Michael S. Cookson

The treated natural history of high risk superficial bladder cancer: 15- year outcome

PURPOSE The long-term outcome of patients with high risk superficial bladder cancer is unknown. We report the results of 15 years of followup of high risk patients treated initially with aggressive local therapy, including transurethral resection alone or combined with intravesical bacillus Calmette-Guerin. MATERIALS AND METHODS Between 1978 and 1981, 86 high risk patients enrolled in a randomized study of transurethral resection alone or with intravesical bacillus Calmette-Guerin for superficial bladder cancer. Of these patients 81% had diffuse carcinoma in situ and 44% had stage T1 tumors before entry into the study. Patients were followed until death (61%) or until the present time (median followup 184 months). RESULTS Disease stage progressed in 46 patients (53%) and 31 (36%) eventually underwent cystectomy for progression (28) or refractory carcinoma in situ (3), while 18 (21%) had upper tract tumors at a median of 7.3 years. The 10 and 15-year disease specific survival rates were 70 and 63%, respectively. At 15 years 34% of patients overall were dead of bladder cancer, 27% were dead of other causes and 37% were alive, including 27% with an intact functioning bladder. CONCLUSIONS Despite aggressive local therapy patients with high risk superficial bladder cancer are at lifelong risk for development of stage progression and upper tract tumors. A third of patients are at risk for death from bladder cancer, justifying careful and vigilant long-term followup. These results support the use of initial aggressive local therapy in patients with high risk superficial bladder cancer.

ANALYSIS OF EARLY COMPLICATIONS AFTER RADICAL CYSTECTOMY: RESULTS OF A COLLABORATIVE CARE PATHWAY

PURPOSE We examined our recent series of patients who underwent radical cystectomy to determine and analyze the early perioperative morbidity of the procedure in a contemporary series treated with the guidance of a clinical pathway. MATERIALS AND METHODS We reviewed the records of 304 consecutive patients who underwent radical cystectomy from December 1995 to July 2000. We specifically evaluated complications that developed within 30 days of the procedure. Potential variables predictive of early morbidity were analyzed, including patient age, gender, race, American Society of Anesthesiologists score, type of urinary diversion, smoking history, estimated blood loss, transfusion requirement, pathological stage and operative time. RESULTS The overall minor complication rate was 30.9% (94 of 304 patients). Postoperative ileus was the most common minor complication, affecting 54 patients (18%). Increased blood loss and major complications predicted a significantly higher likelihood of ileus on multivariate analysis (p = 0.02 and 0.001, respectively). Major complications in 15 patients (4.9%) correlated with higher American Society of Anesthesiologists score, surgical intensive care unit admission and transfusion requirement (p = 0.01, <0.001 and 0.001, respectively). The early mortality rate was 0.3% (1 patient). CONCLUSIONS Within the framework of a clinical pathway, radical cystectomy can be performed safely with an acceptable rate of early minor and major complications. Delay in the return of bowel function is the most common minor complication. Increased estimated blood loss, transfusion requirement and a major complication predicted a higher likelihood of postoperative ileus. The acceptable rate of early morbidity in this series in a 5-year period validates its use in patients undergoing radical cystectomy.

Incidence and clinical significance of false-negative sextant prostate biopsies

PURPOSE Since most patients do not undergo repeat sextant prostate biopsies after a biopsy is positive for prostate cancer, the true incidence of false-negative biopsies is not well defined. We assess the incidence and clinical significance of false-negative sextant prostate biopsies in patients undergoing radical prostatectomy. MATERIALS AND METHODS A total of 118 patients with biopsy proved prostate cancer underwent repeat sextant prostate biopsy before enrollment in a prospective randomized trial of radical prostatectomy with or without neoadjuvant hormonal therapy. Clinical parameters were assessed to determine potential sources of bias. Pathological parameters and prostate specific antigen relapse-free survival rates were compared to determine the clinical significance of false-negative biopsies. RESULTS Of the 118 patients 27 (23%) had a negative repeat sextant biopsy. Except for initial clinical stage, no differences were noted in the clinical or pathological parameters, or prostate specific antigen relapse rates in patients with negative versus positive repeat biopsies. CONCLUSIONS Our findings suggest that this 23% incidence of false-negative biopsies represents significant cancer. This relatively high incidence is important to consider in treatment modalities in which prostate biopsy may be performed to determine response to therapy.

