Sascha Ahyai

Meta-analysis of Functional Outcomes and Complications Following Transurethral Procedures for Lower Urinary Tract Symptoms Resulting from Benign Prostatic Enlargement

CONTEXT There is a continuous decline in the number of transurethral resections of the prostate (TURP) and an increase use of minimally invasive surgical therapy (MIST) for lower urinary tract symptoms resulting from benign prostatic enlargement. Current results from randomised controlled trials (RCT) and methodologically sound prospective studies suggest that some of the proposed procedures have the potential to replace TURP. OBJECTIVE To determine the contemporary status of TURP and of the currently most commonly applied transurethral MISTs: (1) bipolar TURP, (2) bipolar transurethral vaporisation of the prostate (bipolar TUVP), (3) holmium laser enucleation of the prostate (HoLEP), and (4) potassium-titanyl-phosphate (KTP) laser vaporisation of the prostate. EVIDENCE ACQUISITION This meta-analysis was based on a systematic Medline search assessing the period 1997-2009. All RCTs comparing TURP and the most commonly discussed ablative treatments were included. The end points of our analyses were functional outcomes and treatment-related adverse events. EVIDENCE SYNTHESIS Twenty-seven publications involving 23 different RCTs with a total of 2245 patients provided the highest level of evidence available (level 1b) and were fully assessed. Meta-analysis was conducted with SAS v.9.1.3 (SAS Institute, Cary, NC, USA). Forest plots were produced using the R software. Pooled odds ratios and 95% confidence intervals were calculated between various operative techniques versus TURP. Functional results between the specific transurethral procedures versus TURP were summarised as differences in means. CONCLUSIONS This meta-analysis demonstrates statistically comparable efficacy and overall morbidity for MISTs versus contemporary TURP. Type, category (minor vs major), and the number of complications (safety profile) vary specifically for each of the different transurethral techniques. We feel that the individual patients clinical profile should be carefully assessed to identify the most appropriate transurethral technique.

A Systematic Review and Meta-analysis of Functional Outcomes and Complications Following Transurethral Procedures for Lower Urinary Tract Symptoms Resulting from Benign Prostatic Obstruction: An Update

CONTEXT A number of transurethral ablative techniques based on the use of innovative medical devices have been introduced in the recent past for the surgical treatment of benign prostatic obstruction (BPO). OBJECTIVE To conduct a systematic review of the literature and a meta-analysis of available randomized controlled trials (RCTs), and to evaluate the efficacy and safety of transurethral ablative procedures for BPO. EVIDENCE ACQUISITION A systematic literature search was performed for all RCTs comparing any transurethral surgical technique for BPO to another between 1992 and 2013. Efficacy was evaluated after a minimum follow-up of 1 yr based on International Prostate Symptom Score, maximum flow rate, and postvoid residual volume. Efficacy at midterm follow-up, prostate volume, perioperative data, and short-term and long-term complications were also assessed. Data were analyzed using RevMan software. EVIDENCE SYNTHESIS A total of 69 RCTs (8517 enrolled patients) were included. No significant difference was found in terms of short-term efficacy between bipolar transurethral resection of the prostate (B-TURP) and monopolar transurethral resection of the prostate (M-TURP). However, B-TURP was associated with a lower rate of perioperative complications. Better short-term efficacy outcomes, fewer immediate complications, and a shorter hospital stay were found after holmium laser enucleation of the prostate (HoLEP) compared with M-TURP. Compared with M-TURP, GreenLight photoselective vaporization of the prostate (PVP) was associated with a shorter hospital stay and fewer complications but no different short-term efficacy outcomes. CONCLUSIONS This meta-analysis shows that HoLEP is associated with more favorable outcomes than M-TURP in published RCTs. B-TURP and PVP have resulted in better perioperative outcomes without significant differences regarding efficacy parameters after short-term follow-up compared with M-TURP. Further studies are needed to provide long-term comparative data and head-to head comparisons of emerging techniques. PATIENT SUMMARY Bipolar transurethral resection of the prostate, photovaporization of the prostate, and holmium laser enucleation of the prostate have shown efficacy outcomes comparable with conventional techniques yet reduce the complication rate. The respective role of these new options in the surgical armamentarium needs to be refined to propose tailored surgical treatment for benign prostatic obstruction relief.

