Herbert Augustin

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.

Critical assessment of preoperative urinary prostate cancer antigen 3 on the accuracy of prostate cancer staging.

BACKGROUND Knowledge about the staging significance of the prostate cancer antigen 3 (PCA3) score to better identify pathologic features after radical prostatectomy (RP) is limited and controversial. OBJECTIVE Our aim was to study the clinical staging significance of PCA3 to identify pathologic favorable and/or unfavorable features in the RP specimen. DESIGN, SETTING, AND PARTICIPANTS Complete retrospective clinical and pathologic data of consecutive men who had undergone RP from three tertiary referral centers including preoperative PCA3 scores (n=305) and computer-assisted planimetrically measured tumor volume data (n=160) were available. INTERVENTION All patients were treated with RP. MEASUREMENTS PCA3 scores were assessed using the PROGENSA assay (Gen-Probe, San Diego, CA, USA). Beyond standard risk factors (age, digital rectal examination, prostate-specific antigen, prostate volume, biopsy Gleason score, percentage of positive cores), five different PCA3 codings were used in logistic regression models to identify five distinct pathologic end points: (1) low-volume disease (<0.5 ml), (2) insignificant prostate cancer (PCa) according to the Epstein criteria, (3) extracapsular extension (ECE), (4) seminal vesicle invasion (SVI), and (5) aggressive disease defined as Gleason sum ≥7. Accuracy estimates of each end point were quantified using the area under the curve (AUC) of the receiver operator characteristic analysis in models with and without PCA3. RESULTS AND LIMITATIONS PCA3 scores were significantly lower in low-volume disease and insignificant PCa (p ≤ 0.001). AUC of multivariable low-volume disease (+2.4 to +5.5%) and insignificant PCa models (+3 to +3.9%) increased when PCA3 was added to standard clinical risk factors. In contradistinction, regardless of its coding, PCA3 scores were not significantly elevated in pathologically confirmed ECE (p=0.4) or SVI (p=0.5), respectively. Higher PCA3 scores were associated with aggressive disease (p<0.001). Importantly, the addition of PCA3 to multivariable intermediate- and high-grade models did not improve prediction. Despite reporting the largest pathologic PCA3 study, the main limitation resides in its small sample size. CONCLUSIONS PCA3 was confirmed as a valuable predictor of pathologically confirmed low-volume disease and insignificant PCa. Further exploration of its role as an additional marker to select patients for active surveillance may be warranted. In contradistinction, assessment of pathologically advanced or aggressive PCa is not improved using PCA3.

Is repeated transurethral resection justified in patients with newly diagnosed superficial bladder cancer

OBJECTIVES To assess the value of repeated transurethral resection (TUR) in patients with newly diagnosed superficial bladder cancer. METHODS A second TUR was performed in 110 consecutive patients (24 women and 86 men) with newly diagnosed superficial bladder cancer. The mean age was 66 years (range 30 to 85). A second TUR was performed within 4 to 6 weeks after the initial TUR. After the first TUR, the pathologic stage was pTa in 31 patients (28%), pT1 in 76 (70%), and carcinoma in situ in 3 (2%). The pathologic records of the second TUR were reviewed and compared with the findings of the first operation. RESULTS Cystoscopy before the second TUR was negative in 79 patients. Of these cases, 14 (17.7%) had cancer histologically. The second TUR was negative in 70 patients (63.6%). Twenty-two (20%) had residual cancer of the same stage, 9 (8.2%) had a lower stage, and 9 (8.2%) had a higher stage. Of 31 patients with Stage pTa and 76 patients with Stage pT1 at the first TUR, 19 (61.3%) and 51 (67.1%) had a negative second TUR, respectively. CONCLUSIONS We recommend a second TUR for patients with superficial bladder cancer for several reasons. A negative second TUR provides important prognostic information. In addition, removal of residual cancer is achieved early. Finally, patients with pT1 G3 tumors are at high risk of residual, or even invasive, cancer and should be offered definitive therapy as early as possible.

