Health-related Quality of Life After Primary Treatment for Localized Prostate Cancer: A Systematic Review of the Literature

Background: Prostate cancer is the most commonly diagnosed non-cutaneous cancer in American men. In 2007, approximately 218,890 men were diagnosed with and 27,050 men died from prostate cancer. With the advent of PSA screening, younger men are being diagnosed with prostate cancer at the earliest stages of disease. Over 90% of cancers are detected at the localized or regional stage, and early detection allows for a number of treatment options. Currently, there is no consensus on the best treatment for localized prostate cancer, but the most commonly utilized options are prostatectomy, radiation therapy and active surveillance. Without evidence from randomized controlled trials on the mortality benefits of these treatments, health-related quality of life (HRQOL) is becoming an increasingly important factor in treatment decision-making. The purpose of this paper is to systematically review the evidence regarding HRQOL after primary treatment for localized prostate cancer. Methods: Inclusion criteria were English language articles published between 1995 and 2007. The studies must have focused on primary treatment of localized prostate cancer. Any study that addressed metastatic cancer or secondary treatment was excluded. Studies must use the SF-36 questionnaire for measuring general HRQOL. All study types were included in the review. The literature search was conducted using the PubMed MeSH terms Prostatic Neoplasms/therapy [MeSH] and keywords localized or early stage AND (SF-36 OR short form 36). An abstract review was then performed, followed by a full article review. At the end of the selection process, 14 articles met all the inclusion criteria and were considered in this review. Results The 14 studies varied widely in their study designs. The reporting of HRQOL within each study differed between studies, with some reporting only component scores, while others report each of the eight domains of the SF-36. Considering these differences, the review showed that there were some unique trends for recovery of HRQOL by treatment type. For those men undergoing prostatectomy, early decreases in specific domains of HRQOL (bodily pain, role physical, and role emotional) were seen at 3 to 6 months. These deficits usually returned to the patients' baseline by 12 months after treatment. For men choosing radiation, fewer decreases were seen in the immediate post-treatment period. Long term decreases in role physical and role emotional were seen in those studies with follow-up periods longer than 1 to 2 years. The data regarding active surveillance was relatively sparse, with only three studies evaluating HRQOL for those men choosing active surveillance. There was some evidence for decreases in physical function, general health and role emotional. Conclusions: Without convincing randomized controlled evidence showing a mortality benefit for any of the primary treatment options, HRQOL serves as a useful outcome for treatment decision-making. More studies, including upcoming randomized controlled trials, should include robust measures of HRQOL as primary outcomes in their study designs.Master of Public Healt

Modern Pathologic Diagnosis of Renal Oncocytoma

Oncocytoma is a well-defined benign renal tumor, with classic gross and histologic features, including a tan or mahogany-colored mass with central scar, microscopic nested architecture, bland cytology, and round, regular nuclei with prominent central nucleoli. As a result of variations in this classic appearance, difficulty in standardizing diagnostic criteria, and entities that mimic oncocytoma, such as eosinophilic variant chromophobe renal cell carcinoma and succinate dehydrogenase-deficient renal cell carcinoma, pathologic diagnosis remains a challenge. This review addresses the current state of pathologic diagnosis of oncocytoma, with emphasis on modern diagnostic markers, areas of controversy, and emerging techniques for less invasive diagnosis, including renal mass biopsy and advanced imaging

Getting cancer prevalence right: using state cancer registry data to estimate cancer survivors

Cancer incidence and mortality statistics provide limited insight regarding the cancer survivor population and its needs. Cancer prevalence statistics enumerate cancer survivors—those currently living with cancer. Commonly used limited-duration prevalence (LDP) methods yield biased estimates of the number of survivors. National estimates may not allow sufficient granularity to inform local survivorship programs. In this study, complete prevalence (CP) methods are applied to actual North Carolina Central Cancer Registry (NCCCR) data to generate better, more informative prevalence estimates than previous methods

Sav1 Loss Induces Senescence and Stat3 Activation Coinciding with Tubulointerstitial Fibrosis

