Does the extent of lymphadenectomy in radical cystectomy for bladder cancer influence disease-free survival? A prospective single-center study

Background

Controversy exists regarding the optimal extent of lymphadenectomy and the number of lymph nodes to be retrieved at radical cystectomy (RC).

Objective

To compare the disease-free survival of patients with standard lymphadenectomy (endopelvic region composed of the internal, external iliac, and obturator groups of lymph nodes) versus extended lymphadenectomy (up to the level of origin of the inferior mesenteric artery) at RC in a prospective cohort of patients at a single, high-volume center.

Design, setting, and participants

Prospective data were collected from 400 consecutive patients treated with RC for bladder cancer by two high-volume surgeons at Mansoura Urology and Nephrology Center. Of the 400 patients, 200 (50%) received extended lymphadenectomy and the other 200 (50%) underwent standard lymphadenectomy at RC. The patients did not receive any neoadjuvant or adjuvant therapy.

Measurements

Patient characteristics and outcomes are evaluated.

Results and limitations

Median patient age for the entire group was 53.0 yr. Ninety-six patients (24.0%) had lymph node metastases. Median follow-up was 50.2 mo. Estimates of 5-yr disease-free survival in the extended lymphadenectomy group were 66.6% compared with 54.7% for patients with standard lymphadenectomy (p = 0.043). Extended lymphadenectomy was associated with better disease-free survival after adjusting for the effects of standard pathologic features (p = 0.02). When restricting the analyses to lymph node-positive patients, patients with extended lymphadenectomy had much better 5-yr disease-free survival compared with patients with standard lymphadenectomy (48.0% vs 28.2%; p = 0.029). The study was nonrandomized.

Conclusions

Extended lymphadenectomy is associated with better disease-free survival for bladder cancer patients with endopelvic lymph node involvement and should be considered in these patients.     

Is neoadjuvant chemotherapy valid in invasive cancer of the bladder?

The role of neoadjuvant chemotherapy for invasive transitional cell carcinoma (TCC) of the bladder is not determined yet. M-VAC and CMV regimens have a complete response rate of 10-47% with an overall response reaching 80%. In 16.7-35% of all the responders and 42.9-92% of the complete responders a functioning bladder can be preserved. The influence of neoadjuvant chemotherapy on long-term survival is questionable. Nevertheless, the authors conclude that neoadjuvant chemotherapy is feasible in patients with invasive TCC as it improves the results of following surgery and in some cases enables an organ sparing operation.     

Does neoadjuvant chemotherapy improve survival in patients with resectable thoracic oesophageal cancer?

A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was whether neoadjuvant chemotherapy improves survival in patients with resectable oesophageal cancer. Altogether 685 papers were identified using the below mentioned search. Nine represented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group, relevant outcomes and weaknesses were tabulated. We conclude that combining neoadjuvant chemotherapy with surgery for resectable thoracic oesophageal cancer has theoretical appeal and may offer a modest survival advantage compared to surgery alone. The most recent meta-analysis and the largest randomised trial of 804 patients demonstrated an absolute survival advantage of around 7-9% at two years which just reached statistical significance. Benefit was less clear for squamous cell carcinoma than adenocarcinoma and the second largest randomised trial did not demonstrate a significant benefit.     

Does intubated uretero-ureterocutaneostomy provide better health-related quality of life than orthotopic neobladder in patients after radical cystectomy for invasive bladder cancer?

Objectives  

Ileal orthotopic neobladder (ONB) has not proved to provide better health-related quality of life (HRQoL) than other urinary diversion techniques after radical cystectomy. The aim of the study is to compare HRQoL assessed by four questionnaires between ONB and uretero-ureterocutaneostomy (UUC).     

Population-based outcome of muscle-invasive bladder cancer following radical cystectomy: who can benefit from adjuvant chemotherapy?

