Vladimir Novotny

Prediction of 90-day Mortality After Radical Cystectomy for Bladder Cancer in a Prospective European Multicenter Cohort

BACKGROUND Despite recent improvements, radical cystectomy (RC) is still associated with adverse rates for 90-d mortality. OBJECTIVE To validate the performance of the Isbarn nomogram incorporating age and postoperative tumor characteristics for predicting 90-d RC mortality in a multicenter series and to generate a new nomogram based strictly on preoperative parameters. DESIGN, SETTING, AND PARTICIPANTS Data of 679 bladder cancer (BCa) patients treated with RC at 18 institutions in 2011 were prospectively collected, from which 597 patients were eligible for final analysis. INTERVENTION RC for BCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS An established prediction tool, the Isbarn nomogram, was applied to our cohort. For the purpose of external validation, model discrimination was measured using the receiver operating characteristics-derived area under the curve. Calibration plots examined the relationship between predicted and observed probabilities. Univariable and multivariable logistic regression models were fitted to assess the impact of preoperative characteristics on 90-d mortality. RESULTS AND LIMITATIONS The 30-, 60-, and 90-d mortality rates in the development cohort (n=597) were 2.7%, 6.7%, and 9.0%, respectively. The Isbarn nomogram predicted individual 90-d mortality with an accuracy of 68.6%. Our preoperative multivariable model identified age (odds ratio [OR]:1.052), American Society of Anesthesiologists score (OR: 2.274), hospital volume (OR: 0.982), clinically lymphatic metastases (OR: 4.111), and clinically distant metastases (OR: 7.788) (all p<0.05) as independent predictors of 90-d mortality (predictive accuracy: 78.8%). Our conclusions are limited by the lack of an external validation of the preoperative model. CONCLUSIONS The Isbarn nomogram was validated with moderate discrimination. Our newly developed model consisting of preoperative characteristics might outperform existing models. Our model might be particularly suitable for preoperative patient counseling. PATIENT SUMMARY The current report validated an established nomogram predicting 90-d mortality in patients with bladder cancer after radical cystectomy (RC). We developed a new prediction tool consisting of strictly preoperative parameters, thus allowing clinicians an optimal consultation for RC candidates.

Impact of resection margin status after nephron-sparing surgery for renal cell carcinoma

To evaluate whether the negative‐margin width after nephron‐sparing surgery for renal cell carcinoma (RCC) is associated with tumour recurrence.

Treating renal cell cancer in the elderly

To determine whether age and comorbidity are predictors of peri‐operative complications and/or mortality in surgery for renal cell cancer in a retrospective study of patients aged >75 years.

Perioperative Complications after Radical Prostatectomy: Open versus Robot-Assisted Laparoscopic Approach

Background: The best technique of radical prostatectomy - open versus robot-assisted approach - is controversially discussed. In this study, we compared the complication rates of open and robot-assisted radical prostatectomy during the introduction and subsequent routine use of a da Vinci® robotic device while open surgery remained the standard approach. Patients and Methods: Between January 1st, 2006, and June 4th, 2012, 2,754 men underwent radical prostatectomy at our department. Among them, 317 received robot-assisted and 2,438 open surgery. According to the requirements for prostate cancer centers certified by the Deutsche Krebsgesellschaft (German Cancer Society), a prospective database recording perioperative complications was built up. The complication rates of open and robot-assisted radical prostatectomy were compared with the χ2 or Fisher exact test. The distributions of quantitative variables were compared with U tests. Results: Whereas the demographic factors favored patients selected for robot-assisted radical prostatectomy, there were no differences between open and robot-assisted surgery concerning length of stay, autologous blood transfusion rates and the incidence of perioperative complications. Conclusions: Open and robot-assisted radical prostatectomy had comparable complication rates. With better patient- and tumor-related parameters as well as decreasing transfusion rates in the robot-assisted subgroup, this observation might reflect the learning curves of the involved robotic surgeons.