Can Predictive Models for Prostate Cancer Patients Derived in the United States of America Be Utilized in European Patients? A Validation Study of the Partin Tables

OBJECTIVES Prostate cancer patients in the US and Europe differ due to selection and treatment differences. Accuracy of predictive tools derived in the US might therefore suffer when applied to European patients. We tested the validity of the widely accepted Partin tables for their ability to predict pathologic stage in German patients. METHODS Clinical and pathological characteristics were obtained from 1,298 consecutive men with clinically localized prostate cancer undergoing radical prostatectomy at the University Hospital Hamburg between January 1992 and February 2000. Receiver operating characteristic (ROC) curve analysis was performed to compare observed and predicted Partin rates for each pathologic stage. RESULTS The rate for organ confinement was 56% in Hamburg patients compared to 48% in the Partin study. The rates of Hamburg patients for extracapsular extension without seminal vesicle or lymph node involvement were 25%, for seminal vesicle without lymph node involvement 14% and for lymph node metastases 5%. The corresponding rates of the Partin study were 40, 7 and 5%, respectively. The accuracy of Partin table derived probability was high with an area under the ROC curve of 0.817 (95% CI, 0.757-0.876) for organ confinement and 0.807 (95% CI, 0.781-0.833) for lymph node involvement. CONCLUSION Our study demonstrated that predictive tools for prostate cancer developed in the US could be applied to European patients with comparable accuracy to that reported for validation studies performed with US patients.

Patient Self-Reporting Questionnaire on Urological Morbidity and Bother after Radical Retropubic Prostatectomy

OBJECTIVES We assessed the incidence of morbidity and bother on quality-of-life (QL) after radical retropubic prostatectomy for prostate cancer. METHODS At least 12 months after surgery, self-reporting questionnaires were completed and returned by 368 (77.8%) of 473 eligible patients. Surgery related morbidity was evaluated by adhoc constructed questions. QL was assessed by the European Organization for Research and Treatment of Cancer QL core questionnaire (EORTC QLQ-C30). Multivariate and univariate analysis as well as regression analysis were used to assess the bother factors. RESULTS Postoperative urinary incontinence significant enough for the patient to use some kind of protection was reported by 27.2%. After surgery, 14.2% of preoperative potent men were able to get and maintain an erection sufficient enough for sexual intercourse without any aid. Overall 10.6% of respondents had undergone surgery for anastomotic stricture and 23.6% reported on adjuvant therapy. Furthermore, 43.2% reported on fear of not being cured from cancer. Postoperative urinary incontinence and fear of not being cured were associated with significant lower global QL scores and turned out as independent predictors for global QL. In contrast, postoperative erectile dysfunction, anastomotic stricture and adjuvant therapy were not independent predictors. In addition, 82.1% would vote for surgery again. CONCLUSION The majority of the patients would opt for surgical treatment again, although morbidity is common after radical prostatectomy and may impair QL. Particularly urinary incontinence and fear of not being cured are independent predictors for global QL after surgery. Therefore, surgical techniques with a low morbidity are requested as well as some kind of psychological support in order to cope with existential fear.

Accuracy of 3-Tesla Magnetic Resonance Imaging for the Staging of Prostate Cancer in Comparison to the Partin Tables

