Transition zone PSA density enhances prostate cancer prediction in patients with serum prostate specific antigen (PSA) below 10 NG/ML

The value of Prostate Specific Antigen Density (PSAD) to enhance prostate cancer (PCa) detection remains controversial. Most PSA leakage from the benign prostate into the serum was demonstrated to come from the transition zone (TZ). Therefore, in patients with PSA levels<10 ng/ml and proved benign or cancer disease, we compared PSAD and Prostate Specific Antigen Density of the TZ (PSA-TZ), dividing serum PSA by TZ volume. Measuring total prostate and TZ volume by ultrasound using the prolate ellipsoid method, PSAD and PSA-TZ were calculated in 162 patients, 88 diagnosed with localized PCa and operated by radical prostatectomy and 74 patients with BPH and proven benign disease (sextant biopsies and in 19 patients retropubic adenomectomy). PSAD in benign disease averaged 0.11 (SD 0.09) and 0.21 ng/ml/cc (SD 0.11) in PCa (p<0.01). PSA-TZ averaged 0.20 ng/ml/cc (SD 0.14) in BPH and 1.05 ng/ml/cc (SD 0.70) in PCa (p<.0001). If a PSAD of 0.15 had been chosen, the cancer would have been missed in 34% of the patients compared to 10% if a cut-off value of 0.35 for PSA-TZ had been chosen (p<0.001). Overall, in patients with a PSA of 0.25-10 ng/ml, the sensitivity and specificity of PSA-TZ for PCa prediction at a 0.35 cut-off value were 90 and 93% respectively, compared to 94 and 89%, respectively, for those with a PSA of 4 to 10 ng/ml. In this study, PSA-TZ was much more accurate in predicting PCa than PSAD for PSA< 10 ng/ml. The validity of this concept must be further evaluated in large populations seen for early diagnosis. If confirmed in large prospective studies, PSA-TZ could become a routine tool for urologists in the prediction of prostate cancer in men with a PSA< 10 ng/ml.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Repeat prostate biopsy: Who, how and when? A review

Urologists are frequently faced with the dilemma of treating a patient with a high index of suspicion of prostate cancer (PCa), but an initial set of negative biopsies. In this review, we evaluated the current knowledge on repeat prostate biopsies, focusing on when to perform them and in which patients, how many samples to take, where to direct the biopsies and what morbidity should be expected. We focussed on the available literature and the multicenter European Prostate Cancer Detection (EPCD) study. The EPCD study included 1051 men with a total PSA from 4 to 10 ng/ml who underwent a transrectal ultrasound (TRUS) guided sextant biopsy and a repeat biopsy in case of a negative initial biopsy. Most studies support that increasing the number of biopsy cores as compared to the sextant technique and improving prostate peripheral zone (PZ) sampling result in a significant improvement in the detection of prostate cancer without increase in morbidity or effects on quality of life. Re-biopsy can be performed 6 weeks later with no significant difference in pain or morbidity. At least 10% of patients with negative sextant prostatic biopsy results in the EPCD study were diagnosed with PCa on repeat biopsy, percent free PSA and PSA density of the transition zone being the most accurate predictors. Despite differences in location (more apicodorsal) and multifocality, pathological and biochemical features of cancers detected on initial and repeat biopsy were similar, suggesting similar biological behavior and thus advocating for a repeat prostate biopsy in case of a negative finding on initial biopsy. Indications and ideal number of biopsy cores to take when repeating biopsies in patients who already underwent extensive biopsy protocols on the first biopsy remains to be determined. © 2002 Elsevier Science B.V. All rights reserved.SCOPUS: re.jinfo:eu-repo/semantics/publishe

La densité du PSA de la zone transitionnelle: un nouveau marqueur particulièrement fiable pour la détection du cancer prostatique.

