Management Of Invasive Bladder Cancer Research Articles

Super Extended Versus Extended Pelvic Lymph Node Dissection in Patients Undergoing Radical Cystectomy for Bladder Cancer: A Comparative Study

There is evidence from retrospective studies that radical cystectomy with extended pelvic lymph node dissection provides better staging and outcomes than limited lymph node dissection. However, the optimal limits of extended lymph node dissection remain unclear. We compared oncological outcomes at 2 cystectomy centers where 2 different extended lymph node dissection templates are practiced to determine whether removing lymphatic tissue up to the inferior mesenteric artery confers an additional survival advantage. Patients undergoing radical cystectomy and extended lymph node dissection with curative intent from 1985 to 2005 were included in analysis if they met certain criteria, including clinically organ confined urothelial bladder carcinoma (cN0M0), pathological stage pT2-pT3, negative surgical margins and no neoadjuvant therapy. Survival and recurrence data were analyzed. Demographic data and pathological subgroup distribution (pT2 and pT3) were similar in the 554 University of Southern California and 405 University of Bern patients. University of Southern California patients had higher median number of lymph nodes removed than University of Bern patients (38 vs 22, p <0.0001) and a higher incidence of lymph node metastasis (35% vs 28%, p = 0.02). However, the University of Southern California and University of Bern groups had similar 5-year recurrence-free survival for pT2pN0-2 (57% vs 67%) and pT3pN0-2 (32% vs 34%) disease (p = 0.55 and 0.44, respectively). The overall recurrence rate was equal at the 2 institutions (38%). Meticulous extended lymph node dissection up to the mid-upper third of the common iliac vessels appears to provide survival and recurrence outcomes similar to those of a super extended template up to the inferior mesenteric artery. Complete skeletonization in the extended lymph node dissection template is more important than nodal yield. This does not exclude the possibility that certain patient subgroups with suspicious nodes or after neoadjuvant chemotherapy may benefit from more extensive lymph node dissection.

Management of invasive bladder cancer in patients who are not candidates for or decline cystectomy

Bladder cancer is a common malignancy seen in older adults with coexisting medical illnesses. The management of patients with muscle invasive disease includes perioperative chemotherapy and radical cystectomy; however, patients may decline surgery and older patients with comorbid conditions may not be candidates for surgery and thus alternative treatment strategies are needed. Trimodality bladder preservation protocols for muscle invasive bladder cancer have generally included only those patients who are candidates for a salvage cystectomy. In this review, we discuss the current status of bladder preservation treatment options for patients with muscle-invasive disease who are not candidates for cystectomy or who decline surgery and highlight the need for clinical trials investigating novel treatment approaches in this older patient population.

Lymphadenectomy in Management of Invasive Bladder Cancer

Radical cystectomy with pelvic lymphadenectomy represents the gold standard for treatment of muscle-invasive bladder cancer. Extent of the lymph node dissection and lymph node involvement during radical cystectomy are the most powerful prognostic factors associated with poor oncological outcome. However, the optimal boundaries of the lymph node dissection during a radical cystectomy are controversial. The published literature based mostly on retrospective studies suggests that increasing the number of nodes excised may have therapeutic and diagnostic benefits without significantly increasing the surgical morbidity. These conclusions are, however, influenced by selection and surgeon biases, inconsistencies in the quality of the surgery, and node count variability. In this paper, we establish the current understanding about the utility of lymphadenectomy during a radical cystectomy for muscle-invasive bladder cancer.

How Do Commonly Performed Lymphadenectomy Templates Influence Bladder Cancer Nodal Stage?

Determining pathological nodal stage in patients with bladder cancer is important for prognosis. We determined how the extent of lymphadenectomy and the lymph node count influence accurate nodal staging. The study included 120 patients who underwent at least extended lymphadenectomy at radical cystectomy. Different anatomical templates for lymphadenectomy were evaluated for nodal staging accuracy. The cumulative percent was plotted to determine a lymph node count that confidently identified node positive cases. The mean +/- SD total lymph node count in the study population was 36.9 +/- 14.8 at extended lymphadenectomy. Of the patients 36 (30%) had lymph node metastasis, including 14 (39%) with metastasis involving the common iliac and/or presacral lymph nodes. Limited, standard and extended lymphadenectomy accurately identified 75%, 88.9% and 100% of node positive cases, respectively. Removing 23 and 27 lymph nodes provided 80% and 90% confidence, respectively, that a case was accurately staged as pN0. No patient had lymph node metastasis above the aortic bifurcation without nodal metastasis below the aortic bifurcation and none had a change in pN stage by extending lymphadenectomy above the aortic bifurcation. To accurately identify node positive and negative cases, and correctly assign pN stage in node positive cases it is necessary to perform extended lymphadenectomy. Identifying at least 23 to 27 lymph nodes on final pathological evaluation provides a high level of confidence that a case is correctly staged as node positive or negative.

