Impact of previous radiotherapy for prostate cancer on clinical outcomes of patients with bladder cancer.

PURPOSE: The impact of prostate cancer radiotherapy on the biological behavior of bladder cancer remains unclear. We compared the outcomes of patients with bladder cancer previously treated for prostate cancer with radiotherapy vs other treatment modalities. MATERIALS AND METHODS: We identified 144 patients diagnosed with bladder cancer between January 1992 and June 2007 with a previous prostate cancer diagnosis. Clinicopathological data and outcomes were compared between patients with irradiated (brachytherapy and/or external beam radiation therapy 83) and nonirradiated (androgen deprivation therapy, radical prostatectomy and/or surveillance 61) disease. RESULTS: Median time between prostate and bladder cancer diagnoses was longer in the irradiated vs nonirradiated group (59 months, IQR 25 to 88, vs 24 months, IQR 2 to 87, p = 0.007). Patients in the irradiated group presented with higher tumor grade (high 92% vs 77%, p = 0.016) and had progression to higher stage disease (muscle invasive 70% vs 43%, p = 0.001) than those in the nonirradiated group. Of the patients undergoing cystectomy those previously treated with radiation had a numerically higher rate of nonorgan confined disease (75% vs 56% for nonirradiated, p = 0.1). Among all patients with bladder cancer 5-year cancer specific survival was 73% (95% CI 59-87) for irradiated vs 83% (95% CI 71-95) for nonirradiated (p = 0.07). Median followup was 53 months (IQR 24 to 75). CONCLUSIONS: More time elapsed between prostate and bladder cancer diagnoses for patients treated with radiation, and these patients also presented with more advanced disease. Future studies are needed to further establish clinical differences in bladder cancer between irradiated and nonirradiated cases, and whether biological differences exist.

Comprehensive standardized report of complications of retropubic and laparoscopic radical prostatectomy.

BACKGROUND: The lack of standardized reporting of the complications of radical prostatectomy in the literature has made it difficult to compare incidences across institutions and across different surgical approaches. OBJECTIVE: To define comprehensively the incidence, severity, and timing of onset of medical and surgical complications of open retropubic prostatectomy (RP) and laparoscopic radical prostatectomy (LP) using a standardized reporting methodology to facilitate comparison. DESIGN, SETTING, AND PARTICIPANTS: Between January 1999 and June 2007, 4592 consecutive patients underwent RP or LP without prior radiation or hormonal therapy. Median follow-up was 36.9 mo (interquartile range: 20.3-60.6). INTERVENTION: Open or laparoscopic radical prostatectomy. MEASUREMENTS: All medical and surgical complications of radical prostatectomy were captured and graded according to the modified Clavien classification and classified by timing of onset. RESULTS AND LIMITATIONS: There were 612 medical complications in 467 patients (10.2%) and 1426 surgical complications in 925 patients (20.1%). The overall incidences of early minor and major medical and surgical complications for RP were 8.5% and 1.5% for medical and 11.4% and 4.9% for surgical complications, respectively. The overall incidences of early minor and major medical and surgical complications for LP were 14.2% and 2.3% for medical and 23.1% and 6.6% for surgical complications, respectively. On multivariate analysis, LP approach was associated with a higher incidence of any grade medical and surgical complications but a lower incidence of major surgical complications than RP. Six hundred fifty-two men (14.2%) visited the emergency department, and 240 men (5.2%) required readmission. The main limitation is the retrospective nature. CONCLUSIONS: With standardized reporting, the incidence of some complications is higher than recognized in the literature. Although most complications are minor in severity, medical and surgical complications are observed in approximately 10% and 20% of patients, respectively. Accurate reporting of complications through a standardized methodology is essential for counseling patients regarding risk of complications, for identifying modifiable risk factors, and for facilitating comparison across institutions and approaches.

Biochemical recurrence rate in patients with positive surgical margins at radical prostatectomy with further negative resected tissue.

