Peter Hammerer

International Validation of a Preoperative Nomogram for Prostate Cancer Recurrence After Radical Prostatectomy

PURPOSE We evaluated the predictive accuracy of a recently published preoperative nomogram for prostate cancer that predicts 5-year freedom from recurrence. We applied this nomogram to patients from seven different institutions spanning three continents. METHODS Clinical data of 6,754 patients were supplied for validation, and 6,232 complete records were used. Nomogram-predicted probabilities of 60-month freedom from recurrence were compared with actual follow-up in two ways. First, areas under the receiver operating characteristic curves (AUCs) were determined for the entire data set according to several variables, including the institution where treatment was delivered. Second, nomogram classification-based risk quadrants were compared with actual Kaplan-Meier plots. RESULTS The AUC for all institutions combined was 0.75, with individual institution AUCs ranging from 0.67 to 0.83. Nomogram predictions for each risk quadrant were similar to actual freedom from recurrence rates: predicted probabilities of 87% (low-risk group), 64% (intermediate-low-risk group), 39% (intermediate-high-risk group), and 14% (high-risk group) corresponded to actual rates of 86%, 64%, 42%, and 17%, respectively. The use of neoadjuvant therapy, variation in the prostate-specific antigen recurrence definitions between institutions, and minor differences in the way the Gleason grade was reported did not substantially affect the predictive accuracy of the nomogram. CONCLUSION The nomogram is accurate when applied at international treatment institutions with similar patient selection and management strategies. Despite the potential for heterogeneity in patient selection and management, most predictions demonstrated high concordance with actual observations. Our results demonstrate that accurate predictions may be expected across different patient populations.

Urodynamic Evaluation of Changes in Urinary Control After Radical Retropubic Prostatectomy

PURPOSE Urodynamic evaluations were done in patients before and after radical prostatectomy to obtain more information about the factors that affect continence. MATERIALS AND METHODS Urodynamic testing was done in 82 patients before, and 6 to 8 weeks and 6 months (9 cases) after radical prostatectomy. Evaluation included measurement of cystometric bladder capacity, compliance, functional profile length, maximal urethral closure pressure, maximal urethral closure pressure during voluntary contraction of the external sphincter, residual urine, maximal flow rate and bladder instability. RESULTS The continence rate was 33.4, 69.4, 84.7 and 90.9% at 1, 3, 6 and 12 months after radical prostatectomy, respectively. Mean functional urethral length decreased from 61 mm. preoperatively to 25.9 mm. postoperatively, maximal urethral pressure from 89.6 to 65.2 cm. water and bladder capacity from 338.7 to 278.8 ml. Bladder instability was found in 17 and 41% of cases before and directly after radical prostatectomy, respectively. There was a statistically significant difference in maximal urethral closure pressure (68.1 versus 53.1 cm. water) as well as functional urethral length (27.6 versus 20.5 mm.) in continent versus incontinent patients, respectively. Urodynamic examination 6 months after prostatectomy showed an increase in functional profile length and maximal urethral pressure, while bladder measurements did not change significantly. CONCLUSIONS After radical prostatectomy significant changes in bladder and sphincter measurements are noted. Urethral closure pressure, functional urethral length and bladder stability are significant urodynamic factors that influence continence after radical prostatectomy.

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.

Systematic Sextant Biopsies in 651 Patients Referred for Prostate Evaluation

In 651 patients mapping of the prostate by 6 systematic sextant ultrasonography guided biopsies was performed without major side effects using the automatic biopsy gun. The histological findings provided data on patients with normal and abnormal prostates as determined by digital rectal examination. Only 3 of 72 nonurological patients (4%) with normal prostate specific antigen (PSA) levels of less than 4 ng./ml. had prostate cancer. Of the 259 patients with a firm prostate on digital rectal examination 105 (41%) had prostate cancer. For those with a PSA level of less than 4 and 4 ng./ml. or greater the positive biopsy rates were 13% and 58%, respectively. Of 56 patients with clinical stage B or C disease and a PSA level of less than 4 ng./ml. 20 (36%) had prostate cancer, compared to 155 of 187 (83%) with a PSA level of 4 ng./ml. or greater. Transrectal ultrasound was not helpful in screening for prostate cancer due to the low positive biopsy rate for hypoechoic lesions. However, among 175 patients with clinical stage B or C disease transrectal ultrasound identified 157 (90%) with prostate cancer.

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.

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.

Is There Evidence of a Relationship between Benign Prostatic Hyperplasia and Prostate Cancer? Findings of a Literature Review

CONTEXT More than half the male population aged >50 yr have histologic evidence of benign prostatic hyperplasia (BPH), while prostate cancer (PCa) is among the most common male cancers according to recent registry data. Understanding the aetiologies of both conditions is crucial to reduce the resulting burden of mortality and morbidity. OBJECTIVE This review aims to examine the available data on the epidemiology, pathology, risk factors, and genetic markers involved in BPH and PCa; to discuss their clinical implications for management of both conditions; and to discuss their implications for PCa prevention. Our primary objective was to clarify the relationship between BPH and PCa by bringing together evidence from diverse areas of research. EVIDENCE ACQUISITION The primary source of data was PubMed, which was searched using Boolean strategies and by scanning lists of related articles. We also examined secondary sources from reference lists of retrieved articles and data presented at recent congresses. EVIDENCE SYNTHESIS Accumulating evidence suggests that BPH and PCa share important anatomic, pathologic, and genetic links in addition to the well-established epidemiologic association between these conditions. We also found data that suggest interactions between apparently diverse factors, such as dihydrotestosterone levels and inflammation. Recent publications support the hypothesis that both BPH and PCa are part of the metabolic syndrome, while inflammation is emerging as a major contributor to the development of both BPH and PCa. Although many of the findings are preliminary and require further research, they offer new insight into the mechanisms of disease underlying the development of BPH and PCa. CONCLUSIONS Available data suggest that epidemiologic and pathologic links exist between BPH and PCa. Evidence of links between the conditions and contributory factors may offer common preventative strategies for BPH and PCa and common therapeutic approaches to their management.

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.

Management of prostate-specific antigen relapse in prostate cancer: A European consensus

A European Consensus on the management of prostate‐specific antigen (PSA) relapse in patients with prostate cancer has been formulated. The key recommendations proposed are that total PSA is the best detection tool for prostate cancer, with free and complexed PSA having a role in the PSA range 1–4 ng/ml. PSA relapse after radical prostatectomy (RP) has been defined as a value of 0.2 ng/ml with one subsequent rise, while the ASTRO definition should be used after radiotherapy. A PSA level of less than 0.4 ng/ml after hormonal therapy can be considered an indicator of a positive response. Continuous assessment using nomograms or artificial neural networks will help to determine whether progression after local therapy is distant or local, which is the basis for treatment decisions. Secondary treatment after local failure of RP should be initiated when PSA levels reach 1.0–1.5 ng/ml and salvage radiotherapy can be considered with or without hormonal therapy. Local failure after radiotherapy can be treated with a choice of high‐intensity‐focused ultrasound, salvage RP (only in highly selected patients), cryotherapy or external beam radiation. Treatment of distant failure involves hormonal manipulation, the type and the timing of which is based on both physician and patient preferences.

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.