Alexandre Zlotta - Academia.edu (original) (raw)

Papers by Alexandre Zlotta

Research paper thumbnail of Recurrence and Progression of Disease in Non–Muscle-Invasive Bladder Cancer: From Epidemiology to Treatment Strategy

European Urology, 2009

E U R O P E A N U R O L O G Y 5 6 ( 2 0 0 9 ) 4 3 0 -4 4 2 a v a i l a b l e a t w w w . s c i e ... more E U R O P E A N U R O L O G Y 5 6 ( 2 0 0 9 ) 4 3 0 -4 4 2 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m

Research paper thumbnail of An artificial neural network to predict the outcome of repeat prostate biopsies

Urology, 2003

Objectives. To develop an advanced artificial neural network (ANN) to predict the presence of pro... more Objectives. To develop an advanced artificial neural network (ANN) to predict the presence of prostate cancer (PCa) and to predict the outcome of repeat prostate biopsies. The predictive accuracy was compared with the accuracy obtained using standard cutoffs for the free/total (f/t) prostate-specific antigen (PSA) ratio, PSA density (PSAD), PSA density of the transition zone (PSA-TZ), and the total and transition zone volumes. Clinical and biochemical diagnostic tests have been shown to improve PCa detection. When these tests are combined using an ANN, significant increases in specificity at high sensitivity are observed. Methods. The Vienna-based multicenter European referral database for early PCa detection of 820 men with a PSA level between 4 and 10 ng/mL was used. The presence of PCa was determined using transrectal ultrasound-guided octant needle repeat biopsy. Variables in the database consisted of age, PSA, f/t PSA ratio, digital rectal examination findings, PSA velocity, and the transrectal ultrasound-guided variables of prostate volume, transition zone volume, PSAD, and PSA-TZ. The ANN used in the analysis was an advanced multilayer perceptron selected for accuracy by a genetic algorithm. Results. The repeat biopsy PCa detection rate was 10% (n ϭ 83). At 95% sensitivity, the specificity for ANN was 68% compared with 54%, 33.5%, 21.4%, 14.7%, and 8.3% for multivariate logistic regression analysis, f/t PSA ratio, PSA-TZ, PSAD, and total PSA, respectively. The ANN reduced unnecessary repeat biopsies by 68% in this study. The area under the curve was 83% for the ANN versus 79%, 74.5%, 69.1%, 61.8%, and 60.5% for multivariate analysis, f/t PSA ratio, PSA-TZ, PSAD, and total PSA, respectively. Conclusions. The current ANN found a strong pattern predictive of PCa in patients with a negative initial biopsy. By combining the individual clinical and biochemical markers into the ANN, 68% specificity at 95% sensitivity was achieved. The ANN allows more accurate and individual counseling of patients with a negative initial biopsy. UROLOGY 62: 456-460, 2003.

Research paper thumbnail of Radical prostatectomy: a prospective comparison of oncological and functional results between open and laparoscopic approaches

World Journal of Urology, 2003

We prospectively compared, within the same center and during the same period of time, the periope... more We prospectively compared, within the same center and during the same period of time, the perioperative parameters as well as the oncological and functional results of both open retropubic (ORP) and laparoscopic radical prostatectomy (LRP). From September 1999 to September 2001, 162 patients with prostate cancer were treated with radical prostatectomy, 77 using an open retropubic technique, and 85 by the laparoscopic extraperitoneal approach. We prospectively recorded pre-, per- and postoperative parameters and complications, and evaluated the carcinological and functional results, comparing both approaches. There were no significant differences in the preoperative characteristics of the two groups. Mean operative time was statistically longer with LRP than with ORP (288 vs 168 min, P<0.0001) but median blood loss was decreased (400 vs 1,300 ml, P<0.0001). Major complications occurred in a similar number of cases (5% vs 2.4%, NS) while minor complications occurred more frequently with ORP (24.6 vs 11.8%, P=0.003). Pathological examination revealed a similar distribution of Gleason scores and stages in each group. Positive surgical margins in pT2 cases occurred in 7.8% of LRP and 7.3% of ORP. Continence rates (no pad and no leakage at all) were similar (83.9% in ORP vs 80.7% in LRP, NS). Potency rates were similar after 1 year in patients undergoing bilateral nerve sparing (55% in ORP vs 65% in LRP, NS). However, patients operated by LRP had more spontaneous erections. We conclude that this prospective, comparative study shows that LRP, when performed in specialized centers, gives oncological and functional results comparable to open surgery.

Research paper thumbnail of SAFETY AND MORBIDITY OF FIRST AND REPEAT TRANSRECTAL ULTRASOUND GUIDED PROSTATE NEEDLE BIOPSIES: RESULTS OF A PROSPECTIVE EUROPEAN PROSTATE CANCER DETECTION STUDY

Journal of Urology, 2001

We prospectively evaluate the safety, morbidity and complication rates for first and repeat trans... more We prospectively evaluate the safety, morbidity and complication rates for first and repeat transrectal ultrasound guided prostate needle biopsies. In this prospective European Prostate Cancer Detection Study 1,051 men, with total prostate specific antigen between 4 and 10 ng./ml., underwent transrectal ultrasound guided sextant biopsy plus 2 additional transition zone biopsies. Biopsy samples were also obtained from suspicious areas identified during transrectal ultrasound and digital rectal examination. All 820 patients with biopsy samples negative for prostate cancer underwent re-biopsy after 6 weeks. Immediate and delayed (range 1 to 7 days) morbidity, patient satisfaction and complication rates were recorded. Of the 1,051 subjects the initial biopsy was positive for prostate cancer in 231 and negative, including benign prostatic hyperplasia or benign tissue, in 820. Of these 820 patients prostate cancer was detected in 10% (83) on re-biopsy. Minor or no discomfort was observed in 92% and 89% of patients at first and re-biopsy, respectively (p = 0.29). Immediate morbidity was minor and included rectal bleeding (2.1% versus 2.4%, p = 0.13), mild hematuria (62% versus 57%, p = 0.06), severe hematuria (0.7% versus 0.5%, p = 0.09) and moderate to severe vasovagal episodes (2.8% versus 1.4%, respectively, p = 0.03). Delayed morbidity of first and re-biopsy was comprised of fever (2.9% versus 2.3%, p = 0.08), hematospermia (9.8% versus 10.2%, p = 0.1), recurrent mild hematuria (15.9% versus 16.6%, p = 0.06), persistent dysuria (7.2% versus 6.8%, p = 0.12) and urinary tract infection (10.9% versus 11.3%, respectively, p = 0.07). Major complications were rare and included urosepsis (0.1% versus 0%) and rectal bleeding that required intervention (0% versus 0.1%, respectively). Furthermore, an age dependent pattern of pain apprehension during biopsy was observed with the highest scores in patients younger than 60 years. Transrectal ultrasound guided biopsy is generally well tolerated with minor morbidity only rarely requiring treatment. Re-biopsy can be performed 6 weeks later with no significant difference in pain or morbidity. Patients younger than 60 years should be counseled in regard to a higher level of discomfort, and local and topical anesthesia if desired.

