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.     

ICUD-EAU International Consultation on Bladder Cancer 2012: Chemotherapy for Urothelial Carcinoma—Neoadjuvant and Adjuvant Settings

Context

We present a summary of the Second International Consultation on Bladder Cancer recommendations on chemotherapy for the treatment of bladder cancer using an evidence-based strategy.

Objective

To review the data regarding chemotherapy in patients with clinically localized and metastatic bladder cancer with a focus on its use for patients in the neoadjuvant and adjuvant settings.

Evidence acquisition

Medline databases were searched for original articles published prior to April 1, 2012, using the following search terms: bladder cancer, urothelial cancer, metastatic, advanced, neoadjuvant, and adjuvant therapy. Proceedings of major conferences from the last 5 yr also were searched. Novel and promising drugs currently in clinical trials were included.

Evidence synthesis

The major findings are addressed in an evidence-based manner. Prospective trials and important cohort data were analyzed.

Conclusions

Cisplatin-based combination chemotherapy for advanced and metastatic bladder cancer is an established standard, improving overall survival. In the advanced setting, cisplatin-ineligible patients may benefit from gemcitabine and carboplatin. Meta-analyses undertaken for neoadjuvant cisplatin-based combination chemotherapy show a 5% benefit in overall survival. Pathologic complete remission may be an intermediate surrogate for survival, but requires further validation. Use of neoadjuvant chemotherapy is low, and is attributable to patient and physician choice because of limited benefit, advanced age, and comorbidities including renal and/or cardiac dysfunction. Sufficient data to support adjuvant chemotherapy are lacking.     

ICUD-EAU International Consultation on Bladder Cancer 2012: Screening,Diagnosis, and Molecular Markers

Context and objective

To present a summary of the 2nd International Consultation on Bladder Cancer recommendations on the screening, diagnosis, and markers of bladder cancer using an evidence-based strategy.

Evidence acquisition

A detailed Medline analysis was performed for original articles addressing bladder cancer with regard to screening, diagnosis, markers, and pathology. Proceedings from the last 5 yr of major conferences were also searched.

Evidence synthesis

The major findings are presented in an evidence-based fashion. Large retrospective and prospective data were analyzed.

Conclusions

Cystoscopy alone is the most cost-effective method to detect recurrence of bladder cancer. White-light cystoscopy is the gold standard for evaluation of the lower urinary tract; however, technology like fluorescence-aided cystoscopy and narrow-band imaging can aid in improving evaluations. Urine cytology is useful for the diagnosis of high-grade tumor recurrence. Molecular medicine holds the promise that clinical outcomes will be improved by directing therapy toward the mechanisms and targets associated with the growth of an individual patient's tumor. The challenge remains to optimize measurement of these targets, evaluate the impact of such targets for therapeutic drug development, and translate molecular markers into the improved clinical management of bladder cancer patients. Physicians and researchers eventually will have a robust set of molecular markers to guide prevention, diagnosis, and treatment decisions for bladder cancer.     

ICUD-EAU International Consultation on Bladder Cancer 2012: Urinary Diversion

Context

A summary of the 2nd International Consultation on Bladder Cancer recommendations on the reconstructive options after radical cystectomy (RC), their outcomes, and their complications.

Objective

To review the literature regarding indications, surgical details, postoperative care, complications, functional outcomes, as well as quality-of-life measures of patients with different forms of urinary diversion (UD).

Evidence acquisition

An English-language literature review of data published between 1970 and 2012 on patients with UD following RC for bladder cancer was undertaken. No randomized controlled studies comparing conduit diversion with neobladder or continent cutaneous diversion have been performed. Consequently, almost all studies used in this report are of level 3 evidence. Therefore, the recommendations given here are grade C only, meaning expert opinion delivered without a formal analysis.

Evidence synthesis

Indications and patient selection criteria have significantly changed over the past 2 decades. Renal function impairment is primarily caused by obstruction. Complications such as stone formation, urine outflow, and obstruction at any level must be recognized early and treated. In patients with orthotopic bladder substitution, daytime and nocturnal continence is achieved in 85–90% and 60–80%, respectively. Continence is inferior in elderly patients with orthotopic reconstruction. Urinary retention remains significant in female patients, ranging from 7% to 50%.

