Cytology and Urinary Markers for the Diagnosis of Bladder Cancer

Primary detection and follow-up of patients with non–muscle-invasive (NMI) bladder cancer (BC) is done by urethro-cystoscopy (UCS) and, in most cases, cytology. Many urine-based tests have been developed, and in general, these tests have a higher sensitivity than cytology but a lower specificity. In this review, we assessed the value of urine tests for screening, primary detection, and surveillance of NMIBC. Considering the frequency of UCS for follow-up, having markers for recurrent BC would be especially useful. Therefore, we updated our systematic review to include five commonly studied urine markers (BTA stat, NMP22, uCyt + /Immunocyt, FISH UroVysion, and microsatellite analysis) and cytology for surveillance. The sensitivity and/or specificity of cytology and these five markers were more than 5% lower for patients under surveillance compared to the numbers reported in other reviews, confirming that the performance of urine markers and cytology is lower for the detection of recurrent BC than is UCS. Recent data from the first randomized trial to investigate the possibility of lowering UCS frequency with urinary microsatellite analysis showed substantial underestimation of sensitivity and specificity if the urologist was not aware of the urine test outcome. These results question but do not replace UCS as the gold standard for NMIBC surveillance. In conclusion, cytology is still important as an adjunct for the evaluation of patients with hematuria and the surveillance of patients with high-risk NMIBC. Urine markers other than cytology may play a role in future screening studies and the follow-up of patients with low-grade (G1–2) NMIBC.     

Old and New Urinary Markers: Which One is the PSA for Bladder Cancer?

ObjectivesTo review the role of urinary-based markers in the management of bladder cancer.MethodsA literature search was performed to examine the field of urinary-based markers for bladder cancer. The principles for an ideal test to detect bladder cancer using a urinary assay were defined. Reported biomarkers were evaluated for their potential to fulfil these principles.ResultsMany of the criteria defined by Wilson and Junger for a screening program can be applied to urinary-based bladder cancer markers. Biomarkers can be used to either diagnose the disease or survey patients to detect progression or recurrence following initial endoscopic surgery. These roles are separate and different biomarkers may be needed to reflect the biology of these processes. To date, NMP22 appears as one of the best evaluated biomarkers, but its role needs to be clearly defined. Most biomarkers detect one form of bladder cancer, either invasive or noninvasive, and thus have a lower sensitivity than needed to replace cystoscopy.ConclusionsMany reported urinary-based biomarkers can be used within appropriate management regimens to reduce cystoscopic burden and produce economic savings. No biomarker reported to date is sufficiently accurate to replace the need for cystoscopy.     

Immunotherapy for Urothelial Carcinoma: Current Evidence and Future Directions

Purpose of Review

Until recently, effective treatment options for patients with advanced urothelial carcinoma were limited to platinum-based chemotherapy. In the post-platinum setting and for patients ineligible for cisplatin, minimally effective second-line chemotherapy was used and outcomes were poor. The approval of immune checkpoint inhibitors has significantly changed the treatment landscape of urothelial carcinoma. Here, we review current data demonstrating their efficacy in advanced disease and ongoing trials investigating novel combination strategies.

Recent Findings

Since May 2016, five agents targeting the programmed cell death 1 (PD-1) pathways have been approved for use after progression on platinum-based chemotherapy. Further, atezolizumab and pembrolizumab are approved for use in cisplatin-ineligible patients with high programmed death-ligand 1 (PD-L1) expression. Preliminary studies have shown their safety and efficacy as neoadjuvant therapy in muscle-invasive bladder cancer. Several ongoing trials are investigating these agents in combination with radiation therapy, platinum-based chemotherapy, other immune checkpoint inhibitors, and targeted agents.

Summary

Immune checkpoint inhibitors have demonstrated durable efficacy in patients with advanced urothelial carcinoma as first- and second-line therapy. Ongoing studies will help define the optimal sequence, combination strategies, and predictive biomarkers of response.

