Arto E. Boeken Kruger

Complications of transrectal ultrasound-guided systematic sextant biopsies of the prostate: evaluation of complication rates and risk factors within a population-based screening program

OBJECTIVES Screening for prostate cancer to reduce the mortality and morbidity from this disease has become an important issue in recent years. Of all procedures used to diagnose prostate cancer, biopsy of the prostate is the cause of most complications. To evaluate the safety of the screening procedure, we have studied the complications and risk factors for complications within the screened population of the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam section. METHODS Between June 1994 and July 1996, 1687 transrectal ultrasound-guided systematic sextant biopsies were performed after screening 6198 men through prostate-specific antigen level, digital rectal examination, and transrectal ultrasonography. RESULTS From these 1687 biopsies, 302 cases of prostate cancer were diagnosed. Mild complications such as hematuria and hematospermia were reported frequently with rates of 23.6% and 45.3%, respectively. More severe complications were far less frequently seen. Fever, usually of low grade, was seen after 4.2% of biopsies. Seven men (0.4%) were admitted to a hospital after biopsy. Risk factors for complications could not be identified. CONCLUSIONS Review of the literature concerning transrectal biopsies of the prostate shows that the complication rates within this screened population are comparable to those reported within referred patients. The admittance rate is slightly lower. Transrectal ultrasound-guided systematic sextant biopsy of the prostate is a safe procedure for the diagnosis of prostate cancer within the general population; however, identification of risk factors for complications might further improve the safety of the screening procedure.

THE CHANGING PATTERN OF PROSTATE CANCER AT THE TIME OF DIAGNOSIS: CHARACTERISTICS OF SCREEN DETECTED PROSTATE CANCER IN A POPULATION BASED SCREENING STUDY

PURPOSE We describe the clinical and pathological features of prostate cancer diagnosed through serum prostate specific antigen (PSA), digital rectal examination and transrectal ultrasonography in a population based randomized screening study. MATERIALS AND METHODS Between November 1993 and June 1997, 20,632 volunteers 55 to 76 years old were included in the study. In the screening arm 9,776 men underwent digital rectal examination, transrectal ultrasound and serum PSA determination. Biopsies were taken if the digital rectal examination and/or transrectal ultrasound findings were abnormal or if PSA was 4 ng/ml or greater. A total of 2,262 men underwent biopsy and 474 cases of prostate cancer were diagnosed. RESULTS The pretreatment data were complete in 459 men, of whom 78% had clinically organ confined disease. Bone or lymph node metastases were seen in 8 cases (1.7%). Of 172 men who underwent radical prostatectomy 2 had lymph node metastases. Overall 66.3% of men treated with radical prostatectomy had organ confined disease. CONCLUSIONS Comparison of the characteristics of prostate cancer detected through screening of the general population with those in a population based cohort of men in which there was no organized screening revealed stage reduction, primarily with regard to number of metastatic cases. Whether this stage reduction will lead to a decrease in disease specific mortality remains unknown until the study is completed and the end point of prostate cancer specific mortality is evaluated.

REPEAT SCREENING FOR PROSTATE CANCER AFTER 1-YEAR FOLLOWUP IN 984 BIOPSIED MEN: CLINICAL AND PATHOLOGICAL FEATURES OF DETECTED CANCER

PURPOSE We describe the yield of a repeat examination and biopsy procedure 1 year after initial biopsy was negative. We also assessed the parameters responsible for the failure to diagnose these cancers at the primary screening. MATERIALS AND METHODS We screened 8,103 men randomized to the screening arm of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer using prostate specific antigen measurement, digital rectal examination and transrectal ultrasound. At the primary screening biopsy of 1,875 men was positive for prostate cancer in 374. Of the remaining 1,501 men 984 underwent repeat screening. RESULTS Biopsy at repeat screening diagnosed prostate cancer in 49 of 442 men (11%), a rate significantly lower than the 19.9% true positive biopsy rate at the primary screening. Pathological characteristics of the tumors diagnosed were not significantly different in the 2 groups. However, prostate volume in men diagnosed with prostate cancer was significantly greater at repeat versus primary screening (mean 42.6 versus 34.9 cc, p = 0.003). The clinical characteristics were more favorable because of an increased proportion of stage T1C tumors. Prostate volume in men with stage T1C cancer was significantly greater than in those with palpable or visible tumors in whom prostate specific antigen values were in the same range. CONCLUSIONS The most important factor responsible for the failure to diagnose these cancers at the primary screening was significantly greater prostate volume. Tumor characteristics were not significantly different in the groups. If prostate cancer screening were to become a routine health care policy, efforts would have to be made to improve the chances of diagnosing prostate cancer in larger prostates by repeat biopsy or by increasing the number of cores obtained.