Research paper thumbnail of Evolution and Clinical Significance of the T Cell Proliferative and Cytokine Response Directed Against the Fibronectin Binding Antigen 85 Complex of Bacillus Calmette-Guerin During Intravesical Treatment of Superficial Bladder Cancer

Journal of Urology, 1997

Purpose: The antitumorigenic effect of intravesical bacillus Calmette-Guerin (BCG) in superficial... more Purpose: The antitumorigenic effect of intravesical bacillus Calmette-Guerin (BCG) in superficial bladder cancer was reported to be initiated by the attachment of BCG to the bladder wall via fibronectin. The antigen 85 complex secreted in BCG culture filtrate binds specifically to fibronectin and is a powerful T cell stimulus. Therefore, we investigated the evolution and clinical significance of the cellular proliferative response and cytokine production during intravesical BCG therapy against this purified antigen 85 complex.

Research paper thumbnail of Transurethral needle ablation of the prostate: a new treatment of benign prostatic hyperplasia using interstitial low-level radiofrequency energy

Current Opinion in Urology, 1995

The review aims at reviewing the evidence published in the peer review literature or otherwise av... more The review aims at reviewing the evidence published in the peer review literature or otherwise available with particular focus on articles published over the last 2 years on the transurethral needle ablation of the prostate in the treatment of benign prostatic hyperplasia. Prospective noncomparative and comparative studies as well as meta-analyses were considered. Information from the European Real Life database on transurethral needle ablation was also included. The evidence currently available confirms a clinically relevant improvement of lower urinary tract symptoms and quality of life. Impact on voiding dynamics including flow rates, detrusor pressure at maximum flow and postvoid residual, as well on prostate volume, remains marginal. All major guidelines in the management of lower urinary tract symptoms in patients with benign prostatic enlargement include transurethral needle ablation of the prostate as a valuable treatment option in patients with severe symptoms and low degree of bladder outlet obstruction, patients at high risk for surgery and patients who wish to avoid surgery or regional/general anaesthesia.

Research paper thumbnail of Prostate Specific Antigen Density of the Transition Zone: A New Effective Parameter for Prostate Cancer Prediction

Journal of Urology, 1997

Purpose: Use of prostate specific antigen (PSA) density to enhance the predictive value of detect... more Purpose: Use of prostate specific antigen (PSA) density to enhance the predictive value of detecting prostate cancer at intermediate PSA levels has been limited due to contradictory results in large scale studies. Most PSA leakage from the benign prostate into the serum comes from the transition zone. Therefore, in patients with benign prostatic hyperplasia (BPH) and prostate cancer with a serum PSA of less than 10 ng./ml. we studied and compared the values of PSA density of the total prostate and the transition zone. We examined the ability of PSA density of the transition zone to enhance prostate cancer detection in patients with intermediate PSA

Research paper thumbnail of Transperineal radiofrequency interstitial tumor ablation of the prostate: Correlation of magnetic resonance imaging with histopathologic examination

Urology, 1997

(RF) energy has recently been employed to destroy human tissue in vivo. The purpose of this study... more (RF) energy has recently been employed to destroy human tissue in vivo. The purpose of this study was to investigate the safety of this approach in localized carcinoma of the prostate (Cap) and specifically, the predictability of lesions obtained with radiofrequency interstitial tumor ablation (RITA). Methods.

Research paper thumbnail of OPTIMAL PREDICTORS OF PROSTATE CANCER IN REPEAT PROSTATE BIOPSY: A PROSPECTIVE STUDY IN 1051 MEN

Research paper thumbnail of CORRELATION AND PROGNOSTIC SIGNIFICANCE OF p53, p21 WAF1/CIP1 AND Ki67 EXPRESSION IN PATIENTS WITH SUPERFICIAL BLADDER TUMORS TREATED WITH BACILLUS CALMETTE-GUERIN INTRAVESICAL THERAPY

Journal of Urology, 1999

We determine if, before intravesical bacillus-Calmette Guerin (BCG) therapy, p53, p21WAF-1-CIP1 (... more We determine if, before intravesical bacillus-Calmette Guerin (BCG) therapy, p53, p21WAF-1-CIP1 (a critical downstream effector of p53 pathway of cell growth control, inhibiting cyclin dependent kinases) and the cell proliferation marker Ki-67 (MIB-1) could be used as prognostic markers of response to BCG in patients with superficial bladder tumors. The study included 47 patients with superficial bladder tumors at high risk for recurrence or progression treated with 6 weekly intravesical BCG instillations. We analyzed p53, p21 and Ki-67 on paraffin embedded samples by immunohistochemistry and the percentage of positive cells was determined in a blinded fashion. Quantitative immunostaining was analyzed in relation to time to recurrence and progression using univariate or multivariate analysis and the Kaplan-Meier method. During a mean followup of 24.6 months 23 of the 47 patients (48.9%) presented with tumor recurrence and 10 (21.2%) had later progression to invasive disease. A p21 over expression (greater than 10%) was observed in 23 tumors (48.9%) and positively correlated with p53 (p = 0.0097) but not with Ki-67 (p = 0.327). Of the tumors 18 (38.2%) were p53 and p21 negative. Among p21 positive tumors 15 (65.2%) were p53 and p21 positive, suggesting that p21 may also be regulated by p53 independent pathways. However, p53 did not act as a predictor of recurrence or progression. In contrast, using Kaplan-Meier curves p21 over expression (greater than 10%) and Ki-67 at a 25% cutoff were associated with shorter recurrence-free survival (both p = 0.02 log rank test) but they did not predict additional information about risk of progression. However, multivariate analysis failed to demonstrate any independent prognostic value for p21 or Ki-67 in contrast to tumor stage. Our results indicate that p21WAF-1-CIP1 seems to be regulated by p53 independent pathways in superficial bladder cancer. The present study did not indicate an independent prognostic significance in patients treated with BCG for p53, p21WAF-1-CIP1 or Ki-67 markers. Larger prospective studies are needed to evaluate further the independent value of these biological markers in superficial bladder cancer management.