Transurethral Holmium Laser Enucleation of the Prostate Compared with Transvesical Open Prostatectomy: 18-Month Follow-Up of a Randomized Trial

PURPOSE This ongoing randomized study aims to find out whether transurethral holmium laser enucleation of the prostate (HoLEP) could be an alternative to open transvesical prostatectomy in patients with prostates >100 g. PATIENTS AND METHODS A series of 120 urodynamically obstructed patients were randomized to HoLEP or open prostatectomy, 60 patients to each group. The HoLEP was performed with high-powered Ho:YAG lasers at 80 to 100 W (2.0 J, 40-50 Hz) and 550-nm bare laser fibers. The American Urological Association Symptom Scores, peak urinary flow rates, and postvoiding residual urine volumes were evaluated preoperatively and at 1, 3, 6, 12, and 18 months postoperatively. All complications were noted. RESULTS By the Mann-Whitney test, there was no significant difference between the HoLEP and open surgery groups in patient age (69.0 years HoLEP v 71.0 years open surgery), prostate volume (115 cc [range 100-230 cc] v 113 cc [100-230 cc], or weight of resected tissue (94 g [range 57-220 g] v 96 g [range 61-220 g]). There were significant differences in the mean operative time (136 v 91 minutes; P< 0.0001), mean hemoglobin loss (1.9 v 2.8 g/dL; P< 0.0001), median catheter time (1 day v 6 days; P< 0.0001), and median hospital stay (2 days v 10 days; P< 0.0001). Both HoLEP and open prostatectomy resulted in pronounced and lasting postoperative improvements in Symptom Scores, peak urinary flow rates, and postvoiding residual volumes (P< 0.0001). The differences between HoLEP and open prostatectomy were not significant at any interval for any parameter. Blood transfusions were required in 0 HoLEP patients v 8 open surgery patients. Arterial bleeding occurred in three patients in each group. Secondary apical resection was required in two HoLEP patients and no open surgery patients. Bladder neck contracture occurred in none of the HoLEP patients and two of those having open surgery. Thus, the total number of patients having complications was 7 with HoLEP and 13 with open surgery. There were no deaths in either group. CONCLUSIONS The HoLEP appears to be an endourologic alternative to open surgical enucleation of the prostate for large glands. It entails significantly less blood loss and a much shorter catheter time and hospital stay. The perioperative outcome strongly favors the holmium procedure. The rate of late complications is equally low with each procedure. The postoperative micturition improvement was significant and lasting and was equivalent in the two groups.

Radical prostatectomy improves progression‐free and cancer‐specific survival in men with lymph node positive prostate cancer in the prostate‐specific antigen era: a confirmatory study

Study Type – Therapy (outcomes research)
Level of Evidence 2b

Critical assessment of tools to predict clinically insignificant prostate cancer at radical prostatectomy in contemporary men

Overtreatment of prostate cancer (PCa) is a concern, especially in patients who might qualify for the diagnosis of insignificant prostate cancer (IPCa). The ability to identify IPCa prior to definitive therapy was tested.

Initial Prostate Biopsy: Development and Internal Validation of a Biopsy-specific Nomogram Based on the Prostate Cancer Antigen 3 Assay

