Ulrike Heberling

Relationship of the Number of Removed Lymph Nodes to Bladder Cancer and Competing Mortality After Radical Cystectomy

UNLABELLED The extent of lymph node dissection in radical cystectomy is a subject of controversy. A more extended dissection has been reported to be associated with superior survival. We analyzed the relationship between the lymph node count and different causes of death in a sample of 735 patients who underwent radical cystectomy for recurrent or muscle-invasive urothelial or undifferentiated carcinoma of the bladder. The median follow-up was 7.8 yr. The median lymph node count was 17, and the median age was 67 yr. Although there was a clear association between lymph node count and overall survival (≥21 vs. <10 lymph nodes: 10-yr rates: 59% vs. 32%, respectively; hazard ratio: 0.63; 95% confidence interval, 0.46-0.87; log-rank test: p=0.0056), there was no detectable relationship between bladder cancer mortality and lymph node count (narrowly congruent cumulative mortality curves, Pepe-Mori test, p values ranging between 0.40 and 0.93). The differences were virtually entirely attributable to differences in competing mortality. These observations indicate that serious bias may occur when the lymph node count is used to stratify patients undergoing radical cystectomy. The results of the ongoing randomized trials should be awaited to reliably answer the question of the degree to which more extensive dissection may improve outcome. PATIENT SUMMARY Survival differences in patients stratified by lymph node count may be attributed to competing mortality. The results of ongoing randomized trials should be awaited to answer the question of the degree to which more extensive lymph node dissection may improve outcome.

Decreased Overall and Bladder Cancer–Specific Mortality with Adjuvant Chemotherapy After Radical Cystectomy: Multivariable Competing Risk Analysis

UNLABELLED Adding chemotherapy to radical cystectomy (RC) may improve outcome. Neoadjuvant treatment is advocated by guidelines based on meta-analysis data but is severely underused in clinical practice. Adjuvant treatment of patients at risk could be an alternative. We analyzed a sample of 798 patients who underwent RC between 1993 and 2011 for high-risk superficial or muscle-invasive urothelial or undifferentiated bladder cancer, of which 23% received adjuvant cisplatin-based chemotherapy and %5 received neoadjuvant chemotherapy. The use of adjuvant chemotherapy was an independent predictor of decreased overall mortality (hazard ratio [HR]: 0.50; 95% confidence interval [CI], 0.38-0.66; p<0.0001) and bladder cancer-specific mortality (HR: 0.71; 95% CI, 0.52-0.97; p=0.0321), but it was not associated with competing mortality. Similar figures were obtained when analyzing the number of cisplatin-containing cycles administered or when restricting the analysis to patients with lymph node-positive or extravesical but lymph node-negative disease, suggesting a mortality-reducing treatment effect after adjusting for several patient- and tumor-related confounders. Future trials should directly compare the concepts of neoadjuvant and adjuvant application of chemotherapy in candidates for RC. PATIENT SUMMARY Adjuvant chemotherapy may decrease overall and bladder cancer-specific mortality after radical cystectomy (RC). Future trials should directly compare the concepts of neoadjuvant and adjuvant application of chemotherapy in candidates for RC.

An easily applicable single condition–based mortality index for patients undergoing radical prostatectomy or radical cystectomy

PURPOSE There is no generally accepted instrument to measure comorbidity in patients with cancer. We determined which single comorbid conditions are independently associated with competing mortality after radical prostatectomy or radical cystectomy in order to develop a mortality index. METHODS The study samples consisted of 2,961 consecutive patients who underwent radical prostatectomy between 1992 and 2007 for clinically localized prostate cancer and 932 consecutive patients who underwent radical cystectomy between 1993 and 2012 for high-risk non-muscle-invasive or muscle-invasive urothelial or undifferentiated bladder cancer. Competing mortality was the study endpoint. Proportional hazard models for the subdistribution of competing risks were used for analysis. RESULTS Age, angina pectoris, peripheral vascular disease, cerebrovascular disease, chronic lung disease, diabetes mellitus, moderate or severe renal disease, current smoking, and American Society of Anesthesiologists (ASA) physical status class 3 to 4 were independent predictors of competing mortality after radical prostatectomy. After identifying radical cystectomy, age, angina pectoris, chronic lung disease, diabetes mellitus, current smoking, ASA class 3 to 4, and male sex as independent predictors of competing mortality, a combined mortality index using the conditions independently associated with competing mortality in both samples stratified the patients into risk groups with 0% 10-year competing mortality in the lowest and approximately 50% in the highest-risk classes. CONCLUSIONS This simple and plausible combined mortality index based on age, ASA class, smoking status, and the presence of the conditions such as angina pectoris, chronic lung disease, and diabetes mellitus may be used to predict competing mortality in candidates for radical prostatectomy or radical cystectomy.

