Screening for early prostate cancer in Germany. Preliminary results of a prospective multicenter trial

Summary To compare the efficacy of digital rectal examination (DRE) and serum prostate specific antigen (PSA) in early detection of prostate cancer, we initiated a prospective multicenter screening trial. In 12 542 men choosen at random with a mean age of 62 ( ± 7.5) a suspect DRE or a PSA level > 4.0 ng/ml was found in 2343 (20 %). Of the presently performed 744 biopsies, 157 revealed diagnosis of prostate cancer. Although further biopsies as well as the follow up of the 12 542 men are still missing, combination of DRE and PSA value > 4.0 ng/ml appears to be superior to DRE alone with a positive predictive value of 50 % versus 19 % in early detection of prostate cancer.      

Résultats de la biopsie prostatique chez les patients algériens avec un PSA élevé et/ou un toucher rectal suspect

Objectiveto report on prostatic biopsy results in Algerian patients presenting with a suspicious Digital Rectal Examination (DRE) and\or an elevated total PSA.Methodsdata collected on prepared index cards were age, result of DRE, rate of PSA and number of cores, as well as the histological result. The biopsies were performed by two urologist surgeons from Oran city, Algeria.Results331 patients had prostatic transrectal ultrasound-guided biopsies, the average (SD) age was 70.4 (8.7) years with a range 33 - 94 years. The most important age bracket was the one with subjects over 60 years. The DRE was suspicious in 41.69% of patients (138 of 331), and 44.20% of the suspect prostates on DRE were malignant. The average PSA was 42.2 ng/ml the rate of PSA >10 ng/ml constituted 72.57%. The number of biopsy cores was 12 for 129 biopsies, 49.2% of the biopsies revealed prostatic adenocarcinoma. The percentage of positive biopsies was 41.66% (21/48) when the PSA was between 4 and 10 ng/ml, and 33.33% (45/135) when the PSA exceeded 10 ng/ml. Among 47 scores of Gleason 59.7% patients had a score 7, 8.6% had a score < 7, and 31.8% had scores >7.Conclusion49.2% of 331 biopsies were positive for prostatic adenocarcinoma. Significant associations were found between age and cancer, between digital rectal examination and prostate biopsy results, and between PSA and number of positive cores.     

The prognostic value of transrectal ultrasound guided biopsy in patients over 70 years old with a prostate specific Antigen (PSA) level ≤15 ng/ml and normal digital rectal examination: A 10-year prospective follow-up study of 427 consecutive patients

IntroductionAs a urologist, it is common to review a patient above the age of 70 being referred to a prostate assessments clinic with an elevated PSA. We evaluate the prognosis of these patients clinically as there is no international consensus on the exact PSA cutoff level or a single international guideline as to when these patients should be offered a prostate biopsy.Patients and methodsOn receiving ethic committee approval, we recruited 427 consecutive patients aged 70 years and above referred with a PSA of ≥4 ng/ml, from January 1996 to December 2000, into our study. All patients were assessed, examined with a digital rectal examination (DRE) of the prostate, and a subsequent prostate biopsy. We followed up on their histologic diagnosis for up to 10 years and analyzed their outcome. The main outcome measures were disease-free survival and overall survival, stratified according to the PSA level (≤15 vs. >15 ng/ml) and DRE findings (normal vs. sbnormal).ResultsThere was a statistically significant difference in the overall survival (P value < 0.011) and disease specific survival (P value < 0.0001) of cancer patients with a PSA was >15 ng/ml and an abnormal DRE. However, in patients with a PSA ≤15 ng/ml and normal DRE, the incidence of cancer was low and they had no disease-specific or overall survival benefit.ConclusionsA policy of deferring prostate biopsy in patients with a PSA ≤15 ng/ml and normal DRE (Group A) would significantly decrease the need of unnecessary prostate biopsies. Within this group, patients did not have any survival advantage compared with those without cancer. We conclude that up to 20% of the prostate biopsies performed in this age group could have been avoided.     