BackgroundThe benefit of adjuvant chemotherapy remains controversial in muscle-invasive bladder cancer (MIBC) after radical cystectomy. The present study’s primary objective was to construct a predictive tool for the reasonable application of adjuvant chemotherapy.MethodsAll of the patients analyzed in the present study were recruited from the Surveillance Epidemiology and End Results program between 2004 and 2015. Propensity score matching (PSM) was used to reduce inherent selection bias. Cox proportional hazards models were applied to identify the independent prognostic factors of overall survival (OS) and cancer-specific survival (CSS), which were further used to construct prognostic nomogram and risk stratification systems to predict survival outcomes. The prognostic nomogram’s performance was assessed by concordance index (C-index), receiver-operating characteristic (ROC) and calibration curves. Decision curve analysis (DCA) was performed to evaluate the clinical net benefit of the prognostic nomogram.ResultsA total of 6,384 patients with or without adjuvant chemotherapy were included after PSM. Several independent predictors for OS and CSS were identified and further applied to establish a nomogram for 3-, 5- and 10-year, respectively. The nomogram showed favorable discriminative ability for the prediction of OS and CSS, with a C-index of 0.709 [95% confidence interval (CI): 0.699–0.719] for OS and 0.728 (95% CI: 0.718–0.738) for CSS. ROC and calibration curves showed satisfactory consistency. The DCA revealed high clinical positive net benefits of the prognostic nomogram. The different risk stratification systems showed that adjuvant chemotherapy resulted in better OS (P<0.001) and CSS (P<0.001) than without adjuvant chemotherapy for high-risk patients; while the OS (P=0.350) and CSS (P=0.260) for low-risk patients were comparable.ConclusionsWe have constructed a predictive model and different risk stratifications for selecting a population that could benefit from postoperative adjuvant chemotherapy. Adjuvant chemotherapy was found to be beneficial for high-risk patients, while low-risk patients should be carefully monitored.     

Is there an indication for adjuvant or neoadjuvant systemic chemotherapy in bladder cancer?

Two recent meta-analyses demonstrated a significant influence of adjuvant as well as neoadjuvant cisplatin-based chemotherapy regimens on survival of patients undergoing radical cystectomy for bladder cancer. Therefore, the introductory question can be answered with "yes". However, while providing the best evidence available to date on the subject, both analyses are based on clinical trials of dubious quality. Thus, the question today is not whether perioperative chemotherapy is advantageous in some patients undergoing radical cystectomy, but rather which subgroups will actually benefit from additional systemic treatment. Instead of a detailed literature overview, this article discusses potential advantages and disadvantages of perioperative chemotherapy and outlines basic principles for the design of future studies investigating both strategies in bladder cancer.     

Is robot-assisted radical cystectomy justified in the elderly? A comparison of robotic versus open radical cystectomy for bladder cancer in elderly ≥75 years old

Abstract Background and Purpose: Open radical cystectomy (ORC) or minimally invasive radical cystectomy with pelvic lymph node (LN) dissection carries significant morbidity to the elderly because they often have several medical comorbidities that make a surgical approach more challenging. The objective of this study is to compare robot-assisted radical cystectomy (RARC) and ORC in elderly patients. Patients and Methods: A prospective bladder cancer cystectomy database was queried to identify all patients age ≥75 years. A total of 20 patients were identified for each of the RARC and ORC cohorts. A retrospective analysis was performed on these 40 patients undergoing radical cystectomy for curative intent. Results: Patients in both groups had comparable preoperative characteristics and demographics. Patients had significant medical comorbidities with 80% in each cohort having American Society of anesthesiologists classification of 3 and 50% having had previous abdominal surgery. Complete median operative times for RARC was 461 (interquartile range [IQR] 331, 554) vs 370 minutes for ORC (IQR 294, 460) (P=0.056); however, median blood loss for RARC was 275?mL (IQR 150, 450) vs 600?mL for ORC (IQR 500, 1925). The median hospital stay for RARC was 7 days (IQR 5, 8) vs 14.5 days for ORC (IQR 8, 22) (P<0.001). The major complication (Clavien≥III) rate for RARC was 10% compared with 35% for ORC (P=0.024). There were two positive margins in the ORC group compared with one in the RARC group with median LN yields of 15 nodes (IQR 11, 22) and 17 nodes (IQR 10, 25) (P=0.560) respectively. Conclusions: In a comparable cohort of elderly patients, RARC can achieve similar perioperative outcomes without compromising pathologic outcomes, with less blood loss and shorter hospital stays. For an experienced robotic team, RARC should be considered in elderly patients because it may offer significant advantage with respect to perioperative morbidity over ORC.     

Does early cystectomy improve the survival of patients with high risk superficial bladder tumors?