Organ-sparing strategies in the management of invasive bladder cancer

Bladder cancer is the second most common genitourinary malignancy. Radical cystectomy and pelvic lymphadenectomy is the standard of care in the management of muscle-invasive bladder cancer. However, recently, bladder-preservation trials conducted by both single- and multi-institutional groups have gained momentum because of comparable survival and recurrence rates in select patients. While single-modality therapies have failed to provide adequate results, multimodal combination therapies consisting of a thorough transurethral resection with radiotherapy and concomitant chemotherapy have been promising. Careful patient selection, maximum transurethral resection of bladder tumor, cystoscopic evaluation of response with prompt salvage cystectomy for nonresponders and strict long-term follow-up for complete responders constitute the hallmarks of optimal bladder-preservation protocols. Advances in molecular-targeted therapy, chemotherapy and radiotherapy hold promise to improve survival and local control and decrease side effects and toxicity.

Practice patterns and recurrence after partial cystectomy for bladder cancer

Partial cystectomy (PC) remains a viable alternative to radical cystectomy (RC) for management of invasive bladder cancer in approximately 5% of patients. We used a population-based database to examine practice patterns and recurrence after partial cystectomy. We obtained billing records of all partial and radical cystectomies performed for bladder cancer in Quebec from 1983 until 2005. Analysis included age, gender, year of surgery, surgeon's age, hospital type, preoperative and postoperative visits with accompanying diagnoses and dates of recurrences salvage RC, and death. A total of 714 (30.4%) patients with invasive bladder cancer underwent PC. Majority of PC (65%) were performed in non-academic institutions. Pelvic lymphadenectomy was performed in only 163 patients (23%) and concomitant ureteral reimplantation was performed in 89 patients (13%). Of 714 patients, 52 (23.7%) required a salvage RC. Median time from PC to salvage RC was 17.6 months (range 1-240 months), respectively. Patients who underwent PC had similar 5-year overall survival compared with patients who underwent upfront RC (49.8% vs. 51%, p = 0.21). Rate of PC for invasive bladder cancer is significantly higher than expected. Pelvic lymphadenectomy is underutilized in bladder cancer patients treated with PC. Whether prevalent use of PC is due to less stringent selection criteria remains unknown. Since late recurrence is not uncommon, lifelong follow-up is recommended.

Follow-up of nonmuscle invasive transitional cell carcinoma of the bladder: how and how often?

Nonmuscle invasive bladder cancer represents a heterogeneous disease due to different natural history of its various appearances. The purpose of this article is to review recent literature regarding follow-up strategies. Management of nonmuscle invasive bladder cancer has become more complex in respect to diagnosis, treatment and follow-up. Follow-up should therefore be based on individual patient-risk assessment. In addition to improved diagnosis by fluorescence-guided cystoscopy and other new diagnostic tools like optical-coherence tomography management has concentrated on optimizing different concepts of intravesical therapy. The intent of nonmuscle invasive bladder cancer management is to control recurrence and progression and to identify invasive tumours at the earliest possible stage. To obtain exact staging, besides a proper transurethral resection of bladder, a restaging transurethral resection of bladder should be performed in T1 patients. Data from the literature supports the immediate postoperative intravesical instillation of different chemotherapeutic agents in low-risk patients. Multifocal papillary lesions might necessitate a more intensive adjuvant regimen, whereas intravesical immunotherapy using bacillus Calmette-Guerin is recommended in patients who are at a high-risk of progression. Early cystectomy should be considered in patients with recurrent T1 tumours or refractory carcinoma in situ to avoid unfavourable tumour progression.