Early detection of prostate cancer in the ESRD population

BACKGROUND: There are currently no prostate cancer screening guidelines specific to the end-stage renal disease (ESRD) population. With this in mind, we evaluated the clinical usefulness of digital rectal examination (DRE), serum total prostate-specific antigen (PSA), prostate-specific antigen density (PSAD) and transrectal ultrasound (TRUS) in predicting prostate cancer in men with ESRD. METHODS: Fifty male ESRD patients age 40 years and older with no prior history of prostate cancer were enrolled in the study. All patients underwent PSA measurement and a DRE followed by a TRUS. PSAD was calculated as the total PSA divided by the prostate volume. Ultrasound-guided prostate biopsies were performed on any patient with 1 or more of the following abnormal findings: a nodule detected on DRE; an abnormal TRUS; PSA > 4.0 ng/ml, or a PSAD > 0.15 ng/ml/cm3. RESULTS: Abnormal findings were detected in 19 patients. Two (4%) had an abnormal DRE, 3 (6%) had PSA > 4.0 ng/ml, 3 (6%) had PSAD > 0.15 ng/ml/cm3 and 16 (32%) had abnormal findings on TRUS. Three patients had 2 abnormal findings and 1 had 3. Of the 15 prostate biopsies performed, 4 (27%) revealed prostate cancer and 3 (20%) high-grade prostatic intraepithelial neoplasm (HGPIN) comprising 8% and 6%, respectively, of the studied population. Of the 4 patients diagnosed with prostate cancer, none had abnormal DRE, 2 (50%) had PSA > 4.0 ng/ml (sensitivity = 66.7% and PPV = 50% (p = 0.236)), 3 (75%) had PSAD > 0.15 ng/ml/cm3 (sensitivity = 100% and PPV = 75% (p < 0.018)), and 3 (75%) had abnormal findings on TRUS (sensitivity = 30% and PPV = 75% (p = 1.000)). CONCLUSION: Routine screening with PSA and DRE does not seem sensitive enough to predict the presence of the disease. Although TRUS detected abnormalities in 16 patients (32%), sensitivity was very low (30%). In our patients, PSAD increased the sensitivity and positive predictive value (PPV) of detecting prostate cancers compared to PSA alone.     

Is the diagnostic yield of prostate needle biopsies affected by prostate volume?

ObjectivesTo determine the effect of prostate volume on the diagnostic yield of prostate biopsies.Materials and methods155 consecutive patients underwent 12-core transrectal ultrasound guided needle biopsies. Data were collected prospectively on age, serum PSA, digital rectal examination (DRE), previous prostate biopsies, prostate volume and pathologic result. Univariate and multivariate logistic regressions were undertaken to determine the effect of prostate volume on the risk for a positive biopsy.Results45 patients (29%) were diagnosed with cancer. The median patient age was 63 (range 48–82) years, the median PSA level was 6.7 ng/ml (0.5–156 ng/ml), and the median prostate volume was 57 ml (16–273 ml). 42 patients (27%) had an abnormal DRE and 51 (33%) had undergone previous prostate biopsies. Positive biopsy rates were 39%, 33%, and 14% for prostate volume below 46 ml, between 45 and 73 ml, and above 72 ml, respectively. Univariate analysis showed that age, serum PSA, DRE and prostate volume were all associated with a positive biopsy. Multivariate analysis adjusted for age, PSA and DRE showed a significant risk increase for a positive biopsy in smaller prostates. (OR = 5.6 95% CI 1.75–17.89; and 8.86 95% CI 2.72–28.82, for prostate volume between 45 and 72 ml and below 45 ml, respectively).ConclusionThe diagnostic yield of prostate biopsies is significantly lower in large prostates. As the result the standard 12-core biopsy may be insufficient for the diagnosis of cancer in large prostates.     

Digital rectal examination as a prostate cancer-screening method in a country with a low incidence of prostate cancer

The objective of this study was to evaluate the value of using digital rectal examination (DRE) for prostate cancer diagnosis in an Asian population. Patients with serum prostate-specific antigen (PSA) levels ranging from 2.5 to 19.9 ng/ml underwent transrectal ultrasonography-guided prostate biopsies. Patients were divided into two groups: the normal DRE group (n=721) and the abnormal DRE group (n=192). The cancer detection rate was higher in the abnormal DRE group (47.4%) than in the normal DRE group (23.0%) (P<0.001). However, the detection rates in these two groups were not significantly different in men 45-59 years old as well as in men with low PSA levels (2.5-3.9 ng/ml). In all subjects, the areas under the receiver operating characteristic curves for positive biopsies were 60.0% (95% confidence interval (CI), 55.7-64.3%, P<0.001). However, in the subgroup analysis, the predictive power of the DRE was not significant in men 45-59 years old. In addition, DREs of patients with low PSA levels had no discriminative ability. The pathological features of the prostate biopsies were not significantly different between the two groups in subjects 45-59 years old and in subjects with PSA levels from 2.5 to 3.9 ng/ml. Our data indicate that DREs increase the probability of cancer detection. However, our findings also raise the question, 'Are DREs really useful for cancer detection in younger men and men with low PSA levels in the Asian population?'     

