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Background and Objectives: Previous studies have shown that variability in surgical technique can affect the outcomes of cooperative group trials. We analyzed measures of surgical quality and clinical outcomes in patients enrolled in the p53-MVAC trial. Methods: We performed a post-hoc analysis of patients with pT1-T2N0M0 urothelial carcinoma of the bladder following radical cystectomy (RC) and bilateral pelvic and iliac lymphadenectomy (LND). Measures of surgical quality were examined for associations with time to recurrence (TTR) and overall survival (OS). Results: We reviewed operative and/or pathology reports for 440 patients from 35 sites. We found that only 31% of patients met all suggested trial eligibility criteria of having15 lymph nodes identified in the pathologic specimen (LN#) and having undergone both extended and presacral LND. There was no association between extent of LND, LN#, or presacral LND and TTR or OS after adjustment for confounders and multiple testing. Conclusions: We demonstrated that there was substantial variability in surgical technique within a cooperative group trial. Despite explicit entry criteria, many patients did not undergo per-protocol LNDs. While outcomes were not apparently affected, it is nonetheless evident that careful attention to study design and quality monitoring will be critical to successful future trials. J. Surg. Oncol. fl 2015 Wiley Periodicals, Inc.

Background: Sensitivity of standard urine cytology for detecting urothelial carcinoma of the bladder (UCB) is low, attributable largely to its inability to process entire samples, paucicellularity and presence of background cells. Objective: Evaluate performance and practical applicability of a novel portable microfiltration device for capture, enumeration and characterisation of exfoliated tumour cells in urine, and compare it with standard urine cytology for UCB detection. Methods: A total of 54 urine and bladder wash samples from patients undergoing surveillance for UCB were prospectively evaluated by standard and microfilter-based urine cytology. Head-to-head comparison of quality and performance metrics, and cost effectiveness was conducted for both methodologies. Results: Five samples were paucicellular by standard cytology; no samples processed by microfilter cytology were paucicellular. Standard cytology had 33.3% more samples with background cells that limited evaluation (p < 0.001). Microfilter cytology was more concordant (κ = 50.4%) than standard cytology (κ = 33.5%) with true UCB diagnosis. Sensitivity, specificity and accuracy were higher for microfilter cytology compared to standard cytology (53.3%/100%/79.2% versus 40%/95.8%/69.9%, respectively). Microfilter-captured cells were amenable to downstream on-chip molecular analyses. A 40 ml sample was processed in under 4 min by microfilter cytology compared to 5.5 min by standard cytology. Median microfilter cytology processing and set-up costs were approximately 63% cheaper and 80 times lower than standard cytology, respectively. Conclusions: The microfiltration device represents a novel non-invasive UCB detection system that is economical, rapid, versatile and has potentially better quality and performance metrics than routine urine cytology, the current standard-of-care.

In light of the aging population and the high incidence of urologic malignancies in the elderly in the United States, we review issues surrounding radical urologic surgery in the elderly. Specifically, we examine the safety, efficacy, techniques, and special concerns related to elderly patients. We found in multiple series that well selected, elderly patients can safely undergo major, extirpative urologic surgery with acceptable morbidity, comparable to their younger counterparts. Tools, such as the ASA score, Karnofsky index, and Charlson index may help guide patient selection and counseling.

Lymph node metastasis in patients who undergo radical cystectomy for bladder transitional cell carcinoma is considered a poor prognostic factor. However, patients with minimal lymph node involvement likely have a better outcome than those with extensive disease. We examined outcomes in patients with low volume lymph node metastasis and identified variables associated with disease recurrence.Our institution maintains a database of 1,600 patients with bladder transitional carcinoma who underwent radical cystectomy from 1971 to 2005 with intent to cure. All patients with low volume lymph node metastasis, defined as 1 or 2 positive lymph nodes, without concomitant distant metastasis were included in study.A total of 181 patients were identified. Median followup was 12.8 years, during which 96 patients experienced recurrence. Estimated 5 and 10-year recurrence-free survival was 43.8% and 40.9%, respectively. Multivariate analysis indicated that pathological stage/subgroup (RR 1.733, p = 0.015), lymph node density (RR 1.935, p = 0.014) and adjuvant chemotherapy (RR 0.538, p = 0.004) were significant independent predictors of recurrence-free survival.A considerable proportion of patients with low volume lymph node metastasis in our cohort remained free of recurrence during followup. Extravesical tumor extension and lymph node density greater than 4% were associated with a higher recurrence risk and adjuvant chemotherapy was associated with a lower risk. Although some patients with low volume lymph node metastasis may be cured by surgery alone, these data support adjuvant chemotherapy in these patients.

Purpose The standard treatment of high-grade, invasive bladder cancer is radical cystectomy. Prostate-sparing techniques have recently become an alternative surgical approach for the treatment of the disease. We review the literature regarding the oncologic and functional outcomes for prostate-sparing approaches. Materials and methods The literature pertaining to prostate-sparing cystectomy was reviewed. The oncologic issues of preserving the prostate in patients undergoing cystectomy for bladder cancer along with the functional outcomes were evaluated. Results There is a significant incidence of bladder and prostate cancer involving the prostate, and prostate apex in men requiring cystectomy for transitional cell carcinoma of the bladder at the time of surgery. This involvement of the prostate with cancer maybe difficult to determine preoperatively. Importantly, although prostate-sparing procedures provide good potency results, the functional outcomes following cystectomy and orthotopic diversion to the urethra are not significantly different, particularly regarding daytime continence. Lastly, several studies suggest the oncologic outcomes following prostate-sparing cystectomy may be compromised with this surgical approach. Conclusions The significant incidence of bladder and prostate cancer involving the prostate at the time of cystectomy, which is difficult to determine preoperatively, may preclude the general application of prostate-sparing techniques in most men requiring cystectomy. Concerns regarding the oncologic outcomes with prostate-sparing techniques, coupled with the excellent results seen with traditional radical cystectomy and orthotopic diversion, suggest that prostate-sparing procedure should be performed only in well-selected individuals.

