Purpose The frequency of febrile urinary tract infection was determined after outpatient flexible cystoscopy in antibiotic naïve patients with bladder tumor. Materials and Methods A total of 3,108 ...outpatient cystoscopies were performed in 1,110 patients with bladder tumor. Immediately before cystoscopy patients submitted a voided urine sample for culture. Significant bacteriuria was defined as greater than 104 cfu/ml of a single organism. Patients received no antibiotics immediately before or after cystoscopy. They were followed for 30 days for onset of febrile urinary tract infection. Results Of the 3,108 patient cystoscopies 673 (22%) had asymptomatic bacteriuria and 2,435 (78%) had sterile urine. A febrile urinary tract infection developed within 30 days of cystoscopy in 59 patients (1.9%), including in 3.7% of infected and 1.4% of uninfected patients (p = 0.01). All cases resolved within 12 to 24 hours with oral antibiotics. No patient was hospitalized for bacterial sepsis. Conclusions Antibacterial therapy before outpatient flexible cystoscopy does not appear necessary in patients who have no clinical signs or symptoms of acute urinary tract infection, including bacteriuria.
Open radical cystectomy (ORC) has proven to be an important component in the treatment of high-risk bladder cancer (BCa). ORC surgical morbidity remains high; therefore, minimally invasive surgical ...techniques have been introduced in an attempt to improve patient outcomes.
To compare cancer outcomes in BCa patients managed with ORC or robotic-assisted radical cystectomy (RARC).
A prospective, randomized trial was completed between 2010 and 2013. Patients were randomized to ORC/pelvic lymphadenectomy (PLND) or RARC/PLND, with all undergoing open/extracorporeal urinary diversion. Median follow-up was 4.9 (IQR: 3.9–5.9) yr after surgery among surviving patients.
Secondary outcomes to the trial included recurrence-free, cancer-specific, and overall survival.
The trial randomized 118 patients who underwent RC/PLND and urinary diversion. Sixty were randomized to RARC and 58 to ORC. Four RARC-assigned patients refused randomization and received ORC; however, an intention to treat analysis was performed. No differences were observed in recurrence (hazard ratio HR: 1.27; 95% confidence interval CI: 0.69–2.36; p=0.4) or cancer-specific survival (p=0.4). No difference in overall survival was observed (p=0.8). However, the pattern of first recurrence demonstrated a nonstatistically significant increase in metastatic sites for those undergoing ORC (sub-HR sHR: 2.21; 95% CI: 0.96–5.12; p=0.064) and a greater number of local/abdominal sites in the RARC-treated patients (sHR: 0.34; 95% CI: 0.12–0.93; p=0.035). The major limitation to this study is that the trial was not powered to determine differences in cancer recurrences, survival outcomes, or patterns of recurrence.
The secondary outcomes from our randomized trial did not definitively demonstrate differences in cancer outcomes in patients treated with ORC or RARC. However, differences in observed patterns of first recurrence highlight the need for future studies.
Of 118 patients randomly assigned to undergo radical cystectomy/pelvic lymphadenectomy and urinary diversion, half were assigned to open surgery and half to robot-assisted techniques. We found no difference in risk of recurring or dying of bladder cancer between the two groups.
In this secondary analysis of cancer outcomes from our randomized controlled trial, we did not find a difference in overall recurrence rates and cancer-specific survival between open radical cystectomy and robot-assisted radical cystectomy for high-risk bladder cancer. Variations in patterns of recurrence require further study.
Purpose We review how the bacillus Calmette-Guerin vaccine evolved to become standard therapy for superficial bladder cancer. Materials and Methods We reviewed the historical literature describing ...the origin of the bacillus Calmette-Guerin vaccine as an anticancer agent and its singular success as the most effective immunotherapy used against a human neoplasm. Results The association between tuberculosis and cancer, and the demonstration that bacillus Calmette-Guerin invoked immunological reactivity, inhibiting tumor growth in experimental animal models, led to clinical trials showing that intravesical bacillus Calmette-Guerin eradicated and prevented recurrence of superficial bladder tumors. Conclusions For the last 3 decades bacillus Calmette-Guerin therapy has remained the most effective local therapy for superficial bladder cancer, an outstanding example of successful translational medicine in urology.