Diagnosis of advanced prostate cancer at the community level in Rwanda

Background

Prostate cancer is the second most common cancer in men and sixth leading cause of mortality. If not recognized early, patients with advanced prostate cancer can experience debilitating complications which can otherwise be prevented by early androgen deprivation therapy. This research intends to define clear diagnostic tools that will guide practitioners in the rural community setting toward early management of advanced prostate cancer.

Methods

We conducted a cross-sectional observational study at three referral hospitals in Kigali, Rwanda on patients who presented with clinical suspicion of advanced prostate cancer over a period of 6 months. All patients underwent prostate biopsy as well as metastatic work up (CT or MRI), for those who were eligible. Statistical analysis was done using STATA 14.2.

Results

114 patients were included in the study. The median age was 70 years (interquartile range: 65–79 years). In total 14 (12.3%) patients were found to have benign disease, while 100 (87.7%) patients were found to have cancer. Among those who had cancer, 85 (85%) had advanced prostate cancer. 110/114 (96.5%) were symptomatic at presentation. Common presenting symptoms were lower urinary tract symptoms (80.7%), back pain (54.4%), and urinary retention (36.8%). Abnormal digital rectal examination (DRE) was a strong risk factor for both cancer and advanced disease. Prostate cancer was found in 92.2% of those with abnormal DRE compared to 41.7% in those with normal DRE (p?=?0.001). Also, cancer was found in 96.1% of those with multinodular prostate on DRE (p?=?0.02) and had high odds (OR 14.6; CI 3.41–62.25) of having advanced prostate cancer (p?<?0.001). The mean (±?SD) PSA was 643.3?±?1829.8 ng/ml and the median (range) was 100 ng/ml (9.05–10,000 ng/ml) for the whole study population. All patients with prostatic-specific antigen (PSA) of 100 ng/ml or above had advanced prostate cancer.

Conclusion

The results show that there is a significant correlation between clinical findings and advanced prostate cancer. All patients with abnormal DRE and PSA above 100 ng/ml had advanced prostate cancer. Diagnosis of advanced prostate cancer is possible at the community level if PSA testing is utilized and practitioners are well trained.

     

Potential predictive factors of positive prostate biopsy in the Japanese population

Introduction There are numerous arguments for the predictive factors of positive prostate biopsies, differing according to race and region. This study aimed to determine predictive factors for a positive prostate biopsy in East Asian, especially Japanese men, using clinical, laboratory, and transrectal ultrasound (TRUS) findings. Methods Data were collected from 466 men who underwent a prostate biopsy for suspected prostate cancer. Variables analyzed including age, digital rectal examination (DRE) findings, prostate-specific antigen (PSA) level, PSA density, prostate volume, and TRUS findings. Logistic regression analysis and the Mann–Whitney U test were used for this study. Results Logistic regression analysis showed that significant predictors for a positive prostate biopsy for all patients were positive DRE results, prostate volume, and hypoechoic lesions on TRUS. Especially in the patients with PSA levels <10 ng/ml, the significant predictor for positive biopsy was prostate volume. The Mann–Whitney U test showed that significant predictors for a positive prostate biopsy in all patients were PSA density >0.15, positive DRE results, and prostate volume <25 cm³. Especially in patients with PSA levels <10 ng/ml, significant predictors for a positive prostate biopsy were prostate volume <25 cm³ and PSA density >0.15. Additionally, even if the data were confined to those patients with seven or more core biopsies, all the predictive factors shown in all patients were significant predictors in this category. Conclusion This study investigated potential predictors for positive prostate biopsy and demonstrated that prostate volume was an independent predictive factor for positive prostate biopsy in patients with PSA levels <10 ng/ml. In the future, we may be able to use our findings to create a nomogram for predicting positive prostate biopsy in Japanese men.     

