Abstract Context Urothelial bladder cancer (UBC) is a disease of significant morbidity and mortality. It is important to understand the risk factors of this disease. Objective To describe the ...incidence, prevalence, and mortality of UBC and to review and interpret the current evidence on and impact of the related risk factors. Evidence acquisition A literature search in English was performed using PubMed. Relevant papers on the epidemiology of UBC were selected. Evidence synthesis UBC is the 7th most common cancer worldwide in men and the 17th most common cancer worldwide in women. Approximately 75% of newly diagnosed UBCs are noninvasive. Each year, approximately 110 500 men and 70 000 women are diagnosed with new cases and 38 200 patients in the European Union and 17 000 US patients die from UBC. Smoking is the most common risk factor and accounts for approximately half of all UBCs. Occupational exposure to aromatic amines and polycyclic aromatic hydrocarbons are other important risk factors. The impact of diet and environmental pollution is less evident. Increasing evidence suggests a significant influence of genetic predisposition on incidence. Conclusions UBC is a frequently occurring malignancy with a significant impact on public health and will remain so because of the high prevalence of smoking. The importance of primary prevention must be stressed, and smoking cessation programs need to be encouraged and supported.
Abstract Context Tobacco smoke includes a mix of carcinogens implicated in the etiology of bladder cancer (BC) and renal cell cancer (RCC). Objective We reviewed the impact of tobacco exposure on BCC ...and RCC incidence and mortality, and whether smoking cessation decreases the risk. Evidence acquisition A systematic review of original articles in English was performed in August 2013. Meta-analysis of risks was performed using adjusted risk ratios where available. Publication bias was assessed using Begg and Egger tests. Evidence synthesis We identified 2683 papers, of which 107 fulfilled our inclusion criteria, of which 83 studies investigated BC and 24 investigated RCC. The pooled relative risk (RR) of BC incidence was 2.58 (95% confidence interval CI 2.37–2.80) for all smokers, 3.47 (3.07–3.91) for current smokers, and 2.04 (1.85–2.25) for former smokers. The corresponding pooled RR of BC disease-specific mortality (DSM) was 1.47 (1.24–1.75), 1.53 (1.12–2.09) and 1.44 (0.99–2.11). The pooled RR of RCC incidence was 1.31 (1.22–1.40) for all smokers, 1.36 (1.19–1.56) for current smokers, and 1.16 (1.08–1.25) for former smokers. The corresponding RCC DSM risk was 1.23 (1.08–1.40), 1.37 (1.19–1.59), and 1.02 (0.90–1.15). Conclusions We present an up-to-date review of tobacco smoking and BC and RCC incidence and mortality. Tobacco smoking significantly increases the risk of BC and RCC incidence. BC incidence and DSM risk are greatest in current smokers and lowest in former smokers, indicating that smoking cessation confers benefit. We found that secondhand smoke exposure is associated with a significant increase in BC risk. Patient summary Tobacco smoking affects the development and progression of bladder cancer and renal cell cancer. Smoking cessation reduces the risks of developing and dying from these common cancers. We quantify these risks using the most up-to-date results published in the literature.
The Mutational Landscape of Prostate Cancer Barbieri, Christopher E; Bangma, Chris H; Bjartell, Anders ...
European urology,
10/2013, Letnik:
64, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Abstract Context Prostate cancer (PCa) is a clinically heterogeneous disease with marked variability in patient outcomes. Molecular characterization has revealed striking mutational heterogeneity ...that may underlie the variable clinical course of the disease. Objective In this review, we discuss the common genomic alterations that form the molecular basis of PCa, their functional significance, and the potential to translate this knowledge into patient care. Evidence acquisition We reviewed the relevant literature, with a particular focus on recent studies on somatic alterations in PCa. Evidence synthesis Advances in sequencing technology have resulted in an explosion of data regarding the mutational events underlying the development and progression of PCa. Heterogeneity is the norm; few abnormalities in specific genes are highly recurrent, but alterations in certain signaling pathways do predominate. These alterations include those in pathways known to affect tumorigenesis in a wide spectrum of tissues, such as the phosphoinositide 3-kinase/phosphatase and tensin homolog/Akt pathway, cell cycle regulation, and chromatin regulation. Alterations more specific to PCa are also observed, particularly gene fusions of ETS transcription factors and alterations in androgen signaling. Mounting data suggest that PCa can be subdivided based on a molecular profile of genetic alterations. Conclusions Major advances have been made in cataloging the genomic alterations in PCa and understanding the molecular mechanisms underlying the disease. These findings raise the possibility that PCa could soon transition from being a poorly understood, heterogeneous disease with a variable clinical course to being a collection of homogenous subtypes identifiable by molecular criteria, associated with distinct risk profiles, and perhaps amenable to specific management strategies or targeted therapies.
