[Prostate cancer detection rates: comparison of standard biopsy with prompt rebiopsy and a one-time extended biopsy]. / Prostatakarzinomdetektionsraten : Vergleich zwischen der Standardbiopsie mit zeitnaher Rebiopsie und einer einmaligen extendierten Biopsie.

INTRODUCTION: Prostate biopsy is the gold standard for the detection of prostate cancer (PCA). While national and international guidelines recommend the extraction of 10-12 cores at initial biopsy, some authors plead to initially perform more extensive biopsy protocols. We assessed the PCA detection and complication rates of different biopsy schemes. MATERIALS AND METHODS: We relied on the data of 425 men who underwent their first prostate biopsy from April 2005 to May 2013. Exclusion criteria consisted of PSA > 20 ng/ml, prior surgery of the prostate, or intake of 5-α-reductase inhibitors. Overall 357 underwent a 10- to 12-core biopsy, while 68 patients underwent 20-core biopsy. In case of a negative biopsy in the 10-12 cohort, rebiopsy was performed within 6 months, while in the 20-core group clinical follow-up determined further course of action. Endpoints of the study were the overall PCA detection rate and the rate of severe complications, which were defined as complications requiring hospital admission. The effect of the respective biopsy scheme on the PCA detection rate was assessed using uni- and multivariable logistic regression analysis. In the subanalysis, the PCA detection rates between the two groups were compared solely in patients with PSA values ≤10 ng/ml. RESULTS: At initial biopsy, the overall PCA detection rate was 50.4% (214/425). In the 10-12 core group, the PCA detection rate at first biopsy was 52.4% (187/357) and rebiopsy detected a further 19 (11.2%) PCA cases, resulting in a cumulative PCA detection rate of 57.7% (206/357). In the 20-core group, the PCA detection rate was 39.7% (27/68). While the different PCA detection rates were not statistically different when the initial biopsies were compared, biopsy scheme reached independent predictor status when the cumulative PCA detection rate of the 10- to 12-core scheme was compared to the 20-core scheme (p=0.01). Comparable results were obtained only when patients with PSA ≤10 ng/ml were considered. The rate of severe complications was statistically higher in the 20-core group (6.1 vs. 2.4%; p=0.01). CONCLUSION: Our data indicate that an initial 20-core biopsy does not lead to a higher PCA detection rate compared to an initial 10- to 12-core biopsy. Moreover, the cumulative PCA detection rate of a 10- to 12-core biopsy and prompt repeat biopsy was significantly higher compared to a single 20-core biopsy.

Prediction of metastatic status in non-seminomatous testicular cancer.

PURPOSE: To examine the significance of 90 biomarkers for predicting metastatic status in non-seminomatous germ cell tumors (NSGCT). By predicting metastatic status, it may be possible to eliminate unnecessary therapeutic or diagnostic efforts. MATERIALS AND METHODS: We investigated 552 males who were diagnosed with non-metastatic (n = 273) and metastatic (n = 279) NSGCT between 2000 and 2011. The sample included cancers of different histologies: embryonal cell carcinoma (n = 131), teratoma (n = 55), and mixed histology (n = 366). We collected and analyzed more than 90 parameters via logistic regression: demographic characteristics, medical history, histopathological parameters, and levels of tumor markers and hormones. RESULTS: Testis histology (p = 0.004), clinical symptoms (p = 0.0005), tumor length (p = 0.005), infiltration of the rete testis (p = 0.008), invasion of lymphatic (pL1) and blood vessels (pV1) (p < 0.0001), and levels of enzymes such as LDH, ßHCG, AFP, and FSH (p values as small as <0.0001) were associated with metastatic status. With one model, we identified 14 out of 76 (18.4 %) metastatic NSGCT cases with 93-100 % certainty (positive predictive value) at 99 % specificity by the peripheral blood levels of LDH (day of operation) in combination with FSH measurements (1 day after operation). A second model included pV, tumor length, and FSH (1 day after operation). It identified 25 out of 90 (27.8 %) non-metastatic NSGCT with approximately 90 % certainty (negative predictive value) at 94-98 % sensitivity. CONCLUSIONS: No single parameter was able to discriminate metastatic from non-metastatic NSGCT, but combinations of parameters in two predictive models accurately identified the metastatic status in 23 % of the cases in our sample.

