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INTRODUCTION: Our aim was to determine whether androgen deprivation therapy (ADT) with abiraterone acetate (AA) or ADT with docetaxel chemotherapy (DC) resulted in improved quality-adjusted life years (QALYs) among men with de novo metastatic castration-sensitive prostate cancer (mCSPC) and the cost effectiveness of the preferred strategy using decision analytic techniques. METHODS: A microsimulation model with a lifetime time horizon was constructed. Our primary outcome was QALYs. Secondary outcomes included cost, incremental cost effectiveness ratio (ICER), unadjusted overall survival (OS), rates of second- and third-line therapy, and adverse events. A systematic literature review was used to generate probabilities and utilities to populate the model. The base case was a 65-year-old patient with de novo mCSPC. RESULTS: A total of 100 000 microsimulations were generated. Initial AA resulted in a gain of 0.45 QALYs compared to DC (3.36 vs. 2.91 QALYs) with an ICER of $276 251.82 per QALY gained with initial AA therapy. Median crude OS was 51 months with AA and 48 months with DC. Overall, 46.6% and 42.6% of patients received second-line therapy and 8.7% and 7.9% patients received third-line therapy in the AA and DC groups, respectively. Grade 3/4 adverse events were experienced in 17.6% of patients receiving initial AA and 22.3% of patients receiving initial DC. CONCLUSIONS: Although ADT with AA results in a gain in QALYs and crude OS compared to DC, AA therapy is not a cost-effective treatment strategy to apply uniformly to all patients. The availability of AA as a generic medication may help to close this gap. The ultimate choice should be based on patient and tumor factors.

INTRODUCTION AND OBJECTIVE:Among the most common symptoms of patients undergoing flexible cystoscopy are pain and discomfort. Hydrodistension of prostate is a commonly utilized, yet unproven techni...

INTRODUCTION AND OBJECTIVE:Alternatives to radical cystectomy (RC) are critically needed for the treatment of high-risk BCG-unresponsive NMIBC. Vicinium is a recombinant fusion protein comprised of...

Background The chemopreventive effect of various medications in prostate cancer (PCa) has gained interest. Specifically, the potential impact of statins on PCa incidence has been studied, but solely as a “drug family” overlooking the distinctive pharmacological properties of its two main subgroups: hydrophilic and hydrophobic statins. Objective To assess the impact of statin subgroups on PCa-specific mortality (PCSM), PCa diagnosis, and undergoing another prostate biopsy. Design, setting, and participants This is a population-based cohort study in Ontario identifying all men aged ≥66 yr with a history of a single negative prostate biopsy (representing healthy men at risk for PCa) between 1994 and 2016, who were not on any of the analyzed medications prior to the study, with a median follow-up of 9.42 yr (interquartile range 8.03 yr). Outcome measurements and statistical analysis Using multivariable cause-specific hazard models with time-dependent covariates, the association of hydrophobic and hydrophilic statins with all study outcomes was analyzed. Other putative chemopreventive medications (including alpha-blockers, 5-alpha-reductase inhibitors, and proton-pump inhibitors), age, rurality, comorbidities, and study inclusion year were included in the models. Results and limitations Overall, 21 512 men were identified. Statins were taken by 11 401 patients (50.3%), 5184 men (24.1%) were diagnosed with PCa, and 805 (3.7%) died from it. Overall, 7556 patients (35.1%) underwent another biopsy. Any use of hydrophilic statins was associated with a 32.4% (95% confidence interval [CI] 12.9–47.5%), a 20% (95% CI 10–28%), and an 18% (95% CI 6.1–27.3%) decreased risk of PCSM, undergoing another prostate biopsy, and being diagnosed with PCa, respectively. Hydrophobic statins were associated with 17% (95% CI 2–31%) decreased PCSM. The study is limited by its retrospective nature, selection bias, and accompanying health-administrative database inaccuracies. Conclusions Use of any statin may be associated with a lower hazard of PCSM, with hydrophilic statins showing a greater association with decreased PCa diagnosis rates. Preferentially prescribing one statin subgroup over another in men needs further exploration. Patient summary Use of any statin may be associated with a lower probability of dying from prostate cancer. Hydrophilic statins (rosuvastatin and pravastatin) may also be more positively associated with a lower risk of undergoing an additional prostate biopsy and being diagnosed with prostate cancer in men aged ≥66 yr.

Proton pump inhibitors (PPIs) are commonly prescribed medications that have been shown to have contradicting effects on cancer. We aimed to investigate the effect of pantoprazole and other PPIs on prostate cancer (PCa) specific mortality (PCSM), use of androgen deprivation therapy (ADT), and PCa diagnosis using a large Canadian population-based cohort.We identified 21,512 men aged ≥ 66, with a history of a single negative prostate biopsy and no previous use of any of the analyzed medications between 1994 and 2016. Multivariable Cox regression models with time-dependent covariates were used to assess the associations of PPIs with PCa outcomes. All models included other medications with a putative chemopreventative effect on PCa-outcomes, and were adjusted for age, rurality, comorbidity, and study inclusion year.Over a mean follow-up of 8.06 years (SD 5.44 years), 10,999 patients (51.1%) used a PPI, 5187 patients (24.1%) had PCa, 2043 patients (9.5%) were treated with ADT, and 805 patients (3.7%) died from PCa. For every 6 months of cumulative use, pantoprazole was associated with a 3.0% (95% CI 0.3-6.0%) increased rate of ADT use, while any use of other PPIs was associated with a 39.0% (95% CI 18.0-64.0%) increased risk of PCSM. No association was found with PCa diagnosis.Upon validation of the potentially negative association of PPIs with PCa, PPI use may need to be reassessed in PCa patients.

Introduction: Advanced urothelial carcinoma has been challenging to treat due to limited treatment options, poor response rates, and poor long-term survival. New treatment options hold the promise of improved outcomes for these patients. Methods: A multidisciplinary working group drafted a management algorithm for advanced urothelial carcinoma using “consensus development conference” methodology. A targeted literature search identified new and emerging treatments for inclusion in the management algorithm. Published clinical data were considered during the algorithm development process, as well as the risks and benefits of the treatment options. Biomarkers to guide patient selection in clinical trials for new treatments were incorporated into the algorithm. Results: The advanced urothelial carcinoma management algorithm includes newly approved first-line anti- programmed death receptor-1 (PD1)/ programmed death-ligand 1 (PD-L1) therapies, a newly approved anti- fibroblast growth factor receptors (FGFR) therapy, and an emerging anti-Nectin 4 therapy, which have had encouraging results in phase 2 trials for secondline and third-line therapy, respectively. This algorithm also incorporates suggestions for biomarker testing of PD-L1 expression and FGFR gene alterations. Conclusions: Newly approved and emerging therapies are starting to cover an unmet need for more treatment options, better response rates, and improved overall survival in advanced urothelial carcinoma. The management algorithm provides guidance on how to incorporate these new options, and their associated biomarkers, into clinical practice.

