Purpose Although associated with an overall favorable survival rate, the heterogeneity of non-muscle invasive bladder cancer (NMIBC) affects patients’ rates of recurrence and progression. Risk ...stratification should influence evaluation, treatment and surveillance. This guideline attempts to provide a clinical framework for the management of NMIBC. Materials and Methods A systematic review utilized research from the Agency for Healthcare Research and Quality (AHRQ) and additional supplementation by the authors and consultant methodologists. Evidence-based statements were based on body of evidence strength Grade A, B, or C and were designated as Strong, Moderate, and Conditional Recommendations with additional statements presented in the form of Clinical Principles or Expert Opinions. Results A risk-stratified approach categorizes patients into broad groups of low-, intermediate-, and high-risk. Importantly, the evaluation and treatment algorithm takes into account tumor characteristics and uniquely considers a patient’s response to therapy. The 38 statements vary in level of evidence, but none include Grade A evidence, and many were Grade C. Conclusion The intensity and scope of care for NMIBC should focus on patient, disease, and treatment response characteristics. This guideline attempts to improve a clinician’s ability to evaluate and treat each patient, but higher quality evidence in future trials will be essential to improve level of care for these patients.
We performed an updated systematic review and meta-analysis of outcomes important to patients in those undergoing robot-assisted and open radical cystectomy.
Multiple scientific databases were ...searched up to July 2018 for randomized, controlled trials comparing robot-assisted and open radical cystectomy. The primary outcomes of interest were disease progression, major (Clavien III-V) complications and 90-day quality of life. The quality of evidence was evaluated according to the framework in the Cochrane Handbook for Systematic Reviews of Interventions.
Five studies with a total of 540 participants were included in this review. There was no difference between robot-assisted and open radical cystectomy in disease progression (RR 0.94, 95% CI 0.69-1.29), major complications (RR 1.06, 95% CI 0.75-1.49) or quality of life (standardized mean difference -0.03, 95% CI -0.27-0.21). However, robot-assisted radical cystectomy demonstrated a reduced risk of perioperative blood transfusion (RR 0.58, 95% CI 0.43-0.80) and a marginally shorter hospital stay (RR -0.63 days, 95% CI -1.21-0.05). Operative time was longer in the robot-assisted group (mean difference 68.51 minutes, 95% CI 30.55-105.48). There was no statistically significant difference in local recurrence rates between the procedures (RR 2.08, 95% CI 0.96-4.50) but this difference may be clinically significant and it favored open radical cystectomy. The overall quality of evidence was judged to be moderate.
Surgical approach does not have a considerable impact on oncologic, safety and quality of life outcomes in patients who undergo radical cystectomy. The benefits conferred by robot-assisted radical cystectomy are a decreased need for blood transfusion and earlier hospital discharge.
Purpose The guideline purpose is to provide the urologist with a framework for the early detection of prostate cancer in asymptomatic average risk men. Materials and Methods A systematic review was ...conducted and summarized evidence derived from over 300 studies that addressed the predefined outcomes of interest (prostate cancer incidence/mortality, quality of life, diagnostic accuracy and harms of testing). In addition to the quality of evidence, the panel considered values and preferences expressed in a clinical setting (patient-physician dyad) rather than having a public health perspective. Guideline statements were organized by age group in years (age <40; 40 to 54; 55 to 69; ≥70). Results Except prostate specific antigen-based prostate cancer screening, there was minimal evidence to assess the outcomes of interest for other tests. The quality of evidence for the benefits of screening was moderate, and evidence for harm was high for men age 55 to 69 years. For men outside this age range, evidence was lacking for benefit, but the harms of screening, including over diagnosis and overtreatment, remained. Modeled data suggested that a screening interval of two years or more may be preferred to reduce the harms of screening. Conclusions The Panel recommended shared decision-making for men age 55 to 69 years considering PSA-based screening, a target age group for whom benefits may outweigh harms. Outside this age range, PSA-based screening as a routine could not be recommended based on the available evidence. The entire guideline is available at www.AUAnet.org/education/guidelines/prostate-cancer-detection.cfm.
Standard treatment for high-risk non-muscle-invasive bladder cancer is transurethral resection of bladder tumour followed by intravesical BCG immunotherapy. However, despite high initial responses ...rates, up to 50% of patients have recurrence or become BCG-unresponsive. PD-1 pathway activation is implicated in BCG resistance. In the KEYNOTE-057 study, we evaluated pembrolizumab, a PD-1 inhibitor, in BCG-unresponsive non-muscle-invasive bladder cancer.