Research paper thumbnail of Repeat Prostate Biopsy: Who, How and When

European Urology, 2002

Urologists are frequently faced with the dilemma of treating a patient with a high index of suspi... more 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 signi®cant 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 signi®cant 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 ®nding 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 ®rst biopsy remains to be determined. #

Research paper thumbnail of Long-Term Evaluation of Transurethral Needle Ablation of the Prostate (TUNA) for Treatment of Symptomatic Benign Prostatic Hyperplasia: Clinical Outcome up to Five Years from Three Centers

European Urology, 2003

Objective: TUNA has been demonstrated to be a safe and effective therapy for BPH. However the maj... more Objective: TUNA has been demonstrated to be a safe and effective therapy for BPH. However the major criticism, as with all alternative treatments for BPH, was the lack of long-term data. We present the clinical outcome of patients treated by TUNA and followed for 5 years. Methods: 188 consecutive patients with symptomatic BPH treated with TUNA were followed for five years in three different centers. All patients were treated using the TUNA II or TUNA III catheters under local anesthesia only without general or spinal anesthesia. Baseline and 5-year follow-up evaluation included urinary peak flow, International Prostate Symptom Score (IPSS) and post-void residual urine (PVR). The number of patients requiring additional medical or surgical treatment was recorded. Statistics were performed using the t-test. Results: At a mean follow-up of 63 months, mean urinary peak flow rate increased from 8.6 ml/s to 12.1 ml/s ( p < 0:01, t-test), IPSS and PVR decreased from 20.9 and 179 ml to 8.7 and 122 ml, respectively (both p < 0:001, t-test). The percentage of patients who improved by at least 50% their peak uroflow and IPSS was 24% and 78% respectively. Mean prostate volume and PSA levels did not change significantly (53.9 cc vs. 53.8 cc and 3.3 vs. 3.6 ng/ml, respectively at 5 years, both p values > 0.05, t-test). Two patients died of unrelated comorbidities and 10 were lost for follow-up. Medical treatment was given to 12 patients (6.4%), a second TUNA performed in 7 patients (3.7%) and surgery indicated in 22/186 (11.1%). Overall 41/176 patients (188 at start, 2 deaths and 10 lost to follow-up) or 23.3% required additional treatment at 5 years follow-up following the original TUNA procedure. Conclusions: TUNA is effective and provides good long-term clinical improvement at 5-year follow-up. TUNA treatment stands the test of time at 5-year follow-up with low and acceptable failure rates. More than 75% of the patients do not need additional treatment for BPH on the long run. #

Research paper thumbnail of OPTIMAL PREDICTORS OF PROSTATE CANCER ON REPEAT PROSTATE BIOPSY: A PROSPECTIVE STUDY OF 1,051 MEN

Journal of Urology, 2000

We compare the ability of total prostate specific antigen (PSA), percent free PSA, PSA density an... more 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. 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. 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. 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.

Research paper thumbnail of Prostatic Intraepithelial Neoplasia: Influence of Clinical and Pathological Data on the Detection of Prostate Cancer

Journal of Urology, 1996

Prostatic intraepithelial neoplasia (PIN) is the histologic lesion most strongly associated with ... more Prostatic intraepithelial neoplasia (PIN) is the histologic lesion most strongly associated with prostate cancer and has been postulated to be a pre-malignant lesion. However, much of the natural history of PIN remains unknown. A more fundamental understanding of the relationship between PIN and invasive tumors at the molecular level is critically needed and represents an important future challenge for investigators. The importance of their recognition are based on the correlation between their presence and the existence of prostatic adenocarcinomas. It seemed significant to us to point out the criteria of the diagnosis and the action to be taken in front of the discovery of such lesions on biopsies in prostate sufferers.

Research paper thumbnail of CORRELATION AND PROGNOSTIC SIGNIFICANCE OF p53, p21WAF1/CIP1 AND Ki67 EXPRESSION IN PATIENTS WITH SUPERFICIAL BLADDER TUMORS TREATED WITH BACILLUS CALMETTE-GUERIN INTRAVESICAL THERAPY

Journal of Urology, 1999

We determine if, before intravesical bacillus-Calmette Guerin (BCG) therapy, p53, p21WAF-1-CIP1 (... more We determine if, before intravesical bacillus-Calmette Guerin (BCG) therapy, p53, p21WAF-1-CIP1 (a critical downstream effector of p53 pathway of cell growth control, inhibiting cyclin dependent kinases) and the cell proliferation marker Ki-67 (MIB-1) could be used as prognostic markers of response to BCG in patients with superficial bladder tumors. The study included 47 patients with superficial bladder tumors at high risk for recurrence or progression treated with 6 weekly intravesical BCG instillations. We analyzed p53, p21 and Ki-67 on paraffin embedded samples by immunohistochemistry and the percentage of positive cells was determined in a blinded fashion. Quantitative immunostaining was analyzed in relation to time to recurrence and progression using univariate or multivariate analysis and the Kaplan-Meier method. During a mean followup of 24.6 months 23 of the 47 patients (48.9%) presented with tumor recurrence and 10 (21.2%) had later progression to invasive disease. A p21 over expression (greater than 10%) was observed in 23 tumors (48.9%) and positively correlated with p53 (p = 0.0097) but not with Ki-67 (p = 0.327). Of the tumors 18 (38.2%) were p53 and p21 negative. Among p21 positive tumors 15 (65.2%) were p53 and p21 positive, suggesting that p21 may also be regulated by p53 independent pathways. However, p53 did not act as a predictor of recurrence or progression. In contrast, using Kaplan-Meier curves p21 over expression (greater than 10%) and Ki-67 at a 25% cutoff were associated with shorter recurrence-free survival (both p = 0.02 log rank test) but they did not predict additional information about risk of progression. However, multivariate analysis failed to demonstrate any independent prognostic value for p21 or Ki-67 in contrast to tumor stage. Our results indicate that p21WAF-1-CIP1 seems to be regulated by p53 independent pathways in superficial bladder cancer. The present study did not indicate an independent prognostic significance in patients treated with BCG for p53, p21WAF-1-CIP1 or Ki-67 markers. Larger prospective studies are needed to evaluate further the independent value of these biological markers in superficial bladder cancer management.