Introduction: Bladder cancer is the 9th most common cancer in the world and the 4th and 8th most common cancer diagnosed in men in the United States and United Kingdom respectively. The standard of care for the treatment of MIBC is radical cystectomy. Bladder preserving treatment approaches are emerging for select patients and should be considered strongly in patients who decline a radical cystectomy.Areas covered: In this review we look at the European and American recommended guidelines, the current standard of care, bladder-preserving options in MIBC, trimodal therapy and discuss future developments in the identification of molecular biomarkers that can predict therapeutic outcomes.Expert opinion: We strongly advocate bladder preservation for the right patient with strict criteria for enrolling patients in bladder preservation. The development of a specialized bladder cancer clinic could facilitate the selection of patients to be offered trimodal therapy. We believe that the future of bladder cancer will involve individualized care plans based upon clinical, radiological, endoscopic and molecular assessments.

In urothelial bladder cancer (UBC), risk stratification remains an important unmet need. Limitless self‐renewal, governed by TERT expression and telomerase activation, is crucial for cancer progression. Thus, telomerase activation through the interplay of mutations (TERTpMut) and epigenetic alterations in the TERT promoter may provide further insight into UBC behavior. Here, we investigated the combined effect of TERTpMut and the TERT Hypermethylated Oncological Region (THOR) status on telomerase activation and patient outcome in a UBC international cohort (n = 237). We verified that TERTpMut were frequent (76.8%) and present in all stages and grades of UBC. Hypermethylation of THOR was associated with higher TERT expression and higher‐risk disease in nonmuscle invasive bladder cancers (NMIBC). TERTpMut alone predicted disease recurrence (HR: 3.18, 95%CI 1.84 to 5.51, p < 0.0001) but not progression in NMIBC. Combined THORhigh/TERTpMut increased the risk of disease recurrence (HR 5.12, p < 0.0001) and progression (HR 3.92, p = 0.025). Increased THOR hypermethylation doubled the risk of stage progression of both TERTpwt and TERTpMut NMIBC. These results highlight that both mechanisms are common and coexist in bladder cancer and while TERTpMut is an early event in bladder carcinogenesis THOR hypermethylation is a dynamic process that contributes to disease progression. While the absence of alterations comprises an extremely indolent phenotype, the combined genetic and epigenetic alterations of TERT bring additional prognostic value in NMIBC and provide a novel insight into telomere biology in cancer., What's new? Telomerase reverse transcriptase (TERT) activation is central to cancer cell immortalization. It acts, however, through relatively unknown mechanisms. In urothelial bladder cancer (UBC) in particular, TERT activation can occur in the presence or absence of mutation, raising questions about alternative activation mechanisms. Our study shows that hypermethylation of the TERT promoter (THOR) plays a key part in UBC, being a dynamic and progressive process, with hypermethylation levels increasing with bladder cancer severity. Moreover, both hypermethylation and TERT promoter mutation contributed to increased telomerase expression. The findings provide insight into telomere biology in UBC and may be applicable to other tumors.

We investigated the characteristics and outcomes of patients with muscle invasive bladder cancer treated with transurethral resection plus chemotherapy alone in a large observational cohort reflecting the continuum of practice settings in the United States.In the National Cancer Database from 2004 to 2015 we identified 1,538 patients treated with transurethral resection plus multi-agent chemotherapy as definitive treatment of cT2-T4aN0M0 urothelial carcinoma of the bladder. For comparison purposes we included in study 17,866 patients treated with radical cystectomy with or without perioperative chemotherapy. Baseline characteristics were compared between the 2 groups by multivariable logistic regression. Treatment outcomes were assessed using Kaplan-Meier analysis and a Cox regression model.On multivariate analysis several variables, including patient demography (older age, African American race, prior malignancy and lack of insurance), tumor characteristics (higher cT stage) and facility type (nonacademic facilities and lower radical cystectomy volume) were associated with a higher probability of transurethral resection plus chemotherapy for muscle invasive bladder cancer compared to the standard of care. Two and 5-year survival rates in all patients treated with transurethral resection plus chemotherapy were 49.0% and 32.9%, and in patients with cT2 disease the rates were 52.6% and 36.2%, respectively.This large population level cohort of unselected patients shows that long-term survival can be achieved in a subset of patients treated with transurethral resection plus chemotherapy alone for muscle invasive bladder cancer. However, the best candidates for this approach remain to be defined. Ongoing clinical trials are now being launched to evaluate the ability of biomarkers to accurately select patients who could be treated with this bladder sparing strategy.

Item does not contain fulltext PURPOSE: To provide a summary of the Third International Consultation on Bladder Cancer recommendations for the management of non-muscle invasive bladder cancer (NMIBC). METHODS: A detailed review of the literature was performed focusing on original articles for the management of NMIBC. An international committee assessed and graded the articles based on the Oxford Centre for Evidence-based Medicine system. The entire spectrum of NMIBC was covered such as prognostic factors of recurrence and progression, risk stratification, staging, management of positive urine cytology with negative white light cystoscopy, indications of bladder and prostatic urethral biopsies, management of Ta low grade (LG) and high risk tumors (Ta high grade [HG], T1, carcinoma in situ [CIS]), impact of BCG strain and host on outcomes, management of complications of intravesical therapy, role of alternative therapies, indications for early cystectomy, surveillance strategies, and new treatments. The working group provides several recommendations on the management of NMIBC. RESULTS: Recommendations were summarized with regard to staging; management of primary and recurrent LG Ta and high risk disease, positive urine cytology with negative white light cystoscopy and prostatic urethral involvement; indications for timely cystectomy; and surveillance strategies. CONCLUSION: NMIBC remains a common and challenging malignancy to manage. Accurate staging, grading, and risk stratification are critical determinants of the management and outcomes of these patients. Current tools for risk stratification are limited but informative, and should be used in clinical practice when determining diagnosis, surveillance, and treatment of NMIBC.

Purpose: Health related quality of life is important in bladder cancer care and clinical decision making because patients must choose between diverse treatment modalities with unique morbidities. A patient reported outcome measure of overall health related quality of life for bladder cancer regardless of disease severity and treatment could benefit clinical care and research.Materials and Methods: Prospective questionnaire development was completed in 3 parts. In study 1 the BUSS (Bladder Utility Symptom Scale) questions were created by experts using a conceptual framework of bladder cancer health related quality of life generated through patient focus groups. In study 2 patients with bladder cancer, including those treated with surgery, radiation and chemotherapy, completed the BUSS and 5 health related quality of life instruments at baseline and 4 weeks to assess validity and test-retest reliability. External validity was then explored in study 3 by administering the BUSS to 578 patients online and at c...