Postoperative nomogram predicting risk of recurrence after radical cystectomy for bladder cancer

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.

Randomized Prospective Evaluation of Extended Versus Limited Lymph Node Dissection in Patients With Clinically Localized Prostate Cancer

PURPOSE The low rate of pelvic node metastasis in most contemporary series of patients undergoing radical prostatectomy for carcinoma of the prostate has been attributed to earlier and better patient selection than historical series. Alternatively, it has been suggested that the limited dissection commonly performed misses nodal metastasis in a substantial number of patients. To assess the value of an extended node dissection in detecting nodal metastasis, we performed a randomized prospective study. MATERIALS AND METHODS A total of 123 patients undergoing radical prostatectomy were randomized to an extended node dissection on the right versus the left side of the pelvis with the other side being a limited dissection. The extended dissection included removal of all external iliac nodes to a point above the bifurcation of the common iliac artery, the obturator nodes and the presacral nodes. The limited dissection included only the nodes along the external iliac vein and obturator nerve. RESULTS Mean patient age was 61 years. Clinical stage was T1c in 88 patients (72%), T2a in 26 (21%), T2b in 7 (6%) and T3 in 2 (1%). Mean preoperative prostate specific antigen was 7.4 ng./ml. Pelvic lymph node metastasis was histologically confirmed in 8 patients (6.5%). Positive nodes were found on the side of the extended dissection in 4 patients, on the side of the limited dissection in 3 and on both sides in 1. Complications possibly attributable to the node dissection included lymphocele in 4 patients, lower extremity edema in 5, deep venous thrombosis in 2, ureteral injury in 1 and pelvic abscess in 1. These complications occurred 3 times more often on the side of the extended dissection (p = 0.08). CONCLUSIONS Extended node dissection in contemporary series of patients undergoing radical prostatectomy identifies few with nodal metastases not found by a more limited dissection. A trend toward an increased risk of complications attributable to the lymphadenectomy occurs with an extended dissection.

Clinical under staging of high risk nonmuscle invasive urothelial carcinoma treated with radical cystectomy.

PURPOSE The role of radical cystectomy in patients with nonmuscle invasive urothelial carcinoma of the bladder remains controversial. The risk of overtreatment must be balanced against the potential benefit of aggressive therapy. We reviewed our results in these patients with a particular emphasis on clinical under staging. MATERIALS AND METHODS We reviewed the records of 214 consecutive patients who underwent radical cystectomy for urothelial carcinoma between April 1995 and August 1999, focusing on those with nonmuscle invasive, stages T1 or less disease. We assessed clinical and pathological data as well as outcomes based on pathological disease extent. RESULTS A total of 78 patients (36%) underwent radical cystectomy for clinical stages T1 or less disease. Indications included disease refractory to intravesical therapy in 29 cases (37%), pathological findings reflective of high grade stage T1 or multifocal disease in 26 (33%), radiographic suspicion of invasive disease in 15 (20%) and severe symptoms in 8 (10%). Cancer was clinically under staged with stages pT2 or greater disease in 31 patients (40%) according to final pathology results. Under staging was most pronounced in the 10 patients (67%) with suspicious radiography and in the 18 (64%) with absent muscle in the biopsy specimen. Of the 78 patients with pathological stages pT1 disease or less 98% had no evidence of disease compared to 65% with stages pT2 or greater disease (p <0.01). CONCLUSIONS Despite the intent to perform early cystectomy a significant percent of patients harbored occult muscle invasive and/or metastatic disease. In clinical and pathological, superficial stages T1 or less cases disease-free survival was excellent. Due to these results, the selection of high risk superficial transitional cell carcinoma cases for continued bladder sparing treatment should include uninvolved muscle on biopsy and absent radiographic suspicion of invasion.

Correlation between Gleason score of needle biopsy and radical prostatectomy specimen: accuracy and clinical implications.