[Two-stage urethral reconstruction with buccal mucosa for hypospadias cripples : Long-term results]. / Zweizeitige Harnröhrenrekonstruktion mit Mundschleimhaut bei Hypospadiekrüppeln : Langzeitergebnisse.

So-called hypospadias cripples are a challenging group of patients who present with multiple previous repair operations with unsatisfactory functional and cosmetic results. Attempts at renewed correction can be carried out with various techniques and different materials and staged repair with buccal mucosa according to Bracka has shown good results.

The search for biomarkers of metastatic seminoma.

PURPOSE: We screened 90 potential parameters as biomarkers of metastatic seminoma to facilitate detection and eliminate unnecessary therapeutic or diagnostic efforts. MATERIALS AND METHODS: A total of 527 men with pure seminoma (diagnosed 2000 to 2011) were followed during therapy. More than 90 demographic/anamnestic (eg age, height, weight) histopathological parameters (testicular/tumor size, testicular intraepithelial neoplasia) and levels of tumor markers (eg α-fetoprotein, ß-human chorionic gonadotropin, lactate dehydrogenase) in peripheral blood and testicular vein were collected for analysis via logistic regression. Previously described risk factors (tumors larger than 4 cm, infiltration of rete testis) were assessed separately. RESULTS: Established parameters such as tumor length (p = 0.0003), involvement of lymphatic (p <0.0001) or vascular channels (p = 0.0009), extent of primary tumor (p <0.0001) and infiltration of the tunica albuginea (p = 0.02) as well as new biomarkers such as absence of testicular intraepithelial neoplasia in tumor bearing testis (p = 0.03), testicular volume (p = 0.04) and tumor volume (p = 0.02) showed a significant association with metastatic disease. This association was also true of lactate dehydrogenase, human chorionic gonadotropin and α-fetoprotein (p <0.0001 at maximum). However, the discriminatory capacity of these biomarkers (concordance or ROC area) did not exceed 65% when examined alone or in combination, and higher values (up to 80%) were detected for enzyme levels. A subset of metastatic seminoma (2% to 27%) was detectable with high accuracy (positive predictive value 92% to 100%) based on enzyme measurements (p <0.0006). CONCLUSIONS: New biomarkers of metastatic seminoma were identified and previously described risk factors were validated. Further prospective studies of these novel parameters are warranted to verify our findings and to explore a potential use for detecting occult metastases.

Predicting the risk of lymph node invasion during radical prostatectomy using the European Association of Urology guideline nomogram: a validation study.

BACKGROUND: The 2011 European Association of Urology (EAU) guidelines for prostate cancer recommend a pelvic lymph node dissection (PLND) at radical prostatectomy (RP) in all individuals with a nomogram predicted lymph node invasion (LNI) risk of >7%. METHODS: To test the performing characteristics for several thresholds (1-14%) and to examine the overall accuracy and calibration plot of the EAU nomogram at our institution. The study population consisted of 3081 patients treated with RP and PLND limited to the obturator fossa and the external iliac vein between 2008 and 2010 at a single European institution from Germany. More extensive PLNDs were performed at the surgeon's discretion. RESULTS: Overall, 260 patients (9.2%) had LNI. The 7% threshold would have avoided 30% of PLNDs, at the cost of missing 8% of patients with LNI. The use of 8% and 9% threshold would have allowed the avoidance of respectively 39% and 48% of PLNDs, at the cost of missing respectively 12% and 14% of patients with LNI. The accuracy of the LNI nomogram was 78%, and the unadjusted departure from ideal calibration was 5.3%. CONCLUSIONS: We confirmed adequate accuracy and calibration of the LNI nomogram. The 7% cut-off may be overly conservative. Better trade-offs between avoided PLNDs and missed LNI cases may be achieved with a limit of 8 or even 9%.

Impact of annual surgical volume on length of stay in patients undergoing minimally invasive prostatectomy: a population-based study.

