Postradical prostatectomy prostate-specific antigen outcomes after 6 versus 18 months of perioperative androgen-deprivation therapy in men with localized, unfavorable intermediate-risk or high-risk prostate cancer: Results of part 2 of a randomized phase 2 trial.

BACKGROUND: Patients with localized, unfavorable intermediate-risk and high-risk prostate cancer have an increased risk of relapse after radical prostatectomy (RP). The authors previously reported on part 1 of this phase 2 trial testing neoadjuvant apalutamide, abiraterone, prednisone, plus leuprolide (AAPL) or abiraterone, prednisone, and leuprolide (APL) for 6 months followed by RP. The results demonstrated favorable pathologic responses (tumor <5 mm) in 20.3% of patients (n = 24 of 118). Herein, the authors report the results of part 2. METHODS: For part 2, patients were randomized 1:1 to receive either AAPL for 12 months (arm 2A) or observation (arm 2B), stratified by neoadjuvant therapy and pathologic tumor classification. The primary end point was 3-year biochemical progression-free survival. Secondary end points included safety and testosterone recovery (>200 ng/dL). RESULTS: Overall, 82 of 118 patients (69%) enrolled in part 1 were randomized to part 2. A higher proportion of patients who were not randomized to adjuvant therapy had a favorable prostatectomy pathologic response (32.3% in nonrandomized patients compared with 17.1% in randomized patients). In the intent-to-treat analysis, the 3-year biochemical progression-free survival rate was 81% for arm 2A and 72% for arm 2B (hazard ratio, 0.81; 90% confidence interval, 0.43-1.49). Of the randomized patients, 81% had testosterone recovery in the AAPL group compared with 95% in the observation group, with a median time to recovery of <12 months in both arms. CONCLUSIONS: In this study, because 30% of patients declined adjuvant treatment, part B was underpowered to detect differences between arms. Future perioperative studies should be biomarker-directed and include strategies for investigator and patient engagement to ensure compliance with protocol procedures.

Impact of Family History and Germline Genetic Risk Single Nucleotide Polymorphisms on Long-Term Outcomes of Favorable-Risk Prostate Cancer.

PURPOSE: Family history and germline genetic risk single nucleotide polymorphisms (SNPs) have been separately shown to stratify lifetime risk of prostate cancer. Here, we evaluate the combined prognostic value of family history of prostate and other related cancers and germline risk SNPs among patients with favorable-risk prostate cancer. MATERIALS AND METHODS: A total of 1367 participants from the prospective Health Professionals Follow-up Study diagnosed with low- or favorable intermediate-risk prostate cancer from 1986 to 2017 underwent genome-wide SNP genotyping. Multivariable Cox regression was used to estimate the association between family history, specific germline risk variants, and a 269 SNP polygenic risk score with prostate cancer‒specific death. RESULTS: Family history of prostate, breast, and/or pancreatic cancer was observed in 489 (36%) participants. With median follow-up from diagnosis of 14.9 years, participants with favorable-risk prostate cancer with a positive family history had a significantly higher risk of prostate cancer‒specific death (HR 1.95, 95% CI 1.15-3.32, P = .014) compared to those without any family history. The rs2735839 (19q13) risk allele was associated with prostate cancer‒specific death (HR 1.81 per risk allele, 95% CI 1.04-3.17, P = .037), whereas the polygenic risk score was not. Combined family history and rs2735839 risk allele were each associated with an additive risk of prostate cancer‒specific death (HR 1.78 per risk factor, 95% CI 1.25-2.53, P = .001). CONCLUSIONS: Family history of prostate, breast, or pancreatic cancer and/or a 19q13 germline risk allele are associated with an elevated risk of prostate cancer‒specific death among favorable-risk patients. These findings have implications for how family history and germline genetic risk SNPs should be factored into clinical decision-making around favorable-risk prostate cancer.

NCCN Guidelines® Insights: Bladder Cancer, Version 3.2024.

Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non-muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guérin (BCG)-unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.

Free PSA and Clinically Significant and Fatal Prostate Cancer in the PLCO Screening Trial.