Abstract Background Antimicrobial resistance is a major health problem, caused primarily by overuse of antibiotics in clinical situations in which they are not necessary. Practice guidelines ...recommend that antibiotics be given before outpatient cystoscopy to prevent symptomatic urinary tract infection (UTI). Objective To determine the frequency of febrile UTI after outpatient flexible cystoscopy in antibiotic-naive bladder tumor patients. Design, setting, and participants A total of 2010 consecutive outpatients with bladder tumors were entered into a prospective registry study. All patients underwent cystoscopy after they submitted a voided urine sample for culture. Significant bacteriuria was defined as >104 colony-forming units per milliliter with a single organism. Patients were stratified for known risk factors for UTI. Intervention Patients underwent flexible cystoscopy and received no antibiotics immediately before or after cystoscopy. They were followed for 30 d for onset of febrile UTI. Outcome measurements and statistical analysis The end point was incidence of febrile UTI within 30 d of cystoscopy. Febrile UTI was defined as temperature >38 °C and dysuria, or having received antibiotics from an outside physician for urinary symptoms. Results and limitations Of the 2010 patient cystoscopies, 489 (24%) had asymptomatic bacteriuria, and 1521 (76%) had sterile urine. Thirty-nine patients (1.9%) developed febrile UTI ≤30 d after cystoscopy—4.5% in colonized patients and 1.1% in uninfected patients ( p = 0.02). All UTIs resolved in ≤12–24 h with oral antibiotics. None of the patients was admitted for bacterial sepsis. Limitations of the study are that it is a single-surgeon experience in one institution, and results may not apply to other patient populations. Conclusions Antibacterial therapy before outpatient flexible cystoscopy does not appear necessary in bladder tumor patients who have no clinical signs or symptoms of acute UTI, including asymptomatic bacteriuria. Antibiotic stewardship is the responsibility of all urologists.
Abstract Background Open radical cystectomy (ORC) and urinary diversion in patients with bladder cancer (BCa) are associated with significant perioperative complication risk. Objective To compare ...perioperative complications between robot-assisted radical cystectomy (RARC) and ORC techniques. Design, setting, and participants A prospective randomized controlled trial was conducted during 2010 and 2013 in BCa patients scheduled for definitive treatment by radical cystectomy (RC), pelvic lymph node dissection (PLND), and urinary diversion. Patients were randomized to ORC/PLND or RARC/PLND, both with open urinary diversion. Patients were followed for 90 d postoperatively. Intervention Standard ORC or RARC with PLND; all urinary diversions were performed via an open approach. Outcome measurements and statistical analysis Primary outcomes were overall 90-d grade 2–5 complications defined by a modified Clavien system. Secondary outcomes included comparison of high-grade complications, estimated blood loss, operative time, pathologic outcomes, 3- and 6-mo patient-reported quality-of-life (QOL) outcomes, and total operative room and inpatient costs. Differences in binary outcomes were assessed with the chi-square test, with differences in continuous outcomes assessed by analysis of covariance with randomization group as covariate and, for QOL end points, baseline score. Results and limitations The trial enrolled 124 patients, of whom 118 were randomized and underwent RC/PLND. Sixty were randomized to RARC and 58 to ORC. At 90 d, grade 2–5 complications were observed in 62% and 66% of RARC and ORC patients, respectively (95% confidence interval for difference, −21% to −13%; p = 0.7). The similar rates of grade 2–5 complications at our mandated interim analysis met futility criteria; thus, early closure of the trial occurred. The RARC group had lower mean intraoperative blood loss ( p = 0.027) but significantly longer operative time than the ORC group ( p < 0.001). Pathologic variables including positive surgical margins and lymph node yields were similar. Mean hospital stay was 8 d in both arms (standard deviation, 3 and 5 d, respectively; p = 0.5). Three- and 6-mo QOL outcomes were similar between arms. Cost analysis demonstrated an advantage to ORC compared with RARC. A limitation is the setting at a single high-volume, referral center; our findings may not be generalizable to all settings. Conclusions This trial failed to identify a large advantage for robot-assisted techniques over standard open surgery for patients undergoing RC/PLND and urinary diversion. Similar 90-d complication rates, hospital stay, pathologic outcomes, and 3- and 6-mo QOL outcomes were observed regardless of surgical technique. Patient summary Of 118 patients with bladder cancer who underwent radical cystectomy, pelvic lymph node dissection, and urinary diversion, half were randomized to open surgery and half to robot-assisted laparoscopic surgery. We compared the rate of complications within 90 d after surgery for the open group versus the robotic group and found no significant difference between the two groups. Trial Registration ClinicalTrials.gov identifier NCT01076387 , www.clinicaltrials.gov.