Radical cystectomy is inherently associated with morbidity. We assess the timing and incidence of venous thromboembolism, review current guideline recommendations and provide evidence for considering extended venous thromboembolism prophylaxis in all patients undergoing radical cystectomy.We searched PubMed® for available literature on radical cystectomy and venous thromboembolism, focusing on incidence and timing, evidence supporting extended venous thromboembolism prophylaxis in patients undergoing radical cystectomy or abdominal oncologic surgery, current guideline recommendations, safety considerations and direct oral anticoagulants. Search terms included "radical cystectomy," "venous thromboembolism," "prophylaxis," and "extended oral anticoagulants" and "direct oral anticoagulants" alone and in combination. Relevant articles were reviewed, including original research, reviews and clinical guidelines. References from review articles and guidelines were also assessed to develop a narrative review.The incidence of symptomatic venous thromboembolism in short-term followup after radical cystectomy is 3% to 11.6%, of which more than 50% of cases will occur after hospital discharge. Meta-analyses of clinical trials in patients undergoing major abdominal oncologic operations suggest a decreased risk of venous thromboembolisms for patients receiving extended (4 weeks) venous thromboembolism prophylaxis. Extended prophylaxis should be considered in all radical cystectomy cases. Although the relative risk of bleeding also increases, the overall net benefit of extended prophylaxis clearly favors use for at least 28 days postoperatively. Extrarenal eliminated prophylaxis agents are preferred given the risk of renal insufficiency in radical cystectomy cases, with newer oral anticoagulants providing an alternative route of administration.Patients undergoing radical cystectomy are at high risk for venous thromboembolism after hospital discharge. There is strong evidence that extended prophylaxis significantly decreases the risk of venous thromboembolism in oncologic surgery cases. Use of extended prophylaxis after radical cystectomy has been poorly adopted, emphasizing the need for better adherence to current urology procedure specific guidelines as extended prophylaxis for radical cystectomy is the standard of care. Specific and rare circumstances may require case by case assessment.

Objective To assess the toxicity and effectiveness of contemporary metastatic castrate-resistant prostate cancer (mCRPC) treatments at a population level, among all patients in Ontario particularly treated with newer agents, including abiraterone, enzalutamide, docetaxel, and cabazitaxel. Methods We performed a population-based, retrospective cohort study of 2439 men aged ≥65 years treated for mCRPC with abiraterone, enzalutamide, docetaxel, or cabazitaxel from 2003 to 2015 in Ontario, Canada. Our primary outcome was treatment-related toxicity, defined as hospitalizations and emergency room (ER) visits during mCRPC treatment. Based on toxicity profiles identified during phase III trials, we further identified specific treatment-related toxicity. We calculated hazard ratios (HRs) using multivariable Cox proportional hazards models with time-varying exposures. Results Abiraterone and enzalutamide exposure were not associated with any-cause ( P = .19 and .52, respectively) or treatment-related ( P = .45 and .64, respectively) toxicities. In contrast, docetaxel exposure was associated with an increased risk of any-cause (HR 1.29, 95% confidence interval [CI] 1.15-1.44) and treatment-related (HR 1.52, 95% CI 1.33-1.74) toxicities. Cabazitaxel exposure was associated with a significant risk of treatment-related toxicity (HR 5.94, 95% CI 1.87-18.92) but not any-cause toxicity (HR 2.37, 95% CI 0.59-9.63). Conclusion Among patients with mCRPC, we failed to show any increased risk of hospitalizations and ER visits for treatment-related complications for abiraterone or enzalutamide. In contrast, treatment with intravenous chemotherapeutic agents was associated with an increased risk of hospitalizations and ER visits to manage these complications.

239 Background: Baseline prostate specific antigen (PSA) is a strong predictor of clinically significant prostate cancer. In a large cohort of patients undergoing opportunistic testing, our objective was to assess the association between first serum PSA in combination with other PSA predictors and risk of prostate cancer. Methods: This was a retrospective, population-based study in Ontario, Canada between 2010-2019. Men 40-75 years of age who underwent incident PSA testing with at least two PSA tests during the study period were included. Among men who underwent PSA testing, the PSA levels of patients who were diagnosed with prostate cancer were compared to patients who were not. Univariable and multivariable logistic regression analysis was used to compare any prostate cancer and clinically significant prostate cancer diagnosis (International Society of Urological Pathology [ISUP] grade group 2-5) between groups. Results: A total of 508,238 patients were included in our cohort (12,444 cases and 495,794 controls). The median follow-up time was 8.2 years (IQR: 7.0-9.1). Patients who were diagnosed with prostate cancer were older (median age 62 [IQR: 56-67] versus 56 years [IQR:50-63], standardized difference [SD]:0.61) and had a higher first PSA than patients who were not (median 4.79 [IQR:3.29-6.96] versus 0.96 ng/mL [IQR:0.58-1.69], SD:1.93). Fewer than 0.1% (248/261,463) of patients with a first PSA less than 1.0 ng/mL were diagnosed with prostate cancer during the study period. Our final multivariable model revealed that a first PSA above 2.0 ng/mL (adjusted odds ratio [OR] 6.64, 95%CI: 6.13-7.20, p < 0.001), a final PSA between 4.0 to 9.9 ng/mL and 10.0 to 20.0 ng/mL (adjusted OR 22.09, 95%CI: 20.58-23.71, p < 0.001 and adjusted OR 47.46, 95%CI: 43.28-52.05, p < 0.001, respectively) and change from first to final PSA per 365 days of 20.0 to 99.9% (adjusted OR 3.40, 95%CI: 3.21-3.60, p < 0.001) and more than 100% (adjusted OR 6.91, 95%CI: 6.29-7.59, p < 0.001) were strongly associated with the diagnosis of prostate cancer. The model performed well when predicting any prostate cancer, clinically significant prostate cancer, and when stratified by age. Conclusions: This study suggests that first PSA in combination with final PSA and rate of change can be used to predict prostate cancer diagnosis. Future studies will be conducted to determine the association with metastatic and lethal prostate cancer.

224 Background: High-risk prostate cancer has a significant risk of recurrence when treated with unimodal therapy. The utility of neoadjuvant therapy prior to radical prostatectomy (RP) has yet to be defined. The ACDC-RP study investigated the use of abiraterone acetate (AA) + prednisone (P) + leuprolide (LHRH) with or without cabazitaxel prior to RP in high-risk patients. Methods: This phase II trial randomized patients to Arm A (AA/P + LHRH + cabazitaxel 20 mg/m2 with peg-filgrastim 6 cycles) or Arm B (AA/P + LHRH) for 6 months prior to RP. The primary objective was to compare the rate of pathological complete response (CR) or minimal residual disease (MRD) between treatment arms. MRD was defined as ≤5% of prostate volume involved by tumor. We present RP pathological outcomes, safety signals, and early biochemical response data. Results: Out of 78 randomized participants, 70 completed the full course of study treatment and underwent RP. Across both treatment arms, 31 (44%) men achieved either CR or MRD; 5 men had CR (2 in Arm A) and an additional 26 men exhibited MRD (15 in Arm A), p = 1 between Arm A and B. Kaplan-Meier analysis demonstrated no difference in biochemical-free survival (BFS) rate between the two treatment groups. Patients who achieved a CR/MRD experienced significantly longer BFS. Conclusions: Study findings indicate significant tumor response with 44% of patients exhibiting CR/MRD, with no significant difference observed between the two treatment arms. Patients who exhibit CR/MRD experienced better BFS rates. Genomic efforts are underway to determine predictors of response. Clinical trial information: NCT02543255. [Table: see text]