PURPOSE: We compared survival after early versus delayed cystectomy in patients with high risk superficial bladder tumors. MATERIALS AND METHODS: Of 307 patients with high risk superficial bladder tumors who were treated initially with transurethral resection and bacillus Calmette-Guerin (BCG) therapy 90 (29%) underwent cystectomy for recurrent tumor during a followup of 15 to 20 years. Disease specific survival distribution of these 90 patients was determined relative to the indications for and time of cystectomy. RESULTS: Of the 90 patients who underwent cystectomy 44 (49%) survived a median of 96 months. Of 35 patients with recurrent superficial bladder tumors 92% and 56% survived who underwent cystectomy less than 2 years after initial BCG therapy and after 2 years of followup, respectively. Of 55 patients with recurrent muscle invasive bladder disease 41% and 18% survived when cystectomy was performed within and after 2 years, respectively. Multivariate analysis showed that survival was improved in patients who underwent earlier rather than delayed cystectomy for nonmuscle invasive tumor relapse. CONCLUSIONS: Earlier cystectomy improves the long-term survival of patients with high risk superficial bladder tumors in whom BCG therapy fails.     

Does extended lymphadenectomy increase the morbidity of radical cystectomy?

OBJECTIVE: To report the events during and after radical cystectomy and urinary diversion for bladder cancer, in terms of major and minor complications, comparing a minimal with an extended lymphadenectomy, as more lymph nodes obtained during radical cystectomy may improve staging and thus the outcome. PATIENTS AND METHODS: We reviewed 92 consecutive patients who underwent radical cystectomy from March 1998 to February 2002; 46 had a minimal (group A) and 46 an extended lymphadenectomy (group B). Cases were selected according to the American Society of Anesthesiologists classification, only including those graded 2 or 3. We specifically evaluated the incidence and type of complications within 30 days after surgery. RESULTS: Because of extending the lymphadenectomy the operative duration was a median of 63 min longer in group B (P < 0.01). Complications requiring surgical interventions occurred in four (9%) patients in group A and five (11%) in group B (P = 0.28). Complications requiring no surgical intervention were also similar in both groups. Three patients died, two in group A and one in group B (P = 0.57). CONCLUSION: Extended lymphadenectomy in radical cystectomy does not increase the morbidity within 30 days of surgery.     

Lymph node metastases in bladder cancer disease. Is there an indication for radical cystectomy?

Summary Bladder carcinomas with lymph node metastases are a systemic disease with a poor long term survival (< 10 %) [7]. Surgery has no proofen impact on patients survival. Outcome depends on the extent of lymph node disease [8]. Surgery combined with systemic chemotherapy is controversely discussed. Neoadjuvant chemotherapy has no proofen survival impact [4]. Adjuvant chemotherapy is under investigation in prospective randomized phase III trials. Lymph node metastases are no exclusion criteria for orthotopic bladder replacement [2]. Extended lymph node dissection is not superior to lymph node dissection limited to the fossa obturatoria [6]. Despite excellent long term results of radical cystectomy and lymphadenectomy in selected patients with node positive disease [8], surgery seems to be an individual approach, without no proofen impact on patients survival and quality of life.      

Significance of radical cystectomy for bladder cancer in patients over 80 years old

Objectives The objective of this study was to evaluate the usefulness of radical cystectomy for bladder cancer in elderly patients. Materials and methods This study included 72 patients aged ≥80 years (group A) who underwent radical cystectomy and urinary diversion between January 1995 and December 2003, and the clinical outcome of these patients were compared with those of 557 patients aged <80 years (group B) undergoing radical cystectomy during the same period as group A. Results As the procedure for urinary diversion, ureterocutaneostomy was most frequently performed in group A (87.5%), while neobladder creation was most common in group B (43.8%). Despite the absence of significant differences in tumor grade and incidence of lymph node metastasis between these two groups, pathological stage in group A was significantly greater than that in group B. The perioperative mortality rate in group A was significantly higher than that in group B, whereas the incidences of both early and late postoperative complications in group A were similar to those in group B. Cancer-specific survival in group A was significantly lower than that in group B; however, among patients with disease ≤pT2, there was no significant difference in cancer-specific survival between these two groups. Conclusions These findings suggest that an aggressive surgical approach may be an optimal therapeutic strategy for properly selected elderly patients who require definitive therapy for locally invasive bladder cancer, particularly in those with disease ≤pT2.