Research paper thumbnail of BPH and Sexuality

European Urology, 1999

Quality of life has become a very important parameter in benign prostatic hyperplasia (BPH) and o... more Quality of life has become a very important parameter in benign prostatic hyperplasia (BPH) and one of the major concepts identified by the patients to be important is related to sexuality after BPH therapy. The impact on sexuality resulting from the various treatment modalities of BPH, either medical, surgical or instrumental has been too often neglected in the past and poorly investigated. The present article reviews the influence on sexual function of current therapies for symptomatic BPH.

Research paper thumbnail of An Artificial Neural Network for Prostate Cancer Staging when Serum Prostate Specific Antigen is 10 NG./ML. or Less

Journal of Urology, 2003

An artificial neural network was developed to improve the prediction of pathological stage before... more An artificial neural network was developed to improve the prediction of pathological stage before radical prostatectomy based on variables available at biopsy and clinical parameters. We used the prospectively accrued European prostate cancer detection data base to train an artificial neural network to predict pathological stage in 200 men with serum prostate specific antigen (PSA) 10 ng./ml. or less who underwent radical prostatectomy. Variables included in the artificial neural network were patient age, serum PSA, free-to-total PSA ratio, PSA velocity, transrectal ultrasound calculated total and transition zone volumes with their associated PSA parameters (transition zone PSA density and PSA density), digital rectal examination and Gleason score on biopsy. Two multilayer perceptron neural networks were trained on the remaining variables. Data on the 200 patients were divided randomly into a training set, a test set and a validation or prospective set. Overall classification accuracy of the artificial neural network was 92.7% and 84.2% for organ confined and advanced prostate cancer staging, respectively. For preoperatively predicting local versus advanced stage the area under the ROC curve for the artificial neural network was significantly larger (0.91) compared with logistic regression analysis (0.83), Gleason score (0.69), PSA density (0.68), prostate transition zone volume (0.63) and serum PSA (0.62) (all p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). The artificial neural network outperformed logistic regression analysis and correctly predicted pathological stage in more than 90% of the validation patients with serum PSA 10 ng./ml. or less based on clinical, biochemical and biopsy data. In the future artificial neural networks may represent a significant step for improved staging of prostate cancer when counseling patients referred for radical prostatectomy or other curative treatments.

Research paper thumbnail of Total and transition zone prostate volume and age: how do they affect the utility of PSA-based diagnostic parameters for early prostate cancer detection

Urology, 1999

Objectives. To define the role of total prostate (TP) volume, transition zone (TZ) volume, and ag... more Objectives. To define the role of total prostate (TP) volume, transition zone (TZ) volume, and age as determinants of the utility of prostate-specific antigen (PSA)-based diagnostic parameters for early detection of prostate cancer (PCa) in a prospective multicenter study. Methods. The study participants were 974 consecutive men with serum total PSA (tPSA) levels of 4 to 10 ng/mL who were referred for early PCa detection or lower urinary tract symptoms. All patients underwent prostate ultrasound examination and sextant biopsy with two additional TZ biopsies. In patients with negative initial biopsies, repeated biopsies were performed at 6 weeks. tPSA, the free/total PSA ratio (f/t PSA), PSA density of the TZ (PSA-TZ), PSA density (PSAD), and PSA velocity (PSAV) were determined and compared across TP volume strata of 30 cm 3 or less and greater than 30 cm 3 , TZ volume strata of 20 cm 3 or less and greater than 20 cm 3 , and various age groups to evaluate the need for volume and/or age-specific reference ranges. Results. PCa was found in 345 (35.4%) of 974 patients and benign prostatic tissue was found in 629 (64.6%) of 947 patients. Across TP volume strata, significantly higher values of tPSA (P Ͻ0.01), PSA-TZ, PSAD (P Ͻ0.001), and PSAV (P Ͻ0.05) and lower values of f/t PSA (P Ͻ0.001) were observed in patients with PCa than in those without PCa. Similar results were obtained with respect to TZ volume strata, except in the case of PSAV (P Ͻ0.05). tPSA, PSA-TZ, and PSAD were significantly higher (P Ͻ0.05) in patients with PCa than in those without PCa for all corresponding age ranges. In patients with PCa, f/t PSA was significantly lower (P Ͻ0.001) within the same age ranges. Within each group (PCa or benign), f/t PSA, PSAD, PSA-TZ, and PSAV values were unaffected by age strata. However, PSA parameters dependent on prostate volume (PSAD, PSA-TZ) were statistically lower (P Ͻ0.001) in prostates with a higher TP volume (greater than 30 cm 3 ) and TZ volume (greater than 20 cm 3 ); f/t PSA values were unaffected by TP and TZ volumes. Conclusions. f/t PSA and PSA-TZ were the most powerful parameters to differentiate between benign prostatic tissue and PCa. f/t PSA was the sole parameter unaffected by age and prostate volume. We believe new volume-specific cutpoints, as presented in the current study, should be employed when using PSAD and PSA-TZ for the early detection of PCa. UROLOGY 54: 846-852, 1999. © 1999,

Research paper thumbnail of Is one single prostate biopsy helpful for choosing a medical treatment of benign prostatic hyperplasia? a quantitative computerized morphometric study

Urology, 1996

Objectives. Individual differences in proportion of stroma, epithelium, and luminal space compone... more Objectives. Individual differences in proportion of stroma, epithelium, and luminal space components in benign prostatic hyperplasia (BPH) may explain the differences in clinical outcome of the patients treated with a-reductase inhibitors or a-blocking agents and other alternative treatments. Knowledge of the individual proportions of these elements may orient the clinician toward different therapeutic approaches. To determine whether a single prostate biopsy is representative of the whole adenoma, using quantitative morphometry, we have compared the percentage of smooth muscle cells and glandular cells in one prostate needle biopsy and in the corresponding prostate adenoma removed by open surgery.

Research paper thumbnail of PSA Progression Following Radical Prostatectomy and Radiation Therapy: New Standards in the New Millenium

European Urology, 2003

Prostate-speci®c antigen (PSA) progression following radical treatments of clinically localized p... more Prostate-speci®c antigen (PSA) progression following radical treatments of clinically localized prostate cancer is a common problem facing both the patient and the urologist. Not all patients with relapsing disease have an equal risk of death due to prostate cancer.