Conclusions

RC and subsequent UD have been assessed as the most difficult surgical procedure in urology. Significant disparity on how the surgical complications were reported makes it impossible to compare postoperative morbidity results. Complications rates overall following RC and UD are significant, and when strict reporting criteria are incorporated, they are much higher than previously published. Fortunately, most complications are minor (Clavien grade 1 or 2). Complications can occur up to 20 yr after surgery, emphasizing the need for lifelong monitoring. Evidence suggests an association between surgical volume and outcome in RC; the challenge of optimum care for elderly patients with comorbidities is best mastered at high-volume hospitals by high-volume surgeons. Preoperative patient information, patient selection, surgical techniques, and careful postoperative follow-up are the cornerstones to achieve good long-term results.     

EAU Guidelines on Renal Cell Carcinoma: The 2010 Update

Context and objectives

The European Association of Urology Guideline Group for renal cell carcinoma (RCC) has prepared these guidelines to help clinicians assess the current evidence-based management of RCC and to incorporate the present recommendations into daily clinical practice.

Evidence acquisition

The recommendations provided in the current updated guidelines are based on a thorough review of available RCC guidelines and review articles combined with a systematic literature search using Medline and the Cochrane Central Register of Controlled Trials.

Evidence synthesis

A number of recent prospective randomised studies concerning RCC are now available with a high level of evidence, whereas earlier publications were based on retrospective analyses, including some larger multicentre validation studies, meta-analyses, and well-designed controlled studies.

Conclusions

These guidelines contain information for the treatment of an individual patient according to a current standardised general approach. Updated recommendations concerning diagnosis, treatment, and follow-up can improve the clinical handling of patients with RCC.     

ICUD-EAU International Consultation on Kidney Cancer 2010: treatment of metastatic disease

Context

Until the development of novel targeted agents directed against angiogenesis and tumour growth, few treatment options have been available for the treatment of metastatic renal-cell carcinoma (mRCC).

Objective

This review discusses current targeted therapies for mRCC and provides consensus statements regarding treatment algorithms.

Evidence acquisition

Medical literature was retrieved from PubMed up to April 2011. Additional relevant articles and abstract reviews were included from the bibliographies of the retrieved literature.

Evidence synthesis

Targeted treatment for mRCC can be categorized for the following patient groups: previously untreated patients, those refractory to immunotherapy, and those refractory to vascular endothelial growth factor (VEGF)-targeted therapy. Sunitinib and bevacizumab combined with interferon alpha are generally considered first-line treatment options in patients with favourable or intermediate prognoses. Temsirolimus is considered a first-line treatment option for poor-risk patients. Either sorafenib or sunitinib may be valid second-line treatments for patients who have failed prior cytokine-based therapies. For patients refractory to treatment with VEGF-targeted therapy, everolimus is now recommended. Pazopanib is a new treatment option in the first- and second-line setting (after cytokine failure). Sequential and combination approaches, and the roles of nephrectomy and tumour metastasectomy will also be discussed.

Conclusions

Increasing clinical evidence is clarifying appropriate first- and second-line treatments with targeted agents for patients with mRCC. Based on phase 2 and 3 trials, a sequential approach is most promising, while combination therapy is still investigational. The role of nephrectomy in mRCC is being evaluated in ongoing phase 3 clinical trials.     

Tongue Metastasis from a Poorly Differentiated Urothelial Carcinoma of the Bladder

Chemotherapy may cause oral ulceration but a thorough investigation of symptoms and signs is important to determine the underlying diagnosis accurately. We describe a case of a patient with a poorly differentiated urothelial carcinoma of the bladder developing a tongue metastasis. This is a challenging diagnosis to make given the rarity of the presentation but it illustrates the need to evaluate any new symptoms fully.     

Urothelial Bladder Cancer: An Update on Molecular Pathology with Clinical Implications

Urothelial bladder cancer is a heterogenous disease with distinct clinical and histopathological features. In the last few years it became clear that papillary, mostly noninvasive, disease with few molecular changes and aggressive urothelial carcinoma are genomically separate diseases. Recently, several studies found that invasive bladder cancer can also be separated into several molecular subgroups. In the present review we summarize molecular alterations, diagnostic markers, and molecular subgroups in urothelial bladder cancer and discuss their clinical relevance for prognosis, prediction of recurrence and progression, and therapeutic response to chemotherapy, radiotherapy, and immunotherapy.     