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Prevention and screening

Preventative medicine is well established in different areas, but it is still a relatively new concept in urology. Nutrition and environmental factors are suspected to play a major role in the prevention and/or progression of many cancers, including prostate cancer. Increasing evidence suggests that several dietary elements, particularly animal fat, vitamin E, vitamin D, selenium, and calcium, can interfere with the disease process. Large, prospective, randomised trials examining the effect of diet on prostate cancer should clarify these different aspects, allowing more specific dietary recommendations to be made. Extensive efforts have been made in recent years to facilitate the early detection of prostate cancer. Prostate-specific antigen testing has enabled the diagnosis of prostate cancer to be made 5-10 years earlier and shifted the disease stage at diagnosis towards more localised disease. However, screening for prostate cancer remains controversial. The results of large, ongoing, randomised trials, such as the European Randomised Study of Screening for Prostate Cancer, are awaited to determine the benefit of screening in terms of decreased mortality. Even if a benefit is shown, this must be balanced against changes in quality of life related to the potential morbidity of treatment before screening can be advocated. Over-diagnosis is also a significant potential problem from screening programmes; screening must become more specific for those men at risk of morbidity and death. © 2002 Elsevier Science B.V. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Is one set of transrectal sextant biopsies enough to rule out prostate cancer? A prospective evaluation

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Transition zone volume on transrectal ultrasonography is more accurate and reproducible than the total prostate volume

Transrectal ultrasound (TRUS) is a valuable daily tool for urologists. Prostate volume imaging by TRUS has been shown to be highly variable between different observers and this may lead to important differences in prostate specific antigen density values. We have recently shown that the prostate specific antigen density related to the transition zone (TZ) of the prostate was a new accurate parameter for cancer prediction. The aim of the study was to assess the reliability and accuracy of TZ volume measurement. In 19 patients with benign prostatic hyperplasia (BPH) and 20 patients with prostate cancer, TRUS was performed prior to retropubic adenomectomy or radical prostatectomy. TZ volume and total volume were calculated with the prolate ellipsoid formula. For each distance, minimal and maximal values were recorded, both for TZ and total volume. TZ volume and specimen volume (adenoma) as well as total prostate volume and radical prostatectomy specimen were compared. The weight of the operated BPH specimens was 34.41 ±6.08 g while the calculated TZ volume was 31. L7 ±5.50 ce (p>0.05, NS). The weight of the radical prostatectomy specimens was 30.40 ±8.72 g while calculated volume of the entire gland was 26.90 ± 7.53 cc (p<0.05). When calculating maximum and minimum TZ volume, a difference of -9 to +7% was observed while for total prostate volume this difference reached -11 to +17% (p<0.05). One single difference of 1 cm in the cephalocaudal distance of the total prostate volume leads to more than 20% difference in the volume of the total prostate. TZ volume measurement is easy, reliable and reproducible. Because of the absence of the hypoechoic triangle at the apex of the TZ in the cephalocaudal plane, variability in TZ measurement is decreased. TZ volume measurement can be therefore reliably used to calculate the TZ related PSA density, which seems to be a promissing parameter in cancer prediction or when assessing the volume of an adenoma prior to medical or surgical treatment for BPH.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Optimal predictors of prostate cancer on repeat prostate biopsy: A prospective study of 1,051 men