Urinary tract-related quality of life after radical prostatectomy: open retropubic versus robot-assisted laparoscopic approach.

Background: The best technique of radical prostatectomy – open retropubic versus robot-assisted surgery – is a subject of controversy. Patients and Methods: Between January 1st, 2007 and December 31st, 2011, 2,177 men underwent radical prostatectomy at our department. 252 (12%) cases were laparoscopic robot-assisted, the remainder open retropubic procedures. In Germany, certified prostate cancer centers are required to collect urinary tract-related outcome data after radical prostatectomy using the International Consultation of Incontinence Questionnaire Male Lower Urinary Tract Symptoms. The questionnaire data were used to compare both surgical approaches concerning the urinary tract-related outcome 1, 2 and 3 years postoperatively. Results: Neither the voiding score nor the incontinence score or the bother scale sum differed between the two cohorts at any of the measurement times. Conclusions: Concerning continence recovery, in this series, there were no detectable differences between robot-assisted and open radical prostatectomy.

Prognostic Value of Perinodal Lymphovascular Invasion Following Radical Cystectomy for Lymph Node-positive Urothelial Carcinoma

BACKGROUND Metastasis of urothelial carcinoma of the bladder (UCB) into regional lymph nodes (LNs) is a key prognosticator for cancer-specific survival (CSS) after radical cystectomy (RC). Perinodal lymphovascular invasion (pnLVI) has not yet been defined. OBJECTIVE To assess the prognostic value of histopathologic prognostic factors, especially pnLVI, on survival. DESIGN, SETTING, AND PARTICIPANTS A total of 598 patients were included in a prospective multicentre study after RC for UCB without distant metastasis and neoadjuvant and/or adjuvant chemotherapy. En bloc resection and histopathologic evaluation of regional LNs were performed based on a prospective protocol. The final study group comprised 158 patients with positive LNs (26.4%). INTERVENTION Histopathologic analysis was performed based on prospectively defined morphologic criteria of LN metastases. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariable Cox proportional hazard regression models determined prognostic impact of clinical and histopathologic variables (age, gender, tumour stage, surgical margin status, pN, diameter of LN metastasis, LN density [LND], extranodal extension [ENE], pnLVI) on CSS. The median follow-up was 20 mo (interquartile range: 11-38). RESULTS AND LIMITATIONS Thirty-one percent of patients were staged pN1, and 69% were staged pN2/3. ENE and pnLVI was present in 52% and 39%, respectively. CSS rates after 1 yr, 3 yr, and 5 yr were 77%, 44%, and 27%, respectively. Five-year CSS rates in patients with and without pnLVI were 16% and 34% (p<0.001), respectively. PN stage, maximum diameter of LN metastasis, LND, and ENE had no independent influence on CSS. In the multivariable Cox model, the only parameters that were significant for CSS were pnLVI (hazard ratio: 2.47; p=0.003) and pT stage. However, pnLVI demonstrated only a minimal gain in predictive accuracy (0.1%; p=0.856), and the incremental accuracy of prediction is of uncertain clinical value. CONCLUSIONS We present the first explorative study on the prognostic impact of pnLVI. In contrast to other parameters that show the extent of LN metastasis, pnLVI is an independent prognosticator for CSS.

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.

Systematic assessment of complications and outcome of radical cystectomy undertaken with curative intent in patients with comorbidity and over 75 years of age.