Research paper thumbnail of Recurrence and Progression of Disease in Non–Muscle-Invasive Bladder Cancer: From Epidemiology to Treatment Strategy

European Urology, 2009

E U R O P E A N U R O L O G Y 5 6 ( 2 0 0 9 ) 4 3 0 -4 4 2 a v a i l a b l e a t w w w . s c i e ... more E U R O P E A N U R O L O G Y 5 6 ( 2 0 0 9 ) 4 3 0 -4 4 2 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o m

Research paper thumbnail of An artificial neural network to predict the outcome of repeat prostate biopsies

Urology, 2003

Objectives. To develop an advanced artificial neural network (ANN) to predict the presence of pro... more Objectives. To develop an advanced artificial neural network (ANN) to predict the presence of prostate cancer (PCa) and to predict the outcome of repeat prostate biopsies. The predictive accuracy was compared with the accuracy obtained using standard cutoffs for the free/total (f/t) prostate-specific antigen (PSA) ratio, PSA density (PSAD), PSA density of the transition zone (PSA-TZ), and the total and transition zone volumes. Clinical and biochemical diagnostic tests have been shown to improve PCa detection. When these tests are combined using an ANN, significant increases in specificity at high sensitivity are observed. Methods. The Vienna-based multicenter European referral database for early PCa detection of 820 men with a PSA level between 4 and 10 ng/mL was used. The presence of PCa was determined using transrectal ultrasound-guided octant needle repeat biopsy. Variables in the database consisted of age, PSA, f/t PSA ratio, digital rectal examination findings, PSA velocity, and the transrectal ultrasound-guided variables of prostate volume, transition zone volume, PSAD, and PSA-TZ. The ANN used in the analysis was an advanced multilayer perceptron selected for accuracy by a genetic algorithm. Results. The repeat biopsy PCa detection rate was 10% (n ϭ 83). At 95% sensitivity, the specificity for ANN was 68% compared with 54%, 33.5%, 21.4%, 14.7%, and 8.3% for multivariate logistic regression analysis, f/t PSA ratio, PSA-TZ, PSAD, and total PSA, respectively. The ANN reduced unnecessary repeat biopsies by 68% in this study. The area under the curve was 83% for the ANN versus 79%, 74.5%, 69.1%, 61.8%, and 60.5% for multivariate analysis, f/t PSA ratio, PSA-TZ, PSAD, and total PSA, respectively. Conclusions. The current ANN found a strong pattern predictive of PCa in patients with a negative initial biopsy. By combining the individual clinical and biochemical markers into the ANN, 68% specificity at 95% sensitivity was achieved. The ANN allows more accurate and individual counseling of patients with a negative initial biopsy. UROLOGY 62: 456-460, 2003.

Research paper thumbnail of Radical prostatectomy: a prospective comparison of oncological and functional results between open and laparoscopic approaches

World Journal of Urology, 2003

We prospectively compared, within the same center and during the same period of time, the periope... more We prospectively compared, within the same center and during the same period of time, the perioperative parameters as well as the oncological and functional results of both open retropubic (ORP) and laparoscopic radical prostatectomy (LRP). From September 1999 to September 2001, 162 patients with prostate cancer were treated with radical prostatectomy, 77 using an open retropubic technique, and 85 by the laparoscopic extraperitoneal approach. We prospectively recorded pre-, per- and postoperative parameters and complications, and evaluated the carcinological and functional results, comparing both approaches. There were no significant differences in the preoperative characteristics of the two groups. Mean operative time was statistically longer with LRP than with ORP (288 vs 168 min, P<0.0001) but median blood loss was decreased (400 vs 1,300 ml, P<0.0001). Major complications occurred in a similar number of cases (5% vs 2.4%, NS) while minor complications occurred more frequently with ORP (24.6 vs 11.8%, P=0.003). Pathological examination revealed a similar distribution of Gleason scores and stages in each group. Positive surgical margins in pT2 cases occurred in 7.8% of LRP and 7.3% of ORP. Continence rates (no pad and no leakage at all) were similar (83.9% in ORP vs 80.7% in LRP, NS). Potency rates were similar after 1 year in patients undergoing bilateral nerve sparing (55% in ORP vs 65% in LRP, NS). However, patients operated by LRP had more spontaneous erections. We conclude that this prospective, comparative study shows that LRP, when performed in specialized centers, gives oncological and functional results comparable to open surgery.

Research paper thumbnail of SAFETY AND MORBIDITY OF FIRST AND REPEAT TRANSRECTAL ULTRASOUND GUIDED PROSTATE NEEDLE BIOPSIES: RESULTS OF A PROSPECTIVE EUROPEAN PROSTATE CANCER DETECTION STUDY

Journal of Urology, 2001

We prospectively evaluate the safety, morbidity and complication rates for first and repeat trans... more We prospectively evaluate the safety, morbidity and complication rates for first and repeat transrectal ultrasound guided prostate needle biopsies. In this prospective European Prostate Cancer Detection Study 1,051 men, with total prostate specific antigen between 4 and 10 ng./ml., underwent transrectal ultrasound guided sextant biopsy plus 2 additional transition zone biopsies. Biopsy samples were also obtained from suspicious areas identified during transrectal ultrasound and digital rectal examination. All 820 patients with biopsy samples negative for prostate cancer underwent re-biopsy after 6 weeks. Immediate and delayed (range 1 to 7 days) morbidity, patient satisfaction and complication rates were recorded. Of the 1,051 subjects the initial biopsy was positive for prostate cancer in 231 and negative, including benign prostatic hyperplasia or benign tissue, in 820. Of these 820 patients prostate cancer was detected in 10% (83) on re-biopsy. Minor or no discomfort was observed in 92% and 89% of patients at first and re-biopsy, respectively (p = 0.29). Immediate morbidity was minor and included rectal bleeding (2.1% versus 2.4%, p = 0.13), mild hematuria (62% versus 57%, p = 0.06), severe hematuria (0.7% versus 0.5%, p = 0.09) and moderate to severe vasovagal episodes (2.8% versus 1.4%, respectively, p = 0.03). Delayed morbidity of first and re-biopsy was comprised of fever (2.9% versus 2.3%, p = 0.08), hematospermia (9.8% versus 10.2%, p = 0.1), recurrent mild hematuria (15.9% versus 16.6%, p = 0.06), persistent dysuria (7.2% versus 6.8%, p = 0.12) and urinary tract infection (10.9% versus 11.3%, respectively, p = 0.07). Major complications were rare and included urosepsis (0.1% versus 0%) and rectal bleeding that required intervention (0% versus 0.1%, respectively). Furthermore, an age dependent pattern of pain apprehension during biopsy was observed with the highest scores in patients younger than 60 years. Transrectal ultrasound guided biopsy is generally well tolerated with minor morbidity only rarely requiring treatment. Re-biopsy can be performed 6 weeks later with no significant difference in pain or morbidity. Patients younger than 60 years should be counseled in regard to a higher level of discomfort, and local and topical anesthesia if desired.