Abstract Context Although open radical cystectomy (ORC) is still the standard approach, laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) have gained popularity. ...Objective To report a systematic literature review and cumulative analysis of perioperative outcomes and complications of RARC in comparison with ORC and LRC. Evidence acquisition Medline, Scopus, and Web of Science databases were searched using a free-text protocol including the terms robot-assisted radical cystectomy or da Vinci radical cystectomy or robot* radical cystectomy . RARC case series and studies comparing RARC with either ORC or LRC were collected. Cumulative analysis was conducted. Evidence synthesis The searches retrieved 105 papers. According to the different diversion type, overall mean operative time ranged from 360 to 420 min. Similarly, mean blood loss ranged from 260 to 480 ml. Mean in-hospital stay was about 9 d for all diversion types, with consistently high readmission rates. In series reporting on RARC with either extracorporeal or intracorporeal conduit diversion, overall 90-d complication rates were 59% (high-grade complication: 15%). In series reporting RARC with intracorporeal continent diversion, the overall 30-d complication rate was 45.7% (high-grade complication: 28%). Reported mortality rates were ≤3% for all diversion types. Comparing RARC and ORC, cumulative analyses demonstrated shorter operative time for ORC, whereas blood loss and in-hospital stay were better with RARC (all p values <0.003). Moreover, 90-d complication rates of any-grade and 90-d grade 3 complication rates were lower for RARC (all p values <0.04), whereas high-grade complication and mortality rates were similar. Conclusions RARC can be performed safely with acceptable perioperative outcome, although complications are common. Cumulative analyses demonstrated that operative time was shorter with ORC, whereas RARC may provide some advantages in terms of blood loss and transfusion rates and, more limitedly, for postoperative complication rates over ORC and LRC. Patient summary Although open radical cystectomy (RC) is still regarded as a standard treatment for muscle-invasive bladder cancer, laparoscopic and robot-assisted RC are becoming more popular. Robotic RC can be safely performed with acceptably low risk of blood loss, transfusion, and intraoperative complications; however, as for open RC, the risk of postoperative complications is high, including a substantial risk of major complication and reoperation.
Recommendations against prostate-specific antigen (PSA) testing in 2012 have increased advanced-stage diagnosis and prostate cancer–specific mortality rates.
To present the position of the European ...Association of Urology (EAU) in 2021 and provide recommendations for the use of PSA testing as part of a risk-adapted strategy for the early detection of prostate cancer.
The authors combined their review of relevant literature, including the EAU prostate cancer guidelines 2021 update, with their own knowledge to provide an expert opinion, representing the EAU’s position in 2021.
The EAU has developed a risk-adapted early prostate cancer detection strategy for well-informed men based on PSA testing, risk calculators, and multiparametric magnetic resonance imaging, which can differentiate significant from insignificant prostate cancer. This approach largely avoids the overdiagnosis/overtreatment of men unlikely to experience disease-related symptoms during their lifetime and facilitates an early diagnosis of men with significant cancer to receive active treatment. It also reduces advanced-stage diagnosis, thereby potentially reducing prostate cancer–specific mortality and improving quality of life. Education is required among urologists, general practitioners, radiologists, policy makers, and healthy men, including endorsement by the European Commission to adapt the European Council’s screening recommendations in its 2022 plan and requests to individual countries for its incorporation into national cancer plans.
This risk-adapted approach for the early detection of prostate cancer will reverse current unfavourable trends and ultimately save lives.
The European Association of Urology has developed a patient information leaflet and algorithm for the early diagnosis of prostate cancer. It can identify men who do not need magnetic resonance imaging or a biopsy and those who would not show any symptoms versus those with more aggressive disease who require further tests/treatment. We need to raise awareness of this algorithm to ensure that all well-informed men at risk of significant prostate cancer are offered a prostate-specific antigen test.
A risk-adapted early prostate cancer detection strategy, incorporating prostate-specific antigen testing, multiparametric magnetic resonance imaging, risk calculators, and biomarkers, will avoid overdiagnosis/overtreatment of insignificant cancers and ensure early detection and treatment of significant cancers, thereby improving quality of life and reducing prostate cancer–related deaths.
Little is known about health-related quality of life (HRQOL) following treatment for bladder cancer (BC).
To determine this, we undertook a cross-sectional survey covering 10% of the English ...population.
Participants 1–10 yr from diagnosis were identified through national cancer registration data.
A postal survey was administered containing generic HRQOL and BC-specific outcome measures. Findings were compared with those of the general population and other pelvic cancer patients.
