Transketolase like 1 (TKTL1) expression alterations in prostate cancer tumorigenesis Prostate cancer (CaP) is a heterogeneous disease with high variability in regards to clinical outcome and therapeutic response. While some men will develop an indolent CaP not affecting life expectancy, others might die of CaP. Thus, the process of screening and diagnosing, as well as the therapeutic options and monitoring can be difficult for the urologist—to distinguish between lethal and indolent CaP still remains a challenge.
Development of a translational medicine protocol for an NCTN genitourinary clinical trial: Critical steps, common pitfalls and a basic guide to translational clinical research Translational medicine (TM) components of prospective clinical trials provide an invaluable opportunity to test hypotheses that contribute to our knowledge of human disease biology and/or the mechanism of action of a given therapeutic intervention. Our ability to sample tumors and their microenvironment, and the depth and breadth of biological information that can be extracted from them, has increased exponentially in recent years. This information is critical to guide the next steps clinical research if we are to accelerate the pace of progress in cancer treatment.
Robotic versus open partial nephrectomy for highly complex renal masses: Comparison of perioperative, functional, and oncological outcomes Considerable evidence suggests that partial nephrectomy (PN) for localized renal cell carcinoma has equivalent oncological outcomes when compared to radical nephrectomy [1,2]. Another unique feature of PN over radical nephrectomy relates to better renal functional preservation, which may confer a lower risk of cardiovascular disease, translating into better overall survival [3]. Various surgical approaches for PN have been described, including open (OPN) and minimally invasive techniques, namely laparoscopic (LPN) and the robot-assisted (RAPN).
Mechanisms and funding opportunities in genitourinary cancer clinical research Progress in the prevention, diagnosis, and treatment of genitourinary cancers is dependent on well-conducted clinical trials. The complexity and cost of clinical research continues to escalate, and success is dependent on adequate funding. Opportunities to fund such research include federal, industry, and private sources. The mechanisms whereby larger trials are conducted include contract research organizations, publically- and privately funded consortia, and the National Clinical Trials Network of the National Cancer Institute.
Robust method for isolation of tumor infiltrating lymphocytes with a high vital cell yield from small samples of renal cell carcinomas by a new collagenase-free mechanical procedure Since the last decade, therapeutic options for the treatment of advanced renal cell carcinoma (RCC) increased considerably. The checkpoint-inhibitor therapy has emerged as a new treatment regimen with promising outcome [1–3]. This is exemplified by inhibitors targeting the programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) molecules [4] which have shown impressive improvements in treatment responses and patient survival [5,6]. Despite this success, response rates still remain only in the range of 20% [7], which emphasizes the need for increased knowledge on immunopathogenesis of RCC and on the role and phenotypical and functional characteristics of tumor-infiltrating lymphocytes (TIL).
An immediate, single intravesical instillation of mitomycin C is of benefit in patients with non–muscle-invasive bladder cancer irrespective of prognostic risk groups The treatment of non–muscle-invasive bladder cancer (NMIBC) remains a challenge because of its tendency to recur and progress [1,2]. To decrease the risk of recurrence, an immediate instillation of chemotherapy after transurethral resection (TURBT) is administered. The instillation prevents recurrence through eradication of floating tumor cells and residual tumor at the tumor site and by eradication of small overlooked synchronous tumors [3,4]. A recent systematic review and individual patient data meta-analysis by Sylvester et al.
Radical prostatectomy then and now: Surgical overtreatment of prostate cancer is declining from 2009 to 2016 at a tertiary referral center Overtreatment of prostate cancer (CaP) remains an obstacle in delivering high quality care to these patients. Radical prostatectomy (RP) for nonlethal cancers has been reported in as many as 40% of cases in some series [1–5]. The possibility for undesirable sequelae of RP is well-known [6,7], reinforcing the consensus that the operation be restricted to cancers of serious potential [8]. An appreciation of the overtreatment issue has resulted in increased use of active surveillance for low-risk lesions [8].
Female radical cystectomy patients have a higher risk of surgical site infections Radical cystectomy is associated with frequent and often severe adverse events. As systems for recording patient outcomes have become more sensitive and comprehensive over time, the reported risk of adverse events has increased from 20% to 30% in early 1980s to upward of 80% in recent publications [1–8]. Higher quality data pertaining to adverse events have allowed for more accurate patient counseling and have identified specific complications that may be targeted for improvement with interventions.
Current controversies on the role of lymphadenectomy for bladder cancer Significant evidence exists regarding the diagnostic and therapeutic roles of pelvic lymph node dissection at the time of radical cystectomy for patients with bladder cancer. Despite this, lymphadenectomy for bladder cancer is still underutilized and even where performed, controversies exist in regard to what defines an adequate dissection and whether or not the indications for lymphadenectomy have changed now that we are firmly entrenched in the neoadjuvant chemotherapy era. A comprehensive literature review was performed to touch on these important issues and highlight future directions and current trials that will soon provide more clarity for surgeons and patients dealing with bladder cancer.
