Joachim Noldus

Intraoperative and Perioperative Morbidity of Contemporary Radical Retropubic Prostatectomy in a Consecutive Series of 1243 Patients: Results of a Single Center between 1999 and 2002

OBJECTIVES To up date counselling of patients in an experienced center, we assessed intraoperative and perioperative complications in a consecutive series of contemporary radical retropubic prostatectomy for localized prostate cancer. METHODS In a prospective study, we analyzed all intraoperative and perioperative complications within 30 days in a consecutive series of 1243 patients undergoing radical prostatectomy between January 1999 and February 2002. All adverse events were graduated in major and minor complications by their severity and sequel. RESULTS There were no deaths. Overall, 996 patients (80.2%) were not affected by any complication. Major complications were observed in 50 patients (4.0%), minor complications in 197 (15.8%). Pelvic lymphadenectomy was performed in 861 (69.3%) patients. This procedure was associated with a significantly higher rate of lymphoceles requiring a drainage, 4.2% versus 0.3% (p<0.006) and a higher rate of deep venous thrombosis, 1.4% versus 0.5% (p<0.2), respectively. CONCLUSION Radical retropubic prostatectomy is a safe surgical procedure. Postoperatively the majority of our patients was not compromised by any complication within 30 days. Furthermore, due to a higher rate of lymphoceles and thromboembolic events the indication for pelvic lymphadenectomy should be considered carefully.

A VALIDATED STRATEGY FOR SIDE SPECIFIC PREDICTION OF ORGAN CONFINED PROSTATE CANCER: A TOOL TO SELECT FOR NERVE SPARING RADICAL PROSTATECTOMY

PURPOSE Nerve sparing radical prostatectomy for prostate cancer should be restricted to patients who harbor tumors without capsular penetration. To our knowledge the selection criteria for nerve sparing radical prostatectomy are not clearly defined. We investigated a panel of preoperative tumor characteristics with respect to their ability to predict organ confined tumor growth for each lobe of the prostate to indicate unilateral or bilateral nerve sparing radical prostatectomy. MATERIALS AND METHODS Nine preoperative tumor characteristics in 278 patients with clinically localized prostate cancer were included in retrospective univariate and multivariate tree structured regression analysis. The association of clinical stage, serum prostate specific antigen (PSA), PSA density, and results of transrectal ultrasound and systematic sextant biopsy, including a quantitative assessment of cancer in the biopsies with organ confined tumor growth, was statistically evaluated. Except for serum PSA and PSA density preoperative characteristics were considered separately for each prostate lobe. Multivariate analysis results were validated prospectively in 353 patients. RESULTS On univariate analysis the number of positive biopsies was the most useful single parameter with a positive predictive value of 83% in 274 lobes and a negative predictive value of 55%, followed by mm. of tumor in the biopsy. Of all characteristics included in multivariate analysis only the number of biopsies with high grade cancer, the number of positive biopsies and serum PSA were independent for predicting organ confined cancer. When PSA was less than 10 ng./ml. and not more than 1 biopsy with high grade cancer was identified in a lobe, organ confined tumor growth was present in 86.1% of cases. On prospective validation the same criteria led to an 88.5% incidence of organ confined prostate cancer. Pooling the 2 most favorable groups led to 391 prostate lobes (70.8% of those investigated) with a positive predictive value of 82.1% (95% confidence interval 77.9% to 85.8%). Using the multivariate approach more prostate lobes were assigned to a favorable risk group than on univariate analysis. Clinical stage and simple Gleason grade did not contribute independent information for predicting organ confined disease. CONCLUSIONS Quantifying cancer and high grade cancer by systematic biopsy and serum PSA concentration are useful preoperative characteristics for predicting organ confined prostate cancer. Side specific analysis of these parameters is a flexible and reliable tool for selecting patients for nerve sparing radical prostatectomy.

Activation of an Olfactory Receptor Inhibits Proliferation of Prostate Cancer Cells

Olfactory receptors (ORs) are expressed not only in the sensory neurons of the olfactory epithelium, where they detect volatile substances, but also in various other tissues where their potential functions are largely unknown. Here, we report the physiological characterization of human OR51E2, also named prostate-specific G-protein-coupled receptor (PSGR) due to its reported up-regulation in prostate cancer. We identified androstenone derivatives as ligands for the recombinant receptor. PSGR can also be activated with the odorant β-ionone. Activation of the endogenous receptor in prostate cancer cells by the identified ligands evoked an intracellular Ca2+ increase. Exposure to β-ionone resulted in the activation of members of the MAPK family and inhibition of cell proliferation. Our data give support to the hypothesis that because PSGR signaling could reduce growth of prostate cancer cells, specific receptor ligands might therefore be potential candidates for prostate cancer treatment.