ROLE OF PROSTATE-SPECIFIC ANTIGEN AND DIGITAL RECTAL EXAMINATION IN THE DETECTION OF PROSTATE CANCER

Prostate-specific antigen (PSA) is a kallikrein-like serine protease that is secreted exclusively by the epithelial cells of all types of prostatic tissue, benign and malignant. Its serum concentration is raised in men with prostatic disease including cancer. We have evaluated its usefulness in the diagnosis of prostate cancer by measuring serum PSA concentrations in 260 men aged 50 years or over. All had abnormalities at digital rectal examination (DRE) involving suspected cancer, signs and symptoms of benign prostatic hyperplasia and equivocal findings on DRE, and miscellaneous other conditions, including hematospermia, chronic prostatitis and microscopic hematuria. Transrectal prostatic needle biopsies were performed in the men with abnormal findings on DRE or elevated serum PSA (above 4ng/ml). Serum PSA ranged from 4.0 to 9.9ng/ml in 14 (5%) of the 260 men. Four of the men in this group (31%) who underwent prostatic biopsy had prostate cancer. Serum PSA levels greater than or equal to 10.0 ng/ml were found in 8 (3%) of the 260 men. 5 of these 8 (63%) who underwent prostatic biopsy had cancer. If DRE alone had been used to screen the men having biopsies, 4 of the 10 cancers (40%) would have been missed. If PSA alone had been used to screen these men, only 1 of the 10 cancers would have been missed. Serum PSA measurement was more reliable than DRE for detecting prostate cancer. Since these two methods do not always detect the same malignant tumor, the combined use of DRE and PSA testing affords a more complete evaluation of the prostate gland for malignant involvement.     

Follow-up of men obtaining a six-core versus a ten-core benign prostate biopsy 7 years previously

The aim of this study is to evaluate the proportion of repeat biopsies after 7 years in men with an initial benign six- or ten-core biopsy as well as the incidence of prostate cancer (PC) in the repeat biopsies. In this retrospective longitudinal study, 116 men with an elevated prostate-specific antigen (PSA) and/or a suspicious digital rectal examination (DRE) who have had a benign prostate biopsy between January 1997 and September 1997 were included. Fifty-eight men had an initial benign six-core biopsy (median PSA 7.5 ng/ml, range 0.3–67) (group A), and 58 men had an initial benign ten-core biopsy (median PSA 7.5 ng/ml, range 0.8–91.4) (group B). We analysed men with a pathological PSA velocity, a persistently elevated PSA, an abnormal DRE, a high-grade prostatic intraepithelial neoplasia or atypical adenomatous hyperplasia, or atypical small acinar proliferation as indication for rebiopsy. Furthermore, we analysed a subgroup with exclusively an increased PSA velocity (>0.75 ng/ml per year) as indication for rebiopsy. In group A, 14 men had a follow-up biopsy. In this group, follow-up biopsies yielded PC in eight men (13.8%), six (10.3%) had a negative follow-up biopsy. In contrast, in group B only four men (3.4%) had a follow-up biopsy (P=0.005). Two of them (3.4%) had PC (P=0.02), two cases (3.4%) showed a benign histology (P=0.06). The use of an extended biopsy protocol at the initial evaluation reduces the number of repeat biopsies required and decreases the number of PC detection in the follow-up biopsy cohort.     

Outcome prediction for prostate cancer detection rate with artificial neural network (ANN) in daily routine

BackgroundWe evaluated the use of the artificial neural network (ANN) program “ProstataClass” of the Department of Urology and the Institute of Medical Informatics at the Charité-Universitätsmedizin Berlin in daily routine to increase prostate cancer (CaP) detection rate and to reduce unnecessary biopsies.Materials and methodsFrom May 2005 to April 2007, a total of 204 patients were included in the study. The Beckman Access PSA assay was used, and pretreatment prostate specific antigen (PSA) was measured prior to digital rectal examination (DRE) and 12 core systematic transrectal ultrasound (TRUS) guided biopsies. The individual ANN predictions were generated with the use of the ANN application for the Beckman Access PSA and free PSA assays, which relies on age, PSA, percent free prostate specific antigen (%fPSA), prostate volume, and DRE. Diagnostic validity of total prostate specific antigen (tPSA), %fPSA, and the ANN was evaluated by ROC curve analysis.ResultsPSA and %fPSA ranged from 4.01 to 9.91 ng/ml (median: 6.65) and 5% to 48% (median: 15%), respectively. Of all men, 46 (22.5%) demonstrated suspicious DRE findings. Total prostate volume ranged from 7.1 to 119.2 cc (median: 35). Overall, 71 (34.8%) CaP were detected. Of men with suspicious DRE, 28 (60.9%) had CaP on initial biopsy. The ANN was 78% accurate in the original report. The AUC of ROC curve analysis was 0.51 for PSA, 0.66 for %PSA, and 0.72 for the ANN-Output, respectively.ConclusionsOur results in this independent cohort show that ANN is a very helpful parameter in daily routine to increase the CaP detection rate and reduce unnecessary biopsies.     