Tubulointerstitial fibrosis (TIF) is recognized as a final phenotypic manifestation in the transition from chronic kidney disease (CKD) to end-stage renal disease (ESRD). Here we show that conditional inactivation of Sav1 in the mouse renal epithelium resulted in upregulated expression of profibrotic genes and TIF. Loss of Sav1 induced Stat3 activation and a senescence-associated secretory phenotype (SASP) that coincided with the development of tubulointerstitial fibrosis. Treatment of mice with the YAP inhibitor verteporfin (VP) inhibited activation of genes associated with senescence, SASPs, and activation of Stat3 as well as impeded the development of fibrosis. Collectively, our studies offer novel insights into molecular events that are linked to fibrosis development from Sav1 loss and implicate VP as a potential pharmacological inhibitor to treat patients at risk for developing CKD and TIF

Racial differences in PSA screening interval and stage at diagnosis

This study examined PSA screening interval of black and white men aged 65 or older and its association with prostate cancer stage at diagnosis

MYC activation cooperates with Vhl and Ink4a/Arf loss to induce clear cell renal cell carcinoma

Renal carcinoma is a common and aggressive malignancy whose histopathogenesis is incompletely understood and that is largely resistant to cytotoxic chemotherapy. We present two mouse models of kidney cancer that recapitulate the genomic alterations found in human papillary (pRCC) and clear cell RCC (ccRCC), the most common RCC subtypes. MYC activation results in highly penetrant pRCC tumours (MYC), while MYC activation, when combined with Vhl and Cdkn2a (Ink4a/Arf) deletion (VIM), produce kidney tumours that approximate human ccRCC. RNAseq of the mouse tumours demonstrate that MYC tumours resemble Type 2 pRCC, which are known to harbour MYC activation. Furthermore, VIM tumours more closely simulate human ccRCC. Based on their high penetrance, short latency, and histologic fidelity, these models of papillary and clear cell RCC should be significant contributions to the field of kidney cancer research

Going Bone Deep: Osseous Rosai–Dorfman Disease in an Adult with Recurrent, Culture-Negative Osteomyelitis

A patient presented for medical care on three separate occasions over the course of two years with recurrent right knee pain attributed to chronic osteomyelitis. Careful assessment revealed that his symptoms were caused by osseous Rosai–Dorfman disease. This case presents an alternative diagnostic possibility for culture-negative chronic osteomyelitis

Molecular characterization of plasmacytoid urothelial carcinoma and the impact on treatment implications

Bladder cancer researchers and clinicians have increasingly viewed tumor biology through the lens of genomic and molecular alterations, drastically improving our knowledge of the underlying disease biology. This understanding has led to significant advances in treatment options that allow implementation of a personalized approach to cancer treatment. Large-scale genomic studies initially focused on the most common forms of bladder cancer. However, as genomic and molecular technologies become more widespread and are applied to less common variant histologies, we are gaining additional insight into the unique molecular and genomic characteristics driving the biology of variant histologies of bladder cancer. In this review, we summarize the current state of knowledge of molecular alterations underlying the distinct tumor biology of plasmacytoid urothelial carcinoma and how these alterations may impact treatment options

Development and validation of a NanoString BASE47 bladder cancer gene classifier.

BackgroundRecent molecular characterization of urothelial cancer (UC) has suggested potential pathways in which to direct treatment, leading to a host of targeted therapies in development for UC. In parallel, gene expression profiling has demonstrated that high-grade UC is a heterogeneous disease. Prognostic basal-like and luminal-like subtypes have been identified and an accurate transcriptome BASE47 classifier has been developed. However, these phenotypes cannot be broadly investigated due to the lack of a clinically viable diagnostic assay. We sought to develop and evaluate a diagnostic classifier of UC subtype with the goal of accurate classification from clinically available specimens.MethodsTumor samples from 52 patients with high-grade UC were profiled for BASE47 genes concurrently by RNAseq as well as NanoString. After design and technical validation of a BASE47 NanoString probeset, results from the RNAseq and NanoString were used to translate diagnostic criteria to the Nanostring platform. Evaluation of repeatability and accuracy was performed to derive a final Nanostring based classifier. Diagnostic classification resulting from the NanoString BASE47 classifier was validated on an independent dataset (n = 30). The training and validation datasets accurately classified 87% and 93% of samples, respectively.ResultsHere we have derived a NanoString-platform BASE47 classifier that accurately predicts basal-like and luminal-like subtypes in high grade urothelial cancer. We have further validated our new NanoString BASE47 classifier on an independent dataset and confirmed high accuracy when compared with our original Transcriptome BASE47 classifier.ConclusionsThe NanoString BASE47 classifier provides a faster turnaround time, a lower cost per sample to process, and maintains the accuracy of the original subtype classifier for better clinical implementation