433 Background: Prior randomized controlled trials (RCT) comparing bladder preservation to radical cystectomy (RC) for muscle invasive bladder cancer (MIBC) closed early due to lack of accrual. Given that no future RCTs are foreseen, and in the absence of level 1 data, we aimed to provide the best evidence possible on outcomes of matched cohorts comparing trimodality therapy (TMT, maximal transurethral resection of bladder tumor followed by concurrent chemoradiation) to RC in order to guide management. Methods: This retrospective analysis included 703 patients with MIBC clinical stage T2-T3/4aN0M0 MIBC urothelial carcinoma of the bladder, 421 RC and 282 TMT who would have been eligible for both TMT or RC, treated at the Massachusetts General Hospital, Boston; Princess Margaret Cancer Centre, Toronto; and University of Southern California, Los Angeles between 2005-2017. To compare homogeneous cohorts, all patients included in this analysis had solitary tumors < 7 cm, no or unilateral hydronephrosis, and no multifocal carcinoma in situ. Treatment propensity scores were estimated using logistic regression, and patients were matched 3:1 with replacement. Covariates included age, sex, clinical T stage, hydronephrosis, (neo)adjuvant chemotherapy, body mass index, smoking history, and ECOG status. Overall survival (OS) was estimated with adjusted Cox models; cancer-specific survival (CSS), distant failure-free survival, pelvic nodal failure-free survival and metastasis-free survival (combined distant and pelvic nodal failure) were estimated with adjusted competing risk models. Our primary endpoint of interest was metastasis-free survival. The analysis was performed as intent-to-treat. Results: The 3:1 matched cohort comprised of 1,116 patients (834 RC vs 282 TMT). After matching, age (71.3 vs 71.6), cT2 clinical stage (88 vs 90%), presence of hydronephrosis (12 vs 10%), and use of (neo)adjuvant chemotherapy (60 vs 65%) were similar between RC and TMT cohorts. Salvage cystectomy was performed in 38 patients (13%) treated by TMT. At 5 years, metastasis-free (73 vs 78%, p = 0.07), distant failure-free (78 vs 82%, p = 0.14), and pelvic nodal failure-free (96 vs 94%, p = 0.33) survival were not statistically different between RC and TMT, whereas CSS and OS favored TMT (78 vs 85%, p = 0.02; 70 vs 78%, p < 0.001). Outcomes for RC and TMT were not different among centers. Final pT stage in the RC patients was: pT0 14%, pT1 7%, pT2 29%, pT3/4 42% and N+ 24%. Peri RC mortality was 2.1% and median number of nodes removed was 40. NMIBC recurrence occurred in 57/278 (20.5%) TMT patients. Conclusions: This large multi-institutional contemporary study provides the best evidence to date, in the absence of randomized trials, supporting TMT for select patients with MIBC. Oncologic outcomes seem to be equivalent between TMT and RC, affirming the position that TMT should be offered as an effective alternative.

65 Background: The natural history of non-metastatic castrate resistant prostate cancer (nmCRPC) prior to the introduction of novel anti-androgen agents in a real-world setting is largely unknown. Methods: This was a retrospective population-based cohort study of men with nmCRPC in Ontario, Canada. Patients with a diagnosis of prostate cancer, castrate level of testosterone ( < 1.7nmol/L) and a PSA > 2.0nmol/L with a subsequent rise > 25% from the nadir, and without diagnostic or treatment codes for metastasis were included. Annual prevalence of nmCRPC was calculated. Crude time from nmCRPC to metastasis and death are presented as medians with interquartile range (IQR). Predictors of time from nmCRPC to prostate cancer death were compared using univariable and multivariable Fine and Gray subdistributional hazard models to account for the competing risk of non-prostate cancer death. Results: From January 2007 until March 2018, we identified 2045 patients with nmCRPC. Median age was 79 years (IQR: 72-84). A total of 984 patients (48.1%) received upfront hormonal therapy while 584 (25.8%) received initial radiotherapy (RT) and 478 (23.4%) underwent radical prostatectomy. Median time from primary treatment to nmCRPC was 6 years (IQR: 3-10). PSA at the time of meeting nmCRPC criteria was a median of 3.0 ng/L. Patients were followed for a median 31.1 months (IQR: 19.8-47.9). The overall annual prevalence of nmCRPC ranged from 1,519-1,913 patients, representing 7-12% of men with prostate cancer prescribed androgen deprivation therapy each year. Crude median time from nmCRPC to all-cause death was 37.6 months (IQR: 22.1-55.4). Median time from nmCRPC to metastasis and metastasis to all-cause death was 20.0 and 8.3 months, respectively. On regression analysis, older age, ADT use with primary treatment, higher PSA at the time of meeting nmCRPC criteria, and grade group predicted time from nmCRPC to prostate cancer death. Conclusions: This is the largest analysis of the prevalence and natural history of nmCRPC. The current study can be used as a historical cohort to compare how novel imaging modalities and advancements in systemic therapy for patients with nmCRPC impact prevalence estimates and disease trajectory over time.

Introduction: Non-muscle-invasive bladder cancer (NMIBC) accounts for 75‒85% of all urothelial bladder cancers (UBC). Many UBC patients are also afflicted by diabetes mellitus (DM). It has been postulated that several oral hypoglycemic agents could impact disease-specific survival (DSS), but the data are sparse among NMIBC patients. Our primary objective was to evaluate the impact of metformin on DSS and overall survival (OS) in NMIBC patients.Methods: This is a retrospective, population-based study that used linked administrative databases to identify diabetic patients ≥66 years who were subsequently diagnosed with NMIBC in Ontario between 1992 and 2012. Cumulative use of metformin and other hypoglycemic agent were calculated before and after NMIBC diagnosis. DSS and OS were estimated using multivariable competing risk and Cox proportional hazards models, respectively.Results: A total of 1742 subjects were included in the study. After a median followup of 5.2 years, 1122 (64%) had died, including 247 (15%) deaths as a result of UBC. On multivariable analysis, cumulative duration of metformin use after NMIBC diagnosis did not appear to impact DSS (hazard ratio [HR] 1.1; 95% confidence interval [CI] 0.92‒1.2), whereas glyburide use appeared to have a detrimental effect (HR 1.17; 95% CI 1.02‒1.3). None of the other hypoglycemic agents had an impact on OS.Conclusions: In this large, population-based study, we have provided further evidence that metformin use does not significantly impact DSS among diabetic patients diagnosed with NMIBC. However, our findings demonstrate that glyburide use inversely affects DSS. The detrimental effect of glyburide on DSS will require further validation.

Several studies demonstrate that use of commonly prescribed medications is associated with improved survival in various malignancies. Methods of classifying medication use in many of these studies, however, do not account for intermittent or cumulative use. Moreover, there are limited data in kidney cancer. Therefore, we performed a population-based cohort study utilizing healthcare databases in Ontario, Canada. We identified patients aged ≥65 with an incident diagnosis of kidney cancer between 1997 and 2013 and examined use of nine putative anti-neoplastic medications using prescription claims. Cox proportional hazard models evaluated the association of medication exposure on cancer-specific and overall survival. We conducted three separate analyses: the effect of cumulative duration of exposure to the study medications on outcomes, the effect of current exposure (in a binary nature) and the effect of exposure at diagnosis. During the 16-year study period, we studied 9,124 patients. Increasing cumulative use of angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs) and selective serotonin reuptake inhibitors were associated with markedly improved cancer-specific survival; increasing use of NSAIDs was associated with markedly improved overall survival. These results were generally discordant with analyses evaluating the effect of current use and exposure at diagnosis. In conclusion, pharmacoepidemiology studies may be sensitive to the method of analysis; cumulative use analyses may be the most robust as it accounts for intermittent use and supports a dose-outcome relationship. Prospective studies are needed to confirm whether patients diagnosed with kidney cancer should be started on an angiotensin-converting enzyme inhibitor, NSAID or selective serotonin reuptake inhibitor to improve survival.