Objective: To evaluate the complications, survival and oncological outcome of patients ≥75 years of age after radical cystectomy for muscle-invasive bladder cancer. Patients and Methods: Between April 1993 and August 2010, 765 patients with muscle-invasive bladder cancer underwent radical cystectomy at one high-volume center. Of these, 70 patients were ≥75 years of age. All 70 patients had at least one severe systemic comorbidity with an American Society of Anesthesiologists score of 3. Primary endpoints of this retrospective study were overall and recurrence-free survival with a mean follow-up of 22 months (1-159). Perioperative parameters such as need for blood transfusions, hospital stay, mortality, short- and long-term complications were also assessed. Complications were graded according to the Clavien-Dindo classification. Results: Perioperative complications occurred in 23/70 patients (33%) with a 30-day mortality rate of 1.4%. 16/70 patients (23%) developed late complications requiring hospitalization. Within 30 days of surgery, according to the Clavien-Dindo grading, 27% had no complications, 3% grade 1, 49% grade 2, 14% grade 3, 6% grade 4 and 1.4% grade 5 complications. Within 31-90 days after surgery, 76% had grade 1 complications, 3% grade 2, 6% grade 3, 9% grade 4 and 6% grade 4 complications. The calculated 5- and 8-year overall survival rates were 30 and 25%, respectively, with a recurrence-free survival rate of 52% at 5 and 42% at 8 years. Conclusions: Radical cystectomy is an appropriate and effective treatment for comorbid elderly patients. The oncological long-term outcome is the same as in younger patients while overall survival is comparatively lower. Mortality and complication-related morbidity are comparable to those in younger patients with modern perioperative management.

Treatment of metastatic renal cell cancer with sunitinib during chronic hemodialysis.

OBJECTIVES To report on 2 cases of metastatic renal cell cancer treated with sunitinib during chronic hemodialysis. METHODS Two patients who were receiving chronic hemodialysis were treated with escalating doses of sunitinib with close clinical and laboratory surveillance. RESULTS The treatment toxicities were tolerable even after dose escalation. The first patient had a complete response after 5 treatment cycles and the second patient had stable disease after 13 treatment cycles. CONCLUSIONS Sunitinib treatment is feasible and effective against metastatic renal cell cancer with the patient receiving chronic hemodialysis. Patients with terminal renal failure can be offered sunitinib treatment with close clinical and laboratory monitoring.

The Use of Neoadjuvant Chemotherapy in Patients With Urothelial Carcinoma of the Bladder: Current Practice Among Clinicians

Micro‐Abstract Neoadjuvant chemotherapy before radical cystectomy is recommended in patients with bladder cancer in clinical stages T2‐T4a, cN0M0. We analyzed the frequency and current practice of neoadjuvant chemotherapy in 679 patients using uni‐ and multivariable regression analyses and using a questionnaire. We found a great discrepancy between guideline recommendations and practice patterns, despite medical indication and interdisciplinary tumor board discussion. Introduction: Guidelines recommend neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in patients with urothelial carcinoma of the bladder in clinical stages T2‐T4a, cN0M0. We examined the frequency and current practice of NAC and sought to identify predictors for the use of NAC in a prospective contemporary cohort. Materials and Methods: We analyzed prospective data from 679 patients in the PROMETRICS (PROspective MulticEnTer RadIcal Cystectomy Series 2011) database. All patients underwent RC in 2011. Uni‐ and multivariable regression analyses identified predictors of NAC application. Furthermore, a questionnaire was used to evaluate the practice patterns of NAC at the PROMETRICS centers. Results: A total of 235 patients (35%) were included in the analysis. Only 15 patients (2.2%) received NAC before RC. Younger age (< 70 years; P = .035), lower case volume of the center (< 30 RC/year; P < .001), and advanced tumor stage (≥ cT3; P = .038) were identified as predictors for NAC. Of the 200 urologists who replied to the questionnaire, 69% (n = 125) declared tumor stage cT3‐4 a/o N1M0 to be the best indication for NAC application, although 45% of the urologists stated that they would not perform NAC despite recommendations. The decision for NAC was made by the individual urologist in 69% of cases, and only 29% reported that all cases were discussed in an interdisciplinary tumor board. Conclusion: NAC was rarely applied in the present cohort. We observed a discrepancy between guideline recommendations and practice patterns, despite medical indication and pre‐therapeutic interdisciplinary discussion. The potential benefit of NAC within a multimodal approach seems to be neglected by many urologists.