Predictors of subsequent prostate cancer in men with a prostate specific antigen of 2.6 to 4.0 ng/ml and an initially negative biopsy

PURPOSE: Almost 75% of men with a prostate specific antigen (PSA) of 2.6 to 4.0 ng/ml have no evidence of prostate cancer on biopsy. Deciding whether and when to repeat the biopsy is challenging. We determined if patient specific variables might identify men at increased risk for the subsequent detection of prostate cancer. MATERIALS AND METHODS: We analyzed the records of 24,893 men from a community based prostate cancer screening study. Our study group consisted of 1,202 men with PSA 2.6 to 4.0 ng/ml and a previously negative prostate biopsy. Patient specific variables were analyzed for their value in predicting a future diagnosis of prostate cancer. RESULTS: Of 1,011 men with adequate followup 136 (13.5%) were subsequently diagnosed with prostate cancer. Mean followup +/- SD in men without prostate cancer was 72 +/- 36 months. Prostate cancer was subsequently diagnosed in 35% of men with high grade prostatic intraepithelial neoplasia (HGPIN) on initial biopsy (p <0.0001), in 18% with abnormal or suspicious digital rectal examination (DRE) (p = 0.02) and 16% with an annual PSA velocity of 0 ng/ml (p = 0.002). Multivariate analysis identified HGPIN, initial PSA 3.6 to 4.0 ng/ml, abnormal DRE, family history of prostate cancer and annual PSA velocity 0 ng/ml as predictors of prostate cancer. CONCLUSIONS: Men with a PSA of 2.6 to 4.0 ng/ml and negative biopsy should be advised to undergo repeat biopsy if they have HGPIN, initial PSA 3.6 to 4.0 ng/ml, abnormal DRE, a family history of prostate cancer or a PSA velocity of 0 ng/ml or greater.     

¿Impacta el criterio para indicar la biopsia prostática sobre su exactitud? Estudio prospectivo llevado a cabo sobre una población de pacientes ambulantes

IntroductionProstate specific antigen (PSA) and digital rectal examination (DRE) are the main tests for initial prostate investigation; there is no consensus about the best criterion for prostate biopsies. We aim to check the accuracy of different criteria in this context including PSA derivatives to detect prostate cancer.Material and methodsFour different criteria for indication of prostate biopsy were compared: (A) PSA-density (>15 ng/ ml/ cc); (B) PSA > 2,5ng/ml; (C) PSA-velocity (> 0.7 ng/ ml/ year); (D) free/total PSA ratio (<15%). All biopsies and histopathological examinations were performed by the same urologist and pathologist, respectively.ResultsThe study was performed on 180 consecutive biopsies with 37.7% overall cancer detection rate: 29 (16.1%) performed following criterion A, 42 (23.3%) criterion B, 65 (36.1%) criterion C and 44 (24.4%) criterion D. Based on PSA criteria alone, the predictive positive value (PPV) was 37.9% for criterion A, 33.3% for B, 32.3% for C and 50.0% for criterion D, respectively, (p > 0.05). Associating positive DRE with changed PSA, the PPV increased to 50%, 50%, 43.9% and 68.2% for criteria A, B, C and D, respectively (p > 0.05). In univariate analysis, DRE (positive versus negative), PSA level (>10 ng/ ml versus <4.0 ng/ ml), free/total PSA ratio (<10% versus >15%) and age were associated with PC. In multivariate analysis only positive DRE was associated with prostate cancer.ConclusionsAll the criteria of PSA derivatives are complementary and useful predictors of cancer risk. However, a positive DRE increased the PPV of PSA derivatives. New tools are needed to improve the accuracy of prostate cancer detection.     

Serum Pro Prostate Specific Antigen Improves Cancer Detection Compared to Free and Complexed Prostate Specific Antigen in Men With Prostate Specific Antigen 2 to 4 Ng/Ml