We determined whether men on continuous androgen deprivation therapy who achieve testosterone less than 0.7 nmol/l demonstrate subsequent testosterone elevations during followup and whether such events predict worse oncologic outcomes.We evaluated a random, retrospective sample of 514 patients with prostate cancer treated with continuous androgen deprivation therapy in whom serum testosterone was less than 0.7 nmol/l at University Health Network between 2007 and 2016. Patients were followed from the date of the first testosterone measurement of less than 0.7 nmol/l to progression to castrate resistance, death or study period end. Study outcomes were the development of testosterone elevations greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, and progression to a castrate resistant state. Survival curves were constructed to determine the rate of testosterone elevations. Multivariate Cox regression analysis was done to assess whether elevations predicted progression to castrate resistance.Median patient age was 74 years and median followup was 20.3 months. Within 5 years of followup 82%, 45% and 18% of patients had subsequent testosterone levels greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, respectively. In 96% to 100% of these patients levels less than 0.7 nmol/l were subsequently reestablished within 5 years. No patient baseline characteristic was associated with elevations and elevations were not a significant predictor of progression to a castrate resistant state.Men on continuous androgen deprivation therapy in whom initial testosterone is less than 0.7 nmol/l frequently show subsequent elevations in serum testosterone. Such a development should not trigger an immediate response from physicians as these events are prognostically insignificant with regard to oncologic outcomes. Levels are eventually reestablished at less than 0.7 nmol/l.

Introduction: We sought to examine the relationship between preoperative platelet to white blood cell ratio (PLT/WBC), a hematological marker of the systemic inflammatory response, and postoperative infectious complications following radical nephrectomy for localized renal cell carcinoma.Methods: We performed a retrospective cohort study of patients treated with radical nephrectomy for localized kidney cancer between January 1, 2005 and December 31, 2014 (n=6235) using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. Univariate and multivariate analyses were used to assess the association between PLT/ WBC ratio and 30-day infectious complications, including surgical site infection, urinary tract infection (UTI), pneumonia, and sepsis. Secondarily, we examined major complications and bleeding requiring transfusion.Results: A lower PLT/WBC ratio was associated with an increased risk of sepsis, pneumonia, and UTI rates (p

Exposure to commonly prescribed medications may be associated with cancer risk. However, there is limited data in kidney cancer. Furthermore, methods of classifying cumulative medication exposure in previous studies may be prone to bias.We conducted a population-based case-control study of 10,377 incident kidney cancer cases aged ≥66 years matched with 35,939 controls on age, sex, history of hypertension, comorbidity score, and geographic location. Cumulative exposure to commonly prescribed medications hypothesised to modulate cancer risk was obtained using prescription claims data. We modelled exposure in four different fashions: (1) as continuous exposures using (a) fractional polynomials (which allow for a non-linear relationship between an exposure and outcome) or (b) assuming linear relationships; and 2) as dichotomous exposures denoting (a) ≥3 years versus 3 years exposure; or (b) "ever" versus "never" exposure. We used conditional logistic regression to estimate the association of medication exposure on incident kidney cancer.The directions of association were relatively consistent across analyses; however, the magnitudes were sensitive to the method of analysis. When utilising fractional polynomials, increasing cumulative exposure to acetylsalicylic acid, selective serotonin reuptake inhibitors, and proton-pump inhibitors was associated with significantly reduced risk of kidney cancer, while increasing exposure to antihypertensive drugs was associated with significantly increased risk.Our study provides impetus to further explore the effect of commonly prescribed medications on carcinogenesis to identify modifiable pharmacological interventions to reduce the risk of kidney cancer.

Objectives To determine whether studies that used propensity score (PS) methods in the urology literature provided sufficient detail to allow scientific reproducibility and whether appropriate statistical tests were used to obtain valid measures of effect. Materials and Methods We searched OVID Medline and the Science Citation Index from inception to November 2016 to identify studies that used PS methods from 5 general urology journals. From each included article, we extracted pertinent information related to the PS methodology such as estimation of the PS, whether balance diagnostics were performed, and the statistical analysis performed. Results We identified 114 articles for inclusion. Matching on the PS was the most common method used (62 studies, 54.4%). Of all studies, 103 (90.4%) described which covariates were used to estimate the PS; however, only 24 provided justification for the selected covariates. Although the majority of studies (70.2%) performed some sort of diagnostic evaluation to assess balance, few studies (24.6%) used appropriate methods for balance assessment. Only 4 (6.4%) studies that used PS matching provided sufficient detail to replicate the matching strategy. Finally, the majority (77.4%) of studies that used PS matching explicitly used inappropriate statistical methods to estimate the effect of an exposure on an outcome. Conclusions Propensity score methods are poorly described and implemented in the urology literature. We provide recommendations for improvement to allow scientific reproducibility and obtain valid measures of effect from their use. This article is protected by copyright. All rights reserved.

Objective To quantify the effect of immortal-time bias in an observational study examining the effect of cumulative testosterone exposure on mortality. Subjects and Methods We used a population-based matched cohort study of men aged 66 and older newly treated with testosterone replacement therapy and matched-controls from 2007-2012 in Ontario, Canada to quantify the effects of immortal-time bias. We used generalized estimating equations to determine the association between cumulative testosterone replacement therapy exposure and mortality. Results produced by models using time-fixed and time-varying exposures were compared. Further, we undertook a systematic review of PubMed to identify studies addressing immortal-time bias or time-varying exposures in the urologic literature and qualitative summated these. Results Among 10,311 TRT-exposed men and 28,029 controls, the use of a time-varying exposure resulted in the attenuation of treatment effects compared with an analysis which did not account for immortal-time bias. While both analyses showed a decreased risk of death for patients in the highest tertile of TRT exposure, the effect was overestimated when using a time-fixed analysis (aHR 0.56, 95% CI 0.52-0.61) when compared to a time-varying analysis (aHR 0.67, 95% CI 0.62-0.73). Of the 1241 studies employing survival analysis identified in the literature, nine manuscripts met criteria for inclusion. Of these, 5 employed time-varying analytic methodology. Each of these was a large, population-based retrospective cohort study assessing potential harms of pharmacologic agents. Conclusions Where exposures vary over time, a time-varying exposure is necessary to draw meaningful conclusions. Failure to employ a time-varying analysis will result in overestimation of a beneficial effect. However, time-varying exposures are uncommonly utilized among manuscripts published in prominent urologic journals. This article is protected by copyright. All rights reserved.