Patient-reported Sexual Function After Nerve-sparing Radical Retropubic Prostatectomy

OBJECTIVE Improved selection criteria have lead to an increasing number of nerve-sparing radical retropubic prostatectomies (RRP) in patients with clinically localised prostate cancer (PCA). Patient questionnaire based outcome analysis on post-operative erectile function after uni- or bilateral nerve-sparing RRP is described. METHODS Between January 1992 and March 1999, 366 patients (mean age 62.5 years) underwent uni- or bilateral nerve-sparing RRP at our institution. Indication for nerve-sparing procedure was based on the results of a multivariate classification and regression tree analysis (CART). For evaluation of post-operative patient-reported rates of sexual and erectile function non-validated and validated questionnaires (IIEF 5) were administered after a follow-up of 12 months. Data of five operation periods were analysed. RESULTS The unilateral procedure resulted in rates of 13-29% of erections sufficient for unassisted intercourse. Some degree of tumescence was reported by 37-73% of the remaining patients. Bilateral nerve-sparing procedures were almost exclusively performed in periods 3-5, only four patients of period 2 received the bilateral procedure. Here, rates of erections sufficient for intercourse were 25% (period 2), 61% (period 3), 50% (period 4), and 52% (period 5), respectively. Patients with grades 4 and 5 erections had IIEF scores of 19.2 and 20.2 and patients without rigidity or tumescence had scores of 5.7 and 7.0 after uni- and bilateral nerve-sparing procedure, respectively. Patients <60 years of age had better erections than those > or =60 (unilateral: 19% versus 13%, bilateral 45% versus 38%). CONCLUSION Compared to a unilateral nerve-sparing procedure, the bilateral nerve-sparing technique revealed much better results inasmuch as about 50% of the patients reported recovery of erections sufficient for sexual intercourse without use of sexual aids.

Early Prostate-Specific Antigen Relapse after Radical Retropubic Prostatectomy:Prediction on the Basis of Preoperative andPostoperative Tumor Characteristics

Objectives: This study was undertaken to distinguish between patients who will and will not benefit from a retropubic radical prostatectomy (RRP) for clinically localized prostatic carcinoma (PCa) on the basis of preoperative and postoperative tumor characteristics. Methods: Data of 318 consecutive patients who underwent RRP for clinically localized PCa were reviewed. Preoperative characteristics used included clinical stage, findings on transrectal ultrasonography, prostate-specific antigen (PSA) values, Gleason grade, number of positive biopsies, number of biopsies containing any Gleason grade 4 and/or 5 cancer, and number of biopsies with predominant (>50% of cancerous tissue) Gleason grade 4 and/or 5 cancer. Postoperative characteristics included pathologic stage, Gleason grade, margin status, cancer volume, and volume of Gleason grade 4 and/or 5 cancer. The impact on biochemical relapse after RRP were calculated by Cox regression and CART (classification and regression tree) analysis to establish low, intermediate, and high risk of recurrence. Results: Of patients who underwent RRP, 66% showed no evidence of relapse after a follow-up of 42 months. All preoperative and postoperative characteristics showed a significant association with biochemical relapse. Cox regression of preoperative characteristics showed the number of positive biopsies with predominant Gleason grade 4 and/or 5 cancer to be the most accurate predictor of failure (p < 0.0001), followed by the number of positive biopsies and PSA. CART analysis distinguished between four risk groups on the basis of the same characteristics as in the Cox regression. The low-risk group consisted of 232 patients (75.1%) and the high-risk group of 17 patients (5.5%); corresponding Kaplan-Meier curves showed a 2-year PSA-free survival rate of 97% for the low-risk group and 20% for the high-risk group. Cox regression of postoperative characteristics recognized the volume of Gleason grade 4 and/or 5 as the characteristic with the strongest association with biochemical failure. CART analysis distinguished between four risk groups, using the volume of high-grade cancer as the most influential characteristic. The corresponding Kaplan-Meier curves showed for the low-risk group (n = 79; 29.6%) a PSA-free survival rate of 96% after 42 months and for the high-risk group (n = 47; 17.6%) a 21% PSA-free survival rate after 42 months. Conclusion: For preoperative and postoperative estimation of biochemical recurrence after RRP, a quantitative analysis of high-grade cancer, expressed by the number of preoperative biopsy cores containing high-grade cancer and the volume of cancer, proved to be the best predictor of relapse. CART analysis might be useful in advising patients for their best therapy options. However, defined characteristics of risk groups should be evaluated with new prospective data before they are used routinely.

Stage Migration in Clinically Localized Prostate Cancer

Objectives: To determine whether migration of pathological tumor stages in patients with clinically localized prostate cancer exists and whether this is due to an increasing frequency of treating patients with clinically insignificant cancer.Methods: 1,063 radical retropubic prostatectomies were performed in patients with clinically localized prostate cancer in one institution within 7.5 years (from 1992 until June 1999). All specimens were prospectively processed according to the Stanford protocol. These were then analyzed regarding the migration of pathological tumor stages and cancer volumes.Results: Within the observation period, the annual rate of radical retropubic prostatectomies increased by 225% from 69 to 224 cases. The authors noted a decline of advanced tumor stages (from 65 to 40%) and an increase in pathological T2 tumors (from 30 to 55%). The rate of small cancers (<0.5 cm3) remained stable between 2 and 5% over the last 5 years.Conclusion: The data confirm trends which were observed in large US centers with increasing detection and treatment of localized prostate cancer without unnecessary treatment of clinically insignificant cancers.