Re: “Current surgical standards of care in Wilms tumor” The authors have published a valuable article that outlines the current status of surgical care in Wilms tumor, highlighting key technical points as well as addressing areas of controversy and future research directions. One point to clarify for the readership [1]:
FGF-2 is a driving force for chromosomal instability and a stromal factor associated with adverse clinico-pathological features in prostate cancer There is mounting evidence to suggest that stromal cells play an integral role in the progression of prostate cancer (PCa). One of the most frequently altered growth factors in PCa is fibroblast growth factor-2 (FGF-2). It has previously been proposed that early stages of PCa are characterized by a primarily exogenous, that is, stromal cell-derived FGF-2 production, whereas advanced tumors rely more on an autocrine FGF-2 production. Prostate cancer progression is characterized by an increase of genomic instability including aneuploidy and structural chromosomal alterations.
Effect of multimodal analgesia with paravertebral blocks on biochemical recurrence in men undergoing open radical prostatectomy Recent studies suggest that anesthetic technique during radical prostatectomy for prostate cancer may affect recurrence or progression. This association has previously been investigated in series that employ epidural analgesia. The objective of this study is to determine the association between the use of a multimodal analgesic approach incorporating paravertebral blocks and risk of biochemical recurrence following open radical prostatectomy.
Intratumor heterogeneity in prostate cancer Prostate cancer (PCa) has long been thought of as a disease with a heterogeneous phenotype. It can manifest in men as benign growths that can be safely watched or as more aggressive malignancies that can prove fatal. Recent investigations at the genomic, histopathological and molecular levels have identified tumor heterogeneity, the phenomenon of individual tumor cells presenting distinct genomic and phenotypic characteristics, as one of the most confounding and complex factors underlying PCa diagnosis, prognosis, and treatment.
Blue light cystoscopy for the diagnosis of bladder cancer: Results from the US prospective multicenter registry Blue light cystoscopy (BLC) using hexaminolevulinate (HAL/Cysview/Hexvix) has been previously shown to improve detection of non–muscle-invasive bladder cancer (NMIBC). Herein, we evaluated the detection of malignant lesions in a heterogenous group of patients in the real world setting and documented the change in risk category due to upstaging or upgrading.
The natural history of large renal masses followed on observation The safety and feasibility of active surveillance in comorbid patients with renal masses ≥4.0cm is uncertain. The aim of this study is to describe our institutional experience with the observation of large renal masses.
Lifestyle and nutritional modifiable factors in the prevention and treatment of bladder cancer Bladder cancer is one of the top 5 most common cancers diagnosed in the U.S. It is also one of the most expensive cancers to treat through the life course given its high rate of recurrence. While cigarette smoking and occupational exposures have been firmly established as risk factors, it is less certain whether modifiable lifestyle factors such as diet and physical activity play roles in bladder cancer etiology and prognosis. This literature review based on a PubMed search summarizes the research to date on key dietary factors, types of physical activity, and smoking in relation to bladder cancer incidence, and discusses the potential public health implications for formalized smoking cessation programs among recently diagnosed patients.
Role of lymph node dissection in renal cell cancer Lymph node metastasis in renal cell cancer (RCC) portends an extremely poor prognosis. Despite proven staging benefit, the therapeutic value of lymph node dissection in RCC remains questionable. The only prospective randomized trial examining its role failed to show any benefit. However, subsequent retrospective publications have attempted to identify high-risk cohorts and clinical scenarios where removal of nodes may improve survival. The aim of this article is to provide a comprehensive review looking at the role of lymph node dissection in RCC if any, the ideal extent of dissection, and also tools a clinician could employ to identify those who would most likely benefit from this exercise.
Key design and analysis principles for quality of life and patient-reported outcomes in clinical trials Advances in early detection and therapy have increased the number of prostate cancer survivors, leading to a greater emphasis on examining patient-reported outcomes (PROs). PROs augment clinical outcomes, providing a more comprehensive assessment of the patient experience, including symptoms and quality of life, that may impact the overall evaluation of new therapies. The successful incorporation of PROs into clinical trials requires adherence to key design and analysis principles. We present these principles and argue that adherence to these principles is vital to ensure valid interpretation of clinical trial findings, identify meaningful differences among investigational strategies, and better translate clinical trial results to diverse stakeholders.
The resounding effect of DNA repair deficiency in prostate cancer An estimated one-fifth or more of metastatic castration-resistant prostate cancer (mCRPC) harbor defects in genes involved in DNA repair pathway (e.g., BRCA2, BRCA1, and others). Early evidence suggests these alterations may be predictive of therapeutic response to PARP inhibitors and platinum chemotherapy, thought to reflect principles of synthetic lethality and are currently being investigated in an increasing number of prospective clinical trials. Other studies have examined these alterations as prognostic biomarkers and in association with response to currently available treatments.
Editorial: Managing locally advanced bladder cancer. Third International Bladder Cancer Network seminars series This third Seminars Series of the IBCN continues to appraise current knowledge, question today's standards and aim at further advancing the current management of patients with bladder cancer [1]. However, in contrast to previous issues, which were comprised largely of review articles, this time original research articles are also included.
