change of 37% from baseline (mean interval 12.8 months). The mean PSA velocity was 0.05 ng./ml. per year. Pretreatment testosterone level, age and testosterone dose did not independently alter the PSA during testosterone replacement. Eleven men required prostate biopsies during treatment. Biopsies were indicated for abnormal digital rectal examination in 10 men and an elevated PSA in 1. All biopsies were benign. CONCLUSIONS: Parenteral testosterone replacement in hypogonadal men with normal pretreatment digital rectal examination and serum PSA levels does not alter PSA or PSA velocity beyond established nontreatment norms. Thus, any significant increase in PSA or PSA velocity should not be attributed to testosterone replacement therapy and should be evaluated.     

Improvement of specificity in PSA-based screening by using PSA-transition zone density and percent free PSA in addition to total PSA levels

BACKGROUND: The clinical value of prostate-specific antigen (PSA) density in differentiating between prostate cancer and benign prostatic hyperplasia has been the subject of several studies. In this context the question has been raised about the diagnostic benefit of PSA transition-zone density (PSA-TZ density = total PSA/transition-zone volume) in the detection of prostate cancer. In the following study the value of PSA-TZ density alone and in combination with free PSA was investigated. METHODS: Between August 1995-May 1996, 308 first-line screening volunteers with elevated total PSA levels ranging from 2.5-10.0 ng/ml were evaluated. All patients underwent digital rectal examination, transrectal ultrasound, and transrectal ultrasound-guided biopsy of the prostate. Prior to these investigations, serum was obtained and total as well as free PSA levels were obtained. PSA transition-zone density (PSA-TZ density) was defined as follows: PSA-TZ density = total PSA/transition-zone volume. RESULTS: ROC curve analyses for PSA-TZ density showed that by using a PSA-TZ density of more than 0.22 ng/ml/cc as a biopsy criterion, 24.4% of negative biopsies could be avoided; ROC curve analyses for free PSA showed that by using percent free PSA <20% as a biopsy criterion, 45.5% of negative biopsies could be eliminated. When combining these two diagnostic tests, 54.2% of negative biopsies could be avoided. CONCLUSIONS: We conclude that PSA-TZ density, in addition to total and free PSA, is a new opportunity which renders it possible to calculate the likelihood of detecting prostate cancer on repeat biopsies in an individual patient.     

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.     

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.     

Prospective characterization of pathological features of prostatic carcinomas detected via serum prostate specific antigen based screening

PURPOSE: Many small (less than 0.5 cc), well differentiated, organ-confined prostate carcinomas remain clinically undetected during the life of the patient and are identified only at postmortem examination. Thus, these cancers are often called latent or autopsy cancers. There is concern that serum prostate specific antigen (PSA) based screening may preferentially detect these cancers. There are limited prospective data concerning the pathological features of carcinomas of the prostate detected in a screening program. We determined if prostatic carcinomas detected via PSA based screening resembled autopsy cancers. MATERIALS AND METHODS: We assessed the pathological features of carcinomas in 100 consecutive, completely embedded radical prostatectomy specimens from men whose cancer was detected in a PSA based screening program. The tumors were evaluated for pathological stage, surgical margin status, Gleason histological grade and intraglandular tumor extent (morphometrically quantified as percentage carcinoma and tumor volume). RESULTS: Of 100 carcinomas 68 (68%) were larger than 0.5 cc in volume (mean 1.7, range 0.1 to 10.7). Mean amount of carcinoma in the surgical specimen was 10.3% (range 0.1 to 41.6). Of the 100 carcinomas 94 had a Gleason score of 5 to 8 (mean 5.7) and only 6 (6%) were well differentiated (Gleason score of 4 or less). Locally advanced disease was noted in 41 cases (41%) as judged by the presence of extracapsular carcinoma and/or cancerous surgical margins. CONCLUSIONS: We concluded that the pathological features of most prostatic carcinomas detected via PSA based screening do not resemble those of autopsy cancers, and that most prostatic cancers detected in screening programs are likely to be clinically important.     

