Soc. Int. Urol. J., Volume 1, Issue 1 (October 2020) – 12 articles , Pages 3-84

Testicular germ cell tumor (GCT) is the most common malignancy in 18- to 40-year-old men. Unlike most other cancers, GCT is frequently curable even when metastatic. These tumors can be classified histologically into seminoma and non-seminoma, which determines treatment. Therefore, successful treatment requires accurate diagnosis, classification, and monitoring. Serum tumor markers, including lactate dehydrogenase, α-fetoprotein, and β-human chorionic gonadotropin, aid in the classification and staging of GCTs. These markers therefore play a critical role in the decision-making process when managing GCT patients. However, there exist many scenarios in which these markers fail to perform adequately. This is particularly true in the case of seminoma, where only 10% to 15% will have elevated serum tumor markers. Non-specific elevation of these markers is also a common occurrence, complicating the interpretation of borderline positive results, particularly in follow-up. To bridge this gap in performance, next generation biomarkers are being investigated. In this review, we consider the role of conventional serum tumor markers in GCT management and discuss recent advances in the next generation of biomarkers, with a focus on circulating microRNAs. We discuss the value that circulating microRNAs could bring as an addition to currently used markers, as well as potential weaknesses, in GCT management. Full article

The development and description of renal cell carcinoma (RCC) subtypes has led to an increase in demand for tissue biomarkers. This has implications not only in informing diagnosis, but also in guiding treatment selection and in prognostication. Although historically, many immunohistochemical (IHC) stains have been widely characterized for RCC subtypes, challenges may arise in interpreting these results. These may include variations in tumor classification, specimen collection and processing, and IHC techniques. In light of the reclassification of RCC subtypes in 2016, there remains a requirement for a comprehensive outline of tissue biomarkers that may be used to differentiate between RCC subtypes and distinguish these from other non-renal neoplasms. In this review, concise summaries of the commonest RCC subtypes, including clear cell, papillary, and chromophobe RCC, have been provided. Important differences have been highlighted between chromophobe RCC and renal oncocytomas. An overview of the current landscape of tissue biomarkers in other RCC subtypes has also been explored, revealing the variable staining results reported for some markers, whilst highlighting the essential markers for diagnosis in other subtypes. Full article

Each year, there are an estimated 550 000 diagnoses of bladder cancer worldwide, and almost 200 000 deaths from bladder cancer. The need for frequent follow-up, including invasive procedures like cystoscopy, repetitive procedures like transurethral resection of bladder tumors and intravesical instillation therapy in non-muscle invasive stages, as well as systemic treatment with or without radical local treatment in advanced stages, makes bladder cancer one of the most expensive cancers to treat. Prognostic and predictive biomarkers have the potential to fundamentally change bladder cancer treatment algorithms, which may result in improved patient comfort and oncological outcomes and may also decrease the socioeconomic burden of the disease. Intense research has resulted in the recent approval by the U. S. Food and Drug Administration of the first agent for this disease that targets a specific mutation (fibroblast-growth factor receptor). Yet, many areas of bladder cancer diagnosis and treatment have remained unchanged for decades, and this is only in part due to their therapeutic success. In order to integrate biomarkers into clinical practice patterns, specific considerations for the different disease stages and settings should be kept in mind. Especially in the setting of screening, work-up of hematuria, as well as surveillance of patients with non-muscle invasive bladder cancer, (urine-)biomarkers may prove useful. They must, however, demonstrate a high enough sensitivity to pick up a cancer diagnosis or recurrence, allow easy handling (preferably a point-of-care setting) and adequate cost–benefit relationships, while also providing additional information to a full work-up. A biomarker to identify patients with muscle invasive bladder cancer who are in need of—and likely to respond to—neoadjuvant therapy would be very useful. In later disease, early detection of recurrence or progression, as well as biomarkers guiding treatment decisions between the available systemic agents, will be paramount for improved patient care. Full article

Background: The use of urine markers for diagnosis and surveillance has been a topic of broad interest and ongoing controversies in the management of patients with bladder cancer. There has been a constant quest for markers that demonstrate clinical utility. Aim: In the framework of the International Consultation on Urological Diseases 2019 on Molecular Biomarkers in Urologic Oncology, a comprehensive review of literature on urinary biomarkers for bladder cancer has been performed. Results: Currently available urinary markers include protein-based markers, RNA-based markers, and DNA-based markers. The introduction of high-throughput analysis technologies provides the opportunity to assess multiple parameters within a short period of time, which is of interest for RNA-based, DNA-based, and protein-based marker systems. A comprehensive analysis of molecular alterations in urine samples of bladder cancer patients may be of interest not only for diagnosis and surveillance but also for non-invasive longitudinal assessment of molecular, potentially therapy-relevant, alterations. However, most systems lack prospective validation within well-designed trials and have not been broadly implemented in daily clinical practice. Conclusions: Because of limited data from prospective trials, the routine use of any urine marker except cytology is not considered as standard of care in international guidelines. There is an urgent need for prospective trials of urine markers to answer specific clinical questions. Full article

