Peter J. Boström

Risk factors for mortality and morbidity related to radical cystectomy

To evaluate the risk factors for mortality and morbidity related to radical cystectomy (RC) in a medium‐sized academic centre, and to analyse the rate and trends of perioperative morbidity and mortality, as although complications related RC to are lower in modern than historic series, RC is still associated with marked risks.

Genomic Predictors of Outcome in Prostate Cancer.

CONTEXT Given the highly variable behavior and clinical course of prostate cancer (PCa) and the multiple available treatment options, a personalized approach to oncologic risk stratification is important. Novel genetic approaches offer additional information to improve clinical decision making. OBJECTIVE To review the use of genomic biomarkers in the prognostication of PCa outcome and prediction of therapeutic response. EVIDENCE ACQUISITION Systematic literature review focused on human clinical studies reporting outcome measures with external validation. The literature search included all Medline, Embase, and Scopus articles from inception through July 2014. EVIDENCE SYNTHESIS An improved understanding of the genetic basis of prostate carcinogenesis has produced an increasing number of potential prognostic and predictive tools, such as transmembrane protease, serine2:v-ets avian erythroblastosis virus E26 oncogene homolog (TMPRSS2:ERG) gene fusion status, loss of the phosphatase and tensin homolog (PTEN) gene, and gene expression signatures utilizing messenger RNA from tumor tissue. Several commercially available gene panels with external validation are now available, although most have yet to be widely used. The most studied commercially available gene panels, Prolaris, Oncotype DX Genomic Prostate Score, and Decipher, may be used to estimate disease outcome in addition to clinical parameters or clinical nomograms. ConfirmMDx is an epigenetic test used to predict the results of repeat prostate biopsy after an initial negative biopsy. Additional future strategies include using genetic information from circulating tumor cells in the peripheral blood to guide treatment decisions at the initial diagnosis and at subsequent decision points. CONCLUSIONS Major advances have been made in our understanding of PCa biology in recent years. Our field is currently exploring the early stages of a personalized approach to augment traditional clinical decision making using commercially available genomic tools. A more comprehensive appreciation of value, limitations, and cost is important. PATIENT SUMMARY We summarized current advances in genomic testing in prostate cancer with a special focus on the estimation of disease outcome. Several commercial tests are currently available, but further understanding is needed to appreciate the potential benefits and limitations of these novel tests.

A New and Highly Prognostic System to Discern T1 Bladder Cancer Substage

BACKGROUND Management of T1 bladder cancer (BCa) is controversial. OBJECTIVE Evaluate the impact of substage on the clinical outcome of T1 BCa. DESIGN, SETTING, AND PARTICIPANTS The T1 diagnosis of 134 first-diagnosis BCa patients from two university hospitals was confirmed. For the T1 substage, we used a new system that discerns T1-microinvasive (T1m) and T1-extensive-invasive (T1e) tumors. We then determined the invasion of the muscularis mucosae-vascular plexus (MM-VP): T1a (invasion above the MM-VP), T1b (invasion in the MM-VP), or T1c (invasion beyond the MM-VP). If the MM-VP was not present at the invasion front, the case was assigned to T1a or T1c. All patients were initially managed conservatively (with bacillus Calmette-Guérin). MEASUREMENTS Multivariable analyses for progression and disease-specific survival (DSS). RESULTS AND LIMITATIONS Median follow-up was 6.4 yr (interquartile range: 3.3-9.2 yr). Progression to ≥ T2 was observed in 40 patients (30%), and 19 patients (14%) died of BCa. The MM-VP was not present at the invasion front in 50 patients (37%). T1 substage was as follows: 40 T1m and 94 T1e; 81 T1a, 18 T1b, and 35 T1c. In multivariable analyses, substage (T1m/T1e) was significant for progression (p=0.001) and DSS (p=0.032), whereas substage according to T1a/T1b/T1c was not significant. Female gender (p=0.006) and carcinoma in situ (p=0.034) were also significant predictors of progression. The main limitation to the study is absence of a repeat transurethral resection. CONCLUSIONS Substage according to the new system (T1m and T1e) was user-friendly, possible in 100% of cases, and very predictive of T1 BCa behavior. Future studies may ultimately lead to the incorporation of this new substaging system in the TNM classification system for urinary BCa.

THE FGFR3 MUTATION IS RELATED TO FAVORABLE PT1 BLADDER CANCER

PURPOSE Stage pT1 bladder cancer comprises a heterogeneous group of tumors for which different management options are advocated. FGFR3 mutations are linked to favorable (low grade/stage) pTa bladder cancer while altered P53 is common in cases of high grade, muscle invasive (pT2 or greater) bladder cancer. We determined the frequency of FGFR3 mutations and P53 alterations in patients with pT1 bladder cancer and correlated these data to histopathological variables and clinical outcomes. MATERIALS AND METHODS We included 132 patients with primary pT1 bladder cancer from a total of 2 academic centers. A uropathologist reviewed the slides for grade and confirmed the pT1 diagnosis. FGFR3 mutation status was examined by SNaPshot® analysis and P53 expression was determined by standard immunohistochemistry. Kaplan-Meier and multivariate analyses were used to assess progression. RESULTS FGFR3 mutations were detected in 37 of 132 pT1 bladder cancer cases (28%) and altered P53 was seen in 71 (54%). Only 8% of patients had the 2 molecular alterations (p = 0.001). FGFR3 mutation correlated with lower grade and altered P53 correlated with high grade pT1 bladder cancer. Median followup was 6.5 years. FGFR3 mutation status and carcinoma in situ were significant for predicting progression on univariate and multivariate analyses but P53 status was not. CONCLUSIONS FGFR3 mutations selectively identify patients with pT1 bladder cancer who have favorable disease characteristics. Further study may confirm that FGFR3 identifies those who would benefit from a conservative approach to the disease.