To describe the tolerability of two chemotherapy regimens, gemcitabine and cisplatin (GC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) for adjuvant treatment of patients with locally advanced urothelial cancer after radical cystectomy. The USC Department of Urology bladder cancer database was searched for subjects who received adjuvant chemotherapy following cystectomy for transitional cell carcinoma with extravesical and/or lymph node involvement, yielding 187 cases. Clinical details regarding toxicity, number of cycles administered, and cancer outcome were analyzed. The majority of subjects had lymph node involvement (70%). Sixty-eight percent of subjects received MVAC and 32% received GC, the latter regimen was predominant after 2000. Fifty-six percent of subjects received all four planned cycles (51% GC and 58% MVAC). With a median follow-up of 11.2 years (range 1.9–19.6), 96 patients (51%) have suffered a relapse, with no significant difference between chemotherapy regimens. Median time to recurrence for the population was 3.7 years and median overall survival is 4.6 years (3.0–9.3). The median time from recurrence to death was 6.7 months and was not significantly different between MVAC and GC. Both MVAC and GC are tolerated after cystectomy for advanced urothelial carcinoma. A significant proportion of high-risk patients survive, free of disease, beyond 10 years. At recurrence, patients previously treated with adjuvant chemotherapy have a survival that appears much shorter than patients who develop metastases in the absence of this exposure, suggesting resistance to salvage chemotherapy.

Invasive T1 bladder cancers are potentially lethal tumours with varying degrees of aggressiveness and progression. The management of invasive tumours can be very difficult and includes bladder-sparing with transurethral resection and intravesical therapy, or a more aggressive approach with radical cystectomy. Certain clinical and pathological factors might provide some risk stratification for invasive T1 tumours, and might better direct the physician towards an earlier cystectomy for some patients. This review provides a rationale for a radical cystectomy in patients with high-risk, invasive T1 bladder cancer.

Radical cystectomy and lymphadenectomy is a standard treatment for patients with high-grade, invasive bladder cancer. Although the absolute limits of lymphadectomy at the time of surgery have not been precisely defined, there is a growing body of evidence to suggest that an extended lymph node dissection may be beneficial for staging and survival in both node-negative and -positive bladder cancer patients. For lymph node-positive patients, several prognostic factors have been identified to provide risk stratification and direct the need for adjuvant treatment. These include: the pathological stage of the bladder tumor, extent of the lymphadenectomy and nodal tumor burden. The concept of lymph node density has also been identified as a prognostic factor. The literature and data on the extent of lymphadenectomy will be reviewed as well as the current prognostic variables and the benefits of adjuvant chemotherapy.

Purpose The p53 gene status (mutation) and protein alterations (nuclear accumulation detectable by immunohistochemistry; p53 protein status) are associated with bladder cancer progression. Substantial discordance is documented between the p53 protein and gene status, yet no studies have examined the relationship between the gene-protein status and clinical outcome. This study evaluated the clinical relationship of the p53 gene and protein statuses. Materials and Methods The complete coding region of the p53 gene was queried using DNA from paraffin-embedded tissues and employing a p53 gene–sequencing chip. We compared p53 gene status, mutation site, and protein status with time to recurrence. Results The p53 gene and protein statuses show significant concordance, yet 35% of cases showed discordance. Exon 5 mutations demonstrated a wild-type protein status in 18 of 22 samples. Both the p53 gene and protein statuses were significantly associated with stage and clinical outcome. Specific mutation sites were associated with clinical outcome; tumors with exon 5 mutations showed the same outcome as those with the wild-type gene. Combining the p53 gene and protein statuses stratifies patients into three distinct groups, based on recurrence-free intervals: patients showing the best outcome (wild-type gene and unaltered protein), an intermediate outcome (either a mutated gene or an altered protein) and the worst outcome (a mutated gene and an altered protein). Conclusion We show that evaluation of both the p53 gene and protein statuses provides information in assessing the clinical recurrence risk in bladder cancer and that the specific mutation site may be important in assessing recurrence risk. These findings may substantially impact the assessment of p53 alterations and the management of bladder cancer.

Purpose of review Radical cystectomy with an appropriate lymph node dissection and an appropriate form of urinary diversion is the standard treatment for muscle-invasive transitional cell carcinoma of the bladder. Optimal outcomes following radical cystectomy require an extended lymph node dissection, negative surgical margins, and a continent urinary diversion. There has been an increasing number of reports describing initial experiences with laparoscopic radical cystectomy. Recent findings Intermediate and long-term oncologic outcomes with laparoscopic radical cystectomy remain undefined, and appropriate lymph node dissections laparoscopically have not been uniformly performed. Furthermore, the long-term functional outcomes associated with laparoscopically performed urinary diversions also remain undefined. There appears to be a recent trend toward performing the urinary diversion portion of the procedure extracorporeally, after laparoscopic removal of the bladder. Some studies suggest a decrease in postoperative analgesic requirements and quicker recovery of bowel function in those undergoing laparoscopic radical cystectomy, but these observations have not been corroborated by others. Summary In the absence of long-term functional and oncologic outcome data, laparoscopic radical cystectomy should be considered an investigative technique, and potential candidates for this operation should be appropriately counseled.

The role of regional lymph node dissection (LND) in surgical management of high-grade, invasive transitional cell carcinoma of the bladder has evolved over the past several decades. The current concepts and rationale for LND in patients undergoing radical cystectomy for bladder cancer are reviewed and discussed. Evidence suggests that a more extended LND (with cephalad extent to include at least the common iliac vessels) for lymph node-positive and -negative patients undergoing radical cystectomy for bladder cancer may provide therapeutic benefits in addition to prognostic information. Lymph node density also provides risk stratification for lymph node-positive patients and may reduce the surgical bias and extent of the LND, both of which are currently not standardized. Although the absolute limits of the LND remain to be determined, an evolving body of data supports a more extended LND at the time of cystectomy in appropriate surgical candidates.

In the second section of a two-part article, the recent literature is reviewed and the management of nonmuscle-invasive transitional cell carcinoma of the bladder is discussed. Particular attention is given to the indications and timing of intravesical chemotherapy and immunotherapy and the differences in efficacy and side-effect profiles of the available agents. The indications and role of second-look transurethral resection are reviewed. Additionally, the role of bacillus Calmette-Guerin in the management of this disease in terms of definitive treatment and maintenance therapy is discussed. We also offer a review of the literature regarding therapies for bacillus Calmette-Guerin-refractory nonmuscle-invasive transitional cell carcinoma of the bladder and their current place in practice.