Recommendations for follow-up of muscle-invasive bladder cancer patients: A consensus by the international bladder cancer network Several guidelines exist that address treatment of patients with nonmetastatic muscle-invasive bladder cancer (MIBC). However, most only briefly mention follow-up strategies for patients and hence the treating physician is often left to infer on what the preferred follow-up schema would be for an individual patient. Herein, we aim to synthesize recommendations for follow-up of patients with MIBC for easy reference.
Contribution of bladder cancer pathology assessment in planning clinical trials Bladder cancer is a heterogeneous disease that demonstrates a wide spectrum of histologic features. The modern classification of bladder cancer is largely based on pathologic analysis, which assesses tumor grade, stage, type, size, and other features that are essential for understanding the biological behavior of bladder cancer. Bladder cancers with similar histologic features are likely to show comparable responses to a new therapeutic agent in clinical trial. Furthermore, pathologic analysis also evaluates the quality of tissue samples in clinical trial to ensure the integrity of various molecular tests.
Molecular correlates of intermediate- and high-risk localized prostate cancer Clinicopathologic parameters, including Gleason score, remain the most validated prognostic factors for patients diagnosed with localized prostate cancer (PCa). However, patients of the same risk groups have exhibited heterogeneity of disease outcomes. To improve risk classification, multiple molecular risk classifiers have been developed, which were designed to inform beyond existing clinicopathologic classifiers. Alterations affecting tumor suppressors and oncogenes, such as PTEN, MYC, BRCA2, and TP53, which have been long associated with aggressive PCa, demonstrated grade-dependent frequency of alterations in localized PCas.
Epigenetic reprogramming: A key mechanism driving therapeutic resistance Prostate cancer initiation, development and progression is driven by androgen receptor (AR) signaling. Androgen deprivation therapy is the primary treatment for patients that present with locally advanced or metastatic disease. However, androgen deprivation therapy is not curative, and patients will progress to castrate-resistant disease (CRPC). Although most patient’s progress to CRPC via restoration of AR signaling (CRPC-Ad), approximately a quarter of patients will progress via mechanisms independent of AR signaling.
Organizing a clinical trial for the new investigator Clinical trials organization can be daunting especially when orienting to a new system. The steps to a successful clinical trial are not concrete and vary based on the system.
Optimizing androgen deprivation therapy with radiation therapy for aggressive localized and locally advanced prostate cancer Radiation therapy with androgen deprivation therapy (ADT) has historically been one of the mainstays of treatment for intermediate- and high-risk prostate cancer. The benefit of ADT likely derives from both enhancing local control and inhibiting micrometastatic disease. While level 1 evidence has demonstrated the benefits of 4–6 months of ADT for all men with intermediate-risk disease, further stratification of intermediate-risk prostate cancer into favorable and unfavorable subgroups indicates that ADT may not be necessary for favorable intermediate-risk disease but likely still provides a survival advantage for unfavorable intermediate-risk disease, even in the dose escalation era.
Predicting therapy response and resistance in metastatic prostate cancer with circulating tumor DNA The treatment of metastatic castration-resistant prostate cancer (mCRPC) is empirical, with progress to a more precision medicine approach hampered by lack of predictive biomarkers. This is due in large part to the historical difficulty of molecularly profiling a bone-predominant metastatic disease. Focus has turned to minimally invasive sources of tumor material to better understand the molecular drivers of therapy resistance. Circulating cell-free tumor DNA (ctDNA) is highly abundant in the bloodstream of mCRPC patients and appears to provide an accurate snapshot of real-time tumor genomics.
Characterizing recurrent and lethal small renal masses in clear cell renal cell carcinoma using recurrent somatic mutations Small renal masses (SRMs) with evidence of clear cell renal cell carcinoma (ccRCC) are understudied. Current algorithms for the management of SRMs include surgical resection, ablation, and active surveillance. We sought to identify genomic biomarkers that could potentially refine the management of ccRCC in SRMs, especially in patients being evaluated for active surveillance.
An update of research evidence on nutrition and prostate cancer Prostate cancer (PCa) remains a leading cause of mortality in US and other countries. Preclinical and clinical studies have examined the role of nutrition and dietary intake on the incidence and progression of PCa with mixed results.
The expanding repertoire of targets for immune checkpoint inhibition in bladder cancer: What lies beneath the tip of the iceberg, PD-L1 Over the last decade, a new understanding of tumor-immune system interplay has been ushered in, lead in large part by the discovery of immune checkpoints mediated through B7-CD28 family interactions. Therapeutic blockade of the PD-L1 immune checkpoint pathway has already shown great success as a cancer immunotherapy for advanced urothelial carcinoma, leading to durable clinical remissions in an otherwise incurable disease. There are newly described members of the B7-CD28 family including B7-H3, B7x, and HHLA2.
Role of ultrasensitive prostate-specific antigen in the follow-up of prostate cancer after radical prostatectomy Prostate-specific antigen (PSA) is an important tool in the follow-up of prostate cancer after radical prostatectomy (RP). However, the relevance of ultrasensitive PSA (uPSA) after RP is not well defined. The aim of this study was to investigate the value of uPSA in follow-up after RP and to determine whether ultrasensitive PSA doubling time (uDT) correlates with traditional PSA doubling time (tDT).
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