Fluoreszenzzystoskopie

Many studies confirm the clinical interest of photodynamic diagnostics (PDD) in non-muscle invasive bladder cancer management. PDD or fluorescence cystoscopy is not only of great value in occult urothelial cancer detection, but may have a positive impact on disease-free survival and prognosis. Yet, its specificity is found to be highly variable between studies mainly in relation to different disease profiles. New imaging techniques aimed at enhancing visualization to assess the bladder wall are under development.

Outcome After Radical Cystectomy With Limited or Extended Pelvic Lymph Node Dissection

We compared recurrence patterns and survival of patients with urothelial bladder cancer undergoing radical cystectomy who either had limited or extended pelvic lymph node dissection at 2 institutions between 1987 and 2000. Two consecutive series of patients treated with radical cystectomy and limited pelvic lymph node dissection (336; Cleveland Clinic) and extended pelvic lymph node dissection (322; University of Bern) were analyzed. All cases were staged N0M0 prior to radical cystectomy, and none were treated with neoadjuvant radiotherapy or chemotherapy. Patients with PTis/pT1 and pT4 disease were excluded from analysis. Pathological characteristics based on the 1997 TNM system and recurrence patterns were determined. The overall lymph node positive rate was 13% for patients with limited and 26% for those who had extended pelvic lymph node dissection. The 5-year recurrence-free survival of patients with lymph node positive disease was 7% for limited and 35% for extended pelvic lymph node dissection. The 5-year recurrence-free survival for pT2pN0 cases was 67% for limited and 77% for extended pelvic lymph node dissection, and the respective percentages for pT3pN0 cases were 23% and 57% (p <0.0001). The 5-year recurrence-free survival for pT2pN0-2 cases was 63% for limited and 71% for extended pelvic lymph node dissection, and for pT3pN0-2 cases the respective figures were 19% and 49% (p <0.0001). Incidence of local and systemic failure correlated closely with pathological stage for both series. Our data suggest that limited pelvic lymph node dissection is associated with suboptimal staging, poorer outcome for patients with node positive and node negative disease, and a higher rate of local progression. Extended pelvic lymph node dissection allows for more accurate staging and improved survival of patients with nonorgan confined and lymph node positive disease.

Radical Cystectomy and Lymphadenectomy for Invasive Bladder Cancer: Towards the Evolution of an Optimal Surgical Standard

The surgical management of invasive bladder cancer has undergone a significant evolution in technique since its initial introduction. Changes in the extent of surgery have largely reflected a better understanding of the natural history of bladder cancer and the recognized pathways of progression. Incorporation of contemporary surgical techniques that target the perivesical soft tissues, regional lymph nodes, and adjacent organs appear to enhance oncologic outcomes. A growing body of evidence indicates that the quality of radical cystectomy (RC) directly affects patient outcome. Recently, quality of life and functional considerations have led to surgical modifications such as nerve-, prostate-, vaginal wall-, and urethra-sparing approaches. While some modifications in appropriate candidates appear not to decrease cancer control, further studies will be needed to establish their role and safety. This ongoing evolution in the technique of RC and pelvic lymph node dissection (PLND) may help define a new surgical standard that provides optimal benefit in patients with invasive bladder cancer.

The prognostic and staging value of lymph node dissection in the treatment of invasive bladder cancer

Regional lymph node dissection (LND) at the time of radical cystectomy is an essential component of the surgical management of invasive bladder cancer and might provide diagnostic and therapeutic benefits for both node-negative and node-positive patients. The benefits obtained in pathologically node-negative patients might result from more complete resection of undetected micrometastases or from a more meticulous surgical technique. Advanced nodal disease also seems to be amenable to thorough surgical resection in a subpopulation of patients with bladder cancer. Despite the growing body of evidence to support the role of a more extended LND, no guidelines regarding the optimal boundaries of LND have been established. An increased number of resected nodes and wider LND boundaries have been associated with improved local disease control and prolonged survival. Additionally, mapping series indicate that the common iliac and presacral nodal regions are more frequently involved with tumor metastases than previously recognized. Efforts to limit any unnecessary dissection in patients at low risk for metastases--a tailored approach--has been proposed, but remains unproven. From the available evidence, the most reliable diagnostic and therapeutic approach to LND includes the routine extended LND in all patients undergoing cystectomy with curative intent.

