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 :
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.
Metabolic changes in bladder cancer Bladder cancer is a common solid tumor. Outcomes are poor in advanced disease, with few novel clinical therapeutics introduced over the previous several decades. Otto Warburg's original hypothesis that cancer cells use aerobic glycolysis to produce ATP instead of traditional oxidative phosphorylation in the mitochondria was a landmark discovery in its time. Recent studies indicate metabolic changes in cancer are far more complex than originally anticipated though. The purpose of this review is to understand metabolic changes that occur in bladder cancer, how targeting these changes could potentially be used therapeutically, and the current treatments that target these metabolic changes
Finasteride does not prevent bladder cancer: A secondary analysis of the Medical Therapy for Prostatic Symptoms Study Preclinical models have demonstrated that androgen receptor modulation can influence bladder carcinogenesis with an inverse association observed between serum androgen levels and bladder cancer (BC) incidence. It is still unclear whether 5α-reductase inhibitors, by preventing the conversion of testosterone to dihydrotestosterone, have a similar effect. This study aims to evaluate whether dihydrotestosterone-mediated androgen activity has an impact on BC incidence in a cohort of men included in a clinical trial of finasteride vs.
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.
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.
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.
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