BACKGROUND Urinary prostate cancer antigen 3 (PCA3) assay in combination with established clinical risk factors improves the identification of men at risk of harboring prostate cancer (PCa) at initial biopsy (IBX). OBJECTIVE To develop and validate internally the first IBX-specific PCA3-based nomogram that allows an individual assessment of a mans risk of harboring any PCa and high-grade PCa (HGPCa). DESIGN, SETTING, AND PARTICIPANTS Clinical and biopsy data including urinary PCA3 score of 692 referred IBX men at risk of PCa were collected within two prospective multi-institutional studies. INTERVENTION IBX (≥ 10 biopsy cores) with standard risk factor assessment including prebiopsy urinary PCA3 measurement. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS PCA3 assay cut-off thresholds were investigated. Regression coefficients of logistic risk factor analyses were used to construct specific sets of PCA3-based nomograms to predict any PCa and HGPCa at IBX. Accuracy estimates for the presence of any PCa and HGPCa were quantified using area under the curve of the receiver operator characteristic analysis and compared with a clinical model. Bootstrap resamples were used for internal validation. Decision curve analyses quantified the clinical net benefit related to the novel PCA3-based IBX nomogram versus the clinical model. RESULTS AND LIMITATIONS Any PCa and HGPCa were diagnosed in 46% (n=318) and 20% (n=137), respectively. Age, prostate-specific antigen, digital rectal examination, prostate volume, and PCA3 were independent predictors of PCa at IBX (all p<0.001). The PCA3-based IBX nomograms significantly outperformed the clinical models without PCA3 (all p<0.001). Accuracy was increased by 4.5-7.1% related to PCA3 inclusion. When applying nomogram-derived PCa probability thresholds ≤ 30%, only a few patients with HGPCa (≤ 2%) will be missed while avoiding up to 55% of unnecessary biopsies. External validation of the PCA3-based IBX-specific nomogram is warranted. CONCLUSIONS The internally validated PCA3-based IBX-specific nomogram outperforms a clinical prediction model without PCA3 for the prediction of any PCa, leading to the avoidance of unnecessary biopsies while missing only a few cases of HGPCa. Our findings support the concepts of a combination of novel markers with established clinical risk factors and the superiority of decision tools that are specific to a clinical scenario.

Prognostic Role and HER2 Expression of Circulating Tumor Cells in Peripheral Blood of Patients Prior to Radical Cystectomy: A Prospective Study

BACKGROUND Preliminary research has suggested the potential prognostic value of circulating tumor cells (CTC) in patients with advanced nonmetastatic urothelial carcinoma of the bladder (UCB). OBJECTIVE Prospectively analyze the clinical relevance and human epidermal growth factor receptor 2 (HER2) expression of CTC in patients with clinically nonmetastatic UCB. DESIGN, SETTING, AND PARTICIPANTS Blood samples from 100 consecutive UCB patients treated with radical cystectomy (RC) were investigated for the presence (CellSearch system) of CTC and their HER2 expression status (immunohistochemistry). HER2 expression of the corresponding primary tumors and lymph node metastasis were analyzed using fluorescence in situ hybridization. INTERVENTION Blood samples were taken preoperatively. Patients underwent RC with lymphadenectomy. MEASUREMENTS Outcomes were assessed according to CTC status. HER2 expression of CTC was compared with that of the corresponding primary tumor and lymph node metastasis. RESULTS AND LIMITATIONS CTC were detected in 23 of 100 patients (23%) with nonmetastatic UCB (median: 1; range: 1-100). Presence, number, and HER2 status of CTC were not associated with clinicopathologic features. CTC-positive patients had significantly higher risks of disease recurrence and cancer-specific and overall mortality (p values: ≤ 0.001). After adjusting for effects of standard clinicopathologic features, CTC positivity remained an independent predictor for all end points (hazard ratios: 4.6, 5.2, and 3.5, respectively; p values ≤ 0.003). HER2 was strongly positive in CTC from 3 of 22 patients (14%). There was discordance between HER2 expression on CTC and HER2 gene amplification status of the primary tumors in 23% of cases but concordance between CTC, primary tumors, and lymph node metastases in all CTC-positive cases (100%). The study was limited by its sample size. CONCLUSIONS Preoperative CTC are already detectable in almost a quarter of patients with clinically nonmetastatic UCB treated with RC and were a powerful predictor of early disease recurrence and cancer-specific and overall mortality. Thus CTC may serve as an indication for multimodal therapy. Molecular characterization of CTC may serve as a liquid biopsy to guide individual targeted therapy in future clinical trials.