Background: Radical cystectomy is the standard treatment for muscle invasive bladder cancer, however the role and appropriate extent of an associated lymphadenectomy continues to change. Methods: We performed a detailed review of the medical literature pertaining to the development and rationale for an extended lymphadenectomy in patients undergoing radical cystectomy. Results: A perspective of lymphadenectomy and an anatomic account of bladder lymphatic drainage are presented. The technique of an extended lymphadenectomy is also highlighted. Autoptic contemporary clinical data are presented to suggest that a more extensive lymphadenectomy has both prognostic and therapeutic utility. Furthermore, the stage of the primary bladder tumor, total number of lymph nodes removed, and the lymph node tumor burden are shown to be important prognostic variables in patients undergoing cystectomy with pathologic evidence of lymph node metastasis. Conclusions: Radical cystectomy provides excellent local cancer control with the Lowe’s pelvic recurrence rates and the best long-term survival. Radical cystectomy with an appropriate extended lymphadenectomy, while surgically more challenging, does not significantly increase the morbidity or mortality of the procedure. The limits of lymph node dissection are still subject to dabate and there is growing evidence that an extended lymphadenectomy provides further diagnostic and therapeutic benefit.

Radical cystectomy is the gold standard for treatment of localized invasive bladder cancer in the United States. In recent years, there has been increasing focus on the importance of surgical technique as a factor that may influence the clinical and oncologic outcome of the operation, beyond the classically recognized patient and tumor-related factors. There is still insufficient high-quality evidence to support the absolute standardization of the surgical technique or the establishment of firm benchmarks by which the individual surgeon can measure performance. However, there is considerable evidence suggesting that 3 aspects of surgical technique have an impact on outcome: (1) Positive surgical margins nearly always result in ultimate cancer death. The rate of positive margins varies with surgeon experience as well as with cancer-specific variables. (2) The extent of lymphadenectomy has a significant impact on recurrence rates of the cancer, regardless of whether the lymph nodes are pathologically positive or not. (3) Higher volume surgeons have lower operative mortality and fewer positive surgical margins than low-volume surgeons. Higher volume hospitals also have lower operative mortalities and shorter hospital stays for patients who have undergone radical cystectomy. In this review, the authors evaluate the evidence supporting each of these statements and suggest potential areas of standardization of surgical technique that could translate into improved patient outcomes.

Previous studies have shown that variability in surgical technique can affect the outcomes of cooperative group trials. We analyzed measures of surgical quality and clinical outcomes in patients enrolled in the p53-MVAC trial.We performed a post-hoc analysis of patients with pT1-T2N0M0 urothelial carcinoma of the bladder following radical cystectomy (RC) and bilateral pelvic and iliac lymphadenectomy (LND). Measures of surgical quality were examined for associations with time to recurrence (TTR) and overall survival (OS).We reviewed operative and/or pathology reports for 440 patients from 35 sites. We found that only 31% of patients met all suggested trial eligibility criteria of having ≥15 lymph nodes identified in the pathologic specimen (LN#) and having undergone both extended and presacral LND. There was no association between extent of LND, LN#, or presacral LND and TTR or OS after adjustment for confounders and multiple testing.We demonstrated that there was substantial variability in surgical technique within a cooperative group trial. Despite explicit entry criteria, many patients did not undergo per-protocol LNDs. While outcomes were not apparently affected, it is nonetheless evident that careful attention to study design and quality monitoring will be critical to successful future trials.

We review our 20-year experience with salvage radical prostatectomy to determine prognostic variables predictive of oncological control of radiorecurrent prostate cancer. Using a standardized questionnaire we also evaluate outcome data regarding the long-term sexual and urinary effects of salvage radical prostatectomy.Between 1983 and 2002 salvage radical prostatectomy was performed in 51 patients with locally recurrent prostate cancer following definitive radiotherapy. Clinical information was obtained from a prospective database. Quality of life data were collected using the UCLA Prostate Cancer Index, a validated, patient administered instrument.At 5 years 47% of patients were progression-free without androgen deprivation therapy. Among patients with pT2 disease 100% were progression-free at 5 years, compared with 35% of patients with pT3N0 disease or higher and 0% of patients with node positive (pTxN+) disease (p0.001). Preoperative PSA 5.0 ng/ml or less was predictive of organ confined disease, and strongly associated with prolonged progression-free and overall survival (p0.001 and 0.01, respectively). Mean urinary function scores for patients with or without an artificial urinary sphincter compared favorably with scores reported after standard, nonsalvage prostatectomy. Sexual dysfunction was nearly uniform in patients undergoing standard salvage radical prostatectomy but implantation of a penile prosthesis was associated with a clinically significant improvement in sexual function.When initiated early in the course of recurrent disease, salvage radical prostatectomy provides excellent oncological control of radiorecurrent prostate cancer without the need for androgen ablation. Implantation of an artificial urinary sphincter and inflatable penile prosthesis devices in patients with postoperative urinary incontinence or erectile dysfunction results in significantly improved quality of life parameters.

Purpose Radical cystectomy and pelvic lymphadenectomy (PLND) remains the standard treatment for localized and regionally advanced invasive bladder cancers. We have constructed an international bladder cancer database from centers of excellence in the management of bladder cancer consisting of patients treated with radical cystectomy and PLND. The goal of this study was the development of a prognostic outcomes nomogram to predict the 5-year disease recurrence risk after radical cystectomy. Patients and Methods Institutional radical cystectomy databases containing detailed information on bladder cancer patients were obtained from 12 centers of excellence worldwide. Data were collected on more than 9,000 postoperative patients and combined into a relational database formatted with patient characteristics, pathologic details of the pre- and postcystectomy specimens, and recurrence and survival status. Patients with available information for all selected study criteria were included in the formation of the final prognostic nomogram designed to predict 5-year progression-free probability. Results The final nomogram included information on patient age, sex, time from diagnosis to surgery, pathologic tumor stage and grade, tumor histologic subtype, and regional lymph node status. The predictive accuracy of the constructed international nomogram (concordance index, 0.75) was significantly better than standard American Joint Committee on Cancer TNM (concordance index, 0.68; P < .001) or standard pathologic subgroupings (concordance index, 0.62; P < .001). Conclusion We have developed an international bladder cancer nomogram predicting recurrence risk after radical cystectomy for bladder cancer. The nomogram outperformed prognostic models that use standard pathologic subgroupings and should improve our ability to provide accurate risk assessments to patients after the surgical management of bladder cancer.