Prostate-specific Membrane Antigen-targeted Ligand Positron Emission Tomography/Computed Tomography and Immunohistochemical Findings in a Patient With Synchronous Metastatic Penile and Prostate Cancer

A 68-year-old man presented with synchronous metastatic penile and prostate cancer. 68Ga-labeled prostate-specific membrane antigen-targeted ligand positron emission tomography/computed tomography (PSMA-PET/CT) revealed tracer uptake in inguinal, pelvic, and retroperitoneal metastases. Lymph node biopsies and immunohistochemical staining revealed that both cancers involved the lymph nodes and expressed PSMA. In the deposits of penile squamous cell carcinoma, PSMA expression was seen in tumor vessels and may explain the PSMA-PET/CT positivity of inguinal nodes involved in squamous cell carcinoma. The interpretation of imaging in synchronous tumors should take this fact into consideration.

Growth of a Level III Vena Cava Tumor Thrombus Within 1 Month

We describe a patient with rapid growth of a vena cava tumor thrombus from level I-II to level III within 1 month. This case illustrates that once the diagnosis of vena cava involvement is established in renal cell carcinoma, surgery should not be delayed without urgent reasons.

Validation of the diagnostic utility of urinary midkine for the detection of bladder cancer

As it has been demonstrated previously that midkine (also known as neurite growth-promoting factor 2) protein levels in urine of bladder cancer (BCa) patients are increased compared to healthy controls, the present study validated the diagnostic utility of midkine in an independent patient cohort and compared the observed values with voided urine cytology (VUC), which is the current reference standard for non-invasive diagnosis of BCa. Voided urine samples were prospectively collected from 92 BCa patients and 70 control subjects. Protein levels of midkine were assessed using a commercially available enzyme-linked immunosorbent assay and normalized to urinary creatinine. The diagnostic performance of urinary midkine was evaluated by receiver operating characteristic curves. The best combinations of sensitivities and specificities were determined by Youdens Index. Midkine concentrations were significantly elevated in urine samples from BCa patients compared to controls (P<0.001; Mann-Whitney U Test). The level of midkine was associated with disease progression, with the highest concentrations in urine specimens of patients with pT1 and ≥pT2a, as well as high-grade tumors (P<0.001; Mann-Whitney U test). Sensitivities of urinary midkine and VUC were 69.7 and 87.6%, respectively. The corresponding specificities for midkine and VUC were 77.9 and 87.7%, respectively. The combined use of VUC and midkine improved the sensitivity to 93.3%, but reduced the specificity to 66.2%. Despite its reduced discriminatory power for low-grade and low-stage BCa, urinary midkine can be utilized for the identification of high-grade pT1 and ≥pT2a tumors. This means that midkine may potentially be suitable for the identification of patients with high risk BCa.

Selection Effects May Explain Smoking-related Outcome Differences After Radical Cystectomy

The impact of smoking on mortality among patients with bladder cancer is subject to controversy. We investigated 1000 patients who consecutively underwent radical cystectomy between 1993 and 2013. Proportional hazards models for competing risks were used to study the combined effects of variables on mortality. Compared to nonsmokers, current smokers were more frequently male (35.7% vs 12.0%, p<0.0001), younger (63.5 vs 70.5 yr, p<0.0001), had a lower body mass index (26.2 vs 27.1kg/m2, p<0.0001), and suffered less frequently from cardiac insufficiency (12.7% vs 19.3%, p=0.0129). Among current smokers there was a trend towards lower bladder cancer mortality and higher competing mortality in comparison to nonsmokers. On multivariable analysis, current smoking was not a predictor of bladder cancer mortality (hazard ratio [HR] in the full model 0.76; p=0.0687) but was a predictor of competing mortality (HR in the optimal model 1.62; p=0.0044). In conclusion, this study did not confirm adverse bladder cancer-related outcome among current smokers after radical cystectomy. With a younger mean age and a male predominance, there was a trend towards lower bladder cancer mortality current smokers that was eventually neutralized by higher competing mortality, illustrating that selection effects may explain some smoking-related outcome differences after radical cystectomy. The single-center design is a study limitation. PATIENT SUMMARY: Current smokers are not at higher risk of bladder cancer after radical cystectomy but have a higher risk of competing mortality.