PurposePro prostate specific antigen (pPSA) is a precursor form of PSA enriched in tumor compared to benign prostate tissues that may be a more specific serum marker for prostate cancer. Serum pPSA was measured in the clinically relevant early detection PSA range of 2 to 10 ng/ml.Materials and MethodsResearch use immunoassays were used to measure native and truncated forms of pPSA. The subject cohort contained 1,091 serum specimens from men enrolled in prostate cancer screening studies at 2 sites who had undergone prostate biopsy and were divided into PSA ranges of 2 to 4 ng/ml (benign 320, cancer 235) and 4 to 10 ng/ml (benign 315, cancer 221).ResultsIn PSA ranges 2 to 4, 2 to 6, 4 to 10 and 2 to 10 ng/ml, pPSA in a ratio with free PSA (%pPSA) gave the highest cancer specificity. At 2 to 4 ng/ml and 90% sensitivity, %pPSA spared 19% of unnecessary biopsies compared to 10% for free PSA and 11% for complexed PSA(p <0.001). Similar results were obtained at PSA 2 to 6 ng/ml. At 90% sensitivity in the PSA 4 to 10 ng/ml range, %pPSA spared 31% of unnecessary biopsies compared to 20% for % free PSA and 19% for complexed PSA (p <0.0001). In the combined 2 to 10 ng/ml range, %pPSA spared 21% of unnecessary biopsies compared to 13% for % free PSA and 9% for complexed PSA (p <0.0001).ConclusionsThe %pPSA significantly improved specificity for cancer detection and decreased the number of unnecessary biopsies in the PSA 2 to 4 ng/ml range. This relative improvement of %pPSA compared to % free PSA and complexed PSA was maintained throughout the PSA range of 2 to 10 ng/ml.     

The value of endorectal MRI in the early diagnosis of prostate cancer

OBJECTIVE: Assess the value of endorectal MR imaging (EMRI) in the early diagnosis of prostate cancer (PCa) and compare this test to prostate specific antigen (PSA) and digital rectal examination (DRE) in the prediction of negative biopsies. MATERIAL AND METHODS: 92 patients with elevated PSA (>4 ng/ml) and/or abnormal DRE were studied. All patients underwent an EMRI previous to transrectal ultrasound guided needle sextant biopsies (3 cores in each peripheral zone), and were followed up. We performed a total of 184 biopsies: 92 patients underwent 1 biopsy; out of them, 61 patients underwent 2 biopsies, 27 patients 3 biopsies, 3 patients 4 biopsies and 1 patient 5 biopsies. 67 patients had a final negative biopsy and 25 had a final positive biopsy. Mean PSA was 10.44 ng/ml, and the mean % fPSA/tPSA was 0.20. Uni- and multivariate analysis and ROC curves were used to compare the accuracy of the different tests. The probability of positive biopsy with each technique was also assessed. RESULTS: EMRI had a high negative predictive value (91.07%) and the highest accuracy (77%) of all tests, higher than PSA (62%). Mean PSA was not statistically different in patients with negative biopsies (9.44 ng/ml) and positive biopsies (11.8 ng/ml) (p=0.064). The association of EMRI-DRE-PSA had the highest accuracy (83%) significantly higher than DRE-PSA (70%). The probability of positive biopsy in patients with negative DRE and EMRI, and PSA values between 5 and 15 ng/ml was 5-10% at first and second biopsies, but decreased progressively on subsequent biopsies (<8% at third biopsy, <5% at fourth biopsy and <3% at fifth biopsy). CONCLUSION: In patients with elevated PSA and/or abnormal DRE with two previous negative biopsies, an EMRI is a useful test to rule out PCa, when negative, and avoid subsequent biopsies, as they have a low chance of positive biopsy.     

Follow-up of men with elevated prostate-specific antigen and one set of benign biopsies at prostate cancer screening

OBJECTIVE: To study the follow-up of men with elevated prostate-specific antigen (PSA) (>3 ng/ml) after one benign set of sextant biopsies. From the G?teborg branch of the European Randomised Study of Screening for Prostate Cancer (ERSPC). METHOD: 456 men with one set of benign sextant biopsies were followed every second year for 4 years with PSA determinations. In cases of elevated PSA, transrectal ultrasound (TRUS) guided sextant biopsies were suggested. Digital rectal examination (DRE), prostate volume, PSA, PSA density (PSAD) and the ratio between free and total PSA (PSA F/T) were recorded. RESULTS: Complete data were available for 322 men. 3 groups were identified. In 84/322 (26%) men cancer was found ("cancer" group). 182/322 (56%) had benign biopsies ("benign" group) and 56/322 (17%) had normalised PSA ("normalised PSA" group). Median prostate volumes were 36, 46, and 33 cc respectively in the three groups. DRE and/or TRUS were abnormal in only 30% of the men in all groups. Cancer was not found in any prostate >70 cc volume. In prostates of <20 cc either cancer was found or PSA was normalised. The "normalised PSA" group had initial PSA, PSAD and PSA F/T similar to cancer, normalising during follow-up. CONCLUSIONS: Patients with one negative sextant biopsy still have a high likelihood of cancer, especially men with persistently elevated PSA and small prostates (<20 cc) while the majority of men with large prostates (>70 cc) have PSA elevation due to benign prostate hyperplasia (BPH) and not to cancer.     