European Association of Urology (@Uroweb) Recommendations on the Appropriate Use of Social Media

Social media use is becoming common in medical practice. Although primarily used in this context to connect physicians, social media allows users share information, to create an online profile, to learn and keep knowledge up to date, to facilitate virtual attendance at medical conferences, and to measure impact within a field. However, shared content should be considered permanent and beyond the control of its author, and typical boundaries, such as the patient-physician interaction, become blurred, putting both parties at risk. The European Association of Urology brought together a committee of stakeholders to create guidance on the good practice and standards of use of social media. These encompass guidance about defining an online profile; managing accounts; protecting the reputations of yourself and your organization; protecting patient confidentiality; and creating honest, responsible content that reflects your standing as a physician and your membership within this profession.

Evaluation of different mathematical models for diffusion-weighted imaging of normal prostate and prostate cancer using high b-values: A repeatability study

To evaluate monoexponential, stretched exponential, kurtosis, and biexponential models for diffusion‐weighted imaging (DWI) of normal prostate and prostate cancer (PCa), using b‐values up to 2000 s/mm2, in terms of fitting quality and repeatability.

Upstaging of urothelial cancer at the time of radical cystectomy: factors associated with upstaging and its effect on outcome

Study Type – Therapy (case series)

Prognostic value of molecular markers, sub-stage and European Organisation for the Research and Treatment of Cancer risk scores in primary T1 bladder cancer

Study Type – Prognosis (case series)

Patients with Lynch syndrome mismatch repair gene mutations are at higher risk for not only upper tract urothelial cancer but also bladder cancer.

BACKGROUND Lynch syndrome (LS), or hereditary nonpolyposis colorectal cancer, is caused by mutations in mismatch repair (MMR) genes. An increased risk for upper tract urothelial carcinoma (UTUC) has been described in this population; however, data regarding the risk for bladder cancer (BCa) are sparse. OBJECTIVE To assess the risk of BCa in MMR mutation carriers and suggest screening and management recommendations. DESIGN, SETTING, AND PARTICIPANTS Cancer data from 1980 to 2007 were obtained from the Familial Gastrointestinal Cancer Registry in Toronto for 321 persons with known MMR mutations: mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) (MLH1); mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) (MSH2); mutS homolog 6 (E. coli) (MSH6); and PMS2 postmeiotic segregation increased 2 (S. cerevisiae) (PMS2). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Standardized incidence ratios from the Ontario Cancer Registry, using the Surveillance Epidemiology and End Results public database, were used to compare cancer risk in patients with MMR mutations with the Canadian population. Microsatellite instability analysis and immunohistochemistry (IHC) of the MMR proteins were also performed and the results compared with matched sporadic bladder tumors. RESULTS AND LIMITATIONS Eleven of 177 patients with MSH2 mutations (6.21%, p<0.001 compared with the Canadian population) were found to have BCa, compared with 3 of 129 patients with MLH1 mutations (2.32%, p>0.05). Of these 11 tumors, 81.8% lacked expression of MSH2 on IHC, compared with the matched sporadic cases, which all displayed normal expression of MSH2 and MLH1. The incidence of UTUC among MSH2 carriers was 3.95% (p<0.001), and all tumors were found to be deficient in MSH2 expression on IHC. Mutations in the intron 5 splice site and exon 7 of the MSH2 gene increased the risk of urothelial cancer. Limitations include possible inflated risk estimates due to ascertainment bias. CONCLUSIONS LS patients with MSH2 mutations are at an increased risk for not only UTUC but also BCa and could be offered appropriate screening.

Imaging renal cell carcinoma with ultrasonography, CT and MRI

The increased use of abdominal imaging techniques for a variety of indications has contributed to more-frequent detection of renal cell carcinoma (RCC). Ultrasonography has been used to characterize the solid versus cystic nature of renal masses. This modality has limitations, however, in further characterization of solid tumors and in staging of malignancy, although contrast-enhanced ultrasonography has shown promise. Cross-sectional imaging with multiplanar reconstruction capability via CT or MRI has become the standard-bearer in the diagnosis, staging and surveillance of renal cancers. The use of specific protocols and the exploitation of different imaging characteristics of RCC subtypes, including variations in contrast agent timing, MRI weighting and digital subtraction, have contributed to this diagnostic capability. Cystic renal masses are a special case, evaluation of which can require multiple imaging modalities. Rigorous evaluation of these lesions can provide information that is crucial to prediction of the likelihood of malignancy. Such imaging is not without risk, however, as radiation from frequent CT imaging has been implicated in the development of secondary malignancies, and contrast agents for CT and MRI can pose risks, particularly in patients with compromised renal function.