Robot-Assisted Laparoscopic Radical Cystoprostatectomy and Totally Intracorporeal Ileal Neobladder

To describe robot-assisted laparoscopic radical cystoprostatectomy and intracorporeal orthotopic ileal neobladder construction. With the use of the daVinci Surgical System (Intuitive Surgical, Sunnyvale, CA), we performed laparoscopic radical cystectomy and intracorporeal construction of an orthotopic ileal neobladder (modified W pouch). The total operative time was 12 hours, and the estimated blood loss was 100 mL. There were no intraoperative or postoperative complications, and the patient?s hospital stay was 5 days. At early follow-up, oncologic and functional results are good. Robot-assisted laparoscopic radical cystoprostatectomy with intracorporeal ileal neobladder construction is technically feasible. However, its role in the management of invasive bladder cancer remains to be defined.

HIGHLIGHTS FROM THE SOCIETY OF UROLOGIC ONCOLOGY, 5TH ANNUAL MEETING, DECEMBER 3–4, 2004, BETHESDA, MARYLAND, UNITED STATES OF AMERICA

The fifth annual meeting of the Society of Urologic Oncology was held December 3 and 4, 2004 in Bethesda, Maryland. The program provides a forum for the discussion of important issues in genitourinary malignancies among urologists, radiation oncologists and medical oncologists. Agenda topics included kidney cancer, bladder cancer and prostate cancer. Several sessions featured new developments in basic, translational and clinical research. Each session was reviewed for content following the meeting and the highlights were summarized. The Young Urologic Oncologists' Forum was again a successful component of the meeting but it is beyond the scope of this summary. Sessions on kidney cancer focused on molecular genetics and advances in molecular therapeutics. Radio frequency ablation of renal masses was also addressed. Topics discussed in bladder cancer included screening and surgical management. Dr. Donald Skinner received the Huggins Medal and he addressed the society on the management of invasive bladder cancer. Reviewed session topics in prostate cancer included neoadjuvant treatment paradigms, radiation treatment and adjuvant therapy in patients in whom primary treatment has failed. A state-of-the-art lecture addressed hereditary prostate cancer. The Society of Urologic Oncology meeting is unique in its multidisciplinary forum and focus on urological oncology. The meeting this year highlighted emerging trends, and the current state-of-the-art in kidney, bladder and prostate cancer. Additional focus was given to new molecular based diagnostic and therapeutic strategies for genitourinary malignancies.

Current status of establishing standards for lymphadenectomy in the treatment of bladder cancer

Pelvic lymph node dissection at the time of radical cystectomy is a crucial component of the surgical management of invasive bladder cancer. No established therapeutic or diagnostic guidelines regarding pelvic lymph node dissection are, however, currently available. We reviewed the past and contemporary literature to clarify the current role of pelvic lymph node dissection both as a staging modality as well as potential therapeutic intervention. The role of pelvic lymph node dissection has evolved over the past 60 years. Although the added benefits of radical cystectomy over simple cystectomy alone are accepted, an optimal template for pelvic lymph node dissection has not been established. Increasing evidence suggesting therapeutic and diagnostic benefits by extending the boundaries of lymphadenectomy or by increasing the number of nodes excised has been reported. Much of the recent literature, however, is based on retrospective studies, and is influenced by factors such as node count variability, inconsistencies in the quality of the surgery, and the biases in patient selection. Currently, the optimal boundaries of pelvic lymph node dissection and the minimum number of nodes to be pathologically examined remain undetermined. The diagnostic and therapeutic benefits obtained by extending the limits of lymphadenectomy are compelling but inconclusive. Establishing standards for pelvic lymph node dissection will not only increase the consistency of staging and improve the design and interpretation of clinical trials in invasive bladder cancer but also help to identify and optimize the therapeutic benefits of lymphadenectomy. Prospective, randomized trials will be needed to properly establish the extent of lymphadenectomy required to obtain such benefits.

Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer

The mainstay in the management of invasive bladder cancer continues to be radical cystectomy. With regard to improvement of quality of life, however, therapies that preserve the bladder are desirable. We investigated the use of intravesical PLK-1 small interfering RNA (siRNA) against bladder cancer. Patients with bladder cancers expressing high levels of PLK-1 have a poor prognosis compared with patients with low expression. Using siRNA/cationic liposomes, the expression of endogenous PLK-1 could be suppressed in bladder cancer cells in a time- and dose-dependent manner. As a consequence, PLK-1 functions were disrupted. Inhibition of bipolar spindle formation, accumulation of cyclin B1, reduced cell proliferation, and induction of apoptosis were observed. In order to determine the efficacy of the siRNA/liposomes in vivo, we established an orthotopic mouse model using a LUC-labeled bladder cancer cell line, UM-UC-3LUC. PLK-1 siRNA was successfully transfected into the cells, reduced PLK-1 expression, and prevented the growth of bladder cancer in this mouse model. This is the first demonstration, to our knowledge, of inhibition of cancer growth in the murine bladder by intravesical siRNA/cationic liposomes. We believe intravesical siRNA instillation against bladder cancer will be useful as a therapeutic tool.

Intravesical administration of small interfering RNA targeting PLK-1 successfully prevents the growth of bladder cancer

The mainstay in the management of invasive bladder cancer continues to be radical cystectomy. With regard to improvement of quality of life, however, therapies that preserve the bladder are desirable. We investigated the use of intravesical PLK-1 small interfering RNA (siRNA) against bladder cancer. Patients with bladder cancers expressing high levels of PLK-1 have a poor prognosis compared with patients with low expression. Using siRNA/cationic liposomes, the expression of endogenous PLK-1 could be suppressed in bladder cancer cells in a time- and dose-dependent manner. As a consequence, PLK-1 functions were disrupted. Inhibition of bipolar spindle formation, accumulation of cyclin B1, reduced cell proliferation, and induction of apoptosis were observed. In order to determine the efficacy of the siRNA/liposomes in vivo, we established an orthotopic mouse model using a LUC-labeled bladder cancer cell line, UM-UC-3(LUC). PLK-1 siRNA was successfully transfected into the cells, reduced PLK-1 expression, and prevented the growth of bladder cancer in this mouse model. This is the first demonstration, to our knowledge, of inhibition of cancer growth in the murine bladder by intravesical siRNA/cationic liposomes. We believe intravesical siRNA instillation against bladder cancer will be useful as a therapeutic tool.

Bladder-Sparing Treatment Modalities in the Management of Invasive Bladder Cancer

Bladder-Sparing Treatment Modalities in the Management of Invasive Bladder Cancer

Management of muscle invasive bladder cancer—British approaches to organ conservation

British groups have long favored a more conservative approach to the management of invasive bladder cancer. They have been involved in several randomized trials looking at the efficacy of these approaches and have also been leaders in the study of neoadjuvant chemotherapy. This article documents the concerns that linger over the efficacy and morbidity of cisplatin-based chemotherapy and describes a national trial investigating a potentially less morbid 5FU and mitomycin alternative.

Non-invasive management of invasive bladder cancer: lectures by professor William U. Shipley.

This report summarizes lectures by Professor William U. Shipley on the non-invasive management of invasive bladder cancer with chemoradiotherapy and transurethral resection, presented at the 60th Meeting of the International Lectureship, in the international lectureship program of the FPCR.

Organ Conservation in Invasive Bladder Cancer by Transurethral Resection, Chemotherapy and Radiation: Results of a Urodynamic and Quality of Life Study on Long-term Survivors

Transurethral resection, chemotherapy and radiation with salvage cystectomy may be used as alternatives to immediate radical cystectomy in the management of invasive bladder cancer. Concern exists about the function of the retained bladder after such therapy. Of 221 patients with clinical T2-4a bladder cancer treated at Massachusetts General Hospital from 1986 to 2000 with trimodality therapy, 71 were alive with native bladders and disease-free in 2001. These patients were asked to undergo a urodynamic study and to complete a quality of life questionnaire. A total of 69% participated in some component of this study with a median time from trimodality therapy of 6.3 years (range 1.6 to 14.9). Of 32 patients 24 had normally functioning bladders by urodynamic study. Decreased bladder compliance was seen in 7. Bladder hypersensitivity, involuntary detrusor contractions and incontinence were present in 2 women. The questionnaire showed that flow symptoms occurred in 6%, urgency in 15% and control problems in 19%. Of all women 11% wore pads. Distress from urinary symptoms was half as common as prevalence. Bowel symptoms occurred in 22% with 14% recording any level of distress. The majority of men retained sexual function. Global health related quality of life was high. The majority of patients treated with trimodality therapy retain good bladder function. A fifth have evidence of bowel dysfunction.