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.     

Observations on the early detection of prostate cancer from the American Cancer Society National Prostate Cancer Detection Project

BACKGROUND: The American Cancer Society National Prostate Cancer Detection Project (ACS-NPCDP) was established in 1987. The experience of the ACS-NPCDP demonstrates the yield and impact of periodic examinations for the early detection of prostate cancer. METHODS: A cohort of 2999 well men ages 55-70 years was tested annually at 10 clinical centers by prostate specific antigen (PSA), transrectal ultrasound (TRUS), and digital rectal examination (DRE). Biopsies were performed on men with suspicious findings. Pathologic findings were reviewed. The initial study outcomes were the detection yield of multimodality testing and the comparative sensitivity and specificity of the different tests employed. Longer term outcomes included patient quality of life and survival. RESULTS: The cancer detection rate declined significantly across the years of intervention. DRE had lower sensitivity than TRUS or PSA, particularly in later years of follow-up. The specificity of TRUS was lower than that of DRE. Fewer than 9% of the cancers detected in this study were clinically advanced at the time of diagnosis. Ninety-four percent of patients in whom cancer was detected are alive after an average follow-up of 54 months. In one case, death occurred after surgery. Two deaths were attributed to prostate cancer, and eleven other deaths were unrelated to prostate cancer or its treatment. CONCLUSIONS: Results of the ACS-NPCDP indicate that a combined-modality approach to prostate cancer detection yields high levels of early detection with infrequent adverse outcomes. Continued follow-up is required to evaluate long term morbidity and mortality.     

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.     

Do prostate specific antigen and prostate specific antigen density enhance the detection of prostate carcinoma after initial diagnosis of prostatic intraepithelial neoplasia without concurrent carcinoma?

BACKGROUND: Prostatic intraepithelial neoplasia (PIN) is considered to be a precursor of prostate carcinoma in which serum levels of prostate specific antigen (PSA) have been correlated with PIN grades. The aim of this study was to determine whether PSA and prostate specific antigen density (PSAD), obtained at the time of initial diagnosis of PIN without concurrent carcinoma, can be used as predictive factors to discriminate patients with subsequent cancer on repeat biopsy. METHODS: We studied, retrospectively, the records of 93 patients with PIN (low and high grade) without concurrent carcinoma at the time of their first needle biopsy. We assessed the relationship between initial PIN grade, PSA, and PSAD with later detection of carcinoma on repeat biopsy. Patients were divided into 3 subgroups for analysis according to their initial PSA level (0-4, 4.1-10, >10 ng/mL). RESULTS: Carcinoma detection rate on repeat biopsy was 13.3% for patients with low grade PIN and 47.7% for patients with high grade PIN (P < 0.006). High grade PIN was frequently associated with subsequent carcinoma whatever the PSA level (33.3-61.9%). Low grade PIN was associated with subsequent carcinoma in 42.8% of the cases when PSA was greater than 10 ng/mL. When PSA was between 4 and 10 ng/mL, low grade PIN carcinoma was found on repeat biopsies in only 10.7% of the cases (P = 0.05). In none of the PSA subgroups did PSAD enhance later cancer detection. CONCLUSIONS: For patients with high grade PIN, the incidence of subsequent carcinoma is high, whatever the PSA values. For these cases repeat biopsies should be recommended. Patients with low grade PIN and PSA greater than 10 ng/mL should have repeat biopsies because the incidence of subsequent carcinoma is high and comparable to high grade PIN. PSAD did not provide additional information.     

Effectiveness of screening for prostate cancer

In this, our second article, we assess the value of screening for prostate cancer. There is insufficient evidence to recommend for or against routine digital rectal examination as an effective screening test for prostate cancer in asymptomatic men. It is recommended that tumour markers, such as prostate specific antigen, and transrectal ultrasound are not used for routine screening purposes.     