Narrow-band imaging (NBI) cystoscopy detects more bladder tumors than standard white-light imaging (WLI) cystoscopy, but it is unclear whether NBI improves transurethral resection (TUR) of bladder ...tumors. This study compares 2-yr recurrence-free survival (RFS) of patients with non-muscle-invasive bladder tumors following restaging TUR using NBI or WLI cystoscopy. Patients were randomized 1:1 to undergo NBI-assisted TUR (NBI-TUR) or WLI-assisted TUR (WLI-TUR). The main outcome was number of patients free of tumor recurrence after 2-yr follow-up and 2-yr RFS times. Of 254 patients, 127 underwent NBI-TUR and 127 had WLI-TUR. Within 2 yr, 22% of the patients in the NBI-TUR group recurred compared with 33% after WLI-TUR (p=0.05). The mean RFS time was 22 mo (95% confidence interval CI, 20-23) for the NBI-TUR group versus 19 mo (95% CI, 18-21) for the WLI-TUR group (p=0.02). Limitations are that this was a single-surgeon study and that a 20% difference in the number of patients free of recurrence was not achieved, suggesting the study was underpowered. In addition, observer bias may have contributed to results because NBI-TUR was performed after both WLI and NBI cystoscopy was used to inspect the bladder. Although the results suggest reduced recurrence rates and improved RFS times after restaging NBI-TUR compared with WLI-TUR, a larger study is needed.
Narrow-band imaging enhances visibility of bladder tumors over conventional white-light cystoscopy. This report compares transurethral resection of bladder tumors using narrow-band cystoscopy with white-light cystoscopy. The results show that narrow-band cystoscopy improves surgical removal of bladder tumors, which reduces the frequency of early and later tumor recurrences.
Abstract Context Despite the effectiveness of bacillus Calmette-Guérin (BCG) therapy in non–muscle-invasive bladder cancer (NIMBC) to delay recurrence and disease progression, the evidence supporting ...maintenance treatment and its optimal duration is unkown. Objective The purposes of this paper are to critically review the evidence supporting the use of maintenance BCG after an initial series of induction instillations and to illustrate the factors contributing to current dilemmas in establishing the optimal duration of BCG treatment. Evidence acquisition The following terms were used in Medline database searches for original articles published before February 1, 2013: bladder cancer, urothelial cancer, bacillus Calmette-Guérin, maintenance , and induction. All randomized controlled trials and meta-analyses, including those based on indirect comparisons, were evaluated. Evidence synthesis Seven randomized studies compared induction BCG plus maintenance to induction alone, with or without retreatment with BCG on recurrence. All but one of these studies were underpowered and the largest study used a broad, composite end point: worsening-free survival. Seven meta-analyses have been conducted, three of which included data from observational cohort studies. They demonstrated the benefit of maintenance BCG to reduce disease recurrence and delay progression compared to various control groups; however, the analyses were based on suboptimal data. Although there is new evidence that 1 yr of maintenance BCG is sufficient treatment in intermediate-risk patients, the optimal duration of BCG maintenance remains unknown. A new randomized trial is proposed, which includes induction BCG with retreatment on recurrence as a control arm, to study this question. Conclusions The optimal duration of BCG treatment in patients with NMIBC remains unknown and should be the subject of further studies. We recommend that in addition to 3 yr of maintenance BCG, guideline panels also include 1 yr of therapy and induction BCG with retreatment on recurrence as a possible treatment options for patients with NMIBC, albeit with a lower level of evidence and grade of recommendation.
Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC). It is unknown whether this ...treatment strategy is appropriate for patients who progress to MIBC after treatment for prior noninvasive disease (secondary MIBC).
To determine whether clinical and genomic differences exist between primary and secondary MIBC treated with NAC and RC.
Clinicopathologic outcomes were compared between 245 patients with clinical T2-4aN0M0-stage primary MIBC and 43 with secondary MIBC treated with NAC and RC at Memorial Sloan Kettering Cancer Center (MSKCC) from 2001 to 2015. Genomic differences were assessed in a retrospective cohort of 385 prechemotherapy specimens sequenced by whole-exome or targeted exon capture by the Cancer Genome Atlas or at MSKCC. Findings were confirmed in an independent validation cohort of 94 MIBC patients undergoing prospective targeted exon sequencing at MSKCC.
Pathologic response rates, recurrence-free survival (RFS), bladder cancer-specific survival (CSS), and overall survival (OS) were measured. Differences in somatic genomic alteration rates were compared using Fisher's exact test and the Benjamini-Hochberg false discovery rate method.
Patients with secondary MIBC had lower pathologic response rates following NAC than those with primary MIBC (univariable: 26% vs 45%, multivariable: odds ratio=0.4 95% confidence interval=0.18−0.84 p=0.02) and significantly worse RFS, CSS, and OS. Patients with secondary MIBC treated with NAC had worse CSS compared with cystectomy alone (p=0.002). In a separate genomic analysis, we detected significantly more likely deleterious somatic ERCC2 missense mutations in primary MIBC tumors in both the discovery (10.9% 36/330 vs 1.8% 1/55, p=0.04) and the validation (15.7% 12/70 vs 0% 0/24, p=0.03) cohort.