Research paper thumbnail of Evolution and Clinical Significance of the T Cell Proliferative and Cytokine Response Directed Against the Fibronectin Binding Antigen 85 Complex of Bacillus Calmette-Guerin During Intravesical Treatment of Superficial Bladder Cancer

Journal of Urology, 1997

Purpose: The antitumorigenic effect of intravesical bacillus Calmette-Guerin (BCG) in superficial... more Purpose: The antitumorigenic effect of intravesical bacillus Calmette-Guerin (BCG) in superficial bladder cancer was reported to be initiated by the attachment of BCG to the bladder wall via fibronectin. The antigen 85 complex secreted in BCG culture filtrate binds specifically to fibronectin and is a powerful T cell stimulus. Therefore, we investigated the evolution and clinical significance of the cellular proliferative response and cytokine production during intravesical BCG therapy against this purified antigen 85 complex.

Research paper thumbnail of Transurethral needle ablation of the prostate: a new treatment of benign prostatic hyperplasia using interstitial low-level radiofrequency energy

Current Opinion in Urology, 1995

The review aims at reviewing the evidence published in the peer review literature or otherwise av... more The review aims at reviewing the evidence published in the peer review literature or otherwise available with particular focus on articles published over the last 2 years on the transurethral needle ablation of the prostate in the treatment of benign prostatic hyperplasia. Prospective noncomparative and comparative studies as well as meta-analyses were considered. Information from the European Real Life database on transurethral needle ablation was also included. The evidence currently available confirms a clinically relevant improvement of lower urinary tract symptoms and quality of life. Impact on voiding dynamics including flow rates, detrusor pressure at maximum flow and postvoid residual, as well on prostate volume, remains marginal. All major guidelines in the management of lower urinary tract symptoms in patients with benign prostatic enlargement include transurethral needle ablation of the prostate as a valuable treatment option in patients with severe symptoms and low degree of bladder outlet obstruction, patients at high risk for surgery and patients who wish to avoid surgery or regional/general anaesthesia.

Research paper thumbnail of Prostate Specific Antigen Density of the Transition Zone: A New Effective Parameter for Prostate Cancer Prediction

Journal of Urology, 1997

Purpose: Use of prostate specific antigen (PSA) density to enhance the predictive value of detect... more Purpose: Use of prostate specific antigen (PSA) density to enhance the predictive value of detecting prostate cancer at intermediate PSA levels has been limited due to contradictory results in large scale studies. Most PSA leakage from the benign prostate into the serum comes from the transition zone. Therefore, in patients with benign prostatic hyperplasia (BPH) and prostate cancer with a serum PSA of less than 10 ng./ml. we studied and compared the values of PSA density of the total prostate and the transition zone. We examined the ability of PSA density of the transition zone to enhance prostate cancer detection in patients with intermediate PSA

Research paper thumbnail of Transperineal radiofrequency interstitial tumor ablation of the prostate: Correlation of magnetic resonance imaging with histopathologic examination

Urology, 1997

(RF) energy has recently been employed to destroy human tissue in vivo. The purpose of this study... more (RF) energy has recently been employed to destroy human tissue in vivo. The purpose of this study was to investigate the safety of this approach in localized carcinoma of the prostate (Cap) and specifically, the predictability of lesions obtained with radiofrequency interstitial tumor ablation (RITA). Methods.

Research paper thumbnail of OPTIMAL PREDICTORS OF PROSTATE CANCER IN REPEAT PROSTATE BIOPSY: A PROSPECTIVE STUDY IN 1051 MEN

Research paper thumbnail of CORRELATION AND PROGNOSTIC SIGNIFICANCE OF p53, p21 WAF1/CIP1 AND Ki67 EXPRESSION IN PATIENTS WITH SUPERFICIAL BLADDER TUMORS TREATED WITH BACILLUS CALMETTE-GUERIN INTRAVESICAL THERAPY

Journal of Urology, 1999

We determine if, before intravesical bacillus-Calmette Guerin (BCG) therapy, p53, p21WAF-1-CIP1 (... more We determine if, before intravesical bacillus-Calmette Guerin (BCG) therapy, p53, p21WAF-1-CIP1 (a critical downstream effector of p53 pathway of cell growth control, inhibiting cyclin dependent kinases) and the cell proliferation marker Ki-67 (MIB-1) could be used as prognostic markers of response to BCG in patients with superficial bladder tumors. The study included 47 patients with superficial bladder tumors at high risk for recurrence or progression treated with 6 weekly intravesical BCG instillations. We analyzed p53, p21 and Ki-67 on paraffin embedded samples by immunohistochemistry and the percentage of positive cells was determined in a blinded fashion. Quantitative immunostaining was analyzed in relation to time to recurrence and progression using univariate or multivariate analysis and the Kaplan-Meier method. During a mean followup of 24.6 months 23 of the 47 patients (48.9%) presented with tumor recurrence and 10 (21.2%) had later progression to invasive disease. A p21 over expression (greater than 10%) was observed in 23 tumors (48.9%) and positively correlated with p53 (p = 0.0097) but not with Ki-67 (p = 0.327). Of the tumors 18 (38.2%) were p53 and p21 negative. Among p21 positive tumors 15 (65.2%) were p53 and p21 positive, suggesting that p21 may also be regulated by p53 independent pathways. However, p53 did not act as a predictor of recurrence or progression. In contrast, using Kaplan-Meier curves p21 over expression (greater than 10%) and Ki-67 at a 25% cutoff were associated with shorter recurrence-free survival (both p = 0.02 log rank test) but they did not predict additional information about risk of progression. However, multivariate analysis failed to demonstrate any independent prognostic value for p21 or Ki-67 in contrast to tumor stage. Our results indicate that p21WAF-1-CIP1 seems to be regulated by p53 independent pathways in superficial bladder cancer. The present study did not indicate an independent prognostic significance in patients treated with BCG for p53, p21WAF-1-CIP1 or Ki-67 markers. Larger prospective studies are needed to evaluate further the independent value of these biological markers in superficial bladder cancer management.