Generic HRQOL was measured using five-level EQ-5D (EQ-5D-5L) and European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ)-C30. BC-specific outcomes were derived from EORTC QLQ-BLM30 and EORTC QLQ-NMIBC24.
A total of 1796 surveys were completed (response rate 55%), including 868 (48%) patients with non–muscle-invasive BC, 893 (50%) patients who received radiotherapy or radical cystectomy, and 35 (1.9%) patients for whom treatment was unknown. Most (69%) of the participants reported at least one problem in any EQ-5D dimension. Age/sex-adjusted generic HRQOL outcomes were similar across all stages and treatment groups, whilst problems increased with age (problems in one or more EQ-5D dimensions: <65 yr 67% {95% confidence interval or CI: 61–74} vs 85+ yr 84% {95% CI: 81–89}, p = 0.016) and long-term conditions (no conditions 53% {95% CI: 48–58} vs more than four conditions 94% {95% CI: 90–97}, p < 0.001). Sexual problems were reported commonly in men, increasing with younger age and radical treatment. Younger participants (under 65 yr) reported more financial difficulties (mean score 20 95% CI: 16–25) than those aged 85+ yr (6.8 4.5–9.2, p < 0.001). HRQOL for BC patients (for comparison, males with problems in one or more EQ-5D dimensions 69% 95% CI: 66–72) was significantly worse than what has been found after colorectal and prostate cancers and in the general population (51% 95% CI: 48–53, all p < 0.05).
HRQOL following BC appears to be relatively independent of disease stage, treatment, and multimodal care. Issues are reported with sexual function and financial toxicity. HRQOL after BC is worse than that after other pelvic cancers.
Patients living with bladder cancer often have reduced quality of life, which may be worse than that for other common pelvic cancer patients. Age and other illnesses appear to be more important in determining this quality of life than the treatments received. Many men complain of sexual problems. Younger patients have financial worries.
Patients living with bladder cancer often have reduced quality of life, which may be worse than that in patients with other common pelvic cancers. Age and other illnesses appear to be more important in determining this quality of life than the treatments received. Many men complain of sexual problems. Younger patients have financial worries.
We present a suggested list of urologic surgeries that should be prioritized if COVID-19 surges warrant cancellation of elective surgeries to free up health care resources. The recommendations should ...be tailored to locally available resources and situations and can be used as a framework for other specialties.
Abstract Context Prostate cancer (PCa) is one of the most common human malignancies and arises through genetic and epigenetic alterations. Epigenetic modifications include DNA methylation, histone ...modifications, and microRNAs (miRNA) and produce heritable changes in gene expression without altering the DNA coding sequence. Objective To review progress in the understanding of PCa epigenetics and to focus upon translational applications of this knowledge. Evidence acquisition PubMed was searched for publications regarding PCa and DNA methylation, histone modifications, and miRNAs. Reports were selected based on the detail of analysis, mechanistic support of data, novelty, and potential clinical applications. Evidence synthesis Aberrant DNA methylation (hypo- and hypermethylation) is the best-characterized alteration in PCa and leads to genomic instability and inappropriate gene expression. Global and locus-specific changes in chromatin remodeling are implicated in PCa, with evidence suggesting a causative dysfunction of histone-modifying enzymes. MicroRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen receptor signaling and apoptosis. There are important connections between common genetic alterations (eg, E twenty-six fusion genes) and the altered epigenetic landscape. Owing to the ubiquitous nature of epigenetic alterations, they provide potential biomarkers for PCa detection, diagnosis, assessment of prognosis, and post-treatment surveillance. Conclusions Altered epigenetic gene regulation is involved in the genesis and progression of PCa. Epigenetic alterations may provide valuable tools for the management of PCa patients and be targeted by pharmacologic compounds that reverse their nature. The potential for epigenetic changes in PCa requires further exploration and validation to enable translation to the clinic.
Multimodal enhanced recovery after surgery (ERAS) regimens have improved outcomes from colorectal surgery.
We report the application of ERAS to patients undergoing radical cystectomy (RC).
...Prospective collection of outcomes from consecutive patients undergoing RC at a single institution.
Twenty-six components including prehabilitation exercise, same day admission, carbohydrate fluid loading, targeted intraoperative fluid resuscitation, regional local anaesthesia, cessation of nasogastric tubes, omitting oral bowel preparation, avoiding drain use, early mobilisation, chewing gum use, and audit.
Primary outcomes were length of stay and readmission rate. Secondary outcomes included intraoperative blood loss, transfusion rates, survival, and histopathological findings.