Purpose The role of a regional lymphadenectomy in the surgical treatment of high-grade, invasive transitional cell carcinoma of the bladder has evolved over the last several decades. Although the application of a lymphadenectomy for bladder cancer is not significantly debated, the absolute extent or level of proximal dissection of the lymphadenectomy remains a controversial issue. Material and Methods A review of the literature should help elucidate the rationale and extent of an appropriate lymphadenectomy in patients undergoing radical cystectomy for bladder cancer. Various surgical issues of lymphadenectomy as well as prognostic factors in patients undergoing radical cystectomy for bladder cancer are examined. Results A growing body of evidence, spanning from early autopsy and cadaveric studies to recent retrospective series and multicenter prospective trials, suggests that an extended lymph node dissection (cephalad extent to include the common iliac arteries) may provide not only prognostic information but also provide a therapeutic benefit for both patients with lymph node-positive and lymph node-negative disease undergoing radical cystectomy for bladder cancer. Although the absolute boundaries of the lymphadenectomy remain a subject of controversy, historical reports confirmed by recent lymphatic mapping studies suggest the inclusion of the common iliac as well as possibly presacral nodes in the routine lymphadenectomy for transitional cell carcinoma of the bladder. The need to extend the dissection higher to include the distal para-aortic and paracaval lymph nodes may be important in select individuals but remains more controversial. The extent of the primary bladder tumor (p-stage), number of lymph nodes removed, the lymph node tumor burden (tumor volume), and lymph node density (number of lymph nodes involved/number of lymph nodes removed) are all important prognostic variables in patients undergoing cystectomy with pathologic evidence of lymph node metastases. Systemic adjuvant chemotherapy remains a mainstay of treatment of patients with lymph node metastases. Conclusions Radical cystectomy with an appropriately performed lymphadenectomy provides the best survival outcomes and lowest local recurrence rates. Although the absolute limits of the lymph node dissection remain to be determined, evidence supports a more extended lymphadenectomy to include the common iliac vessels and presacral lymph nodes at cystectomy in patients who are appropriate surgical candidates. When feasible, adjuvant chemotherapy is warranted in patients with positive nodal metastasis.

Purpose: Vascular endothelial growth factor has a critical role in maintaining tumor microvasculature and, as such, is an attractive target for anti-angiogenic therapy. Aberrant expression of VEGF receptors, especially VEGFR2, on epithelial tumor cells allows VEGF to stimulate growth and migration of tumor cells in an autocrine and/or paracrine manner. Therefore, we studied the expression of VEGF and VEGFR2 in bladder cancer, and the relationship to disease characteristics.Materials and Methods: Expression of VEGF and VEGFR2 was studied in a cohort of 72 patients with transitional cell cancer of the bladder. Tumor tissues from all patients were analyzed by immunohistochemistry and examined by a pathologist blinded to patient outcome. Patient demographics and disease outcome were correlated with expression of these markers. Bladder cancer cell lines that express VEGFR2 were studied in vitro and in vivo to establish the significance of VEGF/VEGFR2 signaling.Results: Expression of VEGF and VEGFR2 was observe...

Radical cystectomy with an appropriate lymphadenectomy remains the standard of therapy for high-grade invasive bladder cancer. This surgical approach provides the best survival rates with the lowest local recurrence rates and orthotopic diversion can be performed safely in most patients with an acceptable outcome and quality of life. Pathologic analysis of the bladder tumor and regional lymph nodes will help direct the need for adjuvant therapy in high-risk individuals. Equivalent long-term local control and survival are not seen with other forms of treatment including radiation therapy, chemotherapy, or a combination of the two. The rationale and clinical results of large, contemporary cystectomy series are presented, which provide a benchmark of outcomes with this form of surgical treatment.

We sought to evaluate the biological function of the receptor tyrosine kinase EphB4 in bladder cancer. All of the nine bladder cancer cell lines examined express EphB4 and the receptor could be phosphorylated following stimulation with its cognate ligand, EphrinB2. Out of the 15 fresh bladder cancer specimens examined, 14 expressed EphB4 with a mean sevenfold higher level of expression compared to adjacent normal urothelium. EphB4 expression was regulated by several mechanisms: EPHB4 gene locus was amplified in 27% tumor specimens and 33% cell lines studied; inhibition of EGFR signaling downregulated EphB4 levels; and forced expression of wild-type p53 reduced EphB4 expression. EphB4 knockdown using specific siRNA and antisense oligodeoxynucleotides molecules led to a profound inhibition in cell viability associated with apoptosis via activation of caspase-8 pathway and downregulation of antiapoptotic factor, bcl-xl. Furthermore, EphB4 knockdown significantly inhibited tumor cell migration and invasion. EphB4 knockdown in an in vivo murine tumor xenograft model led to a nearly 80% reduction in tumor volume associated with reduced tumor proliferation, increased apoptosis and reduced tumor microvasculature. EphB4 is thus a potential candidate as a predictor of disease outcome in bladder cancer and as target for novel therapy.

Although pure testicular seminoma is most often confined to the testis, it can present with advanced-stage bulky retroperitoneal metastases in nearly a quarter of cases. While highly treatable with cisplatin-based chemotherapy, up to 80% of patients with advanced disease are found to have a radiographically detectable residual mass after chemotherapy. The management of these postchemotherapy residual masses remains controversial. Surgical resection is technically challenging due to a desmoplastic reaction resulting from seminoma treatment and regression. In addition, these residual masses often demonstrate a protracted period of regression that can span several months to years. Surveillance protocols, therefore, may be appropriate for most patients. Several retrospective studies have supported surgical resection only for discrete, well-delineated masses over 3 cm in size. Despite the highly radiosensitive nature of seminoma, radiation therapy in this setting has not been shown to provide significant benefit, and may limit the tolerability of subsequent salvage chemotherapy. The incorporation of noninvasive imaging modalities, such as positron emission tomography, into the management algorithm may better delineate the presence of viable residual tumor and thus allow better risk stratification.

Objectives To evaluate the incidence of bacille Calmette-Guerin (BCG)-contracted bladders and attempt to ascertain the potential risk factors for this severe complication. BCG is the most effective intravesical agent for the treatment of high-grade, noninvasive transitional cell carcinoma (TCC) of the bladder. Widely used by urologists for the management of superficial TCC, adverse effects are not uncommon. These adverse effects are most commonly limited to irritative voiding symptoms, hematuria, and fever; however, severe adverse effects may occur. Methods We retrospectively reviewed two cystectomy databases (University of Southern California/Norris Cancer Center and University of Miami Miller School of Medicine) and identified patients who underwent cystectomy and orthotopic neobladder reconstruction for BCG-induced bladder contracture. Results We identified 1 case each in the two institutions’ cystectomy databases of severely contracted bladders. The overall incidence of this complication leading to cystectomy was 0.05% and 0.3% at each institution. Both patients were salvaged with cystoprostatectomy and orthotopic reconstruction with an ileal neobladder. Neither patient had residual cancer at pathologic analysis of the cystectomy specimen, and both patients’ severe lower urinary tract symptoms were alleviated postoperatively. Conclusions A contracted bladder due to extravasation of BCG, although rare, is a serious complication. Cystoprostatectomy with orthotopic neobladder reconstruction may be the optimal solution to alleviate severe lower urinary tract symptoms and remove the risk of subsequent urothelial malignancy.