Are prostatic biopsies necessary in men aged > or =80 years?

OBJECTIVE: To examine whether prostatic biopsies are necessary in all men aged > or =80 years, as men found to have prostate cancer are frequently treated with a 'watch and wait' policy or with hormonal withdrawal alone, and biopsies are associated with a small but significant complication rate. PATIENTS AND METHODS: The findings on a digital rectal examination (DRE), the prostate-specific antigen (PSA) level, the biopsy and staging bone scan results for all men aged > or = 80 years who had prostatic biopsies over a 3-year period were reviewed, together with those in a group of men aged <80 years for comparison. All biopsy samples had been examined in one of three histopathology units, and 33 consultant urological surgeons contributed. RESULTS: In all, 210 biopsies from 205 men aged > or = 80 years were identified, of whom 163 (79%) had biopsy-confirmed prostate cancer. All 29 men with a PSA level of > or = 100 ng/mL, 98% of 47 with > or = 50 ng/mL, 97% of 76 with > or = 30 ng/mL and 92% of 101 with > or = 20 ng/mL had biopsy cores containing cancer; 63% of men with a PSA level of <20 ng/mL had cancer on biopsy. In men with cancer and a PSA level of > or = 30 ng/mL, 92% had Gleason grade > or = 7 and 93% were treated with hormonal withdrawal alone. In all men with cancer the DRE was abnormal in 91%, the mean number of positive cores was 59% and the bone scan was positive in 18%. The DRE was abnormal in 77% of men with benign biopsies. CONCLUSIONS: In men aged > or = 80 years with a PSA level of > or = 30 ng/mL, at least 97% had prostate cancer, >90% of whom had high-grade disease, and nearly all with cancer received active pharmacological treatment. In the vast majority of these men prostate biopsies did not alter their cancer management. The value of prostatic biopsy in this age group, with a PSA level of > or = 30 ng/mL, is questionable.     

The significance of early detection for prostate cancer in mass screening

PURPOSE: In Mitaka city, mass screening for prostate cancer was conducted for 3 years from 1995 to 1997. Clinical stages were compared between patients found by screening and those diagnosed at our clinic during the same time. The significance of serum-free prostate specific antigen (PSA) in mass screening for prostate cancer was examined. MATERIAL AND METHODS: A prospective clinical trial was conducted on men aged 50 years or older. The primary examination consisted of taking the international prostate symptom score, quality of life score, PSA (Tandem-R) and digital rectal examination (DRE). If PSA was greater than 4.0 ng./ml and/or if DRE suggested cancer, transrectal ultrasound-guided sextant prostate biopsies were indicated. RESULTS: Of the men screened, 23.2% (320/1375) had serum PSA greater than 4.0 ng./ml. and/or suspicious findings on DRE. Biopsy was performed in 199 of 320 (62.1%). Cancer was detected in 21 (1.5%, 21/1375). Prostate cancer was found in one case among 154 males (0.65%, 1/154) who were screened twice or more. The cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic (Wilcoxon's rank-sum test: p = 0.0047). Receiver operating characteristics analysis showed that the optimal free PSA-to-PSA ratio was 12%. Positive predictive value increased from 18% to 50% when free PSA-to-PSA ratio was combined with PSA. CONCLUSION: 1. Cancer detection rate was 1.5% in the mass screening in Mitaka City. 2. Cancer stage found by screening was significantly earlier than that diagnosed at the outpatient clinic. 3. Free PSA determination might eliminate unnecessary biopsies in men with PSA above 4.0 ng./ml with minimal loss of cancer detection.     

Early diagnosis of prostate cancer in the Western Cape.