Four hundred and fifty-three consecutive patients underwent RC, including 393 (87%) with ERAS. Length of stay was shorter with ERAS (median interquartile range: 8 6–13 d) than without (18 13–25, p<0.001). Patients with ERAS had lower blood loss (ERAS: 600 383–969 ml vs 1050 900–1575 ml for non-ERAS, p<0.001), lower transfusion rates (ERAS: 8.1% vs 25%, chi-square test, p<0.001), and fewer readmissions (ERAS: 15% vs 25%, chi-square test, p=0.04) than those without. Histopathological parameters (eg, tumour stage, node count, and margin state) and survival outcomes did not differ with ERAS use (all p>0.1). Multivariable analysis revealed ERAS use was (p=0.002) independently associated with length of stay.
The use of ERAS pathways was associated with lower intraoperative blood loss and faster discharge for patients undergoing RC. These changes did not increase readmission rates or alter oncological outcomes.
Recovery after major bladder surgery can be improved by using enhanced recovery pathways. Patients managed by these pathways have shorter length of stays, lower blood loss, and lower transfusion rates. Their adoption should be encouraged.
We found that changes to the radical cystectomy recovery pathway made dramatic improvements to patient outcomes. In particular, changing recovery pathways lead to shorter length of stay, lower blood loss and transfusion rates, and fewer readmissions after surgery, without impacting on cancer treatment outcomes.
Vesical Imaging Reporting and Data System (VI-RADS) score is adopted to provide preoperative bladder cancer (BCa) staging. Repeated transurethral resection of bladder tumor (Re-TURBT) is recommended ...in most of high-risk non–muscle-invasive bladder cancers (HR-NMIBCs) due to possibility of persistent/understaged disease after initial TURBT. No diagnostic tools able to improve patient’s stratification for such recommendation exist.
To (1) prospectively validate VI-RADS for discriminating between NMIBC and muscle-invasive bladder cancer (MIBC) at TURBT, and (2) evaluate the accuracy of VI-RADS for identifying HR-NMIBC patients who could avoid Re-TURBT and detecting those at higher risk for understaging after TURBT.
Patients with BCa suspicion were offered multiparametric magnetic resonance imaging (mpMRI) before TURBT. According to VI-RADS, a cutoff of ≥3 to define MIBC was assumed. TURBT reports were compared with preoperative VI-RADS scores to assess accuracy of mpMRI for discriminating between NMIBC and MIBC. HR-NMIBC Re-TURBT reports were compared with preoperatively recorded VI-RADS scores to assess mpMRI accuracy in predicting Re-TURBT outcomes.
Multiparametric MRI of the bladder before TURBT.
Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated for mpMRI performance in patients undergoing TURBT and for HR-NMIBC patients candidate for Re-TURBT. Performance of mpMRI was assessed by receiver operating characteristic curve analysis. Ƙ statistics was used to estimate inter- and intrareader variability.
A total of 231 patients were enrolled. Multiparametric MRI showed sensitivity, specificity, PPV, and NPV for discriminating NMIBC from MIBC at initial TURBT of 91.9% (95% confidence interval CI: 82.2–97.3), 91.1% (95% CI: 85.8–94.9), 77.5% (95% CI: 65.8–86.7), and 97.1% (95% CI: 93.3–99.1), respectively. The area under the curve (AUC) was 0.94 (95% CI: 0.91–0.97). Among HR-NMIBC patients (n=114), mpMRI before TURBT showed sensitivity, specificity, PPV, and NPV of 85% (95% CI: 62.1–96.8), 93.6% (95% CI: 86.6–97.6), 74.5% (95% CI: 52.4–90.1), and 96.6% (95% CI: 90.5–99.3) respectively, to identify patients with MIBC at Re-TURBT. The AUC was 0.93 (95% CI: 0.87–0.97).
VI-RADS is accurate for discriminating between NMIBC and MIBC. Within HR-NMIBC cases, VI-RADS could, in future, improve the selection of patients who are candidate for Re-TURBT.
We investigated the accuracy of Vesical Imaging Reporting and Data System (VI-RADS) score to asses bladder cancer staging before transurethral resection of bladder tumors, and we explored the performance of VI-RADS score as a future preoperative predictive tool for the selection of high-risk non–muscle-invasive bladder cancer patients who are candidate for undergoing early repeated transurethral resection of the primary tumor site.
Vesical Imaging Reporting and Data System (VI-RADS) score is a novel imaging tool able to differentiate superficial from muscle-invasive bladder cancer before transurethral resection of bladder tumor (TURBT). Within the category of high-risk non–muscle-invasive bladder cancers, VI-RADS could differentiate those not needing repeated TURBT (Re-TURBT) from those who should definitely not miss Re-TURBT.
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