OBJECTIVE: To determine the biochemical recurrence (BCR) rate in patients with positive surgical margins (PSMs) on the prostate specimen who have additional negative tissue resected from that site (M+ -), compared to patients with negative margins (M-) and those with persistent PSM (M+), as those with PSM at radical prostatectomy (RP) are at greater risk of BCR, and in some instances where suspicious tissue is noted in the prostate bed or when frozen-section analysis shows PSM, additional tissue is resected from the suspect site of the PSM. PATIENTS AND METHODS: Between January 1999 and June 2007, 4217 consecutive patients underwent open or laparoscopic RP with no previous radiotherapy or hormonal therapy. The median (interquartile range) follow-up was 37.4 (21.1-60.7) months. RESULTS: Pathological organ-confined (OC) cancer was present in 2901 men, of whom 2659 had M-, 216 had M+, and 26 had M+-. Extracapsular extension (ECE) alone with no seminal vesicle or lymph node involvement was present in 843 men, of whom 657 had M-, 174 had M+ and 12 had M+-. For patients with OC cancer, the 36-month actuarial BCR-free probability was 97.9% (95% confidence interval 97.3-98.5) for M-, vs 89.0 (84.1-93.9)% for M+ vs 100% for M+-. For patients with ECE, the 36-month actuarial BCR-free probability was 83.7 (80.0-87.4)% for M- vs 73.7 (66.1-81.3)% for M+ vs 90.0 (71.4-100)% for M+-. The main limitation of the study was its retrospective nature, with the reason for resection of additional tissue not always well documented. CONCLUSIONS: While the few patients with PSMs and further negative resected tissue limited the statistical analysis, it would appear that in these patients the disease behaves as in those with negative margins.

Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology.

BACKGROUND: Reporting methodology is highly variable and nonstandardized, yet surgical outcomes are utilized in clinical trial design and evaluation of healthcare provider performance. OBJECTIVE: We sought to define the type, incidence, and severity of early postoperative morbidities following radical cystectomy (RC) using a standardized reporting methodology. DESIGN, SETTING, AND PARTICIPANTS: Between 1995 and 2005, 1142 consecutive RCs were entered into a prospective complication database and retrospectively reviewed for accuracy. All patients underwent RC/urinary diversion by high-volume fellowship-trained urologic oncologists. MEASUREMENTS: All complications within 90 d of surgery were analyzed and graded according to the Memorial Sloan-Kettering Cancer Center complication grading system. Complications were defined and stratified into 11 specific categories. Univariate and multivariate regression models were used to define predictors of complications. RESULTS AND LIMITATIONS: Sixty-four percent (735/1142) of patients experienced a complication within 90 d of surgery. Among patients experiencing a complication, 67% experienced a complication during the operative hospital admission and 58% following discharge. Overall, the highest grade of complication was grade 0 in 36% (n=407), grade 1-2 in 51% (n=582), and grade 3-5 in 13% (n=153). Gastrointestinal complications were most common (29%), followed by infectious complications (25%) and wound-related complications (15%). The 30-d mortality rate was 1.5%. CONCLUSIONS: Surgical morbidity following RC is significant and, when strict reporting guidelines are incorporated, higher than previously published. Accurate reporting of postoperative complications after RC is essential for counseling patients, combined modality treatment planning, clinical trial design, and assessment of surgical success.

Pathological upgrading and up staging with immediate repeat biopsy in patients eligible for active surveillance.

PURPOSE: Active surveillance with selective delayed intervention is a treatment regimen used in patients with low risk prostate cancer. Decision making is based on pretreatment prostate specific antigen, clinical stage and prostate biopsy results. We reviewed our experience with immediate repeat biopsy in patients eligible for active surveillance with selective delayed intervention. MATERIALS AND METHODS: A retrospective review was done of the records of consecutive patients who underwent repeat biopsy within 3 months of a first positive biopsy from March 2002 to June 2007. Patients were considered eligible if they had prostate specific antigen less than 10 ng/ml, clinical stage T2a or less, Gleason pattern 3 or less, 3 or fewer positive cores and no single core with 50% or greater cancer involvement. RESULTS: A total of 104 patients met eligibility criteria. Of the 104 repeat biopsies performed 27 (26%) were negative, 59 (57%) had a Gleason score of 6 or less and 17 (16%) had a Gleason score of 7. One patient had a Gleason score of 9, while 10 of 104 (10%) had greater than 3 cores involved on repeat biopsy and 12 (12%) had 50% or greater involvement of at least 1 core. Of 104 cases (27%) 28 were upgraded and/or up staged. Treated cases that were upgraded and/or up staged were more likely to show higher pathological stage and grade at radical prostatectomy than those that were not (p = 0.003 and p = 0.001, respectively). CONCLUSIONS: Immediate repeat biopsy in cases of active surveillance with selective delayed intervention resulted in 27% being upgraded or up staged and those were more likely to show higher grade and stage disease at radical prostatectomy. We recommend repeat biopsy because it improved our discrimination of who are the best candidates for active surveillance with selective delayed intervention.

An analysis of the effect of statin use on the efficacy of bacillus calmette-guerin treatment for transitional cell carcinoma of the bladder.