PURPOSE Despite the reliability of Gleason grading with respect to the same specimen, the correlation between the biopsy and prostatectomy specimen is less well defined. We compared the accuracy of Gleason grading of biopsies in predicting histological grading of radical retropublic prostatectomy specimens. MATERIAL AND METHODS Gleason scores of 18 gauge needle biopsies were compared to those of radical retropublic prostatectomy specimens in 226 consecutive patients. In addition to comparing numeric discrepancies, differences between biopsy and specimen Gleason scores of 2 or more and a change in group from Gleason scores 2 to 4, 5 to 7 or 8 to 10 were evaluated by kappa testing, as well as any change in group from Gleason scores 2 to 4, 5 and 6, 7 and 8 to 10. RESULTS The biopsy score was identical to the specimen score in 31% of cases, while 26% were discrepant by 2 or more Gleason scores. Overall, 54% of biopsies were under graded, while 15% were over graded. If only cases in which discrepancies of 2 or more Gleason scores and a change in group were considered, there was good overall agreement (kappa 0.468, accuracy 80%). Among the cases with any change in group, the accuracy was only 46% with poor agreement (kappa 0.153). CONCLUSIONS Overall, the reliability of Gleason grading of needle biopsies in predicting final pathology was good. However, the limitations of Gleason grading based on biopsy should be considered when discussing treatment options and comparing results based on biopsy data.

ICUD-EAU International Consultation on Bladder Cancer 2012: Radical Cystectomy and Bladder Preservation for Muscle-Invasive Urothelial Carcinoma of the Bladder

CONTEXT New guidelines of the International Consultation on Urological Diseases for the treatment of muscle-invasive bladder cancer (MIBC) have recently been published. OBJECTIVE To provide a comprehensive overview of the current role of radical cystectomy (RC) in MIBC. EVIDENCE ACQUISITION A detailed Medline analysis was performed for original articles addressing the role of RC with regard to indication, timing, surgical extent, perioperative morbidity, oncologic outcome, and follow-up. The analysis also included radiation-based bladder-preserving strategies. EVIDENCE SYNTHESIS The major findings are presented in an evidence-based fashion and are based on large retrospective unicenter and multicenter series with some prospective data. CONCLUSIONS Open RC is the standard treatment for locoregional control of MIBC. Delay of RC is associated with reduced cancer-specific survival. In males, standard RC includes the removal of the bladder, prostate, seminal vesicles, and distal ureters; in females, RC includes an anterior pelvic exenteration including the bladder, entire urethra and adjacent vagina, uterus, and distal ureters. A procedure sparing the urethra and the urethra-supplying autonomous nerves can be performed in case of a planned orthotopic neobladder. Further technical variations (ie, seminal-sparing or vaginal-sparing techniques) aimed at improving functional outcomes must be weighed against the risk of a positive margin. Laparoscopic surgery is promising, but long-term data are required prior to accepting it as an option equivalent to the open procedure. Lymphadenectomy should remove all lymphatic tissue around the common iliac, external iliac, internal iliac, and obturator region bilaterally. Complications after RC should be reported according to the modified Clavien grading system. In selected patients with MIBC, bladder-preserving therapy with cystectomy reserved for tumor recurrence represents a safe and effective alternative to immediate RC.

Health Related Quality of Life Assessment After Radical Cystectomy: Comparison of Ileal Conduit with Continent Orthotopic Neobladder

