Active Surveillance for Prostate Cancer: A Systematic Review of the Literature

Context: Prostate cancer (PCa) remains an increasingly common malignancy worldwide. The optimal management of clinically localized, early-stage disease remains unknown, and profound quality of life issues surround PCa interventions. Objective: To systematically summarize the current literature on the management of low-risk PCa with active surveillance (AS), with a focus on patient selection, outcomes, and future research needs. Evidence acquisition: A comprehensive search of the PubMed and Embase databases from 1980 to 2011 was performed to identify studies pertaining to AS for PCa. The search terms used included prostate cancer and active surveillance or conservative management or watchful waiting or expectant management. Selected studies for outcomes analysis had to provide a comprehensive description of entry characteristics, criteria for surveillance, and indicators for further intervention. Evidence synthesis: Data from seven large AS series were reviewed. Inclusion criteria for surveillance vary among studies, and eligibility therefore varies considerably (4-82%). PCa-specific mortality remains low (0-1%), with the longest published-median follow-up being 6.8 yr. Up to one-third of patients receive secondary therapy after a median of about 2.5 yr of surveillance. Surveillance protocols and triggers for intervention vary among institutions. Most patients are treated for histologic reclassification (27-100%) or prostate-specific antigen doubling time <3 yr (13-48%), while 7-13% are treated with no evidence of progression. Repeat prostate biopsy with a minimum of 12 cores appears to be important for monitoring patients for changes in tumor histology over time. Conclusions: AS for PCa offers an opportunity to limit intervention to patients who will likely benefit the most from radical treatment. This approach confers a low risk of disease-specific mortality in the short to intermediate term. An early, confirmatory biopsy is essential for limiting the risk of underestimating tumor grade and amount. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved

Metastatic signet-ring cell carcinoma of the urinary bladder: A novel management approach to a rare tumor.

Primary signet-ring cell carcinoma (SRCC) of the urinary bladder, a variant of adenocarcinoma, is exceedingly rare and as a result no gold standard exists for its management. We report a case of primary SRCC of the bladder with recurrent metastases; we utilized an innovative diagnostic approach and the patient exhibited a treatment response to palliative FOLFOX-6 chemotherapy

Disulfide-crosslinked nanomicelles confer cancer-specific drug delivery and improve efficacy of paclitaxel in bladder cancer

Chemotherapy commonly used in the treatment of advanced bladder cancer is only moderately effective and associated with significant toxicity. There has been no appreciable improvement in overall survival over the last three decades. The goal of this project is to develop and characterize bladder cancer-specific nanometer-scale micelles loaded with the chemotherapeutic drug paclitaxel (PTX) and determine the anti-tumor activity and toxicity. Micelle-building-material telodendrimers were synthesized through the stepwise conjugation of eight cholic acid units at one terminus of polyethylene glycol (PEG) and a bladder cancer-specific targeting peptide named PLZ4 at the other terminus. To synthesize disulfide-crosslinked PLZ4 nanomicelles (DC-PNM), cysteine was introduced between the cholic acid and PEG. DC-PNM-PTX was synthesized through the evaporation method by loading PTX in the core. The loading capacity of PTX in DC-PNM was 25% (W/W). The loading efficiency was over 99%. DC-PNM-PTX was spherical with the median size of 25 nm. The stability of DC-PNM-PTX was determined in a solution containing sodium docecyl sulfate (SDS). It was stable in a SDS solution, but dissolved within 5 min after the addition of glutathione at the physiological intracellular concentration of 10 mM. In vivo targeting and anti-tumor activity were determined in immunodeficient mice carrying patient-derived bladder cancer xenografts (PDXs). After intravenous administration, DC-PNM specifically targeted the bladder cancer PDXs, but very little to the lung cancer xenografts in the same mice (p &lt; 0.001). DC-PNM loaded with PTX overcame cisplatin resistance, and improved the median survival from 55 d with free PTX to 69.5 d (p = 0.03) of mice carrying PDXs. In conclusion, DC-PNM remained stable in the SDS solution, specifically targeted the bladder cancer xenografts in vivo, and improved the anti-cancer efficacy of PTX

Long non-coding RNAs identify a subset of luminal muscle-invasive bladder cancer patients with favorable prognosis

Background: Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease, and gene expression profiling has identified several molecular subtypes with distinct biological and clinicopathological characteristics. While MIBC subtyping has primarily been based on messenger RNA (mRNA), long non-coding RNAs (lncRNAs) may provide additional resolution. Methods: LncRNA expression was quantified from microarray data of a MIBC cohort treated with neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) (n = 223). Unsupervised consensus clustering of highly variant lncRNAs identified a four-cluster solution, which was characterized using a panel of MIBC biomarkers, regulon activity profiles, gene signatures, and survival analysis. The four-cluster solution was confirmed in The Cancer Genome Atlas (TCGA) cohort (n = 405). A single-sample genomic classifier (GC) was trained using ridge-penalized logistic regression and validated in two independent cohorts (n = 255 and n = 94). Results: NAC and TCGA cohorts both contained an lncRNA cluster (LC3) with favorable prognosis that was enriched with tumors of the luminal-papillary (LP) subtype. In both cohorts, patients with LP tumors in LC3 (LPL-C3) were younger and had organ-confined, node-negative disease. The LPL-C3 tumors had enhanced FGFR3, SHH, and wild-type p53 pathway activity. In the TCGA cohort, LPL-C3 tumors were enriched for FGFR3 mutations and depleted for TP53 and RB1 mutations. A GC trained to identify these LPL-C3 patients showed robust performance in two validation cohorts. Conclusions: Using lncRNA expression profiles, we identified a biologically distinct subgroup of luminal-papillary MIBC with a favorable prognosis. These data suggest that lncRNAs provide additional information for higher-resolution subtyping, potentially improving precision patient management.Medicine, Faculty ofNon UBCUrologic Sciences, Department ofReviewedFacult

Neoadjuvant chemotherapy plus radical cystectomy versus radical cystectomy alone in clinical T2 bladder cancer without hydronephrosis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168363/1/bju15289.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168363/2/bju15289_am.pd