BACKGROUND: On average, patients remain hospitalized no more than 2 days after MIRP. The aim of our study was to examine the temporal trends in length of stay ≥ 3 days and to test the relationship between annual surgical volume (ASV) and annual hospital volume (AHV) and length of stay ≥ 3 days in patients undergoing MIRP. MATERIAL AND METHODS: Within the Florida Hospital Inpatient Datafile, 2439 men who were treated with MIRP for prostate cancer between 2005 and 2008 were identified. Temporal trends were assessed and uni and multi-variable logistic regression models tested the relationship between ASV, AHV and length of stay ≥ 3 days. RESULTS: The average length of stay decreased from 2.4 in 2005 to 1.7 days in 2008. Length of stay ≥ 3 days was recorded in 13.6% of patients and the proportion of patients staying more than ≥ 3 days decreased over time (25.5-12.2%; Chi Square trend p < 0.001). After stratification into low (<1-15 MIRPs) vs. intermediate (16-63 MIRPs) vs. high ASV tertiles (≥ 64 MIRPs) the proportion of patients with length of stay ≥ 3 days were 29.1; 13.2 and 11.1%. In multivariable logistic regression models predicting length of stay ≥ 3 days, ASV, year of surgery and comorbidities achieved independent predictor status and MIRP patients operated by highest ASV tertile surgeons were 71% (p < 0.001) less likely to be hospitalized for more than 3 days. CONCLUSION: The length of stay after MIRP decreased between 2005 and 2008. Surgical expertise represented one of the main determinants of shorter length of stay.

[Type and extent of preoperative imaging before radical prostatectomy]. / Evaluation von Art und Ausmass der präoperativen Bildgebung vor radikaler Prostatektomie.

BACKGROUND: According to current guidelines, in cases of newly diagnosed prostate cancer the type and extent of imaging to be performed should be based on the patient's risk profile. We investigated the rate of computed tomography (CT), magnetic resonance imaging (MRI), and bone scintigraphy carried out before radical prostatectomy (RP) depending on the individual risk profile. PATIENTS AND METHOD: Between 1 January 2006 and 31 December 2007, a total of 1,018 consecutive patients who had not received neoadjuvant hormone therapy were treated with RP in our department. We determined the preoperative rates of CT, MRI, and bone scintigraphy by reviewing the medical charts. The patients were stratified according to the D'Amico criteria into low-risk, intermediate-risk, and high-risk groups. RESULTS: Of the 1,018 subjects, 493 (48%) were classified as low-risk, 403 (40%) as intermediate-risk, and 122 (12%) as high-risk patients, respectively. The rate of preoperative abdominal CT/MRI and bone scintigraphy was 17 and 23% in the low-risk group, 25 and 39% in the intermediate-risk patients, and 39 and 57% in the high-risk group. CONCLUSION: The rate of preoperative CT and bone scintigraphy is extremely high in the low-risk group. In contrast the rate in the high-risk patients more likely appears to be too low. The discrepancy between the rates of preoperative imaging subject to the patient's risk profile shows that precisely formulated guidelines addressing this issue are needed.

[Comparison of the effectiveness between long-term instillation of mitomycin C and short-term prophylaxis with MMC or bacille Calmette-Guérin. Study of patients with non-muscle-invasive urothelial cancer of the urinary bladder]. / Vergleich der Effektivität der Langzeitinstillation mit Mitomycin C gegen Kurzzeitprophylaxen mit MMC oder Bacillus Calmette-Guerin. Untersuchung bei Patienten mit nicht muskelinvasivem Urothelkarzinom der Harnblase.

BACKGROUND: Adjuvant instillation therapy with chemo- or immunotherapeutic agents is an integral component in the treatment of non-muscle-invasive bladder cancer. There is, however, no general consensus on the choice of medication and the optimal duration of therapy. This multicenter trial compared a long-term treatment regimen with mitomycin C (MMC) with two short-term treatment approaches with MMC or bacille Calmette-Guérin (BCG) for intermediate-/high-risk bladder tumor after transurethral resection. In patients with low-risk bladder tumors, the effectiveness of six weekly MMC instillations was determined and compared with the results of patients not receiving adjuvant treatment. MATERIAL AND METHODS: A total of 495 patients with intermediate-/high-risk bladder tumor (recurrent and/or multifocal pTaG1, pTaG2-3, or pT1G1-3) were randomly administered either BCG-RIVM 2x108 CFU in six weekly instillations, MMC 20 mg in six weekly instillations, or MMC 20 mg in six weekly instillations with subsequent monthly instillations for 3 years. A total of 132 low-risk patients (first diagnosis of a unifocal pTaG1 bladder tumor) were randomly allocated to two treatment arms. In the first arm, 20 mg MMC were instilled weekly six times. In the control arm, the patients received no adjuvant therapy. RESULTS: The 3-year recurrence-free rate in the patients of the intermediate-/high-risk group was 65.5% (95% CI: 55.9-73.5%) in the BCG arm and 68.6% (95% CI: 59.9-75.7%) in the MMC short-term arm. In the MMC long-term arm, the 3-year recurrence-free rate was significantly higher at 86.1% (95% CI: 77.9-91.4%, log-rank test: p=0.001). There was no increased toxicity observed with long-term administration of MMC. In the low-risk group, the 3-year recurrence-free rate after adjuvant therapy was 74% (95% CI: 60.0-83.8%) and in the patients receiving no adjuvant treatment 63% (95% CI: 46.6-75.5%, corresponding to a hazard ratio of 0.58 (95% CI: 0.28-1.18%). The difference between the treatment arms was not significant. CONCLUSION: Long-term prophylaxis with MMC results in a significantly reduced recurrence rate in intermediate-/high-risk bladder cancer with a comparable toxicity profile in comparison to short-term MMC or short-term BCG. Our study showed no significant decrease of the recurrence rate in low-risk tumors with six adjuvant MMC instillations. This treatment approach thus does not represent an alternative to early instillation.