     

后腹腔镜下肾输尿管全长切除术治疗上尿路尿路上皮癌

目的探讨后腹腔镜下肾输尿管全长切除术治疗上尿路尿路上皮癌的临床效果。方法临床收集2010年1月至2014年1月间在本院接受后腹腔镜下肾输尿管全长切除术的患者63例,统计相关手术及术后随访数据,评价此术式治疗上尿路尿路上皮癌的临床效果。结果 63例患者手术均顺利完成,术后恢复良好,术后病理检查均为尿路上皮癌,手术时间平均[110(90~180)]分钟,术中出血量平均[70(30~150)]ml,术后引流管留置时间平均[3(2~4)]天,导尿管留置时间平均[7(4~15)]天,住院时间平均[5(4~7)]天,术后59例患者接受随访(失访4例),随访时间平均[8(3~24)]月。所有患者术后均无发热、漏尿等明显并发症发生,接受随访患者在随访期3例患者术后3~6月内出现膀胱肿瘤,并行膀胱肿瘤电切术,1例患者死亡,死于脑血管病,余患者在随访期无肿瘤复发。结论后腹腔镜下肾输尿管全长切除术治疗上尿路上皮癌临床效果确切,手术时间相对较短,创伤小,患者术后恢复快,手术安全易行,可予以临床推广。     

Urinary Pyridinoline and Deoxypyridinoline as Potential Markers of Bone Metastasis in Patients with Prostate Cancer

Purpose

The levels of probable markers of bony metastatic disease were measured to evaluate their efficacy as predictors of disease and therapeutic outcome.

Materials and Methods

Urinary pyridinoline, urinary deoxypyridinoline, serum alkaline phosphatase and serum osteocalcin were measured in patients with benign prostatic hyperplasia, clinically localized prostate cancer and prostate cancer with bone metastases. Also, urinary pyridinoline and deoxypyridinoline were compared in 2 groups of patients with metastatic prostate cancer of the bone who demonstrated progression or positive response to treatment. Urinary pyridinoline and deoxypyridinoline were determined by high performance liquid chromatography and were normalized to urinary creatinine.

Results

Levels of pyridinoline and deoxypyridinoline in urine, and the level of alkaline phosphatase in serum from patients with bone metastatic prostate cancer were significantly greater than levels in patients with benign prostatic hyperplasia or localized prostate cancer. Serum osteocalcin levels failed to separate the 3 groups. Serial measurement of urinary pyridinoline and deoxypyridinoline was correlated with a positive response to treatment (decreased) and with clinical progression of disease (increased) before detection of new bone lesions by bone scintigraphy.

Conclusions

Measurement of urinary pyridinoline and deoxypyridinoline may provide a useful marker of prostate cancer metastatic to bone and may be useful in monitoring the response to treatment.     

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.     

Indications and Oncologic Outcome of Radical Cystectomy for Urothelial Bladder Cancer

ContextRadical cystectomy (RC) offers the best opportunity for ultimate cure of high-grade and high-risk invasive bladder cancer (BCa).ObjectiveTo review the available literature on indications for and oncologic outcomes of RC for urothelial carcinoma of the bladder.Evidence acquisitionA database search of the US National Library of Medicine (PubMed) was performed for relevant medical articles using the Medical Subject Headings invasive bladder cancer and radical cystectomy with restrictions to English-language publications.Evidence synthesisImmediate or early RC should be offered as a treatment of choice to all patients with recurrent or multifocal high-grade T1 tumours, T1 tumours at high risk of progression, failures of bacillus Calmette-Guérin treatment, and muscle-invasive bladder tumours. RC offers excellent recurrence-free survival (RFS) and disease-specific survival rates as well as local tumour control in patients with organ-confined and node-negative disease. Tumour control in non–organ-confined tumours is still satisfactory, with long-term RFS rates of about 50%. For node-positive disease, surgery may only be curative in approximately one-fourth of patients.ConclusionsEvidence from the literature supports early, aggressive surgical management for invasive BCa. Risk stratification of patients with BCa based on pathologic features at initial transurethral resection or at recurrence can select those patients most appropriate for RC early. In patients with organ-confined, lymph node–negative urothelial bladder carcinoma, excellent long-term survival rates can be achieved.     

The Cancer Immunogram as a Framework for Personalized Immunotherapy in Urothelial Cancer

Context

The abysmal outlook of urothelial cancer (UC) has changed with the introduction of immunotherapy. Still, many patients do not respond and distinctive biomarkers are currently lacking. The rise of this novel armamentarium of immunotherapy treatments, in combination with the complex biology of an immunological tumor response, warrants the development of a comprehensive framework that can provide an overview of important immunological processes at play in individual patients.