Tumour molecular features are increasingly linked to treatment response and patient prognosis in advanced prostate cancer. Plasma cell-free circulating tumour DNA (ctDNA) isolated from a minimally invasive blood draw offers a convenient source of tumour material to develop clinical biomarkers. Importantly, the burden of ctDNA in the blood has strong prognostic implications at different points during the natural history of metastatic progression. In prostate cancer, the identification of somatic profiles from ctDNA requires a broad next-generation sequencing approach because of the low mutation rate and frequent structural rearrangements. Nevertheless, comparison of genomic profiles between liquid and tissue biopsies has demonstrated that ctDNA is a surrogate for tumour tissue in the metastatic setting. Our understanding of resistance to androgen receptor (AR) directed therapies has been significantly augmented by the frequent detection of AR gene amplifications, mutations, and structural rearrangements via liquid biopsy. Furthermore, early studies suggest that distinct molecular subtypes derived from ctDNA profiling can help determine the optimal therapeutic regimen for an individual patient and enable real-time monitoring for therapy response and resistance. Indeed, in clinical trials targeting the DNA damage repair pathway in prostate cancer, ctDNA-based assessment of DNA repair status is already under evaluation as a predictive biomarker. Recent advances in the study of circulating DNA fragments now make it possible to interrogate aspects of the epigenome. In this review, we describe the various applications of plasma ctDNA in metastatic prostate cancer, including its potential role as a clinically informative liquid biomarker. Full article

At every stage of the prostate cancer journey from screening and diagnosis to management of advanced disease, patients and clinicians face dilemmas and decisions that can impact long-term outcomes. Although traditional risk stratification in prostate cancer is based on serum prostate specific antigen, clinical stage and Gleason score, in recent years, biomarkers have been developed that may be useful in several clinical scenarios. Biomarkers that can accurately predict an individual patient’s risk, prognosis, and response to specific treatments could lead to improvements in decision-making and clinical care. Although there is evidence to support the use of biomarkers to guide management decisions, the optimal scenario in which to use them, how to interpret the results, and how to incorporate those results into clinical decision-making can be confusing. Nevertheless, in the era of personalized and precision medicine, it is important for clinicians to be aware of what tests are available, what clinical questions they seek to answer, and what limitations they have. This review focuses on the serum and urine biomarkers for the management of prostate cancer that have been under intense investigation in recent years. Full article

The clinical course of localized prostate cancer varies widely, from indolent disease unlikely to need treatment to aggressive disease requiring intensive, multimodal therapy. Traditionally, treatment decisions have been based on clinical and pathologic factors, including serum prostate specific antigen (PSA), clinical stage, and Gleason score. However, these factors have limited ability to describe the underlying tumor biology. Tissue-based genomic tests have emerged as a promising tool to more accurately characterize prostate cancer biology and predict clinical course. Using prostate cancer tissue obtained at pre-treatment biopsy or radical prostatectomy, these tests exploit the expression of specific genes involved in key biological pathways and, as a result, have the potential to aid clinical decision-making. The current review summarizes available data describing the clinical use of 5 commercially available tissue-based genomic assays in a number of clinical scenarios. Full article

Most candidate biomarkers are never adopted into clinical practice. The likelihood that a biomarker with good predictive properties will be incorporated into urologic decision-making and will improve patient care can be enhanced by following established principles of biomarker development. Studies should follow the REMARK guidelines, should have clinically relevant outcomes, and should evaluate the biomarker on the same patients to whom the biomarker would be applied in practice. It is also important to recognize that biomarker research is comparative: the question is not whether a biomarker provides information, but whether it provides better information than is already available. Continuous biomarkers should not be categorized above or below a fixed cutpoint: risk prediction allows for individualization of care. The risk predictions must be calibrated, that is, close to a patient’s true risk, and decision analysis is required to determine whether using the biomarker in clinical practice would change decisions and improve outcomes. Finally, impact studies are needed to evaluate how use of the biomarker in the real world affects outcomes. Full article

A “biomarker” is any measurable characteristic that indicates the presence or absence of disease or the biological response to a stimulus, typically an exposure or intervention. The FDA-NIH Biomarker Working Group has produced a document called Biomarkers, EndpointS and other Tools (BEST), which defines 7 categories of biomarkers according to their clinical usage: susceptibility and risk, diagnostic, monitoring, prognostic, predictive, pharmacodynamic and treatment response, and safety. We approach the classification of biomarkers in 2 additional ways: their bodily source and their measurement type. In the context of their use in genitourinary malignancy, we also consider factors that influence their use and reliability in clinical and research applications. Full article