PURPOSE: We studied whether adding percent free PSA to total PSA improves prediction of clinically significant prostate cancer and fatal prostate cancer. MATERIALS AND METHODS: A total of 6,727 men within the intervention arm of PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial) had baseline percent free PSA. Of this cohort, 475 had clinically significant prostate cancer and 98 had fatal prostate cancer. Cumulative incidence and Cox analyses were conducted to evaluate the association between percent free PSA/PSA and clinically significant prostate cancer/fatal prostate cancer. Harrell's C index evaluated predictive ability. Kaplan-Meier analysis assessed survival. RESULTS: Median follow-up was 19.7 years, median baseline PSA was 1.19 ng/mL, median percent free PSA was 18%. Cumulative incidence of fatal prostate cancer for men with baseline PSA ≥2 ng/mL and percent free PSA ≤10 was 3.2% and 6.1% at 15 and 25 years, respectively, compared to 0.03% and 1.1% for men with percent free PSA >25%. In younger men (55-64 years) with baseline PSA 2-10 ng/mL, C index improved from 0.56 to 0.60 for clinically significant prostate cancer and from 0.53 to 0.64 for fatal prostate cancer with addition of percent free PSA. In older men (65-74 years), C index improved for clinically significant prostate cancer from 0.60 to 0.66, with no improvement in fatal prostate cancer. Adjusting for age, digital rectal exam, family history of prostate cancer, and total PSA, percent free PSA was associated with clinically significant prostate cancer (HR 1.05, P < .001) per 1% decrease. Percent free PSA improved prediction of clinically significant prostate cancer and fatal prostate cancer for all race groups. CONCLUSIONS: In a large U.S. screening trial, the addition of percent free PSA to total PSA in men with baseline PSA ≥2 ng/mL improved prediction of clinically significant prostate cancer and fatal prostate cancer. Free PSA should be used to risk-stratify screening and decrease unnecessary prostate biopsies.

Evaluation of statin use and renal cell carcinoma risk identifies sex-specific associations with RCC subtypes.

Background: The association between statin use and risk of renal cell carcinoma (RCC) has been debated. We aimed to evaluate whether statin use is associated with RCC risk.Material and methods: We studied 100,195 women in the Nurses' Health Study (NHS) from 1994 to 2016; 91,427 women in the Nurses' Health Study II (NHS II) from 1999 to 2015; and 45,433 men in the Health Professionals Follow-up Study (HPFS) from 1990 to 2016. Statins and covariate data were collected at baseline and then biennially. Outcome was measured as incidence of total RCC and clinically relevant disease subgroups. Cox proportional hazards models estimated covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).Results: During follow-up, 661 participants developed RCC. There was no significant association between the use of statins and the risk of overall RCC, fatal RCC, or advanced or localized disease. Across cohorts, the adjusted HR for ever vs. never users was 0.97 (95% CI 0.81-1.16). Female ever users of statins were at increased risk of high-grade disease in the NHS only (HR 1.75, 95% CI 1.07-2.85). Among men only, ≥4 years of statin use was associated with an increased risk of clear cell RCC (HR 1.65, 95% CI 1.10-2.47).Conclusions: Statin use was not associated with the overall risk of RCC. However, it was associated with an increased risk of high-grade disease among women in the NHS cohort and an increased risk of clear cell RCC among men. The reasons for these inconsistent results by sex are unclear.

Impact of COVID-19 pandemic on ambulatory urologic oncology surgeries.

INTRODUCTION: Robot-assisted laparoscopic prostatectomy (RALP) and transurethral resection of bladder tumor (TURBT) are two common surgeries for prostate and bladder cancer. We aim to assess the trends in the site of care for RALP and TURBT before and after the COVID outbreak. MATERIALS AND METHODS: We identified adults who underwent RALP and TURBT within the California Healthcare Cost and Utilization Project State Inpatient Database and the State Ambulatory Surgery Database between 2018 and 2020. Multivariable analysis and spline analysis with a knot at COVID outbreak were performed to investigate the time trend and factors associated with ambulatory RALP and TURBT. RESULTS: Among 17,386 RALPs, 6,774 (39.0%) were ambulatory. Among 25,070 TURBTs, 21,573 (86.0%) were ambulatory. Pre-COVID, 33.5% of RALP and 85.3% and TURBT were ambulatory, which increased to 53.8% and 88.0% post-COVID (both p < 0.001). In multivariable model, RALP and TURBT performed after outbreak in March 2020 were more likely ambulatory (OR 2.31, p < 0.0001; OR 1.25, p < 0.0001). There was an overall increasing trend in use of ambulatory RALP both pre- and post-COVID, with no significant change of trend at the time of outbreak (p = 0.642). TURBT exhibited an increased shift towards ambulatory sites post-COVID (p < 0.0001). CONCLUSIONS: We found a shift towards ambulatory RALP and TURBT following COVID outbreak. There was a large increase in ambulatory RALP post-COVID, but the trend of change was not significantly different pre- and post-COVID - possibly due to a pre-existing trend towards ambulatory RALP which predated the pandemic.

Association between Operative Time and Short-Term Radical Cystectomy Complications.