PURPOSE: Bacillus Calmette-Guerin is an effective immunotherapy for carcinoma in situ of the bladder and it reduces recurrence from resected papillary transitional cell carcinoma of the bladder. Many patients receiving bacillus Calmette-Guerin therapy are concurrently taking statin agents, which have known immunomodulatory properties and may alter the performance of bacillus Calmette-Guerin. Some data have suggested that patients taking a statin while on bacillus Calmette-Guerin therapy experience reduced clinical efficacy. MATERIALS AND METHODS: We conducted a retrospective review of 952 consecutive patients from 1978 through 2006. Time to recurrence and progression to surgery were compared between those taking and those not taking a statin by Kaplan-Meier methods and multivariable Cox regression controlling for stage and grade. RESULTS: There were 245 (26%) patients taking a statin before bacillus Calmette-Guerin therapy and 707 not on statin therapy (74%). A total of 796 patients had recurrence overall with 214 in the statin group and 582 in the other group. Median time to recurrence was similar between those who did and those who did not use a statin. On multivariable analysis statin use was not significantly associated with recurrence (hazard ratio 1.04; 95% CI 0.81, 1.34; p = 0.7) or progression to surgery (hazard ratio 0.77; 95% CI 0.52, 1.13; p = 0.17) after bacillus Calmette-Guerin therapy. CONCLUSIONS: This retrospective study in a large cohort of patients showed no statistically significant association between statin use and recurrence or progression to open surgery in patients treated with bacillus Calmette-Guerin for transitional cell carcinoma of the bladder. Based on these data patients should not be discouraged from taking statins while undergoing bacillus Calmette-Guerin treatment.

Multicenter, randomized, controlled trial of virtual-reality simulator training in acquisition of competency in colonoscopy.

BACKGROUND: The GI Mentor is a virtual reality simulator that uses force feedback technology to create a realistic training experience. OBJECTIVE: To define the benefit of training on the GI Mentor on competency acquisition in colonoscopy. DESIGN: Randomized, controlled, blinded, multicenter trial. SETTING: Academic medical centers with accredited gastroenterology training programs. PATIENTS: First-year GI fellows. INTERVENTIONS: Subjects were randomized to receive 10 hours of unsupervised training on the GI Mentor or no simulator experience during the first 8 weeks of fellowship. After this period, both groups began performing real colonoscopies. The first 200 colonoscopies performed by each fellow were graded by proctors to measure technical and cognitive success, and patient comfort level during the procedure. MAIN OUTCOME MEASUREMENTS: A mixed-effects model comparison between the 2 groups of objective and subjective competency scores and patient discomfort in the performance of real colonoscopies over time. RESULTS: Forty-five fellows were randomized from 16 hospitals over 2 years. Fellows in the simulator group had significantly higher objective competency rates during the first 100 cases. A mixed-effects model demonstrated a higher objective competence overall in the simulator group (P < .0001), with the difference between groups being significantly greater during the first 80 cases performed. The median number of cases needed to reach 90% competency was 160 in both groups. The patient comfort level was similar. CONCLUSIONS: Fellows who underwent GI Mentor training performed significantly better during the early phase of real colonoscopy training.

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.

Efficacy and costs of a one-day hands-on EASIE endoscopy simulator train-the-trainer workshop.

BACKGROUND: The efficacy of an intensive hands-on training in endoscopic hemostasis on the compactEASIE simulator has been previously demonstrated in a randomized prospective trial. In the current study, we evaluated how quickly and effectively new tutors, without simulator training experience, are able to acquire teaching skills in endoscopic hemostasis. METHODS: Five tutors with prior Erlangen Active Simulator for Interventional Endoscopy (EASIE) teaching experience instructed 7 endoscopists without prior EASIE experience on how to teach when using the model. These new tutors then independently conducted a workshop for 8 fellows in 4 hemostasis techniques. Results were compared with a historical control trained similarly by experienced tutors. Two one-day workshops in endoscopic hemostasis on the compactEASIE ex vivo endoscopy simulator were conducted in a category A hospital in New York City, New York. Skill scores at the end of training were compared with baseline skills assessments, and qualitative ratings of the new tutors were obtained from both the trainees and the experienced tutors. RESULTS: Significant improvement was achieved by the fellows in all 4 skills areas. Both the expert tutors and the trainees consistently rated the teaching skill of the new tutors highly. Fellows' skill acquisition using new tutors was of similar magnitude to that achieved in the prior EASIE trial using experienced trainers teaching the fellows. CONCLUSIONS: It is feasible to conduct an effective EASIE train-the-trainer course in one day. Tutors trained in this manner are able to provide a similar educational experience with objective improvement in trainee skill to experts who have conducted many hands-on workshops.