Purpose Multidisciplinary management improves complex treatment decision making in cancer care, but its impact for bladder cancer (BC) has not been documented. Although radical cystectomy (RC) ...currently is viewed as the standard of care for muscle-invasive bladder cancer (MIBC), radiotherapy-based, bladder-sparing trimodal therapy (TMT) that combines transurethral resection of bladder tumor, chemotherapy for radiation sensitization, and external beam radiotherapy has emerged as a valid treatment option. In the absence of randomized studies, this study compared the oncologic outcomes between patients treated with RC or TMT by using a propensity score matched-cohort analysis. Methods Data from patients treated in a multidisciplinary bladder cancer clinic (MDBCC) from 2008 to 2013 were reviewed retrospectively. Those who received TMT for MIBC were identified and matched (for sex, cT and cN stage, Eastern Cooperative Oncology Group status, Charlson comorbidity score, treatment date, age, carcinoma in situ status, and hydronephrosis) with propensity scores to patients who underwent RC. Overall survival and disease-specific survival (DSS) were assessed with Cox proportional hazards modeling and a competing risk analysis, respectively. Results A total of 112 patients with MIBC were included after matching (56 who had been treated with TMT, and 56 who underwent RC). The median age was 68.0 years, and 29.5% had stage cT3/cT4 disease. At a median follow-up of 4.51 years, there were 20 deaths (35.7%) in the RC group (13 as a result of BC) and 22 deaths (39.3%) in the TMT group (13 as a result of BC). The 5-year DSS rate was 73.2% and 76.6% in the RC and TMT groups, respectively ( P = .49). Salvage cystectomy was performed in 6 (10.7%) of 56 patients who received TMT. Conclusion In the setting of a MDBCC, TMT yielded survival outcomes similar to those of matched patients who underwent RC. Appropriately selected patients with MIBC should be offered the opportunity to discuss various treatment options, including organ-sparing TMT.
Abstract Context Non–muscle-invasive bladder cancer (NMIBC) commonly recurs, requiring invasive and costly transurethral resection of bladder tumor (TURBT). A meta-analysis of seven trials published ...in 2004 demonstrated that intravesical chemotherapy (IVC) following TURBT reduces recurrences. Despite European Association of Urology endorsement, adoption of this practice has been modest. Objective To investigate whether immediate postoperative IVC prolongs the recurrence-free interval (RFI) and early recurrences (ERs) in light of new trial data and to explore the quality of evidence supporting its use. Evidence acquisition A systematic literature review of random controlled trials (RCTs) published before March 2013 was performed using the Medline, Embase, and Cochrane databases. Trials examining NMIBC recurrence for adults receiving IVC immediately following TURBT were included. RFI was estimated by hazard ratio (HR), and ER was estimated by absolute risk reduction (ARR) of recurrences within 1 yr of TURBT. Both outcomes were synthesized using random-effects models. Risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool, and quality of evidence for each outcome was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation system. Evidence synthesis Thirteen studies with 2548 patients were included. IVC prolonged RFI by 38% (HR: 0.62; 95% confidence interval CI, 0.50–0.77; p < 0.001; I2 : 69%), and ERs were 12% less likely in the intervention population (ARR: 0.12; 95% CI, −0.18 to −0.06; p < 0.001, I2 : 0%). The number needed to treat to prevent one ER was 9 (95% CI, 6–17 patients). There was high risk of bias present in 12 of 13 publications. Quality of evidence for RFI was very low and low for ERs. Conclusions Our updated meta-analysis supports that IVC prolongs RFI and reduces ERs of NMIBC when administered immediately after TURBT. However, contemporary methodology suggests low evidence quality for examined outcomes. Thus RCTs with careful randomization and blinding are still warranted to clarify the usefulness of immediate postoperative IVC in this population.
To systematically review and meta-analyze the current literature in a methodologically rigorous and transparent manner for quantitative evidence on survival outcomes among patients diagnosed with ...muscle-invasive bladder cancer that were treated by either trimodal therapy or radical cystectomy.
MEDLINE, EMBASE, CENTRAL were systematically searched for comparative observational studies reporting disease-specific survival and/or overall survival on adult patients diagnosed with localized muscle-invasive bladder cancer that were exposed to either trimodal therapy or radical cystectomy. Studies qualified for meta-analysis (random effects model) if they were not at critical risk of bias (RoB).
The literature search identified 12 eligible studies. Three (all rated as "moderate RoB") out of 6 studies reporting on disease-specific survival qualified for quantitative analysis and yielded a pooled hazard ratio (trimodal therapy versus radical cystectomy) of 1.39 (95% confidence interval: 1.03-1.88). Four (mainly rated as "serious RoB") out of 12 studies were included in the meta-analysis of overall survival and estimated a hazard ratio of 1.39 (1.20-1.59).