A laudable trend in urologic surgical oncology is to minimize operative morbidity by anatomic and functional organ preservation without compromising radicality. An increasing number of authors have taken advantage of the sexual-function-preserving cystectomy for bladder cancer. The modified procedure includes cystectomy with sparing of prostate, vasa deferens, seminal vesicles, and resection of a prostatic adenoma to avoid bladder outlet obstruction and bladder reconstruction with an orthotopic reservoir. This article focuses on studies from the last 15 years and includes the results from 13 centers worldwide. Many of them report a pattern of failure (local versus distant) that is highly unusual. Although a local recurrence rate of 7 of 252 patients is to be expected in this combined series the distant failure rate of 34 of 252 patients is at least twice as high as expected for the given series of superficial or organ-confined TCC. The observed distant failure rate of sexuality-preserving cystectomy in this potentially lethal disease is more than 5% higher as compared with standard radical cystectomy. The precise underlying mechanism of this unexpected pattern of failure following sexuality-sparing cystectomy is not fully understood. Furthermore, surgeons considering procedures that preserve a portion of the prostatic urethra, the prostatic capsule, or the entire prostate should recognize a 6% risk of significant prostatic cancer in any residual tissue, and the potential risk of urethral tumor involvement with TCC. Daytime continence following radical versus sexuality-sparing cystectomy is identical. Data on nighttime continence of sexuality-sparing cystectomy are inconclusive. The continuous intermittent catheterization rate following sexuality-sparing cystectomy, however, seems to be higher than after standard cystectomy. The only advantage sexuality-preserving cystectomy has is indeed preservation of these functions in a much higher percentage than following standard or nerve-sparing cystectomy. This is at the cost of radicality, however, and results in a 10% to 15% higher oncologic failure rate. Consequently, sexuality-sparing cystectomy for bladder cancer is a step in the wrong direction and should be abandoned.

Radical cystectomy has become a standard and effective treatment for muscle-invasive bladder cancer, however, the role and appropriate extent of a concomitant lymphadenectomy continues to evolve. We performed a detailed review of the English medical literature pertaining to the historical development and rationale for an extended lymphadenectomy in patients undergoing radical cystectomy. An historical perspective of lymphadenectomy and an anatomic account of bladder lymphatic drainage are presented. The boundaries and technique of an extended lymphadenectomy are also highlighted. Autopsy and contemporary survival data are presented to suggest that a more extensive lymphadenectomy has both prognostic and therapeutic utility. Furthermore, the stage of the primary bladder tumor, total number of lymph nodes removed, and the lymph node tumor burden are shown to be important prognostic variables in patients undergoing cystectomy with pathologic evidence of lymph node metastasis. Radical cystectomy provides not only excellent local cancer control with low pelvic recurrence rates, but also the best long-term survival. Radical cystectomy with an appropriate extended lymphadenectomy, while surgically more challenging, does not significantly increase the morbidity or mortality of the procedure. Although the absolute limits of the lymph node dissection remain to be determined, there is an evolving body of data to support that an extended lymphadenectomy provides further diagnostic and therapeutic benefit.

BACKGROUND. The authors reported their experience with radical cystectomy for transitional cell carcinoma (TCC) of the bladder. They compared pathologic features and survival rates between older and younger patients. METHODS. The authors retrospectively reviewed the records of 1054 patients who underwent radical cystectomy for bladder TCC between 1971 and 1997. Four age groups were compared: < 60 years old at the time of cystectomy (n = 310), 60-69 years old (n = 381), 70-79 years old (n = 313), and ≥ 80 years old (n = 50). RESULTS. There were no significant differences in pathologic features among the groups regarding frequency of carcinoma in situ, high-grade disease, p53 status, and lymph node positivity. However, in the age groups < 60, 60-69, 70-79, and ≥ 80, 45%, 49%, 51%, and 72% of patients, respectively, had extravesical TCC (P=0.004). Significant differences also were seen in the proportion of patients who received adjuvant chemotherapy (26%, 26%, 15%, and 6%, respectively; P < 0.001). The 5-year overall survival rates for patients < 60, 60-69, 70-79, and a 80 years old were 72%, 58%, 54%, and 33%, respectively (P < 0.001). The 5-year disease recurrence-free survival rates were 75%, 65%, 68%, and 45%, respectively (P = 0.003). The elderly had a lower probability of receiving adjuvant chemotherapy. CONCLUSIONS. Elderly patients undergoing cystectomy for TCC had similar pathologic features (except for disease stage) as younger patients. In the current series, elderly patients undergoing cystectomy had a higher pathologic stage and were less likely to receive adjuvant chemotherapy. The elderly hade worse disease recurrence-free survival rates. Further work is needed to identify the causes for this and to develop strategies to improve cancer control in elderly patients.

We evaluated the role of CA 125 as a prognostic marker in patients with transitional cell carcinoma (TCC) of the bladder undergoing uniform radical cystectomy with bilateral pelvic iliac lymphadenectomy.From April 1996 to March 2001, 287 patients with a median age of 68 years (range 34 to 89) had preoperative CA 125 serum assays performed. All patients had high grade or invasive TCC and were scheduled to undergo radical cystectomy. Preoperative CA 125 was evaluated according to tumor grade and pathological subgroups (organ confined, extravesical and lymph node positive) as well as recurrence-free and overall survival.Of the 287 patients 31 (10.8%) demonstrated increased serum CA 125 (greater than 35 U/ml). No significant association was found between increased CA 125 and recurrence-free survival or tumor grade. However, a statistically significant association was found among pathological tumor subgroups, namely 4.9% for organ confined, 11.3% for extravesical and 21.6% for lymph node positive disease (p0.001). Furthermore, patients with lymph node positive disease or high grade tumors (grades III/IV and IV/IV) and increased CA 125 assays demonstrated significantly worse overall survival (p0.001).Increased CA 125 was seen in approximately 11% of patients with high grade or invasive TCC preoperatively. It was more commonly found in patients with locally advanced and lymph node positive disease, and it was associated with overall survival. However, recurrence-free survival was not associated with CA 125. Further studies are required to define the exact role of CA 125 in bladder cancer.