[Active surveillance for prostate cancer]. / Aktive Uberwachung des Prostatakarzinoms.

Active surveillance is a valuable treatment option in patients with newly diagnosed low-risk prostate cancer. Studies considering a watchful waiting approach showed favourable cancer-specific survival rates in such patients and it is assumed that patients benefit from a definitive therapy if life expectancy exceeds 10-15 years. Therefore active surveillance is especially valuable in older men and in patients with an elevated comorbidity profile. Precise identification of histologically and clinically insignificant prostate cancers is still not possible today. Active surveillance includes regular PSA measurements combined with follow-up biopsies; however, no standardized protocol exists so far. Histological progression in the follow-up biopsy and PSA elevation are the most important criteria for initiating definitive therapy. Today only a minority of low-risk patients join an active surveillance protocol and a substantial proportion of these men leave such a protocol early without evidence of progression. The psychological burden of living with an untreated cancer seems to be responsible for this. Active surveillance has the potential to lead to undertreatment as there is some evidence that prolonged treatment delay might adversely affect outcome of definitive therapy.

[DNA methylation on urinalysis and as a prognostic marker in urothelial cancer of the bladder]. / DNA-Methylierung in der Urindiagnostik und als Prognosemarker beim Urothelkarzinom der Harnblase.

INTRODUCTION AND OBJECTIVES: Detection of promoter hypermethylation has been proposed as a promising tool for cancer diagnosis and as a prognostic marker in various cancers. We studied the versatility of DNA methylation for noninvasive diagnosis and as a prognostic marker for non-muscle-invasive bladder carcinoma. METHODS: Tumor specimens were microdissected and DNA was extracted from 105 paraffin-embedded paraffin specimens from patients undergoing transurethral resection for non-muscle-invasive bladder carcinoma. Urine specimens were collected from patients undergoing cystectomy for bladder cancer and from healthy volunteers. Methylation status was assessed with the real-time quantitative methylation-sensitive PCR (MethyLight). We checked a panel of 20 cancer-associated genes (p14ARF, p16 CDKN2A, STAT-1, SOCS-1, DR-3, DR-6, PIG-7, BCL-2, H-TERT, BAX, EDNRB, DAPK, RASSF-1A, FADD, TMS-1, E-CADHERIN, ICAM-1, TIMP-3, MLH-1, COX-2) for DNA methylation. RESULTS: Follow-up data were available in 95 of 105 patients (91.4%). A tumor recurrence was observed in 26 patients (27.3%). We could identify six genes (SOCS-1, STAT-1, BCL-2, DAPK, TIMP-3, E-cadherin), where methylation was associated with tumor recurrence. In Kaplan-Meier analysis, TIMP-3 showed a significant association with recurrence-free survival. Methylation of TIMP-3 predicted prolonged disease-free interval. Regarding urinalysis we could identify a pattern of methylation markers including DAPK, BCL-2, and H-TERT that yielded a sensitivity of 81.1% with a specificity of 100% in a cancer-free control population CONCLUSIONS: We present data on the clinical usefulness of methylation analysis in bladder carcinoma. Our data confirm that methylation analysis is a promising tool for bladder cancer diagnosis and prognosis.