We did this open-label, single-arm, multicentre, phase 2 study in 54 sites (hospitals and cancer centres) in 14 countries. In cohort A of the trial, adults aged 18 years or older with histologically confirmed BCG-unresponsive carcinoma in situ of the bladder, with or without papillary tumours, with an Eastern Cooperative Oncology Group performance status of 0–2, and who were ineligible for or declined radical cystectomy were enrolled. All enrolled patients were assigned to receive pembrolizumab 200 mg intravenously every 3 weeks for up to 24 months or until centrally confirmed disease persistence, recurrence, or progression; unacceptable toxic effects; or withdrawal of consent. The primary endpoint was clinical complete response rate (absence of high-risk non-muscle-invasive bladder cancer or progressive disease), assessed by cystoscopy and urine cytology approximately 3 months after the first dose of study drug. Patient follow-ups were done every 3 months for the first 2 years and every 6 months thereafter for up to 5 years. Efficacy was assessed in all patients who received at least one dose of the study drug and met BCG-unresponsive criteria. Safety was assessed in all patients who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov number, NCT02625961, and is ongoing.
Between Dec 9, 2015, and April 1, 2018, we screened 334 patients for inclusion. 186 patients did not meet inclusion criteria, and 47 patients were assigned to cohort B (patients with BCG-unresponsive high grade Ta or any grade T1 papillary disease without carcinoma in situ; results will be reported separately). 101 eligible patients were enrolled and assigned to receive pembrolizumab. All 101 patients received at least one dose of the study drug and were included in the safety analysis. Five patients had disease that did not meet the US Food and Drug Administration definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore not included in the efficacy analysis (n=96). Median follow-up was 36·4 months (IQR 32·0–40·7). 39 (41%; 95% CI 30·7–51·1) of 96 patients with BCG-unresponsive carcinoma in situ of the bladder with or without papillary tumours had a complete response at 3 months. Grade 3 or 4 treatment-related adverse events occurred in 13 (13%) patients; the most common were arthralgia (in two 2% patients) and hyponatraemia (in three 3% patients). Serious treatment-related adverse events occurred in eight (8%) patients. There were no deaths that were considered treatment related.
Pembrolizumab monotherapy was tolerable and showed promising antitumour activity in patients with BCG-unresponsive non-muscle-invasive bladder cancer who declined or were ineligible for radical cystectomy and should be considered a a clinically active non-surgical treatment option in this difficult-to-treat population.
Merck Sharp & Dohme.
Radical cystectomy is the surgical standard for invasive bladder cancer. Robot-assisted cystectomy has been proposed to provide similar oncological outcomes with lower morbidity. We aimed to compare ...progression-free survival in patients with bladder cancer treated with open cystectomy and robot-assisted cystectomy.
The RAZOR study is a randomised, open-label, non-inferiority, phase 3 trial done in 15 medical centres in the USA. Eligible participants (aged ≥18 years) had biopsy-proven clinical stage T1–T4, N0–N1, M0 bladder cancer or refractory carcinoma in situ. Individuals who had previously had open abdominal or pelvic surgery, or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded. Patients were centrally assigned (1:1) via a web-based system, with block randomisation by institution, stratified by type of urinary diversion, clinical T stage, and Eastern Cooperative Oncology Group performance status, to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion. Treatment allocation was only masked from pathologists. The primary endpoint was 2-year progression-free survival, with non-inferiority established if the lower bound of the one-sided 97·5% CI for the treatment difference (robotic cystectomy minus open cystectomy) was greater than −15 percentage points. The primary analysis was done in the per-protocol population. Safety was assessed in the same population. This trial is registered with ClinicalTrials.gov, number NCT01157676.