Background Non–muscle-invasive bladder cancer (NMIBC) is especially prevalent among the elderly. Many patients with NMIBC also have significant concomitant comorbidities, including cardiovascular diseases and hypercholesterolemia. Statins are the most commonly used cholesterol-depleting agents, and they may possess anticancer properties. The objective of this population-based study was to evaluate the effect of statins on the survival of individuals diagnosed with NMIBC. Methods This is a retrospective population-based cohort study that used administrative databases to identify individuals 66 years of age and older who were diagnosed with NMIBC between 1992 and 2012. Subjects with documented use of statins before they were 66 years of age were excluded from the analysis. Cumulative daily use of statins was calculated before and after the diagnosis of NMIBC. Their effect on cancer-specific survival and overall survival was estimated using a multivariable competing risk and Cox proportional hazards model, respectively. Results The final cohort was composed of 13,811 individuals≥66 years diagnosed with NMIBC. Of these, 4,748 individuals (34%) were exposed to statins during follow-up. The median statin exposure after NMIBC diagnosis was 21.4 months (interquartile range: 7.8–45.4). After a median follow-up of 7.1 years (interquartile range: 4.0–11.3) from NMIBC diagnosis, 8,900 (64%) individuals had died. The cumulative use of statins after NMIBC diagnosis did not significantly affect cancer-specific survival ( P = 0.10). However, its cumulative use after NMIBC diagnosis was associated with a better overall survival ([0.93; 95% CI: 0.91–0.96], per year of use). Conclusions This large population-based study has provided evidence that cumulative statin use was not associated with an improved cancer-specific survival among individuals with NMIBC. However, our findings did demonstrate that statin users had a better overall survival than nonusers.

Purpose: Degarelix, a new gonadotropin-releasing hormone (GnRH) receptor antagonist with demonstrated efficacy as first-line treatment in the management of high-risk prostate cancer, possesses some theoretical advantages over luteinizing hormone–releasing hormone (LHRH) analogues in terms of avoiding “testosterone flare” and lower follicle-stimulating hormone (FSH) levels. We set out to determine whether preoperative degarelix influenced surrogates of disease control in a randomized phase II study. Experimental Design: Thirty-nine patients were randomly assigned to one of three different neoadjuvant arms: degarelix only, degarelix/bicalutamide, or LHRH agonist/bicalutamide. Treatments were given for 3 months before prostatectomy. Patients had localized prostate cancer and had chosen radical prostatectomy as primary treatment. The primary end point was treatment effect on intratumoral dihydrotestosterone levels. Results: Intratumoral DHT levels were higher in the degarelix arm than both the degarelix/bicalutamide and LHRH agonist/bicalutamide arms (0.87 ng/g vs. 0.26 ng/g and 0.23 ng/g, P < 0.01). No significant differences existed for other intratumoral androgens, such as testosterone and dehydroepiandrosterone. Patients in the degarelix-only arm had higher AMACR levels on immunohistochemical analysis (P = 0.01). Serum FSH levels were lower after 12 weeks of therapy in both degarelix arms than the LHRH agonist/bicalutamide arm (0.55 and 0.65 vs. 3.65, P < 0.01), and inhibin B levels were lower in the degarelix/bicalutamide arm than the LHRH agonist/bicalutamide arm (82.14 vs. 126.67, P = 0.02). Conclusions: Neoadjuvant degarelix alone, compared with use of LHRH agonist and bicalutamide, is associated with higher levels of intratumoral dihydrotestosterone, despite similar testosterone levels. Further studies that evaluate the mechanisms behind these results are needed. Clin Cancer Res; 23(8); 1974–80. ©2016 AACR.

Background Exposure to metformin, a medication used to treat diabetes, has been associated with improved survival outcomes in various malignancies. However, studies evaluating the association between metformin use and kidney cancer survival outcomes have demonstrated conflicting results. Patients and Methods We performed a retrospective review of diabetic patients undergoing nephrectomy for M0 renal cell carcinoma from 2000 to 2014 at a tertiary academic center. Medication use at the time of surgery was determined by medical record review. Inverse probability of treatment weights (IPTWs) were derived from a propensity score model that included various clinical, surgical, and pathologic characteristics. Cox proportional hazard models were used to evaluate the association between metformin use and disease-free, cancer-specific, and overall survival in the sample weighted by the IPTWs. Results A total of 158 diabetic patients were identified, 82 (52%) of whom were taking metformin at the time of surgery. Before the application of the propensity score methods, the metformin users were significantly older and were more likely to undergo surgery between 2009 and 2014. After applying the IPTWs, the clinical, surgical, and pathologic characteristics were well balanced between the 2 groups. The median follow-up period was 43 months. Metformin use was not significantly associated with disease-free (hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.36-2.74), cause-specific (HR, 0.38; 95% CI, 0.08-1.86), or overall (HR, 0.86; 95% CI, 0.40-1.85) survival. Conclusion We found no significant association between metformin use and kidney cancer outcomes. Population-based studies are needed to further evaluate the role of metformin in kidney cancer therapy.

Bladder-sparing trimodality therapy (TMT) has become an accepted alternative to cystectomy for selected muscle invasive bladder cancer (MIBC) patients unfit for cystectomy or opting for bladder preservation. This review will summarize recent advances in TMT for MIBC. A growing body of literature has emerged which supports the use of TMT. However, its delivery is yet to be standardized. The role of chemotherapy and predictive biomarkers remain to be elucidated. Novel bladder-sparing approaches, drug combinations including immunotherapy and targeted therapies are under investigation in clinical trials, with the goal of ultimately enhancing survival and quality of life outcomes. Recent advances in TMT have made bladder preservation possible for MIBC patients seeking an alternative local therapy to cystectomy. With careful patient selection, TMT offers comparable survival outcomes to cystectomy, and improved quality of life as patients are able to successfully retain their bladder.

Objective To examine health behaviours in bladder cancer survivors including physical activity (PA), body mass index, diet quality, smoking and alcohol consumption, and to explore their relationship with health‐related quality of life (HRQoL). Subjects/Patients and Methods Cross‐sectional questionnaire packages were distributed to bladder cancer survivors (muscle‐invasive bladder cancer [MIBC] and non‐muscle‐invasive bladder cancer [NMIBC]) aged >18 years, and proficient in English. Lifestyle behaviours were measured using established measures/questions, and reported using descriptive statistics. HRQoL was assessed using the validated Bladder Utility Symptom Scale, and its association with lifestyle behaviours was evaluated using analysis of covariance (ancova) and multivariate regression analyses. Results A total of 586 participants completed the questionnaire (52% response rate). The mean (SD) age was 67.3 (10.2) years, and 68% were male. PA guidelines were met by 20% (n = 117) and 22.7% (n = 133) met dietary guidelines. In all, 60.9% (n = 357) were overweight/obese, and the vast majority met alcohol recommendations (n = 521, 92.5%) and were current non‐smokers (n = 535, 91.0%). Health behaviours did not differ between MIBC and NMIBC, and cancer treatment stages. Sufficient PA, healthy diet, and non‐smoking were significantly associated with HRQoL, and the number of health behaviours participants engaged in was positively associated with HRQoL (P