PURPOSE Health related quality of life after urinary diversion has been increasingly recognized as an important outcome measure. However, few studies have directly compared patients with an ileal conduit with those with a continent orthotopic neobladder and even fewer have used validated quality of life instruments. Therefore, we compared health related quality of life in patients who underwent neobladder versus ileal conduit creation using validated questionnaires. MATERIALS AND METHODS We mailed 2 validated questionnaires that are measures of health related quality of life, namely the RAND 36-Item Health Survey (SF-36) and Functional Assessment of Cancer Therapy-General (FACT-G), to patients who underwent radical cystectomy for urothelial carcinoma between January 1995 and December 1999. Statistical analysis was performed, including univariate and multivariate analysis. RESULTS A total of 112 patients were available for assessment. A total of 72 (64%) questionnaires were returned, including 23 (32%) and 49 (68%) from patients with an ileal conduit and neobladder, respectively. On the SF-36 questionnaire there were significant univariable relationships between treatment and age (p <0.001 and 0.01, respectively). Younger patients and those with a neobladder had higher health related quality of life scores, including significant differences in 5 of the 9 SF-36 domains (general health, physical functioning, physical health, social functioning and energy/fatigue). There was no relationship between health related quality of life and the final pathological stage (p = 0.25). On multivariate analysis adjusting for age led to a suggestive but nonsignificant difference in health related quality of life scores favoring neobladders (p = 0.09). On the FACT-G there were no significant differences in health related quality of life due to treatment (p = 0.28), pathological stage (p = 0.5), age (p = 0.72) or current disease status (p = 0.27). On the FACT-G 2 of the 4 domains (emotional and functional well-being) were significantly in favor of neobladders. Overall satisfaction was high in the 2 groups with 96% and 85% of patients with a neobladder and ileal conduit, respectively, reporting that they would make the same choice of diversion. CONCLUSIONS Based on validated health related quality of life instruments these findings suggest that patients with an orthotopic neobladder have marginal quality of life advantages over those with an ileal conduit. However, differences in health related quality of life in the 2 types of urinary diversion are confounded by age since patients who underwent orthotopic diversion were younger and as a result of age would be expected to have a higher health related quality of life score. A prospective longitudinal study of health related quality of life after adjusting for differences in age among patients undergoing urinary diversion is currently underway to extend further these observations.

Incidence and Location of Prostate and Urothelial Carcinoma in Prostates From Cystoprostatectomies: Implications for Possible Apical Sparing Surgery

PURPOSE Prostatic carcinoma (Pca) at cystoprostatectomy is usually an incidental finding with the majority thought to be clinically insignificant. Most studies have not specifically addressed the location of Pca or the incidence and location of in situ or invasive urothelial carcinoma (Uca) in prostates of cystoprostatectomy specimens. The frequency of involvement of the apex with these processes has clinical implications. Specifically urinary continence following orthotopic diversion may be enhanced by prostate apical sparing. In this study the pathological features of Pca and Uca, and the frequency of apical involvement were investigated in prostates from cystoprostatectomy specimens. MATERIALS AND METHODS Whole mounted prostates from 121 consecutive cystoprostatectomy specimens were analyzed. Pca location, tumor volume, grade, stage, surgical margin and pelvic lymph node status of Pcas were assessed. Clinically insignificant Pcas had a volume of less than 0.5 cc without Gleason pattern 4, extracapsular extension, seminal vesicle invasion, lymph node involvement or positive surgical margins. Prostate involvement by Uca or urothelial carcinoma in situ (CIS)/severe dysplasia and its location were assessed. RESULTS Of 121 prostates 50 (41%) had unsuspected Pca, of which 24 (48%) were clinically significant. Of Pcas 30 of 50 (60%) involved the apex, including 19 of 24 (79%) that were significant and 11 of 26 (42%) that were insignificant. Of 121 prostates 58 (48%) had Uca involving the prostatic stroma, noninvasive Uca or urothelial CIS/severe dysplasia in the prostatic urethra or periurethral ducts, of which 19 (33%) had apical involvement. Overall only 32 of 121 patients (26%) had no Pca or prostate Uca/CIS and only 45 (37%) had no clinically significant Pca or Uca/CIS in the prostate. However, 74 of the 121 patients (61%) had no prostatic apical involvement by Pca or Uca/CIS and 85 (70%) had no apical involvement by clinically significant Pca or Uca/CIS. Patients with prostatic apical involvement by invasive or in situ Uca uniformly had involvement of more proximal (toward the base) portions of the prostate. CONCLUSIONS The majority of prostates from cystoprostatectomies had no involvement of the prostatic apex by Uca or clinically significant Pca. Hence, most patients may be candidates for prostate apical sparing. However, involvement of the apex by Uca in any patient raises concern about procedures that leave portions of the prostate urethra after cystectomy in an effort to improve continence. In candidates for orthotopic neobladder reconstruction removing all of the prostatic urethra and sparing the remainder of the prostatic apex may allow improved preservation of urinary continence with an acceptable low risk of clinical Pca progression. Whether future strategies for preoperative exclusion of apical Pca and intraoperative assessment of more proximal prostate to help exclude apical urothelial disease may identify patients suitable for prostatic apical sparing remains to be determined. The impact on functional outcomes and cancer control also require additional study.