Superglue in the Urethra: Surgical Treatment

We describe a case of superglue application into the male urethra with successful surgical treatment of the glue particles by external urethrotomy.

Radikale Zystektomie und Harnableitung beim Harnblasenkarzinom

ZusammenfassungDie radikale Zystektomie mit regionaler Lymphknotendissektion stellt die Standardtherapie des muskelinvasiven Harnblasenkarzinoms dar. Untersuchungen zum klinischen Verlauf nach Zystektomie zeigen in Abhängigkeit vom Tumorstadium exzellente Langzeitergebnisse in Bezug auf das rezidivfreie und tumorspezifische Überleben. Darüber hinaus zeichnet sich die Zystektomie gegenüber den anderen Therapieoptionen durch eine geringe Rate lokaler Rezidive aus. Verbesserungen der chirurgischen Technik, der Anästhesie und der perioperativen Überwachung haben die Zystektomie zu einem Standardeingriff mit akzeptabler Morbidität und Mortalität gemacht. Trotzdem sollte die Indikation insbesondere bei älteren und multimorbiden Patienten kritisch gestellt werden. Die perioperative Mortalität, postoperative Komplikationen sowie die Krankenhausverweildauer sind in Zentren mit hohem Zystektomie-Aufkommen und erfahrenen Operateuren besonders gering. Die Ersatzblase ist heute das am häufigsten gewählte kontinente Harnableitungsverfahren. Der damit verbundene Erhalt von Kontinenz, Miktion auf natürlichem Wege und des „body image“ haben die Akzeptanz der Patienten für ein radikales operatives Vorgehen zusätzlich erhöht. AbstractRadical cystectomy including pelvic lymph node dissection is the standard treatment for muscle-invasive bladder cancer. Depending on tumor stage, long-term observational studies demonstrate excellent results with regard to recurrence-free and tumor-specific survival. Compared to other treatment modalities radical cystectomy achieves low recurrence rates. Improvements in surgical technique, anaesthesia and perioperative care lead to acceptable morbidity and mortality. However, the indication for radical cystectomy should be carefully assessed especially in the elderly and multimorbid patient. Perioperative mortality, complications and length of hospital stay appear to be lower if treatment is performed in high volume centres with experienced surgeons. Orthotopic bladder replacement is nowadays the most frequently used type of continent urinary diversion. Neobladders maintain continence, normal micturition as well as “body image” to a high degree resulting in better patient acceptance of a radical surgical approach.

Gender and Mortality after Radical Cystectomy: Competing Risk Analysis

Background: Data on the impact of gender on mortality after radical cystectomy is conflicting. We investigated a large single center sample with long-term follow-up in order to determine the relationship between gender and outcome. Patients and Methods: A total of 1,184 consecutive patients who underwent radical cystectomy for high risk superficial or muscle-invasive urothelial or undifferentiated bladder cancer between 1993 and 2015 were stratified by gender. Demographic data was compared using Mann-Whitney U test, chi-square test, or Fisher exact test. Cox proportional hazard models were used for the analysis of competing risks and logit models were used for the prediction of the receipt of adjuvant cisplatin-based chemotherapy. Results: Female patients were older, healthier, less frequently current smokers and had more extravesical tumors. In the multivariate analyses, female gender was an independent predictor of (lower) non-bladder cancer (competing) mortality (hazards ratio [HR] 0.68, 95% CI 0.49–0.95, p = 0.0248) but no predictor of bladder cancer-specific mortality (HR in the full model 1.20, 95% CI 0.94–1.54, p = 0.15). Gender was no predictor of the receipt of adjuvant cisplatin-based chemotherapy. Conclusions: Female gender was associated with an increased risk of extravesical disease but was no independent predictor of bladder cancer-specific mortality. Anatomical differences might be a plausible explanation for these observations.