Significance: Photodynamic therapy (PDT) could become a treatment option for nonmuscle invasive bladder cancer when the current high morbidity rate associated with red light PDT and variable PDT dose can be overcome through a combination of intravesical instillation of the photosensitizer and the use of green light creating a steep PDT dose gradient. Aim: To determine how a high PDT selectivity can be maintained throughout the bladder wall considering other efficacy determining parameters, in particular, the average optical properties of the mucosal layer governing the fluence rate multiplication factor, as well as the bladder shape and the position of the emitter in relationship to the bladder wall. Approach: We present three irradiance monitoring systems and evaluate their ability to enable selective bladder PDT considering previously determined photodynamic threshold values for the bladder cancer, mucosa and urothelium in a preclinical model, and the photosensitizer’s specific uptake ratio. Monte Carlo-based light propagation simulations performed for six human bladders at the time of therapy for a range of tissue optical properties. The performance of one irradiance sensing device in a clinical phase 1B trial is presented to underline the impact of irradiance monitoring, and it is compared to the Monte Carlo-derived dose surface histogram. Results: Monte Carlo simulations showed that irradiance monitoring systems need to comprise at least three sensors. Light scattering inside the bladder void needs to be minimized to prevent increased heterogeneity of the irradiance. The dose surface histograms vary significantly depending on the bladder shape and bladder volume but are less dependent on tissue optical properties. Conclusions: We demonstrate the need for adequate irradiance monitoring independent of a photosensitizer’s specific uptake ratio.

The relationship between metformin use and prostate cancer risk remains controversial. Genetic variation in metformin metabolism pathways appears to modify metformin glycemic control and the protective association with some cancers. However, no studies to date have examined this pharmacogenetic interaction and prostate cancer chemoprevention. Clinical data and germline DNA were collected from our prostate biopsy database between 1996 and 2014. In addition to a genome-wide association study (GWAS), 27 single nucleotide polymorphisms (SNPs) implicated in metformin metabolism were included on a custom SNP array. Associations between metformin use and risk of high-grade (Grade Group ≥ 2) and overall prostate cancer were explored using a case-control design. Interaction between the candidate/GWAS SNPs and the metformin-cancer association was explored using a case-only design. Among 3481 men, 132 (4%) were taking metformin at diagnosis. Metformin users were older, more likely non-Caucasian, and had higher body mass index, Gleason score, and number of positive cores. Overall, 2061 (59%) were diagnosed with prostate cancer, of which 922 (45%) were high-grade. After adjusting for baseline characteristics, metformin use was associated with higher risk of high-grade prostate cancer (OR = 1.76, 95% CI 1.1–2.9, p = 0.02) and overall prostate cancer (OR = 1.77, 95% CI 1.1–2.9, p = 0.03). None of the 27 candidate SNPs in metformin metabolic pathways had significant interaction with the metformin-cancer association. Among the GWAS SNPs, one SNP (rs149137006) had genome-wide significant interaction with metformin for high-grade prostate cancer, and another, rs115071742, for overall prostate cancer. They were intronic and intergenic SNPs, respectively, with largely uncharacterized roles in prostate cancer chemoprevention. In our cohort, metformin use was associated with increased risk of being diagnosed with prostate cancer. While SNPs involved in metformin metabolism did not have modifying effects on the association with disease risk, one intronic and one intergenic SNP from the GWAS study did, and these require further study.

Background: The causal association between radiation and chemotherapy treatment and the development of secondary sarcoma is well known, but the contemporary risk has not been well characterized for patients with cancers of the abdomen and pelvis. Methods: We conducted a population–based retrospective cohort study examining the risk of sarcoma among patients with localized cancer of the prostate, bladder, colorectal, cervical, uterine, and testis between 2002–2016. The primary outcome was the development of sarcoma. Cox proportional hazard analysis was used to estimate the risk of sarcoma after treatment combinations with radiation, chemotherapy, or surgery. Findings: We identified 173,580 patients. Most patients had genitourinary (51∙4%) or colorectal cancer (39∙9%). Overall, 332 (0∙2%) sarcomas developed over a median of 5∙7 years (IQR: 2∙2–8∙9). Compared to a reference group of patients who had surgery alone, the greatest risk for sarcoma was found for patients who underwent a combination of radiation and chemotherapy (HR=4∙1,95%CI:2∙8–6∙0,p

Tumors of the adrenal gland are very common, found incidentally in 5% of CT scans. They can be functional or nonfunctional, benign, or malignant or arise in the adrenal cortex or medulla. The majority of adrenal tumors are benign nonfunctioning adenomas that are found incidentally on abdominal imaging for another cause (adrenal incidentaloma). Due to the risk of malignancy, incidentalomas over 4 cm should be removed while smaller ones may be followed with serial imaging. Benign functioning adrenal adenomas can secrete aldosterone, cortisol, or androgens. After appropriate workup, all functioning adrenal lesions should be surgically removed. Pheochromocytomas are usually benign, however, more than 30% are associated with a genetic syndrome. Traditional components of perioperative management include alpha blockage followed by beta-blockade if tachycardia. This pathway has recently been challenged. Adrenocortical carcinoma is rare, and 60% of cases present with symptoms of hormone excess which may portend a worse prognosis. After workup, localized disease is treated with surgical resection and consideration of adjuvant mitotane in addition to other chemotherapy and radiation options. Adrenal metastases are common and laparoscopic adrenalectomy may improve survival in selected patients. Overall, while the most common approach to minimally invasive adrenalectomy has been the lateral/anterior approach, the posterior approach may provide better visualization, quicker discharge from hospital, less pain, and for pheochromocytoma resection, less hemodynamic lability.

Item does not contain fulltext CONTEXT: Currently, there is no standard of care for patients with non-muscle-invasive bladder cancer (NMIBC) who recur despite bacillus Calmette-Guerin (BCG) therapy. Although radical cystectomy is recommended, many patients decline to undergo or are ineligible to receive it. Multiple agents are being investigated for use in this patient population. OBJECTIVE: To systematically synthesize and describe the efficacy and safety of current and emerging treatments for NMIBC patients after treatment with BCG. EVIDENCE ACQUISITION: A systematic literature search of MEDLINE, Embase, and the Cochrane Controlled Register of Trials (period limited to January 2007-June 2019) was performed. Abstracts and presentations from major conference proceedings were also reviewed. Randomized controlled trials were assessed using the Cochrane risk of bias tool. Data for single-arm trials were pooled using a random-effect meta-analysis with the proportions approach. Trials were grouped based on the minimum number of prior BCG courses required before enrollment and further stratified based on the proportion of patients with carcinoma in situ (CIS). EVIDENCE SYNTHESIS: Thirty publications were identified with data from 23 trials for meta-analysis, of which 17 were single arm. Efficacy and safety outcomes varied widely across studies. Heterogeneity across trials was reduced in subgroup analyses. The pooled 12-mo response rates were 24% (95% confidence interval [CI]: 16-32%) for trials with two or more prior BCG courses and 36% (95% CI: 25-47%) for those with one or more prior BCG courses. In a subgroup analysis, inclusion of >/=50% of patients with CIS was associated with a lower response. CONCLUSIONS: The variability in efficacy and safety outcomes highlights the need for consistent endpoint reporting and patient population definitions. With promising emerging treatments currently in development, efficacious and safe therapeutic options are urgently needed for this difficult-to-treat patient population. PATIENT SUMMARY: We examined the efficacy and safety outcomes of treatments for non-muscle-invasive bladder cancer after bacillus Calmette-Guerin therapy. Outcomes varied across studies and patient populations, but emerging treatments currently in development show promising efficacy.