The aim of this review is to provide a contemporary outline of our current understanding of the molecular and genetic events associated with tumorigenesis and the progression of bladder cancer. A comprehensive review of the literature was performed on the molecular alterations associated with transitional cell carcinoma (TCC) of the bladder. Intense research efforts are being made to better identify and characterize various bladder cancers and their true biologic potential. The need to predict which superficial tumors will recur or progress, and which invasive tumors will metastasize has led to a much better understanding of the molecular pathways associated with bladder cancer. The molecular changes that occur in TCC of the bladder are numerous and can be categorized into: (1) chromosomal alterations leading to carcinogenesis, (2) loss of cell cycle regulation accounting for cellular proliferation, and (3) metastasis, guided by events such as angiogenesis. It is becoming apparent that the accumulation of genetic and molecular changes ultimately determines a tumors phenotype and subsequent clinical behavior. At the present time, conventional histopathologic evaluation of bladder cancer (tumor grade and stage) is inadequate to accurately predict the behavior of most bladder tumors. While new laboratory techniques have allowed us to better understand how bladder cancer develops and ultimately progresses, few of these techniques are currently available for use in the clinical setting. The ultimate goal is to develop reliable prognostic markers which will accurately predict not only the expected clinical course of an individual bladder tumor but also the response of that tumor to currently available therapies. More importantly, this information may be employed in the future to dictate altogether new treatments for the prevention and/or stabilization of the early molecular events that lead to the development of bladder cancer.

Bladder cancer continues to be one of the most common genitourinary malignancies. The mainstay of diagnosis remains cystoscopic visualization with transurethral biopsy or resection. As over two-thirds of bladder tumors recur, vigilant surveillance is required. Due to the invasiveness and expense of frequent cystoscopies and the lack of sensitivity of urinary cytology, especially for low-grade superficial lesions, novel molecular markers have been investigated as a means to detect bladder cancer noninvasively.As our understanding of the pathogenesis of urothelial neoplasia improves, coupled with recent advances in molecular biological techniques, an array of new approaches to the diagnosis of bladder cancer has emerged. Several urine-based markers have been tested against the standard of urinary cytology with promising results. However, lack of standardization of technique and heterogeneity of bladder cancer itself may hinder the widespread dissemination of these diagnostic aids.A host of new molecular markers based on the pathogenesis of bladder cancer have been investigated, such as telomerase, survivin, and multitarget fluorescence in situ hybridization, which may eventually improve detection and management of urothelial malignancies. By improving the sensitivity of urinary cytology for low-grade superficial lesions and detecting recurrent disease noninvasively early in its course, these new molecular markers might someday allow changes in the way bladder cancer is diagnosed and followed. At the present time, however, no single molecular marker provides 100% accuracy. Perhaps panels utilizing the most promising of these markers may alter bladder cancer detection and management policy.

Purpose: A serous lined extramural ileal flap valve technique called the T limb was developed to prevent reflux of urine in an orthotopic bladder substitute called the T pouch. We evaluate our intermediate clinical and functional experience with the orthotopic T pouch ileal neobladder. Materials and Methods: From November 1996 through May 2000, 209 patients (169 men [80%], 40 women), with a mean age of 69 years (range 33 to 93) underwent construction of an orthotopic T pouch ileal neobladder after cystectomy. The indication for cystectomy included bladder cancer in 198 patients (95%). Median followup for the entire cohort was 33 months (range 0 to 69). Data were analyzed according to perioperative mortality, early (within 3 months) and late diversion related and diversion unrelated complications, radiographic evaluation of the upper urinary tract and urinary reservoir, and determination of renal function. Results: Three patients (1.4%) died perioperatively. A total of 63 (30%) early complications occurred, 53 (25%) diversion unrelated and 10 (5%) diversion related. The most common early diversion unrelated complication was dehydration (10 patients). The most common early diversion related complication was urine leak in 6 patients. There were no early complications directly related to the antirefluxing T limb. Late complications occurred in 68 (32%) patients including 30 (14%) diversion unrelated and 38 (18%) diversion related. The most common late diversion unrelated complication was incisional hernia in 16 patients. Of the 38 late diversion related complications the most common were pouch calculi in 17 and ureteroileal obstruction in 9 patients. The only late complication directly related to the T limb was stenosis in 4 patients, 3 of whom received adjuvant pelvic radiation. A total of 181 patients had radiographic evaluation of the upper urinary tract including 162 (90%) with a normal radiographic study or evidence of postoperative decompression. An abnormal upper tract study was seen in 18 patients (10%) including 9 with ureteroileal obstruction and 4 with afferent T limb stenosis. Gravity cystography of the neobladder was normal in 143 of 158 (90%) evaluable patients. Reflux was seen in 15 patients (10%). Renal function as determined by serum creatinine was stable or improved in 96% of patients. Good daytime and nighttime continence was reported in 87% and 72% of evaluable patients, respectively. Overall 75% of patients complete void while 25% required some form of intermittent catheterization to empty the neobladder completely including 20% of men and 43% of women. Conclusions: With intermediate followup the functional results of the T pouch ileal neobladder are acceptable. The antirefluxing T limb provides unobstructed urinary flow in 95% and reflux prevention in 90% of patients. Although these results are encouraging, further followup is required to assess the long-term results of the T pouch ileal neobladder.

Transitional cell carcinoma (TCC) of the bladder that extends directly into contiguous organs (pT4) portends a poor prognosis. The 2002 American Joint Committee on Cancer staging system does not include seminal vesicle involvement by primary TCC of the bladder. In this analysis we evaluated the clinical outcomes and prognostic significance of seminal vesicle involvement with TCC of the bladder after radical cystectomy.From 1971 to 2001, 1,682 patients underwent radical cystectomy and pelvic lymphadenectomy for bladder cancer. Only those tumors that involved adjacent organs through the bladder wall (pT4) were included. Overall 132 male patients with a median age of 68 years (range 36 to 98) qualified for analysis. Patients were stratified into 4 subgroups of 1) direct extravesical prostatic stromal involvement only in 37 patients (28%), 2) prostatic stroma and seminal vesicle involvement in 37 patients (28%), 3) seminal vesicle involvement only in 10 patients (8%) and 4) other contiguous pelvic organ involvement (stage pT4b) in 48 patients (36%). Overall 88 patients (67%) received some form of adjuvant therapy. At a median followup of 12.5 years (range 0 to 15.2) clinical outcomes were analyzed including overall and recurrence-free survival using Kaplan-Meier plots.There was no significant difference in clinical outcomes or prognosis for groups 2 and 3, thus they were combined for analysis. Five-year overall survival for any seminal vesicle involvement (10%) was significantly worse than prostatic stromal involvement only (38%) but was similar to pT4b tumors (7%, p0.0001). The 5-year recurrence-free survival for seminal vesicle involvement (14%) was also significantly worse than prostatic stromal involvement alone (68%) but similar to that pT4b disease (25%, p = 0.01). Results were controlled for lymph node status.Patients with extravesical tumor extension into seminal vesicles and contiguous pelvic organs are at high risk for recurrence and progression. Involvement of the seminal vesicles by direct extension of bladder TCC portends a prognosis similar to that of pT4b disease and should, therefore, be classified as such.