Research paper thumbnail of Repeat Prostate Biopsy: Who, How and When

European Urology, 2002

Urologists are frequently faced with the dilemma of treating a patient with a high index of suspi... more 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 signi®cant 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 signi®cant 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 ®nding 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 ®rst biopsy remains to be determined. #

Research paper thumbnail of Long-Term Evaluation of Transurethral Needle Ablation of the Prostate (TUNA) for Treatment of Symptomatic Benign Prostatic Hyperplasia: Clinical Outcome up to Five Years from Three Centers

European Urology, 2003

Objective: TUNA has been demonstrated to be a safe and effective therapy for BPH. However the maj... more Objective: TUNA has been demonstrated to be a safe and effective therapy for BPH. However the major criticism, as with all alternative treatments for BPH, was the lack of long-term data. We present the clinical outcome of patients treated by TUNA and followed for 5 years. Methods: 188 consecutive patients with symptomatic BPH treated with TUNA were followed for five years in three different centers. All patients were treated using the TUNA II or TUNA III catheters under local anesthesia only without general or spinal anesthesia. Baseline and 5-year follow-up evaluation included urinary peak flow, International Prostate Symptom Score (IPSS) and post-void residual urine (PVR). The number of patients requiring additional medical or surgical treatment was recorded. Statistics were performed using the t-test. Results: At a mean follow-up of 63 months, mean urinary peak flow rate increased from 8.6 ml/s to 12.1 ml/s ( p < 0:01, t-test), IPSS and PVR decreased from 20.9 and 179 ml to 8.7 and 122 ml, respectively (both p < 0:001, t-test). The percentage of patients who improved by at least 50% their peak uroflow and IPSS was 24% and 78% respectively. Mean prostate volume and PSA levels did not change significantly (53.9 cc vs. 53.8 cc and 3.3 vs. 3.6 ng/ml, respectively at 5 years, both p values > 0.05, t-test). Two patients died of unrelated comorbidities and 10 were lost for follow-up. Medical treatment was given to 12 patients (6.4%), a second TUNA performed in 7 patients (3.7%) and surgery indicated in 22/186 (11.1%). Overall 41/176 patients (188 at start, 2 deaths and 10 lost to follow-up) or 23.3% required additional treatment at 5 years follow-up following the original TUNA procedure. Conclusions: TUNA is effective and provides good long-term clinical improvement at 5-year follow-up. TUNA treatment stands the test of time at 5-year follow-up with low and acceptable failure rates. More than 75% of the patients do not need additional treatment for BPH on the long run. #

Research paper thumbnail of OPTIMAL PREDICTORS OF PROSTATE CANCER ON REPEAT PROSTATE BIOPSY: A PROSPECTIVE STUDY OF 1,051 MEN

Journal of Urology, 2000

We compare the ability of total prostate specific antigen (PSA), percent free PSA, PSA density an... more 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. 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. 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. 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.

Research paper thumbnail of Prostatic Intraepithelial Neoplasia: Influence of Clinical and Pathological Data on the Detection of Prostate Cancer

Journal of Urology, 1996

Prostatic intraepithelial neoplasia (PIN) is the histologic lesion most strongly associated with ... more Prostatic intraepithelial neoplasia (PIN) is the histologic lesion most strongly associated with prostate cancer and has been postulated to be a pre-malignant lesion. However, much of the natural history of PIN remains unknown. A more fundamental understanding of the relationship between PIN and invasive tumors at the molecular level is critically needed and represents an important future challenge for investigators. The importance of their recognition are based on the correlation between their presence and the existence of prostatic adenocarcinomas. It seemed significant to us to point out the criteria of the diagnosis and the action to be taken in front of the discovery of such lesions on biopsies in prostate sufferers.

Research paper thumbnail of CORRELATION AND PROGNOSTIC SIGNIFICANCE OF p53, p21WAF1/CIP1 AND Ki67 EXPRESSION IN PATIENTS WITH SUPERFICIAL BLADDER TUMORS TREATED WITH BACILLUS CALMETTE-GUERIN INTRAVESICAL THERAPY

Journal of Urology, 1999

We determine if, before intravesical bacillus-Calmette Guerin (BCG) therapy, p53, p21WAF-1-CIP1 (... more We determine if, before intravesical bacillus-Calmette Guerin (BCG) therapy, p53, p21WAF-1-CIP1 (a critical downstream effector of p53 pathway of cell growth control, inhibiting cyclin dependent kinases) and the cell proliferation marker Ki-67 (MIB-1) could be used as prognostic markers of response to BCG in patients with superficial bladder tumors. The study included 47 patients with superficial bladder tumors at high risk for recurrence or progression treated with 6 weekly intravesical BCG instillations. We analyzed p53, p21 and Ki-67 on paraffin embedded samples by immunohistochemistry and the percentage of positive cells was determined in a blinded fashion. Quantitative immunostaining was analyzed in relation to time to recurrence and progression using univariate or multivariate analysis and the Kaplan-Meier method. During a mean followup of 24.6 months 23 of the 47 patients (48.9%) presented with tumor recurrence and 10 (21.2%) had later progression to invasive disease. A p21 over expression (greater than 10%) was observed in 23 tumors (48.9%) and positively correlated with p53 (p = 0.0097) but not with Ki-67 (p = 0.327). Of the tumors 18 (38.2%) were p53 and p21 negative. Among p21 positive tumors 15 (65.2%) were p53 and p21 positive, suggesting that p21 may also be regulated by p53 independent pathways. However, p53 did not act as a predictor of recurrence or progression. In contrast, using Kaplan-Meier curves p21 over expression (greater than 10%) and Ki-67 at a 25% cutoff were associated with shorter recurrence-free survival (both p = 0.02 log rank test) but they did not predict additional information about risk of progression. However, multivariate analysis failed to demonstrate any independent prognostic value for p21 or Ki-67 in contrast to tumor stage. Our results indicate that p21WAF-1-CIP1 seems to be regulated by p53 independent pathways in superficial bladder cancer. The present study did not indicate an independent prognostic significance in patients treated with BCG for p53, p21WAF-1-CIP1 or Ki-67 markers. Larger prospective studies are needed to evaluate further the independent value of these biological markers in superficial bladder cancer management.