Patients with secondary MIBC treated with NAC had worse clinical outcomes than similarly treated patients with primary MIBC. ERCC2 mutations predicted to result in increased cisplatin sensitivity were enriched in primary versus secondary MIBC. Prospective validation is still needed, but given the lack of clinical benefit with cisplatin-based NAC in patients with secondary MIBC, upfront RC or enrollment in clinical trials should be considered.
A retrospective cohort study of patients with “primary” and “secondary” muscle-invasive bladder cancer (MIBC) treated with chemotherapy before surgical removal of the bladder identified lower response rates and shorter survival in patients with secondary MIBC. Tumor genetic sequencing of separate discovery and validation cohorts revealed that chemotherapy-sensitizing DNA damage repair gene mutations occur predominantly in primary MIBC tumors and may underlie the greater sensitivity of primary MIBC to chemotherapy. Prospective validation is still needed, but patients with secondary MIBC may derive greater benefit from upfront surgery or enrollment in clinical trials rather than from standard chemotherapy.
Patients with secondary muscle-invasive bladder cancer (MIBC) treated with neoadjuvant chemotherapy had worse clinical outcomes than patients treated similarly with primary MIBC. These contrasting clinical outcomes may have resulted from differing rates of cisplatin-sensitizing ERCC2 mutations that were enriched in primary MIBC.
Radical cystectomy (RC) has the potential for profound changes to health-related quality of life (HRQOL).
To evaluate a broad range of HRQOL outcomes in a large RC cohort.
A single-center prospective ...study enrolled RC patients from 2008 to 2014. We collected 14 separate patient-reported outcome measures at the presurgical visit and at 3, 6, 12, 18, and 24 mo after RC.
To visualize the patterns of recovery over time across domains, we used generalized estimating equations (GEEs) with nonlinear terms. Given substantial differences in patient selection for the type of urinary diversion, we separately modeled longitudinal HRQOL within conduit and continent diversion groups. The mean pre-RC scores were compared to illustrate the baseline HRQOL differences between diversion groups.
The analyzed cohort included 411 patients (n = 205 ileal conduit, n = 206 continent diversion). At baseline, patients receiving continent diversion reported better mean physical (p < 0.001), urinary (p = 0.006), and sexual function (p < 0.001), but lower social function (p = 0.015). After RC, GEE modeling showed physical function scores decreasing 5/100 points by 6 mo, and subsequently stabilizing or returning to baseline. By 12 mo, social function improved by 10/100 points among continent diversions, while remaining stable among ileal conduits. Global quality of life exceeded baseline scores by 6 mo. Sexual function scores were low before RC, with limited recovery. Psychosocial domains were stable or improved, except for 10/100-point worsening of body image among ileal conduits.
RC patients reported favorable HRQOL recovery within 24 mo in most areas other than body image (ileal conduits) and sexual function (both). Importantly, large measurable decreases in scores were not reported by 3 mo after RC. These contemporary outcomes and the excellent locoregional control provided by RC further support it as the gold standard therapy for high-risk bladder cancer.
We review quality of life in the 24 mo following radical cystectomy. Large decreases in health-related quality of life were not reported, with most areas returning to, or exceeding, baseline, except for sexual function and body image.
In a large, prospective study, quality of life outcomes after radical cystectomy are favorable within 24 mo. Across most measured domains, scores recovered to preoperative levels. Exceptions were body image (ileal conduits) and sexual function (all diversions) domains.
This study was an evaluation of whether restaging transurethral resection (TUR) of superficial bladder cancer improves the early response to bacillus Calmette-Guerin (BCG) therapy.
A total of 347 ...patients with high risk superficial bladder cancer (high grade Ta and T1 tumors associated with carcinoma in situ) underwent a single transurethral resection (TUR, 132 patients) or restaging TUR (215 patients) before receiving 6 weekly intravesical BCG treatments. The patients were evaluated for response (presence or absence of tumor) at first followup cystoscopy, at 6 and 12 months after treatment, and evaluated for disease stage progression within 3 years of followup.
Of the 132 patients who underwent a single TUR before BCG therapy, 75 (57%) had residual or recurrent tumor at the first cystoscopy and 45 (34%) later had progression, compared with 62 of 215 patients (29%) who had residual or recurrent tumors and 16 (7%) who had progression after undergoing restaging TUR (p = 0.001).
Restaging TUR of high risk superficial bladder cancer improves the initial response rate to BCG therapy, reduces the frequency of subsequent tumor recurrence and appears to delay early tumor progression.
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