Alexandre Zlotta

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.

Extraperitoneal laparoscopic radical prostatectomy. Results after 50 cases.

INTRODUCTION After an initial experience using transperitoneal laparoscopic radical prostatectomy as described by Vallancien and Guillonneau, we developed a pure extraperitoneal approach. This approach seems more comparable to the open technique and avoid potential risks of specific complications due to the transperitoneal approach. We evaluated the perioperative parameters (blood loss, operating time, transfusion rate) and postoperative results (oncological results, continence and potency) after our first 50 cases. MATERIAL AND METHOD Between September 1999 and September 2000, we performed 50 laparoscopic radical prostatectomy. On average, patients were 63.3 years old (range 47-71), had preoperative mean PSA values of 9.14 ng/ml (1.1-23). Median Gleason score was 6 (4-10) with 2.5 (1-6) positive biopsies for a mean prostate volume of 40 cm(3) (17.5-95.0). Clinical stage was T1, T2a, T2b and T3 in 46.3, 41.5, 9.8 and 2.4% of the cases, respectively. We used a pure extraperitoneal approach and we performed a descending technique starting with the dissection at the bladder neck. The seminal vesicles dissection is comparable to the open approach. RESULTS 42 extraperitoneal and 8 transperitoneal procedures were performed (2 in the initial experience, 3 because of previous abdominal surgery and 3 because of incidental peritoneal opening). Mean operative time was 317 min, mean blood loss 680 cm(3), transfusion rate of 13%. 1 patient/50 was converted to an open procedure. Pathological stage was pT1a, pT2a, pT2b, pT2c, pT3a and pT3b in 2.2, 8.5, 42.5, 2.2, 34 and 10.6% of cases, respectively. Positive surgical margins were observed in 22% of cases. The potency rate after neurovascular bilateral bundle preservation was 43% at 3 months (n = 7) and 67% at 6 months and (n = 6) without any further treatment. The continence rate (no pad) was 39% at 3 months and 85% at 6 months. Detectable postoperative PSA at 3 month was observed in 2 patients only. Two major complications occurred: one acute transient renal failure one uretrorectal fistula at day 20. CONCLUSIONS The extraperitoneal laparoscopic radical prostatectomy results seem comparable to transperitoneal laparoscopic radical prostatectomy or open surgery. This approach is reproducible and seems to avoid the potential risks of intraperitoneal injury. Long-term follow up and comparative series are however necessary to further evaluate these new techniques.

Extraperitoneal Laparoscopic Radical Prostatectomy

Introduction: After an initial experience using transperitoneal laparoscopic radical prostatectomy as described by Vallancien and Guillonneau, we developed a pure extraperitoneal approach. This approach seems more comparable to the open technique and avoid potential risks of specific complications due to the transperitoneal approach. We evaluated the perioperative parameters (blood loss, operating time, transfusion rate) and postoperative results (oncological results, continence and potency) after our first 50 cases. Material and Method: Between September 1999 and September 2000, we performed 50 laparoscopic radical prostatectomy. On average, patients were 63.3 years old (range 47–71), had preoperative mean PSA values of 9.14 ng/ml (1.1–23). Median Gleason score was 6 (4–10) with 2.5 (1–6) positive biopsies for a mean prostate volume of 40 cm3 (17.5–95.0). Clinical stage was T1, T2a, T2b and T3 in 46.3, 41.5, 9.8 and 2.4% of the cases, respectively. We used a pure extraperitoneal approach and we performed a descending technique starting with the dissection at the bladder neck. The seminal vesicles dissection is comparable to the open approach. Results: 42 extraperitoneal and 8 transperitoneal procedures were performed (2 in the initial experience, 3 because of previous abdominal surgery and 3 because of incidental peritoneal opening). Mean operative time was 317 min, mean blood loss 680 cm3, transfusion rate of 13%. 1 patient/50 was converted to an open procedure. Pathological stage was pT1a, pT2a, pT2b, pT2c, pT3a and pT3b in 2.2, 8.5, 42.5, 2.2, 34 and 10.6% of cases, respectively. Positive surgical margins were observed in 22% of cases. The potency rate after neurovascular bilateral bundle preservation was 43% at 3 months (n = 7) and 67% at 6 months and (n = 6) without any further treatment. The continence rate (no pad) was 39% at 3 months and 85% at 6 months. Detectable postoperative PSA at 3 month was observed in 2 patients only. Two major complications occurred: one acute transient renal failure one uretrorectal fistula at day 20. Conclusions: The extraperitoneal laparoscopic radical prostatectomy results seem comparable to transperitoneal laparoscopic radical prostatectomy or open surgery. This approach is reproducible and seems to avoid the potential risks of intraperitoneal injury. Long–term follow up and comparative series are however necessary to further evaluate these new techniques.

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 apico-dorsal) 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.

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.