Purpose To determine the combined effects of p53, p21, and pRb alterations in predicting the progression of bladder transitional cell carcinoma. Patients and Methods p53, p21, and pRb expression was examined immunohistochemically on archival radical cystectomy samples from 164 patients with invasive or high-grade recurrent superficial transitional cell carcinoma (TCC; lymph node–negative, 117 patients; lymph node–positive, 47 patients). Median follow-up was 8.6 years. Based on percentage of nuclear reactivity, p53 was considered as wild-type (0% to 10%) or altered (> 10%); p21 was scored as wild-type (>10%) or altered (< 10%); and pRb status was considered wild-type (1% to 50%) or altered (0% or > 50%). Results As individual determinants, the p53, p21, and pRb status were independent predictors of time to recurrence (P < .001, P < .001, and P < .001, respectively), and overall survival (P < .001, P = .002, and P = .001, respectively). By examining these determinants in combination, patients were categorized as group I (no alteration in any determinant, 47 patients), group II (any one determinant altered, 51 patients), group III (any two determinants altered, 42 patients), and group IV (all three determinants altered, 24 patients). The 5-year recurrence rates in these groups were 23%, 32%, 57%, and 93%, respectively (log-rank P < .001), and the 5-year survival rates were 70%, 58%, 33%, and 8%, respectively (log-rank P < .001). After stratifying by stage, the number of altered proteins remained significantly associated with time to recurrence and overall survival. Conclusion This study suggests that alterations in p53, p21, and pRb act in cooperative or synergistic ways to promote bladder cancer progression. Examining these determinants in combination provides additional information above the use of a single determinant alone.

We evaluated clinical outcomes in patients with pathological microscopic (pT3a) and gross (pT3b) extravesical tumor extension with transitional cell carcinoma (TCC) of the bladder following radical cystectomy.A total of 236 patients, including 173 males (73%) and 63 females, underwent radical cystectomy for pathological primary bladder TCC with extravesical extension (pT3), of whom 69 (29%) had pT3a and 167 (71%) had pT3b disease. At a median followup of 8.9 years (range 0 to 19.4) lymph node involvement, local and distant recurrences, and clinical outcomes were determined.Of the 236 patients with pT3 tumors 106 (45%) had lymph node positive disease, including 34 of 69 (49%) with pT3a and 72 of 167 (43%) with pT3b disease. The 10-year recurrence-free survival rate for patients with pT3a tumors was 48% compared with 47% for those with pT3b disease (p = 0.89). Recurrence-free survival was significantly better in patients with lymph node negative disease than in those with positive lymph nodes irrespective of the extent of extravesical involvement (pT3a vs pT3b). Local pelvic recurrence developed in 13 of the 236 patients (6%), while 84 (36%) had distant metastatic disease. Of the patients with recurrence, the type of recurrence (local or distant) was not associated with tumor stage (pT3a vs pT3b, p = 0.71). Lymph node involvement was a significant risk factor for distant tumor recurrence (p0.001).Differentiating between microscopic (pT3a) and gross (pT3b) extravesical tumor involvement of TCC as outlined in the revised 1997 TNM staging system does not appear to have prognostic significance.

Objectives To present our experience with four retroperitoneal schwannomas treated by surgical excision and review the current literature. Retroperitoneal schwannomas are rare, benign tumors and infrequently present to the urologist. Methods From 1997 through 2002, the charts of 164 patients with a diagnosis of benign retroperitoneal soft tissue mass were reviewed. Of those, four had a pathologic diagnosis of retroperitoneal schwannoma. Results Three of the 4 patients were women, with a median age of 54 years (range 46 to 80). The average tumor size was 13.7 cm (range 8.8 to 20). All patients underwent magnetic resonance imaging, computed tomography, or ultrasonography, and 3 of the 4 patients underwent a computed tomography-guided fine needle aspiration biopsy (all were either inaccurate or inconclusive). All patients underwent complete tumor excision with free margins of resection and tolerated surgery without any complications. None of the patients have had any evidence of recurrence at a mean follow-up of 26 months (range 10 to 48). Conclusions Retroperitoneal schwannomas are difficult to diagnose preoperatively. Computed tomography-guided fine needle aspiration biopsy does not appear to provide an accurate preoperative diagnosis. The surgical approach should focus on complete excision of the mass. Patients undergoing complete surgical resection tend to do well without evidence of early recurrence.

BACKGROUND The current TNM classification for bladder carcinoma stratifies extravesical extension into microscopic (pT3a) and macroscopic (pT3b) tumor involvement. The authors evaluated the outcomes of patients with pT3a and pT3b disease after radical cystectomy. METHODS Patients (n = 129) with transitional cell carcinoma of the bladder treated with radical cystectomy alone demonstrated pathologic extravesical tumor extension: 37 (29%) had pT3a disease and 92 (71%) had pT3b disease. No patient received any adjuvant therapy. With a median follow-up of 13.6 years, the presence of lymph node involvement, margin positivity, local (pelvic) and distant disease recurrence, and clinical outcomes were determined. RESULTS Of the 129 patients, 43 (33%) had lymph node tumor involvement: 13 of 37 patients with pT3a disease (35%) and 30 of 92 patients with pT3b disease (33%). The 10-year recurrence-free and overall survival for the entire group was 54% and 20%, respectively. No statistical difference between pT3a and pT3b disease was observed with regard to recurrence-free (P = 0.54) and overall (P = 0.66) survival. Lymph node involvement was predictive of a significantly worse 10-year recurrence-free survival (32%) compared with lymph node-negative disease (60%; P = 0.003). Local disease recurrence was reported to occur in 12 patients (9%), whereas 37 patients (29%) were reported to develop distant metastases. Among those who had disease recurrence, the type of disease recurrence (local or distant) was not found to be associated with tumor stage (pT3a vs, pT3b, P = 0.47). CONCLUSIONS This cohort of surgically managed patients provided insight into the long-term natural history of pathologically confirmed extravesical bladder carcinoma after radical cystectomy. There was no important difference in the incidence of lymph node involvement, survival rates, and disease recurrence rates between patients with microscopic and macroscopic extravesical extension. Adjuvant protocols should be undertaken for these high-risk patients to further improve on these clinical outcomes. Cancer 2003;98:955–61. © 2003 American Cancer Society. DOI 10.1002/cncr.11569

The flap-valve T mechanism in the T pouch provides an effective and reliable antireflux technique. The long-term results of the T pouch are yet to be determined; however, initial and early results have been excellent. This technique can be learned with a little experience. The T mechanism is a versatile flap-valve technique that can also be applied as a continent mechanism in a cutaneous reservoir (double T pouch). Reconstructive surgeons interested in lower urinary tract reconstruction should understand this concept and technique to broaden their surgical armamentarium.