Pooled results were significant in favor of radical cystectomy. The conclusion is mainly driven by large population-based studies that are at high RoB. Hence, the certainty of these treatment estimates can be considered very low and further research will likely have an important impact on these estimates. At present, the ultimate decision between trimodal therapy and radical cystectomy should be left to the patient based on individual preferences and on the recommendation of a multidisciplinary provider team experienced with both approaches.
Summary Background We aimed to investigate the safety and efficacy of dutasteride, a 5α-reductase inhibitor, on prostate cancer progression in men with low-risk disease who chose to be followed up ...with active surveillance. Methods In our 3 year, randomised, double-blind, placebo-controlled study, undertaken at 65 academic medical centres or outpatient clinics in North America, we enrolled men aged 48–82 years who had low-volume, Gleason score 5–6 prostate cancer and had chosen to be followed up with active surveillance. We randomly allocated participants in a one-to-one ratio, stratified by site and in block sizes of four, to receive once-daily dutasteride 0·5 mg or matching placebo. Participants were followed up for 3 years, with 12-core prostate biopsy samples obtained after 18 months and 3 years. The primary endpoint was time to prostate cancer progression, defined as the number of days between the start of study treatment and the earlier of either pathological progression (in patients with ≥1 biopsy assessment after baseline) or therapeutic progression (start of medical therapy). This trial is registered with ClinicalTrials.gov , number NCT00363311. Findings Between Aug 10, 2006, and March 26, 2007, we randomly allocated 302 participants, of whom 289 (96%) had at least one biopsy procedure after baseline and were included in the primary analysis. By 3 years, 54 (38%) of 144 men in the dutasteride group and 70 (48%) of 145 controls had prostate cancer progression (pathological or therapeutic; hazard ratio 0·62, 95% CI 0·43–0·89; p=0·009). Incidence of adverse events was much the same between treatment groups. 35 (24%) men in the dutasteride group and 23 (15%) controls had sexual adverse events or breast enlargement or tenderness. Eight (5%) men in the dutasteride group and seven (5%) controls had cardiovascular adverse events, but there were no prostate cancer-related deaths or instances of metastatic disease. Interpretation Dutasteride could provide a beneficial adjunct to active surveillance for men with low-risk prostate cancer. Funding GlaxoSmithKline.
To assess the patterns and predictors of metastatic disease in renal cell carcinoma (RCC) at the time of diagnosis in a contemporary series.
The Surveillance, Epidemiology, and End Results database ...was queried for all patients with kidney RCC from 2010 to 2013 (N = 50,815). Distribution and predictors of distant metastases at diagnosis were assessed. Multivariate logistic regression hazard analyses were performed to determine covariates associated with the likelihood of having metastases at diagnosis, whereas competing risks regression analysis was used to assess predictors of cancer-specific mortality (CSM) in patients with metastatic disease.
Lung (7.73%) and bone (5.17%) metastases were the most common. The strongest predictors of metastatic disease were disease-specific factors, such as clinical T-stage (cT4 vs. cT1; odds ratio = 43.08; P<0.01) and higher Fuhrman grade (FG4 vs. FG1; odds ratio = 5.09; P<0.01). Papillary RCC and chromophobe RCC were associated with localized disease at the time of diagnosis. For CSM, the presence of brain and liver metastases were associated with worse CSM than lung or bone metastases. Although patient factors did not contribute to the presence of metastases at diagnosis, lower socioeconomic status and being widowed/divorced predicted worse CSM.
Understanding the distribution of distant metastases and associated CSM is important to counseling patients with newly diagnosed metastatic RCC. Although pathologic factors drive the presence of metastases at diagnosis, health care deficits in treatment remain.
•Goal: identify patterns and predictors of metastases at time of diagnosis in RCC.•Lung (7.73%) and bone (5.17%) mets more common than liver (2.6%) and brain (1.5%) mets.•Isolated bone metastases (11.1%) almost as common as isolated lung mets (16.8%).•Lower socioeconomic status and being widowed/divorced predicted higher CSM.•Health care deficit between diagnosis and treatment that still needs to be rectified.
Profiling the heterogeneous phenotypes of rare circulating tumour cells (CTCs) in whole blood is critical to unravelling the complex and dynamic properties of these potential clinical markers. This ...task is challenging because these cells are present at parts per billion levels among normal blood cells. Here we report a new nanoparticle-enabled method for CTC characterization, called magnetic ranking cytometry, which profiles CTCs on the basis of their surface expression phenotype. We achieve this using a microfluidic chip that successfully processes whole blood samples. The approach classifies CTCs with single-cell resolution in accordance with their expression of phenotypic surface markers, which is read out using magnetic nanoparticles. We deploy this new technique to reveal the dynamic phenotypes of CTCs in unprocessed blood from mice as a function of tumour growth and aggressiveness. We also test magnetic ranking cytometry using blood samples collected from cancer patients.