Purpose: We compare the ability of total prostate specific antigen (PSA), percent free PSA, PSA density and transition zone PSA density to predict the outcome of repeat prostatic biopsy in men with serum total PSA 4 to 10 ng./ml. who were diagnosed with benign prostatic hyperplasia after initial biopsy. Materials and Methods: In this prospective study 1,051 men with total PSA 4 to 10 ng./ml. underwent transrectal ultrasound guided sextant biopsy with 2 additional transition zone biopsies. In 254 subjects biopsy specimens were also obtained from suspicious areas identified during transrectal ultrasound and digital rectal examination. All subjects with biopsy specimens negative for prostate cancer underwent repeat biopsy 6 weeks after initial biopsy. The ability of total PSA, percent free PSA, PSA density and transition zone PSA density to improve the diagnostic power of PSA testing was assessed with univariate and multivariate analyses as well as receiver operating characteristics (ROC) curves. Results: Initial biopsy was positive (prostate cancer) in 231 and negative (benign prostatic hyperplasia) in 820 of the 1,051 subjects. Prostate cancer was detected on repeat biopsy in 10% of subjects (83 of 820) with negative initial biopsy. Percent free PSA and transition zone PSA density were the most accurate predictors of prostate cancer in these subjects. At a cutoff of 30% percent free PSA would have detected 90% of cancers (sensitivity) and eliminated 50% of unnecessary repeat biopsies (specificity). Sensitivity and specificity of transition zone PSA density at a cutoff of 0.26 ng./ml./cc was 78% and 52%, respectively. ROC curve analysis also showed that percent free PSA was a significantly better predictor of repeat biopsy results than total PSA, PSA density and transition zone PSA density. The area under the ROC curve was 74.5% for percent free PSA, 69.1% for transition zone PSA density, 61.8% for PSA density and 60.3% for total PSA. Conclusions: At least 10% of patients with negative initial prostatic biopsy results will be diagnosed with prostate cancer on repeat biopsy. Percent free PSA and transition zone PSA density enhance the specificity of PSA testing compared to total PSA or PSA density when determining which patients should undergo repeat biopsy. Repeat biopsy should be performed in patients with percent free PSA less than 30% or transition zone PSA density 0.26 ng./ml./cc or greater. In our study percent free PSA was the most accurate predictor of prostate cancer in repeat biopsy specimens.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A new modality of treatment of localized prostate cancer: Initial experience with radio frequency interstitial tumor ablation (RITA) through a transperineal ultrasound-guided approach

Radiofrequency energy (RF) creates very localized controlled necrotic lesions and has already been used therefore to ablate, among others, liver metastasis and benign prostatic tissue. This study was intended to determine the feasibility, safety and pathology of the lesions induced by RF energy delivered interstitially in patients with prostate cancer (PCa) scheduled for radical prostatectomy. RITA was performed in 16 patients with localized PCa prior to surgery. RF energy was delivered into the prostate by active needles (monopolar or bipolar) placed through a transperineal approach under transrectal ultrasound guidance. Needles are covered by retractable shields thus allowing to deliver the energy on a chosen and controlled area. In 15 patients, the procedure was performed just before radical prostatectomy. The last patient was treated by RITA under spinal anesthesia 1 week prior to surgery. Two lesions were performed per prostate. NADPH staining and Hematoxylin-Eosin (HE) were used to assess the extent of the necrotic lesions. Average energy delivered ranged from 3000 to 11000 Joules with maximum central temperatures reaching 106°C for 12 minutes of ablation. No complications were encountered, especially no damage to the urethral sphincter or rectal wall. Macroscopic examination showed marked lesions including the prostate capsule of up to 2.2×1.5×4.5 cm. Microscopic examination showed clear delineated lesions both with NADPH (in prostates immediately removed after surgery) and HE (at 1 week after RITA). In 1 patient, no residual cancer was found on the specimen. Transperineally delivered RF is capable of creating safely reproducible controlled necrotic lesions in PCa. The data presented provide basic information for the potential future application of RITA for localized prostate cancer.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The importance of measuring the prostatic transition zone: an anatomical and radiological study