Background: An accurate prediction of final pathological stage is essential for proper patient selection to determine who will experience maximum benefit from radical prostatectomy. In this context, the Partin tables represent one of the most widely used statistical prediction tools. Purpose: To compare the accuracy in predicting pathological stage in patients intended for radical prostatectomy between 3-Tesla (T) magnetic resonance imaging (MRI) and the Partin tables in a prospective trial. Material and Methods: 27 men with staging results from 3T MRI using a phased-array coil were compared in terms of staging accuracy with whole-mount-section histopathologic analyses as the standard of reference. Probabilities for pathological stages were estimated according to the Partin tables. Spearman rank correlation and discriminant analysis were calculated to assess relationships. Results: Histopathological evaluation revealed organ-confined disease (OC) in 21 (77.8%) and extracapsular extension (ECE) in six (22.2%) men. Three-Tesla MRI staging was accurate in all patients with OC and in four out of the six men with ECE. Accuracy of local staging was 85.2% (23 of 27). Sensitivity was 66.7% (95% confidence interval [CI] 0.223–0.957) and specificity 100% (95% CI 0.839–1) for the detection of ECE. Findings of MRI and the Partin tables showed a Spearman rho of 0.780 vs. 0.254 for OC and 0.780 vs. 0.363 for ECE, respectively. Compared to the Partin tables, MRI revealed standardized canonical discriminant function coefficients of 0.992 (P<0.001) vs. 0.205 (P=0.432) for OC and 0.965 (P<0.001) vs. 0.329 (P=0.197) for ECE, respectively. Conclusion: 3T MRI showed a high accuracy for the staging of clinically localized prostate cancer, and it was significantly more accurate in predicting the final pathological stage than the Partin tables.

A comparative performance analysis of total prostate-specific antigen, percentage free prostate-specific antigen, prostate-specific antigen velocity and urinary prostate cancer gene 3 in the first, second and third repeat prostate biopsy.

Study Type – Diagnosis (exploratory cohort)

Whole-genome plasma sequencing reveals focal amplifications as a driving force in metastatic prostate cancer

Genomic alterations in metastatic prostate cancer remain incompletely characterized. Here we analyse 493 prostate cancer cases from the TCGA database and perform whole-genome plasma sequencing on 95 plasma samples derived from 43 patients with metastatic prostate cancer. From these samples, we identify established driver aberrations in a cancer-related gene in nearly all cases (97.7%), including driver gene fusions (TMPRSS2:ERG), driver focal deletions (PTEN, RYBP and SHQ1) and driver amplifications (AR and MYC). In serial plasma analyses, we observe changes in focal amplifications in 40% of cases. The mean time interval between new amplifications was 26.4 weeks (range: 5–52 weeks), suggesting that they represent rapid adaptations to selection pressure. An increase in neuron-specific enolase is accompanied by clonal pattern changes in the tumour genome, most consistent with subclonal diversification of the tumour. Our findings suggest a high plasticity of prostate cancer genomes with newly occurring focal amplifications as a driving force in progression.

Prostate cancers in the transition zone: Part 1; pathological aspects

There are several anatomical models of the prostate but the one currently used by pathologists and clinicians was established by McNeal et al. [1]. The landmark is the prostatic urethra, which gives rise to four distinct glandular elements. The largest is the peripheral zone (PZ), which covers the dorsal, lateral and apical parts of the gland. Therefore, most of its glandular units end near the dorsolateral fibrous capsule, and it is the PZ of the prostate that neighbours the neurovascular bundle at each dorsolateral side of the gland. Most adenocarcinomas of the prostate are thought to arise in the PZ, and this region is also prone to inflammation and atrophy. The central zone is cone-shaped with its base at the bladder neck and the tip at the verumontanum. Its glandular units are more complex than those in other parts of the prostate, but seem to be remarkably resistant to both inflammation and the development of neoplasia. The small periurethral zone is formed by tiny ducts and abortive acini next to the proximal urethra. Finally, the transition zone (TZ) consists of two lobes, located anteriorly between the proximal urethra and the lateral parts of the PZ. Its arched ducts turn to the ventral aspect of the gland and give rise to acini that end near the anterior fibromuscular stroma. In the young male, the TZ is rather small, but it continues to grow, as it is the main origin of BPH in later life. In this way the TZ may become the dominant glandular part of the prostate. The TZ is separated from the PZ by a small stromal band (Figs 1 and 2), which may guide the surgeon in determining the extent of TURP for BPH. INCIDENCE

Differences in biopsy features between prostate cancers located in the transition and peripheral zone

To identify the zonal location of prostate cancers before surgery, by analysing the mapping of ultrasonography‐guided systematic sextant biopsies for differences between cancers located in the transition zone (TZ) and peripheral zone (PZ); and to compare the correlation between Gleason scores of needle biopsies and those of radical prostatectomy (RP) specimens.