Physician assistants (PAs) are healthcare professionals who act as physician extenders. PAs are being used more and more in a wide variety of clinic settings throughout Canada to increase access to ...healthcare and reduce cost. We set out to determine the impact of PAs on a tertiary care center urology oncology practice.
We reviewed OHIP billing codes since the introduction of PAs for two attending urologists at Princess Margaret Cancer Centre. Data were grouped into Early experience and Established experience. In addition, questionnaires were electronically distributed among nurses, physicians, residents, and fellows who work with PAs in clinic. Patient visits conducted by PAs were tracked for one quarter to estimate the amount of annual patients seen by PAs. The costs associated with PAs are presented as recommendations for a new graduate PA hire.
On average, PAs increased clinic volume by 11.3 patient visits per day. Furthermore, they individually care for an average of 24 patients per day. PAs did not represent a financial burden on the urology practice plan (revenue gain of $16 800). Our questionnaire demonstrated that PAs were capable healthcare professionals, who decreased workload and contributed to resident/fellow education.
PAs in a Canadian urology practice allow for more patient visits, decrease in physician workload, and positively impact trainee education. PAs saw more patients in clinic than clinic growth, thereby decreasing physician, fellow, and resident workload. The offset of the increase in patient visits made the PAs a cost-neutral investment.
PURPOSE Use of androgen deprivation therapy (ADT) may be associated with an increased risk of diabetes mellitus but the risk of both acute myocardial infarction (AMI) and cardiovascular mortality ...remain controversial because few outcomes and conflicting findings have been reported. We sought to clarify whether ADT is associated with these outcomes in a large, representative cohort. METHODS Using linked administrative databases in Ontario, Canada, men age 66 years or older with prostate cancer given continuous ADT for at least 6 months or who underwent bilateral orchiectomy (n = 19,079) were matched with men with prostate cancer who had never received ADT. Treated and untreated groups were matched 1:1 (ie, hard-matched) on age, prior cancer treatment, and year of diagnosis and propensity-matched on comorbidities, medications, cardiovascular risk factors, prior fractures, and socioeconomic variables. Primary outcomes were development of AMI, sudden cardiac death, and diabetes. Fragility fracture was also examined. Results The cohort was observed for a mean of 6.47 years. In time-to-event analyses, ADT use was associated with an increased risk of diabetes (hazard ratio HR, 1.16; 95% CI, 1.11 to 1.21) and fragility fracture (HR, 1.65; 95% CI, 1.53 to 1.77) but not with AMI (HR, 0.91; 95% CI, 0.84 to 1.00) or sudden cardiac death (HR, 0.96; 95% CI, 0.83 to 1.10). Increasing duration of ADT was associated with an excess risk of fragility fractures and diabetes but not cardiac outcomes. CONCLUSION Continuous ADT use for at least 6 months in older men is associated with an increased risk of diabetes and fragility fracture but not AMI or sudden cardiac death.
Early treatment of patients at risk for developing aggressive prostate cancer is able to delay metastasis and reduce mortality; as such, up-front identification of these patients is critical. Several ...risk classification systems, including CAPRA-S, are currently used for disease prognostication. However, high-risk patients identified by these systems can still exhibit wide-ranging disease outcomes, leading to overtreatment of some patients in this group.
The master methylation regulator TET2 is downregulated in prostate cancer, where its loss is linked to aggressive disease and poor outcome. Using a random forest strategy, we developed a model based on the expression of 38 genes associated with TET2 utilizing 100 radical prostatectomy samples (training cohort) with a 49% biochemical recurrence rate. This 38-gene model was comprised of both upregulated and downregulated TET2-associated genes with a binary outcome, and was further assessed in an independent validation (n = 423) dataset for association with biochemical recurrence.
38-gene model status was able to correctly identify patients exhibiting recurrence with 81.4% sensitivity in the validation cohort, and added significant prognostic utility to the high-risk CAPRA-S classification group. Patients considered high-risk by CAPRA-S with negative 38-gene model status exhibited no statistically significant difference in time to recurrence from low-risk CAPRA-S patients, indicating that the expression of TET2-associated genes is able to separate truly high-risk cases from those which have a more benign disease course.
The 38-gene model may hold potential in determining which patients would truly benefit from aggressive treatment course, demonstrating a novel role for genes linked to TET2 in the prognostication of PCa and indicating the importance of TET2 dysregulation among high-risk patient groups.
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