Objective. To assess the accuracy and reliability of measurements of the volume of the transition zone (TZ, representing the hypertrophied benign component) and whole prostate by TRUS in patients with BPH or cancer, by comparing the radiological with pathological findings after surgery.Patients and methods. The study comprised 36 patients with prostate cancer undergoing radical prostatectomy and 34 patients with symptomatic BPH treated using retropubic adenectomy. The weights of the radical prostatectomy specimens and of the enucleated adenomas were correlated with the corresponding volumes of the TZ and of the whole prostate, respectively, measured by TRUS using the prolate ellipsoid method.Results.The mean (sd) TZ volume measured by TRUS was 36.9 (25.48) mL, whereas the weight of the enucleated specimen was 42.7 (33.58) g (correlation coefficient r=0.95, P<0.001). The TRUS estimate of the volume of the whole prostate was 29.2 (9.24) mL, while the radical prostatectomy specimens weighed 34.5 (10.76) g (r=0.78, P<0.001). The variability in the TZ volume estimate ranged from −17% to +18%, whereas the variability for whole prostate was −21% to +30% (P<0.05).Conclusions. Measurements of the TZ of the prostate by TRUS are more accurate than those for the whole prostate. An assessment of the TZ volume may be sufficiently reliable to be used in the clinical management of BPH and to detect prostate cancer using the prostate-specific antigen density of the TZ as a marker.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jFLWINinfo:eu-repo/semantics/publishe

Complexed prostate-specific antigen, complexed prostate-specific antigen density of total and transition zone, complexed/total prostate-specific antigen ratio, free-to-total prostate-specific antigen ratio, density of total and transition zone prostate-specific antigen: Results of the prospective multicenter European trial

This prospective, multicenter European Prostate Cancer Detection study evaluated the value and performance of the molecular forms of prostate-specific antigen (PSA) and their derivatives in combination with prostate gland and transition zone volumes in early detection of prostate cancer in patients with PSA levels between 4 and 10 ng/mL. Of 750 men enrolled at 7 different European urology centers into the study between November 2001 and March 2002, 340 (45.3%) had a total PSA (tPSA) between 4 and 10 ng/mL (age range, 46 to 87 years). In all patients, the ratio of complexed PSA (cPSA) to tPSA (c/tPSA), cPSA density (cPSAD), cPSAD of the transition zone, PSA, free PSA (fPSA), ratio of fPSA to tPSA (f/tPSA), tPSA density (PSAD), and PSAD of the transition zone were measured and collected 5 to 10 minutes before the sextant biopsy with 2 additional transition zone cores. Measurements of tPSA and fPSA were done with the AxSYM test, whereas cPSA was measured with the ACS 180 cPSA assay. All patients had a transrectal ultrasound-guided sextant prostate biopsy, and 2 additional transition zone biopsies and total and transition zone volumes were measured at the time of biopsy. Histopathologic findings revealed benign histology in 237 patients and prostate cancer in 103 patients (69.7% and 30.3%, respectively). Statistically significant differences included larger total volumes, larger transition zone volumes, and f/tPSA in patients with benign disease (P = 0.0009, P <0.0001, P <0.0001, respectively). At 90% and 95% sensitivity, specificity of cPSA was significantly greater than that for PSA (P <0.0001). At sensitivity levels of 90% and 95%, the specificity of the cPSA assay using cutoff values of 3.06 and 2.52 ng/mL was 20.3% and 9.1%, respectively. A cPSA cutoff value of 6.95 ng/mL and 7.57 ng/mL afforded 90% and 95% specificity for detecting prostate cancer. The area under the curve (AUC) in the receiver operating characteristics curve of cPSA was statistically significantly higher compared with tPSA (60.8 vs 56.9, P = 0.032). AUC for volume-related parameters PSAD, cPSAD, PSAD of the transition zone, and cPSAD of the transition zone were 62.8%, 63.1%, 63.0%, and 63.6%, respectively. cPSA performs better than tPSA in the differentiation between benign disease and prostate cancer and provides similar information to the f/tPSA ratio. In addition, cPSA and cPSA volume-related parameters (cPSAD, cPSAD of the transition zone) further improved the specificity of PSA in early detection of prostate cancer. © 2002, Elsevier Science Inc.SCOPUS: ar.jinfo:eu-repo/semantics/publishe