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

OBJECTIVES Radiofrequency (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 Using RITA, a total of 21 lesions were induced in 10 patients with localized CaP (mean age 70.4 years). RF was delivered transperineally under transrectal ultrasound (TRUS) guidance. All patients underwent endorectal magnetic resonance imaging (MRI) before and after treatment. Radical prostatectomy was performed in all patients 1 to 7 days after RITA. Three of the patients were treated with local anesthesia only. The predictability of the thermal lesion was assessed by correlating the findings of intraoperative TRUS, pre- and post-RITA endorectal MRI, and the histologic examination of the specimen. RESULTS Postoperatively, patients were catheterized for an average of 1.8 days (1 to 3 days). Lesions of 2 x 2 x 2 cm were targeted. Average lesion diameters obtained on MRI were 2.08 +/- 0.23 x 2.09 +/- 0.36 x 2.28 +/- 0.21 cm. Average lesion diameters defined by coagulative necrosis at histologic examination were 2.20 +/- 0.23 x 2.10 +/- 0.31 x 2.38 +/- 0.14 cm. There were no statistically significant differences (P = 0.377) between average lesion volume on MRI (5.37 +/- 1.83 cm3) and average lesion volume at histology (5.86 +/- 1.63 cm3). No complications or adverse events were noted. CONCLUSIONS In this Phase I study, RITA was shown to be safe and feasible, and to result in lesions that were predictable in size and location. MRI accurately visualized and verified the area of coagulative necrosis as documented at histology. The procedure is technically simple and can even be performed under local anesthesia.

Total and transition zone prostate volume and age: How do they affect the utility of PSA-based diagnostic parameters for early prostate cancer detection?

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 cm3 or less and greater than 30 cm3, TZ volume strata of 20 cm3 or less and greater than 20 cm3, 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 <0.01), PSA-TZ, PSAD (P <0.001), and PSAV (P <0.05) and lower values of f/t PSA (P <0.001) 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 <0.05). tPSA, PSA-TZ, and PSAD were significantly higher (P <0.05) 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 <0.001) 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 <0.001) in prostates with a higher TP volume (greater than 30 cm3) and TZ volume (greater than 20 cm3); 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.

Is One Set of Sextant Biopsies Enough to Rule Out Prostate Cancer? Influence of Transition and Total Prostate Volumes on Prostate Cancer Yield

Purpose: Although the sextant biopsy technique has been widely used, concern has arisen that this method may not include an adequate sampling of the prostate, especially for large prostate volumes. We conducted a multicenter study in patients with PSA levels <10 ng/ml to determine the influence of the total and transition zone (TZ) volumes of the prostate for predicting whether one single set of biopsies was sufficient to rule out prostate cancer (PCa). These parameters were evaluated in patients in whom PCa was found after one set of systematic sextant biopsies and those in whom PCa was found after a repeat biopsy.Materials and Methods: A total of 1,018 patients were included in this study. All underwent transrectal ultrasound–guided needle sextant and two TZ biopsies of the prostate. Total and TZ volumes of the prostate were measured (prolate ellipsoid method). From this cohort, all patients in whom a benign disease was found after the first set of biopsies underwent a second similar set of biopsies within 6 weeks. Only patients with PCa were included in this study, whether diagnosed on first or repeat biopsy. Uni– and multivariate statistical analysis using the SAS system (Cary, N.C., USA) and ROC curves were used to compare patients in whom the diagnosis was performed after the first set of biopsies and those who required a second set. Results: Of the 1,018 patients, 344 (33.8%) had PCa diagnosed, 285 (28%) after the first set of biopsies, and 59 (8.1%) on repeat biopsy. As compared to patients diagnosed with PCa after the first set of biopsies, patients diagnosed after the second set had larger total prostate and TZ volumes (43.1±13.0 vs. 32.5±10.6 cm3, p<0.0001 and 20.5±8.3 vs. 12.8±6.0 cm3, p<0.0001). ROC curves showed that total and TZ volumes of 45 and 22.5 cm3, respectively, provided the best combination of sensitivity and specificity for discriminating between patients diagnosed with PCa after the first from those diagnosed after a second set. Conclusion: In patients with total prostate volume >45 cm3 and TZ >22.5 cm3, a single set of sextant biopsies may not be sufficient to rule out PCa. In these patients, a repeat biopsy should be considered in case of a negative first biopsy.

Nutrition and prostate cancer: evidence or suspicion?

This document reviews and assesses evidence-based epidemiologic prospective and laboratory data on the role of diet in prostate cancer using the Medline and Current Contents databases. Studies were classified as randomized prospective cohorts nested case- control studies within larger prospective trials and case-control studies. Although primary chemoprevention of prostate cancer is noted as a promising strategy for preventing and arresting the development of the disease the study also notes the important role of nutrition. Such role is confirmed from the evidence gathered on the interference of dietary compounds in the genesis or promotion of prostate cancer particularly vitamin E selenium soy products and low-animal-fat diets. The results from these studies are important to urologists to help them in advocating scientifically the use of nutritional supplements as standard practice for prostate cancer prevention.

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

 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.