Comparison of prostate-specific antigen corrected for total prostate volume and transition zone volume in a population-based screening study

OBJECTIVES To compare the discriminatory potential between prostate cancer and benign conditions of the prostate in a population-based screening study, of serum prostate-specific antigen levels (PSA) and PSA corrected for both the total prostate volume (PSA-D) and the transition zone volume (PSA-T). METHODS In a randomized population-based screening study (Rotterdam section of the European Randomized Study of Screening for Prostate Cancer), in which 10,865 men have been screened, the biopsy results of 1202 men with PSA levels of 4 ng/mL or more were evaluated. Planimetric and prolate ellipsoid volumes of the total prostate as well as of the transition zone were measured. The measured volumes were compared with the volumes of 57 radical prostatectomy specimens through Spearmans rank correlation coefficient and agreement tests. A receiver operating characteristic (ROC) curve analysis was done of sensitivity and specificity of biopsy indications through PSA and PSA corrected for the volumes measured with transrectal ultrasound. RESULTS In the 1202 men studied, 361 cases of prostate cancer were diagnosed. Both PSA-D and PSA-T showed a significantly higher area under the ROC curve (0.77 and 0.79, respectively) than PSA alone (area 0.65). There was no significant difference between PSA-D and PSA-T. The use of a PSA-D threshold value of 0. 10 ng/mL/cc would have avoided 28% of biopsies at the cost of 10% of detectable cancers. A PSA-D threshold of 0.15 ng/mL/cc would have avoided 73.8% of biopsies at the cost of not diagnosing 43.8% of detectable cancers. CONCLUSIONS The planimetrically obtained prostate volume showed a more favorable agreement with the radical prostatectomy volume than the prolate ellipsoid volume. The discriminatory potential of the corrected PSA value is better at predicting the results of needle biopsy of the prostate when compared with PSA alone. The use of the transition zone volume for this correction results in a higher discriminatory potential when compared to the use of the total prostate volume; however, the observed difference was not statistically significant.

On the Standardization of Total Prostate-Specific Antigen: an Exercise with Two Reference Preparations

Abstract In this study, 112 serum samples were analyzed for total prostate-specific antigen with three well-established assays i.e. Tandem R and Tandem E (both from Hybritech Inc., San Diego, USA) and Prostatus Free/Total from Wallac Oy, Turku, Finland. Thirty-two samples were collected from prostate cancer patients, 32 from patients with benign prostate hyperplasia and 48 from men participating in a screening study for prostate cancer. The aim of the study was to compare the results before and after recalculation with the data obtained with two reference preparations for total prostate-specific antigen: Stanford 90:10 PSA Calibrator and Certified Reference Material 613 Prostate-Specific Antigen. Comparing the actual results revealed almost perfect correlations between Tandem R and Tandem E and between both Tandem assays and Prostatus. We observed statistically significant differences in accuracy between Tandem R and Tandem E: y(Tandem E)= 1.05 × (Tandem R)+0.07, and between Tandem E and Prostatus: y(Prostatus)= 0.94 × (Tandem E)+0.02 In both comparisons prostate-specific antigen values ranged from 0–40 μg/l. Recalculation with both reference preparations did not solve these discrepancies. One exception was the combination Tandem R and Tandem E. The application of either reference preparation solved the differences in accuracy here. In conclusion, even after recalibration, assays for total prostate-specific antigen are still not completely interchangeable.

New developments in the standardization of total prostate-specific antigen

OBJECTIVE Analytical evaluation of the calibration of three recently launched assays for the measurement of total prostate-specific antigen, i.e., IMx Total PSA (Abbott), Elecsys PSA (Roche), and IMMULITE 3rd Generation PSA (DPC). DESIGN AND METHODS For accuracy assessment two reference materials were applied namely, Stanford 90:10 PSA Calibrator and Certified Reference Material 613 Prostate-Specific Antigen. Dilutions of these preparations were analyzed with all assays. In addition, clinical specimens from known prostate cancer or benign prostate hyperplasia patients and samples taken from an ongoing prostate cancer screening study were used for comparison. RESULTS Application of the Stanford Calibrator revealed results well within 10% of the calculated values for all assays. Regarding the CRM Calibrator only the IMx Total PSA proved to approach the line of identity. The IMMULITE results differed about 40% and the Elecsys about 18% from the calculated values. The comparison with clinical specimens showed statistically different results for the combination IMMULITE-IMx and for IMMULITE-Elecsys. The regression lines for both collections were: y(IMx) = 0.86x(IMMULITE) +0.12 (n = 104, r = 0.970, Sy/x = 0.883 microg/L) and y(Elecsys) = 0.98x(IMMULITE) +0.38 (n = 97, r = 0.976, Sy/x = 0.733 microg/L). In the lower measuring range (PSA <5.0 microg/L) as measured with the screening samples (n = 43), these differences were less pronounced. CONCLUSION In analytical sense a difference was found for both reference preparations in the assays studied. Clinically, despite improvements in methodology, results for total prostate-specific antigen are still not interchangeable. The possible consequences need to be elaborated.

Risk factors for progression in patients with prostate cancer treated by radical prostatectomy

The use of radical prostatectomy as a form of treatment in prostate cancer has increased dramatically. In recent years, outcomes of this surgical form of treatment were reported on large series of patients. This gives the opportunity to evaluate the well documented recurrence and survival rates in relation to the widely used factors of prognosis. Although radical prostatectomy is a well established option for curative treatment, both the patient and the urologist should be aware of the fact that randomized trials to compare different forms of treatment (i.e. radiotherapy and radical prostatectomy) for prostate cancer have not been conducted.