前列腺癌诊治体会

本文报告74例前列腺癌的诊治体会。发病年限分析表明前列腺癌的发病人数呈明显的增长趋势,重视本病可提高检出率;诊断方面强调指肛检查的重要性;讨论了经直肠前列腺B超、前列腺穿刺活检及常用治疗方法的应用及意义。     

Epidemiology and Risk Factors of Urothelial Bladder Cancer

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.     

European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2020 Update

ContextThe European Association of Urology (EAU) Guidelines Panel on Upper Urinary Tract Urothelial Carcinoma (UTUC) has prepared updated guidelines to aid clinicians in the current evidence-based management of UTUC and to incorporate recommendations into clinical practice.ObjectiveTo provide an overview of the EAU guidelines on UTUC as an aid to clinicians.Evidence acquisitionThe recommendations provided in the current guidelines are based on a thorough review of available UTUC guidelines and articles identified following a systematic search of Medline. Data on urothelial malignancies and UTUC were searched using the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract carcinoma, renal pelvis, ureter, bladder cancer, chemotherapy, ureteroscopy, nephroureterectomy, neoplasm, adjuvant treatment, instillation, recurrence, risk factors, and survival. References were weighted by a panel of experts.Evidence synthesisOwing to the rarity of UTUC, there are insufficient data to provide strong recommendations. The 2017 tumour, node, metastasis (TNM) classification is recommended. Recommendations are given for diagnosis and risk stratification as well as for radical and conservative treatment, and prognostic factors are discussed. A single postoperative dose of intravesical mitomycin after nephroureterectomy reduces the risk of bladder tumour recurrence. Kidney-sparing management should be offered as a primary treatment option to patients with low-risk tumour and two functional kidneys. After radical nephroureterectomy, cisplatin-based chemotherapy is indicated in locally advanced UTUC.ConclusionsThese guidelines contain information on the management of individual patients according to a current standardised approach. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen, based on the proposed risk stratification of these tumours.Patient summaryUrothelial carcinoma of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis, an appropriate diagnosis is most important. A number of known risk factors exist.     

Prostate Cancer Prevention Trial and European Randomized Study of Screening for Prostate Cancer Risk Calculators: A Performance Comparison in a Contemporary Screened Cohort

Background

Several models can predict the risk of prostate cancer (PCa) on biopsy.

Objective

To evaluate the performance of the Prostate Cancer Prevention Trial (PCPT) and European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculators in detecting PCa in a contemporary screened cohort.

Design, setting, and participants

We analyzed prebiopsy characteristics of 525 consecutive screened patients submitted to biopsy, as required by the risk calculators, in one European center between 2006 and 2007.

Measurements

Comparisons were done using tests of accuracy (area under the receiver operating characteristic curve [AUC-ROC]), calibration plots, and decision curve analysis. Biopsy predictors were identified by univariate and multivariate logistic regression.

Results and limitations

PCa was detected in 35.2% of the subjects. Among predictors included in the calculators, the logarithmic transformations of prostate volume and prostate-specific antigen (PSA), digital rectal examination, previous biopsy status, and age were significantly associated with PCa; transrectal ultrasound abnormalities and family history were not. AUC-ROC for the ERSPC calculator was significantly higher than the PCPT calculator and PSA alone (80.1%, 74.4%, and 64.3%, respectively). Calibration plots showed better performance for the ERSPC calculator; nevertheless, ERSPC may underestimate risk, while PCPT tends to overestimate predictions. Decision curve analysis displayed higher net benefit for the ERSPC calculator; 9% and 23% unnecessary biopsies can be avoided if a threshold probability of 20% and 30%, respectively, is adopted. In contrast, the PCPT model displayed very limited benefit. Our findings apply to a screened European cohort submitted to extended biopsy schemes; consequently, caution should be exerted when considering different populations.

Conclusions

The ERSPC risk calculator, by incorporating several risks factors, can aid in the estimation of individual PCa risk and in the decision to perform biopsy. The ERSPC calculator outperformed the PCPT model, which is of very limited value, in a contemporary cohort of screened patients.     

