[PSA increase after definitive treatment]. / PSA-Anstieg nach definitiver Therapie.

Following definitive treatment with curative intent a subset of patients with prostate cancer experience biochemical recurrence. In these patients clinical parameters are mostly used to decide if a local or systemic disease recurrence is present. While salvage radiation treatment is advocated for local recurrence after radical prostatectomy, no standard recommendations exist in cases of local recurrence after primary radiation therapy although salvage prostatectomy may be considered. Imaging procedures have traditionally not routinely been recommended for the onset of prostate-specific antigen (PSA) relapse; however, prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computed tomography (CT) exhibits high detection rates even at low PSA values. Thus, the current German guidelines state that PSMA PET/CT can be considered if this could result in a decisive change in further treatment management. Currently, a positive influence on oncological long-term outcome, however, has not yet been proven.

Influence of low-molecular-weight heparin dosage on red blood cell transfusion, lymphocele rate and drainage duration after open radical prostatectomy.

BACKGROUND: To assess the rates of red blood cell (RBC) transfusions, pelvic lymphoceles, and prolonged drainage duration in patients after radical prostatectomy (RP) receiving perioperative bridging with low-molecular-weight heparin (LMWH). PATIENTS AND METHODS: Between 2006 and 2009, 114 RP patients receiving bridging therapy with 60 mg (n = 63) or ≥80 mg (n = 51) Enoxaparin/d were compared to 1327 consecutive RP patients receiving 40 mg Enoxaparin/d. Logistic regression models were used to test the effect of LMWH dosage on all three outcomes. Covariables included age, body mass index (BMI), Charlson comorbidity index (CCI), prostate volume, pelvic lymph node dissection, and pathological stage. RESULTS: The RBC transfusion rates in patients treated with 40, 60 and ≥80 mg were 4.9, 9.5 and 19.6%, respectively (p < 0.001). The respective lymphocele rates were 6.4, 3.2 and 2.0% (p = 0.26). The respective rates of drainage duration of ≥4 days were 6.7, 4.8 and 16.7% (p = 0.088). After adjusting for confounding factors, patients receiving ≥80 mg were 4.1-fold more likely to be transfused than patients receiving prophylactic LMWH (p = 0.02). Similarly, patients receiving ≥80 mg were 3.2-fold more likely to have a drainage duration of ≥4 days than patients receiving prophylactic LMWH (p = 0.03). CONCLUSIONS: Patients with a perioperative bridging with LMWH in RP are more likely to receive a RBC transfusion and to have prolonged drainage duration. Conversely, bridging therapy was not associated with an increased risk of lymphocele formation.

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.

[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.