Free-to-total prostate-specific antigen (PSA) ratio improves the specificity for detecting prostate cancer in patients with prostatism and intermediate PSA levels

OBJECTIVE: To investigate the clinical significance of the free-to-total prostate-specific antigen (PSA) ratio in improving the specificity of PSA measurement for detecting prostate cancer within the diagnostic intermediate range (4-10 ng/mL total PSA) in patients referred for the treatment of urinary symptoms. PATIENTS AND METHODS: Serum samples were obtained from 333 consecutive patients with obstructive and irritative urinary symptoms. Of these men, 114 had total PSA levels of 4-10 ng/mL; 22 had prostate cancer (group 1) and 71 had benign prostatic hyperplasia (BPH, group 2). Group 3 consisted of 21 patients with BPH and a chronic indwelling catheter. The concentrations of free and total PSA (ProStatus, Wallac Oy, Turku, Finland) and PSA complexed to alpha-1-antichymotrypsin were measured and the free-to-total PSA ratio calculated. All patients under 70 years of age or with suspicious findings on digital rectal examination or transrectal ultrasonography underwent ultrasound-guided sextant prostate biopsies. Of the 114 patients, 105 (92%) underwent transurethral resection of the prostate and six (5%) radical retropubic prostatectomy. RESULTS: Patients in group 1 had significantly lower median free PSA concentrations (0.78 ng/mL vs 1.13 ng/mL, P < 0.001) and a lower free-to-total PSA ratio (12.1% vs 19.9%, P < 0.001) than those in group 2. The differences were similar between group 1 and group 3 (median free PSA in group 3, 1.06 ng/mL, P = 0.03, and free-to-total PSA ratio 18.7%, P = 0.007). There were no significant differences between patients in groups 2 and 3. The free-to-total PSA ratio had a higher specificity than total PSA at all sensitivity levels, e.g. a threshold free-to-total PSA ratio of 0.20 detected 91% of cancers and spared 48% (group 2) or 46% (group 3) from unnecessary biopsies. The area under the receiver operating characteristic curve for group 1 vs group 2 was 0.56 (total PSA) and 0.78 (free-to-total PSA ratio) and for group 1 vs group 3 was 0.56 (total PSA) and 0.81 (free-to-total PSA ratio). CONCLUSION: In those patients with extensive symptoms from BPH and requiring surgical treatment, the free-to-total PSA ratio improves the specificity for detecting prostate cancer in the diagnostic 'grey zone' of 4-10 ng/mL total PSA. This improvement occurred in patients with or without a chronic indwelling catheter for urinary retention.     

Clinical evaluation of chemiluminescence immunoassay PSA (ACS-PSA) for detection of prostate cancer

Serum prostate specific antigen (PSA) levels were measured using an ACS-PSA kit in 147 systematic biopsy cases (61 with prostate cancer (PC)) and 96 transurethral resection of prostate (TUR-P) cases (2 with PC). In the 147 biopsy cases, the sensitivity for PSA using 3.0 and 10.0 ng/ml as cut-off values was 91.8 and 90.2%, while the specificity was 9.30 and 30.2%, respectively. The sensitivity for PSAD (A) (calculated by transabdominal ultrasound) using 0.25 and 0.5 ng/ml/cm3 as cut-off values was 91.8 and 90.2%, while the specificity was 22.1 and 50.0%, respectively. These data indicated that PSAD (A) provided better information for detecting PC than PSA alone. No statistical difference was found between PSAD (A) and PSAD (R) (calculated by transrectal ultrasound) in the utility of detecting PC. PSA below 15.0 ng/ml was seen in sixteen patients with PC. Five of these sixteen patients had a PSA level of < 3.0, and they underwent prostate biopsy based on the abnormality by digital rectal examination (DRE). The other eleven patients had PSAD (A) level of > 0.3 ng/ml/cm3. In all 243 cases, PC was not found in the 49 patients (PSA < 3.0 ng/ml) or 91 patients (PSAD (A) < 0.25 ng/ml/cm3) who had no abnormal findings by DRE and transabdominal ultrasonography. These results suggested a criterion in the use of the ACS-PSA kit for the indication of prostate biopsy and TUR-P.