The Effect of Prior Biopsy Scheme on Prostate Cancer Detection for Repeat Biopsy Population: Results of the 14-core Prostate Biopsy Technique

OBJECTIVES: To evaluate the diagnostic performance of 14-core repeat biopsy protocol and the impact of prior biopsy scheme on repeat prostate biopsy group. METHODS: 211 patients had repeat biopsy using 14-core protocol consisting of 10-core peripheral zone (classical sextant+4 lateral peripheral cores) and 4-core transitional zone (TZ) biopsies. The diagnostic yield was determined both in patients who had previously undergone sextant or 10-core biopsy protocol. RESULTS: Overall cancer detection rate was 25.6%. 14-core biopsy technique detected cancer in 36.1 and 18.7% of the patients who had a previous sextant biopsy and 10-core biopsy protocol, respectively (P = 0.005). Patients with and without high-grade prostatic intraepithelial neoplasia (HGPIN) in the previous sextant biopsy had 56.5 and 28.3% cancer detection rates on the subsequent extended biopsy, respectively (P = 0.017) Patients who had previous 10-core biopsy with and without HGPIN revealed 22.9 and 17.2% cancer detection rates, respectively (P = 0.465) Additional four lateral peripheral cores detected 33% (3/30) and 17% (4/24) of cancers in patients with previous sextant and 10-core biopsy, respectively. 3.7% of the patients had tumor only in the TZ and none of them had prior extended biopsy. CONCLUSIONS: The yield of extended 14-core repeat biopsy protocol was higher in patients with previous negative sextant biopsy compared to the patients with previous negative 10-core biopsy. HGPIN history found on previous sextant biopsy was a strong cancer predictor on repeat biopsy; same was not true for the patients with previous 10-core biopsy. The yield of lateral peripheral cores and TZ biopsies were lower in patients with prior negative extended biopsy.     

EAU Guidelines on Prostate Cancer. Part 1: Screening,Diagnosis, and Local Treatment with Curative Intent—Update 2013

Context

The most recent summary of the European Association of Urology (EAU) guidelines on prostate cancer (PCa) was published in 2011.

Objective

To present a summary of the 2013 version of the EAU guidelines on screening, diagnosis, and local treatment with curative intent of clinically organ-confined PCa.

Evidence acquisition

A literature review of the new data emerging from 2011 to 2013 has been performed by the EAU PCa guideline group. The guidelines have been updated, and levels of evidence and grades of recommendation have been added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews.

Evidence synthesis

A full version of the guidelines is available at the EAU office or online (www.uroweb.org). Current evidence is insufficient to warrant widespread population-based screening by prostate-specific antigen (PSA) for PCa. Systematic prostate biopsies under ultrasound guidance and local anesthesia are the preferred diagnostic method. Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy. A biopsy progression indicates the need for active intervention, whereas the role of PSA doubling time is controversial. In men with locally advanced PCa for whom local therapy is not mandatory, watchful waiting (WW) is a treatment alternative to androgen-deprivation therapy (ADT), with equivalent oncologic efficacy. Active treatment is recommended mostly for patients with localized disease and a long life expectancy, with radical prostatectomy (RP) shown to be superior to WW in prospective randomized trials. Nerve-sparing RP is the approach of choice in organ-confined disease, while neoadjuvant ADT provides no improvement in outcome variables. Radiation therapy should be performed with ≥74 Gy in low-risk PCa and 78 Gy in intermediate- or high-risk PCa. For locally advanced disease, adjuvant ADT for 3 yr results in superior rates for disease-specific and overall survival and is the treatment of choice. Follow-up after local therapy is largely based on PSA and a disease-specific history, with imaging indicated only when symptoms occur.

Conclusions

Knowledge in the field of PCa is rapidly changing. These EAU guidelines on PCa summarize the most recent findings and put them into clinical practice.

Patient summary

A summary is presented of the 2013 EAU guidelines on screening, diagnosis, and local treatment with curative intent of clinically organ-confined prostate cancer (PCa). Screening continues to be done on an individual basis, in consultation with a physician. Diagnosis is by prostate biopsy. Active surveillance is an option in low-risk PCa and watchful waiting is an alternative to androgen-deprivation therapy in locally advanced PCa not requiring immediate local treatment. Radical prostatectomy is the only surgical option. Radiation therapy can be external or delivered by way of prostate implants. Treatment follow-up is based on the PSA level.