Does Perioperative Outcome of Transurethral Holmium Laser Enucleation of the Prostate Depend on Prostate Size

BACKGROUND AND PURPOSE In conventional transurethral resection of the prostate (TURP), perioperative morbidity resulting from causes such as blood loss and TUR syndrome increases with prostate size. Therefore, TURP is restricted to small and medium-sized glands. The present study aimed to find out whether perioperative parameters of holmium laser enucleation of the prostate (HoLEP) other than operation time and weight of resected tissue were dependent on prostate size. PATIENTS AND METHODS A total of 384 patients were treated with HoLEP (holmium:YAG laser, 2.0 J, 40 or 50 Hz, 80 or 100 W, 550-nm bare fiber) for acute removal of obstructing benign hyperplastic tissue. Among them, 111 patients (28.9%) had prostates of <40 g (group 1), 152 (39.6%) had prostates of 40 to 79 g (group 2), and 121 (31.5%) had prostates of >/=80 g (range 80-260) (group 3). The perioperative outcomes of the three groups were compared. A total of 346 patients completed the 1-month postoperative assessment. RESULTS The mean prostate sizes were 31.8 g, 56 g, and 98.7 g for groups 1, 2, and 3 (P<0.0001 group 1 v group 2 v group 3). The mean resected tissue weight was 19.5 g v 34.4 g (P= 0.009) v 70.1 g (range 50-220) (P< 0.0001). The mean operation time was 64.3 v 84.2 (P= 0.009) v 118.4 minutes (P< 0.0001). The mean hemoglobin loss was 0.9 v 1.2 (NS) v 1.9 g/dL (P< 0.001). The overall correlation between hemoglobin loss and prostate size in all patients was very weak (r = 0.229) and just exceeded the level of significance (r = 0.2). In all three groups, the median postoperative catheter time was 1 day, and the median postoperative hospital stay was 2 days. The HoLEP resulted in an immediate and significant improvement of American Urological Association Symptom Scores, peak urinary flow rates, and postvoiding residual urine volumes (P< 0.0001) 1 month after the operation, without significant differences between the groups. The rate of complications was similar in all three groups. None of the patients needed blood transfusions. There were no perioperative deaths. CONCLUSION In HoLEP, perioperative morbidity and postoperative micturition improvement do not depend on prostate size. Therefore, in contrast to TURP, HoLEP is equally suitable for small, medium-size, and large prostate glands.

Surgical volume is related to the rate of positive surgical margins at radical prostatectomy in European patients

To assess the association between surgical volume (SV) and the rate of positive surgical margins (PSM) after radical prostatectomy (RP) in a large single‐institution European cohort of patients.

Biochemical recurrence after radical prostatectomy: multiplicative interaction between surgical margin status and pathological stage.

PURPOSE A positive surgical margin after radical prostatectomy is considered an adverse prognostic feature. However, few groups have explored the potential interaction between surgical margin status and other cancer characteristics, specifically pathological stage. We addressed the first degree of interaction between positive surgical margins and other established adverse predictors of biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS We used univariate and multivariate analysis to test the effect of surgical margin status on biochemical recurrence in 4,490 patients treated at a single institution between 1992 and 2008. We systematically tested all first-degree interactions between surgical margin status, and pretreatment prostate specific antigen, pT and pN stage, and radical prostatectomy Gleason sum. If interactions were significant, we quantified the effect on the biochemical recurrence rate. RESULTS Overall 850 patients (18.9%) had positive surgical margins. In those with negative vs positive surgical margins the 5-year biochemical recurrence-free survival rate was 95% vs 83%, 74% vs 62% and 47% vs 29% for pT2, pT3a and pT3b disease, respectively. In multivariate models only the pT stage-surgical margin status interaction achieved independent predictor status (p = 0.003). Negative vs positive surgical margin multivariate HRs were 1 vs 2.9, 2.3 vs 4.3 and 4.1 vs 5.6 in pT2, pT3a and pT3b cases, respectively. CONCLUSIONS Compared to negative surgical margins, positive surgical margins increase the absolute biochemical recurrence 5-year rate by 12% to 18%. More importantly, positive surgical margins may substantially worsen the prognosis beyond that of the original pathological disease stage.