Research paper thumbnail of BPH and Sexuality

European Urology, 1999

Quality of life has become a very important parameter in benign prostatic hyperplasia (BPH) and o... more Quality of life has become a very important parameter in benign prostatic hyperplasia (BPH) and one of the major concepts identified by the patients to be important is related to sexuality after BPH therapy. The impact on sexuality resulting from the various treatment modalities of BPH, either medical, surgical or instrumental has been too often neglected in the past and poorly investigated. The present article reviews the influence on sexual function of current therapies for symptomatic BPH.

Research paper thumbnail of An Artificial Neural Network for Prostate Cancer Staging when Serum Prostate Specific Antigen is 10 NG./ML. or Less

Journal of Urology, 2003

An artificial neural network was developed to improve the prediction of pathological stage before... more An artificial neural network was developed to improve the prediction of pathological stage before radical prostatectomy based on variables available at biopsy and clinical parameters. We used the prospectively accrued European prostate cancer detection data base to train an artificial neural network to predict pathological stage in 200 men with serum prostate specific antigen (PSA) 10 ng./ml. or less who underwent radical prostatectomy. Variables included in the artificial neural network were patient age, serum PSA, free-to-total PSA ratio, PSA velocity, transrectal ultrasound calculated total and transition zone volumes with their associated PSA parameters (transition zone PSA density and PSA density), digital rectal examination and Gleason score on biopsy. Two multilayer perceptron neural networks were trained on the remaining variables. Data on the 200 patients were divided randomly into a training set, a test set and a validation or prospective set. Overall classification accuracy of the artificial neural network was 92.7% and 84.2% for organ confined and advanced prostate cancer staging, respectively. For preoperatively predicting local versus advanced stage the area under the ROC curve for the artificial neural network was significantly larger (0.91) compared with logistic regression analysis (0.83), Gleason score (0.69), PSA density (0.68), prostate transition zone volume (0.63) and serum PSA (0.62) (all p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01). The artificial neural network outperformed logistic regression analysis and correctly predicted pathological stage in more than 90% of the validation patients with serum PSA 10 ng./ml. or less based on clinical, biochemical and biopsy data. In the future artificial neural networks may represent a significant step for improved staging of prostate cancer when counseling patients referred for radical prostatectomy or other curative treatments.

Research paper thumbnail of Total and transition zone prostate volume and age: how do they affect the utility of PSA-based diagnostic parameters for early prostate cancer detection

Urology, 1999

Objectives. To define the role of total prostate (TP) volume, transition zone (TZ) volume, and ag... more Objectives. To define the role of total prostate (TP) volume, transition zone (TZ) volume, and age as determinants of the utility of prostate-specific antigen (PSA)-based diagnostic parameters for early detection of prostate cancer (PCa) in a prospective multicenter study. Methods. The study participants were 974 consecutive men with serum total PSA (tPSA) levels of 4 to 10 ng/mL who were referred for early PCa detection or lower urinary tract symptoms. All patients underwent prostate ultrasound examination and sextant biopsy with two additional TZ biopsies. In patients with negative initial biopsies, repeated biopsies were performed at 6 weeks. tPSA, the free/total PSA ratio (f/t PSA), PSA density of the TZ (PSA-TZ), PSA density (PSAD), and PSA velocity (PSAV) were determined and compared across TP volume strata of 30 cm 3 or less and greater than 30 cm 3 , TZ volume strata of 20 cm 3 or less and greater than 20 cm 3 , and various age groups to evaluate the need for volume and/or age-specific reference ranges. Results. PCa was found in 345 (35.4%) of 974 patients and benign prostatic tissue was found in 629 (64.6%) of 947 patients. Across TP volume strata, significantly higher values of tPSA (P Ͻ0.01), PSA-TZ, PSAD (P Ͻ0.001), and PSAV (P Ͻ0.05) and lower values of f/t PSA (P Ͻ0.001) were observed in patients with PCa than in those without PCa. Similar results were obtained with respect to TZ volume strata, except in the case of PSAV (P Ͻ0.05). tPSA, PSA-TZ, and PSAD were significantly higher (P Ͻ0.05) in patients with PCa than in those without PCa for all corresponding age ranges. In patients with PCa, f/t PSA was significantly lower (P Ͻ0.001) within the same age ranges. Within each group (PCa or benign), f/t PSA, PSAD, PSA-TZ, and PSAV values were unaffected by age strata. However, PSA parameters dependent on prostate volume (PSAD, PSA-TZ) were statistically lower (P Ͻ0.001) in prostates with a higher TP volume (greater than 30 cm 3 ) and TZ volume (greater than 20 cm 3 ); f/t PSA values were unaffected by TP and TZ volumes. Conclusions. f/t PSA and PSA-TZ were the most powerful parameters to differentiate between benign prostatic tissue and PCa. f/t PSA was the sole parameter unaffected by age and prostate volume. We believe new volume-specific cutpoints, as presented in the current study, should be employed when using PSAD and PSA-TZ for the early detection of PCa. UROLOGY 54: 846-852, 1999. © 1999,

Research paper thumbnail of Is one single prostate biopsy helpful for choosing a medical treatment of benign prostatic hyperplasia? a quantitative computerized morphometric study

Urology, 1996

Objectives. Individual differences in proportion of stroma, epithelium, and luminal space compone... more Objectives. Individual differences in proportion of stroma, epithelium, and luminal space components in benign prostatic hyperplasia (BPH) may explain the differences in clinical outcome of the patients treated with a-reductase inhibitors or a-blocking agents and other alternative treatments. Knowledge of the individual proportions of these elements may orient the clinician toward different therapeutic approaches. To determine whether a single prostate biopsy is representative of the whole adenoma, using quantitative morphometry, we have compared the percentage of smooth muscle cells and glandular cells in one prostate needle biopsy and in the corresponding prostate adenoma removed by open surgery.

Research paper thumbnail of PSA Progression Following Radical Prostatectomy and Radiation Therapy: New Standards in the New Millenium

European Urology, 2003

Prostate-speci®c antigen (PSA) progression following radical treatments of clinically localized p... more Prostate-speci®c antigen (PSA) progression following radical treatments of clinically localized prostate cancer is a common problem facing both the patient and the urologist. Not all patients with relapsing disease have an equal risk of death due to prostate cancer.