BACKGROUND: Early stage prostate cancer does not cause symptoms, and even metastatic disease may exist for years without causing symptoms or signs. Whereas early stage prostate cancer can be cured with radical prostatectomy or radiotherapy, the prognosis of patients with locally advanced or metastatic cancer is significantly poorer. OBJECTIVES: In view of the high incidence of advanced and therefore incurable prostate cancer seen at the oncology clinic of the Department of Urology, Tygerberg Hospital, we started a prostate clinic with the aim of detecting early stage prostate cancer which is potentially curable. A secondary objective was to investigate the question whether there is a higher incidence of prostate cancer among black African men. PATIENTS AND METHODS: Men aged 50-70 years were invited by means of media communications (newspaper and radio) to attend our prostate clinic for a free physical examination, including a digital rectal examination (DRE) and serum prostate specific antigen (PSA) assay. If the DRE was clinically suspicious of malignancy and/or the serum PSA was > 4 ng/ml, the patient was appropriately counselled and referred for transrectal ultrasound (TRUS)-guided sextant prostate biopsy. RESULTS: In the period June 1997-September 1999 a total of 1,056 men attended the prostate clinic. Biopsies were indicated in 160 cases, and were obtained in 114 (71.3%, i.e. 10.8% of the entire cohort). Prostate cancer was detected on first biopsy in 3.5% of the entire group of men (in 35.9% of those with a clinically abnormal DRE, in 41.3% of those with a serum PSA > 4 ng/ml and in 88.6% of those with an abnormal DRE and serum PSA > 4 ng/ml. In the 37 men with prostate cancer, the clinical tumour stage was T1-2 in 83.8% and T3-4 in 16.2%. In the group of patients with clinical stage T1-2 tumours, the treatment was watchful waiting in 62.5% of cases, radiotherapy in 20.8% and radical prostatectomy in 16.7%. Analysis of the data according to race showed that in the group of 47 black men there was a higher percentage of clinically abnormal DRE, PSA > 4.0 ng/ml and biopsies showing malignancy, and a higher overall prostate cancer detection rate (8.5%). CONCLUSIONS: Our prostate cancer detection rate of 3.5% is slightly lower than that reported in larger studies (4.7%), which may be due to the fact that prostate biopsy was performed in only 71% of those who had an indication for biopsy. In the men diagnosed with clinically localised prostate cancer, potentially curative treatment was given in only 37.5% of cases. This compares unfavourably with the historical cohort of men seen at our oncology clinic, where 53% received potentially curative treatment, and a large European study where potentially curative treatment was given in 89% of cases. Our finding that black men had a higher percentage of clinically abnormal DRE, PSA > 4.0 ng/ml and biopsies showing malignancy and a higher overall detection rate of prostate cancer should be interpreted with caution, since black men comprised only 4.5% of our overall study cohort.     

Early detection of prostate cancer in Germany: a study using digital rectal examination and 4.0 ng/ml prostate-specific antigen as cutoff

OBJECTIVE: While international screening studies for prostate cancer are by now almost reaching the estimated number of recruitments mandatory for the necessary power to investigate an effect on mortality of prostate cancer, no statistical figures on the detection of prostate cancer in Germany - apart from historical data before the use of prostate-specific antigen (PSA) are available. In order to generate a database and to investigate the diagnostic efficacy of the primarily practice-based urological care system, a case finding study designed as a nationwide longitudinal early detection trial was initiated. METHODS: In one week in November 1997, 963 urologists prospectively examined 11,644 men between 45 and 75 years of age by digital rectal examination (DRE) and PSA with 4.0 ng/ml as cutoff. Data of family history and physical examination were collected by questionnaire. At this time participants were not aware of their PSA value. PSA was determined in the study center. Indication for sextant biopsy was a PSA value above 4.0 ng/ml or a suspicious lesion on DRE. Any indicated biopsy not performed had to be clarified. In a second questionnaire results of prostate biopsy, treatment and tumor status were documented. RESULTS: The mean age of the study population was 62 years (median 62). The PSA median was 1.4 ng/ml with 82.8% presenting with < 4.0 ng/ml, 12.8% with 4-10 ng/ml and 4.4% with >10 ng/ml. From 1,115 men (47.7%) biopsied, 262 cancers were detected resulting in a detection rate of 23.5%. While 399 men refused biopsy, further investigation was not recommended in 387 men by their urologist, because prostatitis or benign hyperplasia was thought to be the cause for elevated PSA. From the 143 patients undergoing radical prostatectomy, 93 (65%) cancers were organ confined. T(1c) cancers with elevated PSA > 10 ng/ml could be treated with curative intent in 44% only. The positive predictive value (PPV) was estimated to be 16% for DRE alone (14/90), 17% for PSA alone (143/819) and 51% for the combination of both (105/206). In that cohort, use of age-adjusted PSA values and PSA density increased the PPV of PSA testing nonsignificantly. CONCLUSIONS: Significant higher PPV indicated that utilizing a combination of both DRE and PSA is most effective in the early detection of prostate cancer. Unnecessary biopsies can be avoided using either age-adjusted PSA value or PSA density, but the PPV is not significantly changed and potentially curable cancer is missed in up to 25%. Given the substantial variability of the diagnostic approach despite the study design, uniform guidelines are necessary to ensure countrywide sufficient screening.