Radical cystectomy remains the primary form of therapy for high-grade, invasive bladder cancer. Orthotopic substitution has become the ideal form of urinary diversion in appropriately selected women. Good functional results have been seen with intermediate follow-up in these women. Proper patient selection and surgical technique are critical to optimize the outcome in this group of patients.

Objective To compare the outcome between patients with pT3N0 adenocarcinoma of the prostate treated with radical prostatectomy (RP) and those receiving RP followed by a planned course of postoperative radiation therapy (RT). Patients and methods During a period of 22 years 622 patients with pT3N0 prostate cancer were treated in one medical centre by RP. Of these, 199 (32%) were treated with surgery alone while 423 (68%) received planned postoperative pelvic RT (median 48 Gy). Patients were selected for RT by having a higher incidence of adverse prognostic factors than those undergoing RP alone. These prognostic factors included pathological stage (P = 0.001) preoperative prostate specific antigen (PSA) level (P 25 ng/mL was predictive of DFS (P = 0.02). In a multivariate analysis the Gleason score was the most important predictor for overall survival and DFS (P 0.05 ng/mL). This compared with 13 (6.5%) patients with clinical recurrence, including seven (3.5%) with local recurrence and 23 (11.6%) with PSA > 0.05 ng/mL in the RP-alone group. Postoperative RT was well tolerated and did not add to the incidence of surgical complications. Conclusion We propose that postoperative RT, as described here, helped to reduce the incidence of local recurrence and improved DFS to equal that of a lower-risk group of patients treated with RP alone. A randomized comparison is needed to define the role of adjuvant RT in patients with pT3N0 disease.

PURPOSE: After proctocolectomy for ulcerative colitis or familial adenomatous polyposis, creation of a continent ileostomy is one of the surgical options. Although most patients will be offered a pull-through procedure, the continent ileostomy is a valuable alternative in patients who are either not candidates for or have failed an ileal pouch-anal anastomosis or who—for other reasons—prefer a permanent ileostomy. The traditional continent reservoirs (Kock or Barnett pouch) with an intussuscepted bowel segment as valve mechanism have an unsatisfactorily high incidence of dysfunction and frequent reoperations. The objective of this study was to adapt the T-pouch valve concept, previously used for urinary reservoirs, for a continent stool reservoir and to construct a valve mechanism that omits intussusception of the bowel and maintains the blood supply to the valve segment. METHODS: The technique for the critical valve construction is described in detail. It consists of isolating the terminal segment of the small bowel with its blood supply. The valve mechanism is created by embedding this segment in a serosa-lined tunnel of two apposed limbs of bowel that will form the pouch reservoir. RESULTS: Preliminary results in six patients indicate complete continence of the pouch. CONCLUSION: Although long-term results are not yet available, the new T-pouch concept is suitable as a continent stool reservoir and promises a significant improvement as compared with the traditional Kock pouch.

Objectives To investigate the association between lymphovascular invasion (LVI) and clinical outcome in organ-confined, node-negative urothelial cancer of the bladder (UCB) in a post hoc analysis of a prospective clinical trial. To explore the effect of adjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) on outcome in the subset of patients whose tumours exhibited LVI. Patients and Methods Surgical and tumour factors were extracted from the operative and pathology reports of 499 patients who had undergone radical cystectomy (RC) for pT1–T2 N0 UCB in the p53-MVAC trial (Southwest Oncology Group 4B951/NCT00005047). The presence or absence of LVI was determined by pathological examination of transurethral resection or RC specimens. Variables were examined in univariate and multivariate Cox proportional hazards models for associations with time to recurrence (TTR) and overall survival (OS). Results Among 499 patients with a median follow-up of 4.9 years, a subset of 102 (20%) had LVI-positive tumours. Of these, 34 patients had pT1 and 68 had pT2 disease. LVI was significantly associated with TTR with a hazard ratio (HR) of 1.78 [95% confidence interval (CI) 1.15–2.77; number of events (EV) 95; P = 0.01) and with OS with a HR of 2.02 (95% CI 1.31–3.11; EV 98; P = 0.001) after adjustment for pathological stage. Among 27 patients with LVI-positive tumours who were randomised to receive adjuvant chemotherapy, receiving MVAC was not significantly associated with TTR (HR 0.70, 95% CI 0.16–3.17; EV 7; P = 0.65) or with OS (HR 0.45, 95% CI 0.11–1.83; EV 9; P = 0.26). Conclusions Our post hoc analysis of the p53-MVAC trial revealed an association between LVI and shorter TTR and OS in patients with pT1–T2N0 disease. The analysis did not show a statistically significant benefit of adjuvant MVAC chemotherapy in patients with LVI, although a possible benefit was not excluded.

Radical cystectomy with urinary diversion remains the primary form of therapy for appropriate candidates with high-grade, invasive bladder cancer. Several important advances have been made in an attempt to improve the clinical and functional outcomes of patients following bladder removal. These technical advances primarily have involved improvements in lower urinary tract reconstruction, as well as enhancement of the continence mechanism and preservation of potency. Quality-of-life issues are clearly important factors and are becoming more important, as patients are living longer with higher expectations; however, must not override the need to provide sound oncologic surgical extirpation. Orthotopic lower urinary tract reconstruction to the intact native urethra has revolutionized urinary diversion following cystectomy in male7 and femaleI9 patients. The ultimate goal of lower urinary tract reconstruction has evolved from merely providing a means to divert the urine and protecting the upper urinary tract from significant damage over the patient’s lifespan. Current advantages of orthotopic diversion should allow patients to store urine and void in a nearly normal physiologic manner through the intact urethra. In an effort to provide patients a more normal lifestyle with an improved self-image, preservation of sexual function and potency has also gained increasing importance in the management of patients requiring bladder removal.