Introduction: Our aim was to determine whether androgen-deprivation therapy (ADT) with abiraterone acetate (AA) or ADT with docetaxel chemotherapy (DC) resulted in improved quality-adjusted life years (QALYs) among men with de novo metastatic castration-sensitive prostate cancer (mCSPC) and the cost-effectiveness of the preferred strategy using decision analytic techniques. Methods: A microsimulation model with a lifetime time horizon was constructed. Our primary outcome was QALYs. Secondary outcomes included cost, incremental cost-effectiveness ratio (ICER), unadjusted overall survival (OS), rates of second- and third-line therapy, and adverse events. A systematic literature review was used to generate probabilities and utilities to populate the model. The base case was a 65-year-old patient with de novo mCSPC. Results: A total of 100 000 microsimulations were generated. Initial AA resulted in a gain of 0.45 QALYs compared to DC (3.36 vs. 2.91 QALYs) with an ICER of $276 251.84 per QALY gained with initial AA therapy. Median crude OS was 51 months with AA and 48 months with DC. Overall, 46.6% and 42.6% of patients received second-line therapy and 8.7% and 7.9% patients received third-line therapy in the AA and DC groups, respectively. Grade 3/4 adverse events were experienced in 17.6% of patients receiving initial AA and 22.3% of patients receiving initial DC. Conclusions: Although ADT with AA results in a gain in QALYs and crude OS compared to DC, AA therapy is not a cost-effective treatment strategy to apply uniformly to all patients. The availability of AA as a generic medication may help to close this gap. The ultimate choice should be based on patient and tumor factors.

Key Points Question Was a change in hospital funding policy for radical prostatectomy associated with changes in management of localized prostate cancer in the province of Ontario, Canada? Findings In this population-based interrupted time series study, which included 33 128 patients with incident localized prostate cancer and 17 159 patients treated with radical prostatectomy, no statistically significant association of the change in hospital funding policy with most outcomes was found. However, potential improvement in appropriate patient selection for prostate cancer surgery was observed. Meaning The implementation of a hospital funding policy change aimed at improving health care quality and value was not associated with management of localized prostate cancer., This population-based, interrupted time series study evaluates whether changes in hospital funding policy in Ontario, Canada, aimed at improving health care quality and value were associated with changes in the management of localized prostate cancer or the characteristics of patients receiving radical prostatectomy for localized prostate cancer., Importance Hospital funding reforms for prostate cancer surgery may have altered management of localized prostate cancer in the province of Ontario, Canada. Objective To determine whether changes in hospital funding policy aimed at improving health care quality and value were associated with changes in the management of localized prostate cancer or the characteristics of patients receiving radical prostatectomy (RP) for localized prostate cancer. Design, Setting, and Participants This population-based, interrupted time series study used linked population-based administrative data regarding adults in Ontario with incidental localized prostate cancer and those who underwent RP for localized prostate cancer. Patients who underwent RP were compared with patients who underwent surgical procedures for localized renal cell carcinoma, which was not included in the policy change but was subjected to similar secular trends and potential confounders. Monthly outcomes were analyzed using interventional autoregressive integrated moving average models. Data were collected from January 2011 to November 2017 and analyzed in January 2019. Exposures Funding policy change in April 2015 from flexible block funding for all hospital-based care to prespecified payment amounts per procedure for treatment of localized prostate cancer, coupled with the dissemination of a diagnosis-specific handbook outlining best practices. Main Outcomes and Measures Initial management (RP vs radiation therapy vs active surveillance) and tumor risk profiles per management strategy among incident cases of localized prostate cancer. Additional outcomes were case volume, mean length of stay, proportion of patients returning to hospital or emergency department within 30 days, proportion of patients older than 65 years, mean Charlson Comorbidity Index, and proportion of minimally invasive surgical procedures among patients undergoing RP for localized prostate cancer. Results A total of 33 128 patients with incident localized prostate cancer (median [interquartile range (IQR)] age, 67 [61-73] years; median [IQR] cases per monthly observation interval, 466 [420-516]), 17 159 patients who received radical prostatectomy (median [IQR] age, 63 [58-68] years; median [IQR] cases per monthly observation interval, 209 [183-225]), and 5762 individuals who underwent surgery for renal cell carcinoma (median [IQR] age, 62 [53-70] years; median [IQR] cases per monthly observation interval, 71 [61-77]) were identified. By the end of the observation period, radical prostatectomy and radiation therapy were used in comparable proportions (30.3% and 28.9%, respectively) and included only a small fraction of low-risk patients (6.4% and 2.9%, respectively). No statistically significant association of the funding policy change with most outcomes was found. Conclusions and Relevance The implementation of funding reform for hospitals offering RP was not associated with changes in the management of localized prostate cancer, although it may have encouraged more appropriate selection of patients for RP. Mostly preexisting trends toward guideline-conforming practice were observed. Co-occurring policy changes and/or guideline revisions may have weakened signals from the policy change.

Introduction: Active surveillance (AS) is standard of care in low-risk prostate cancer (PC). This study describes a novel total cancer location (TCLo) density metric and aims to determine its performance in predicting clinical progression (CP) and grade progression (GP). Methods: This was a retrospective study of patients on AS after confirmatory biopsy (CBx). We excluded patients with Gleason ≥7 at CBx and 0.05) was independently associated with time to CP (HR 4.70, 95% CI: 2.62-8.42, p

The choice of urinary diversion at cystectomy is a life altering decision. Patient decision aids are clinical tools that promote shared decision making by providing information about management options and helping patients communicate their values. We sought to develop and evaluate a patient decision aid for individuals undergoing cystectomy with urinary diversion.We used the IPDAS (International Patient Decision Aids Standards) to guide a systematic development process. A literature review was performed to determine urinary diversion options and the incidence of outcomes. We created a prototype using the Ottawa Decision Support Framework. A 10-question survey was used to assess patient decision aid acceptability among patients, allied health professionals and urologists. The primary outcome was acceptability of the patient decision aid.Ileal conduit and orthotopic neobladder were included as primary urinary diversion options because they had the most evidence and are most commonly performed. Continent cutaneous diversion was identified as an alternative option. Outcomes specific to ileal conduit were stomal stenosis and parastomal hernia. Outcomes specific to neobladder were daytime and nighttime urinary incontinence and urinary retention. Acceptability testing was completed by 8 urologists, 9 patients and 1 advanced practice nurse. Of the respondents 94% reported that the language was appropriate, 94% reported that the length was adequate and 83% reported that option presentation was balanced. The patient decision aid met all 6 IPDAS defining criteria, all 6 certification criteria and 21 of 23 quality criteria.We created a novel patient decision aid to improve the quality of decisions made by patients when deciding among urinary diversion options. Effectiveness testing will be performed prospectively.

INTRODUCTION AND OBJECTIVES:There is emerging evidence that oncology patients with pre-existing mental illness may have poorer survival compared to patients without psychiatric disease. Furthermore...