Between July 1, 2011, and Nov 18, 2014, 350 participants were randomly assigned to treatment. The intended treatment was robotic cystectomy in 176 patients and open cystectomy in 174 patients. 17 (10%) of 176 patients in the robotic cystectomy group did not have surgery and nine (5%) patients had a different surgery to that they were assigned. 21 (12%) of 174 patients in the open cystectomy group did not have surgery and one (1%) patient had robotic cystectomy instead of open cystectomy. Thus, 302 patients (150 in the robotic cystectomy group and 152 in the open cystectomy group) were included in the per-protocol analysis set. 2-year progression-free survival was 72·3% (95% CI 64·3 to 78·8) in the robotic cystectomy group and 71·6% (95% CI 63·6 to 78·2) in the open cystectomy group (difference 0·7%, 95% CI −9·6% to 10·9%; pnon-inferiority=0·001), indicating non-inferiority of robotic cystectomy. Adverse events occurred in 101 (67%) of 150 patients in the robotic cystectomy group and 105 (69%) of 152 patients in the open cystectomy group. The most common adverse events were urinary tract infection (53 35% in the robotic cystectomy group vs 39 26% in the open cystectomy group) and postoperative ileus (33 22% in the robotic cystectomy group vs 31 20% in the open cystectomy group).
In patients with bladder cancer, robotic cystectomy was non-inferior to open cystectomy for 2-year progression-free survival. Increased adoption of robotic surgery in clinical practice should lead to future randomised trials to assess the true value of this surgical approach in patients with other cancer types.
National Institutes of Health National Cancer Institute.
Controversy exists regarding the benefit of extended lymphadenectomy at radical prostatectomy for prostate cancer. We sought to determine whether more extended lymphadenectomy, along with radical ...prostatectomy, resulted in a decreased risk of prostate cancer-specific death at 10 years.
Data on all patients undergoing radical prostatectomy (with or without lymphadenectomy) for prostate cancer obtained from the Surveillance, Epidemiology, and End Results Program (1988 to 1991) were examined. All surviving patients had a minimal follow-up of 10 years. Multivariate Cox proportional hazards analysis was used to determine the independent effect of lymphadenectomy on the risk of prostate cancer-specific death.
Patients undergoing excision of at least 4 lymph nodes (node-positive and node-negative patients) or more than 10 nodes (only node-negative patients) had a lower risk of prostate cancer-specific death at 10 years than did those who did not undergo lymphadenectomy. The removal of a greater number of nodes was associated with a greater likelihood of the presence of positive nodes. The presence of more than one positive node was associated with a greater risk of prostate cancer-related death.
Performing more extensive pelvic lymphadenectomy in patients undergoing radical prostatectomy could improve the accuracy of staging and reduce the risk of prostate cancer-specific death in the long term.
The summary presented herein covers recommendations on the early detection of prostate cancer and provides a framework to facilitate clinical decision-making in the implementation of prostate cancer ...screening, biopsy, and follow-up. This is Part I of a two-part series that focuses on prostate cancer screening. Please refer to Part II for discussion of initial and repeat biopsies as well as biopsy technique.
The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. The systematic review was based on searches in Ovid MEDLINE and Embase and Cochrane Database of Systematic Reviews (January 1, 2000-November 21, 2022). Searches were supplemented by reviewing reference lists of relevant articles.
The Early Detection of Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance in prostate cancer screening, initial and repeat biopsy, and biopsy technique.
Prostate-specific antigen (PSA)-based prostate cancer screening in combination with shared decision-making (SDM) is recommended. Current data regarding risk from population-based cohorts provide a basis for longer screening intervals and tailored screening, and the use of available online risk calculators is encouraged.
To determine the morbidity and mortality from radical cystectomy in a nationally representative population-derived sample. Complications after radical cystectomy have been reported from large ...single-institution series but population-based representative data are lacking.
All patients undergoing radical cystectomy for bladder cancer were identified from the National Inpatient Sample data set of the Health Care Utilization Project (1998 to 2002). The prevalence of different complications coded according to the International Classification of Diseases, version 9, after cystectomy were determined. Independent hospital and patient-related factors associated with the occurrence of a complication were determined by logistic regression analysis. The prevalence of complication by type and frequency were compared with that in other large reported series.
The in-hospital mortality rate was 2.57%, and at least one complication other than death occurred in 28.4% of patients. These rates were comparable to those reported in published studies. Younger patients had a lower likelihood of complications. Younger patients and those undergoing cystectomy at large bed size, urban, teaching hospitals were less likely to have secondary complications after surgery, and younger patients, women, and those undergoing cystectomy at high-volume hospitals were less likely to have primary complications directly related to their surgery.
The overall morbidity and mortality rates after radical cystectomy in a population-based sample were comparable to those reported from individual centers. Larger centers in urban locations may have lower complication rates but only hospitals performing a high volume of cystectomies were associated with fewer primary surgery-related complications.
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