The Impact of Real-Time Elastography Guiding a Systematic Prostate Biopsy to Improve Cancer Detection Rate: A Prospective Study of 353 Patients

PURPOSE We evaluated whether real-time elastography guided biopsy improves prostate cancer detection compared to conventional systematic gray scale ultrasound guidance. MATERIALS AND METHODS A total of 353 consecutive patients suspicious for prostate cancer were prospectively randomized for real-time elastography (178) or gray scale ultrasound (175). Each patient enrolled in the study underwent a 10-core prostate biopsy. Six lateral prostate sectors (base, mid, apex) were scanned for cancer suspicious areas, defined as stiffer blue lesions using real-time elastography and hypoechoic lesions using gray scale ultrasound. Suspicious areas were sampled by a single targeted biopsy and considered representative of a defined prostate sector. If real-time elastography or gray scale ultrasound did not visualize a suspicious area in a sector, the biopsy core was taken systematically. Imaging findings were correlated with histopathological reports. Real-time elastography and gray scale ultrasound cases were compared in terms of cancer detection rate and imaging guidance accuracy. RESULTS Characteristics of patients undergoing real-time elastography and gray scale ultrasound, including age, prostate specific antigen, prostate volume and digital rectal examination, were not significantly different (p>0.05). Prostate cancer was detected in 160 of 353 patients (45.3%). The prostate cancer detection rate was significantly higher in patients who underwent biopsy with the real-time elastography guided approach compared to the gray scale ultrasound guided biopsy at 51.1% (91 of 178) vs 39.4% (69 of 175) (p=0.027). Overall sensitivity and specificity to detect prostate cancer was 60.8% and 68.4% for real-time elastography vs 15% and 92.3% for gray scale ultrasound, respectively. CONCLUSIONS Sensitivity to visualize and detect prostate cancer improved using real-time elastography in addition to gray scale ultrasound during prostate biopsy. Overall sensitivity did not reach levels to omit a systematic biopsy approach.

Prediction of 90-day Mortality After Radical Cystectomy for Bladder Cancer in a Prospective European Multicenter Cohort

BACKGROUND Despite recent improvements, radical cystectomy (RC) is still associated with adverse rates for 90-d mortality. OBJECTIVE To validate the performance of the Isbarn nomogram incorporating age and postoperative tumor characteristics for predicting 90-d RC mortality in a multicenter series and to generate a new nomogram based strictly on preoperative parameters. DESIGN, SETTING, AND PARTICIPANTS Data of 679 bladder cancer (BCa) patients treated with RC at 18 institutions in 2011 were prospectively collected, from which 597 patients were eligible for final analysis. INTERVENTION RC for BCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS An established prediction tool, the Isbarn nomogram, was applied to our cohort. For the purpose of external validation, model discrimination was measured using the receiver operating characteristics-derived area under the curve. Calibration plots examined the relationship between predicted and observed probabilities. Univariable and multivariable logistic regression models were fitted to assess the impact of preoperative characteristics on 90-d mortality. RESULTS AND LIMITATIONS The 30-, 60-, and 90-d mortality rates in the development cohort (n=597) were 2.7%, 6.7%, and 9.0%, respectively. The Isbarn nomogram predicted individual 90-d mortality with an accuracy of 68.6%. Our preoperative multivariable model identified age (odds ratio [OR]:1.052), American Society of Anesthesiologists score (OR: 2.274), hospital volume (OR: 0.982), clinically lymphatic metastases (OR: 4.111), and clinically distant metastases (OR: 7.788) (all p<0.05) as independent predictors of 90-d mortality (predictive accuracy: 78.8%). Our conclusions are limited by the lack of an external validation of the preoperative model. CONCLUSIONS The Isbarn nomogram was validated with moderate discrimination. Our newly developed model consisting of preoperative characteristics might outperform existing models. Our model might be particularly suitable for preoperative patient counseling. PATIENT SUMMARY The current report validated an established nomogram predicting 90-d mortality in patients with bladder cancer after radical cystectomy (RC). We developed a new prediction tool consisting of strictly preoperative parameters, thus allowing clinicians an optimal consultation for RC candidates.

Standardized assessment of complications in a contemporary series of European patients undergoing radical cystectomy.

To examine postoperative complications in a contemporary series of patients after radical cystectomy using a standardized reporting system, and to identify readily available preoperative risk factors.

Comparison of real-time elastography with grey-scale ultrasonography for detection of organ-confined prostate cancer and extra capsular extension: a prospective analysis using whole mount sections after radical prostatectomy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b