INTRODUCTION: The aim of this study was to examine the relationship between duration of surgical intervention and postoperative complications in radical cystectomy (RC). We hypothesized that the complication rate increases with longer operative time. METHODS: We analyzed the National Surgical Quality Improvement Program database 2011-2017 to identify all patients who underwent RC. Clinicodemographic characteristics, operative time, and perioperative complications using the Clavien-Dindo Classification (CDC) were abstracted. We fit a generalized linear model with linear splines for operative time to analyze if the relationship between operative time and probability of complication changed over time. RESULTS: A total of 10,520 RC patients were identified with a mean operative time of 5.5 h (standard deviation 2.03). In 55% and 18.2%, any complication and major complications (CDC ≥3) occurred within 30 days postoperatively, respectively. The spline regression model for any complication showed an almost linear relationship between the complication rate and operative time, ranging from 55% at 2.5 h to 82% at 10 h. For major complications, the model revealed the inflection point (knot) at 4.5 h, which corresponds to the lowest complication rate with 15%. Operative times at the extremes of the distribution had higher complication rates: 17.5% if <2.5 h and 28% if >10 h. DISCUSSION/CONCLUSION: Operative time of RC is associated with postoperative complications. Though many factors impact the duration of surgery, surgeries that lasted between 4 and 5 h had trend toward the lowest complication rates. Attention to factors impacting operative time may allow surgeons to identify strategies for optimizing surgical care and reducing complications after RC.

NCCN Guidelines® Insights: Bladder Cancer, Version 2.2022.

The NCCN Guidelines for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer and other urinary tract cancers (upper tract tumors, urothelial carcinoma of the prostate, primary carcinoma of the urethra). These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines regarding the treatment of non-muscle-invasive bladder cancer, including how to treat in the event of a bacillus Calmette-Guérin (BCG) shortage; new roles for immune checkpoint inhibitors in non-muscle invasive, muscle-invasive, and metastatic bladder cancer; and the addition of antibody-drug conjugates for metastatic bladder cancer.

A Phase 2/3 Prospective Multicenter Study of the Diagnostic Accuracy of Prostate Specific Membrane Antigen PET/CT with 18F-DCFPyL in Prostate Cancer Patients (OSPREY).

PURPOSE: Prostate specific membrane antigen-targeted positron emission tomography/computerized tomography has the potential to improve the detection and localization of prostate cancer. OSPREY was a prospective trial designed to determine the diagnostic performance of 18F-DCFPyL-positron emission tomography/computerized tomography for detecting sites of metastatic prostate cancer. MATERIALS AND METHODS: Two patient populations underwent 18F-DCFPyL-positron emission tomography/computerized tomography. Cohort A enrolled men with high-risk prostate cancer undergoing radical prostatectomy with pelvic lymphadenectomy. Cohort B enrolled patients with suspected recurrent/metastatic prostate cancer on conventional imaging. Three blinded central readers evaluated the 18F-DCFPyL-positron emission tomography/computerized tomography. Diagnostic performance of 18F-DCFPyL-positron emission tomography/computerized tomography was based on imaging results compared to histopathology. In cohort A, detection of pelvic nodal disease (with specificity and sensitivity as co-primary end points) and of extrapelvic metastases were evaluated. In cohort B, sensitivity and positive predictive value for prostate cancer within biopsied lesions were evaluated. RESULTS: A total of 385 patients were enrolled. In cohort A (252 evaluable patients), 18F-DCFPyL-positron emission tomography/computerized tomography had median specificity of 97.9% (95% CI: 94.5%-99.4%) and median sensitivity of 40.3% (28.1%-52.5%, not meeting prespecified end point) among 3 readers for pelvic nodal involvement; median positive predictive value and negative predictive value were 86.7% (69.7%-95.3%) and 83.2% (78.2%-88.1%), respectively. In cohort B (93 evaluable patients, median prostate specific antigen 11.3 ng/ml), median sensitivity and positive predictive value for extraprostatic lesions were 95.8% (87.8%-99.0%) and 81.9% (73.7%-90.2%), respectively. CONCLUSIONS: The primary end point for specificity was met while the primary end point for sensitivity was not. The high positive predictive value observed in both cohorts indicates that 18F-DCFPyL-positive lesions are likely to represent disease, supporting the potential utility of 18F-DCFPyL-positron emission tomography/computerized tomography to stage men with high-risk prostate cancer for nodal or distant metastases, and reliably detect sites of disease in men with suspected metastatic prostate cancer.

Results of a Randomized Phase II Trial of Intense Androgen Deprivation Therapy prior to Radical Prostatectomy in Men with High-Risk Localized Prostate Cancer.

PURPOSE: This multicenter randomized phase 2 trial investigates the impact of intense androgen deprivation on radical prostatectomy pathologic response and radiographic and tissue biomarkers in localized prostate cancer (NCT02903368). MATERIALS AND METHODS: Eligible patients had a Gleason score ≥4+3=7, prostate specific antigen >20 ng/mL or T3 disease and lymph nodes <20 mm. In Part 1, patients were randomized 1:1 to apalutamide, abiraterone acetate, prednisone and leuprolide (AAPL) or abiraterone, prednisone, leuprolide (APL) for 6 cycles (1 cycle=28 days) followed by radical prostatectomy. Surgical specimens underwent central review. The primary end point was the rate of pathologic complete response or minimum residual disease (minimum residual disease, tumor ≤5 mm). Secondary end points included prostate specific antigen response, positive margin rate and safety. Magnetic resonance imaging and tissue biomarkers of pathologic outcomes were explored. RESULTS: The study enrolled 118 patients at 4 sites. Median age was 61 years and 94% of patients had high-risk disease. The combined pathologic complete response or minimum residual disease rate was 22% in the AAPL arm and 20% in the APL arm (difference: 1.5%; 1-sided 95% CI -11%, 14%; 1-sided p=0.4). No new safety signals were observed. There was low concordance and correlation between posttherapy magnetic resonance imaging assessed and pathologically assessed tumor volume. PTEN-loss, ERG positivity and presence of intraductal carcinoma were associated with extensive residual tumor. CONCLUSIONS: Intense neoadjuvant hormone therapy in high-risk prostate cancer resulted in favorable pathologic responses (tumor <5 mm) in 21% of patients. Pathologic responses were similar between treatment arms. Part 2 of this study will investigate the impact of adjuvant hormone therapy on biochemical recurrence.

The association of diabetes with risk of prostate cancer defined by clinical and molecular features.

BACKGROUND: To prospectively examine the association between diabetes and risk of prostate cancer defined by clinical and molecular features. METHODS: A total of 49,392 men from the Health Professionals Follow-up Study (HPFS) were followed from 1986 to 2014. Data on self-reported diabetes were collected at baseline and updated biennially. Clinical features of prostate cancer included localised, advanced, lethal, low-grade, intermediate-grade, and high-grade. Molecular features included TMPRSS2: ERG and PTEN subtypes. Cox proportional hazards regression models were used to evaluate the association between diabetes and incidence of subtype-specific prostate cancer. RESULTS: During 28 years of follow-up, we documented 6733 incident prostate cancer cases. Relative to men free from diabetes, men with diabetes had lower risks of total (HR: 0.82, 95% CI: 0.75-0.90), localised (HR: 0.82, 95% CI: 0.74-0.92), low-and intermediate-grade prostate cancer (HR: 0.77, 95% CI: 0.66-0.90; HR: 0.77, 95% CI: 0.65-0.91, respectively). For molecular subtypes, the HRs for ERG-negative and ERG-positive cases were 0.63 (0.42-0.95) and 0.72 (0.46-1.12); and for PTEN-intact and PTEN-loss cases were 0.69 (0.48-0.98) and 0.52 (0.19-1.41), respectively. CONCLUSION: Besides providing advanced evidence for the inverse association between diabetes and prostate cancer, this study is the first to report associations between diabetes and ERG/PTEN defined prostate cancers.

A model combining clinical and genomic factors to predict response to PD-1/PD-L1 blockade in advanced urothelial carcinoma.

BACKGROUND: In metastatic urothelial carcinoma (mUC), predictive biomarkers that correlate with response to immune checkpoint inhibitors (ICIs) are lacking. Here, we interrogated genomic and clinical features associated with response to ICIs in mUC. METHODS: Sixty two mUC patients treated with ICI who had targeted tumour sequencing were studied. We examined associations between candidate biomarkers and clinical benefit (CB, any objective reduction in tumour size) versus no clinical benefit (NCB, no change or objective increase in tumour size). Both univariable and multivariable analyses for associations were conducted. A comparator cohort of 39 mUC patients treated with taxanes was analysed by using the same methodology. RESULTS: Nine clinical and seven genomic factors correlated with clinical outcomes in univariable analysis in the ICI cohort. Among the 16 factors, neutrophil-to-lymphocyte ratio (NLR) ≥5 (OR = 0.12, 95% CI, 0.01-1.15), visceral metastasis (OR = 0.05, 95% CI, 0.01-0.43) and single-nucleotide variant (SNV) count < 10 (OR = 0.04, 95% CI, 0.006-0.27) were identified as independent predictors of NCB to ICI in multivariable analysis (c-statistic = 0.90). None of the 16 variables were associated with clinical benefit in the taxane cohort. CONCLUSIONS: This three-factor model includes genomic (SNV count >9) and clinical (NLR <5, lack of visceral metastasis) variables predictive for benefit to ICI but not taxane therapy for mUC. External validation of these hypothesis-generating results is warranted to enable use in routine clinical care.

Bladder Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non-muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non-muscle-invasive bladder cancer in the event of a bacillus Calmette-Guérin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.

Impact of tumor, treatment, and access on outcomes in bladder cancer: Can equal access overcome race-based differences in survival?

BACKGROUND: There are race-based differences in bladder cancer survival. To better understand this phenomenon, this study was designed to assess the statistical contributions of tumor, treatment, and access variables to race-based differences in survival. METHODS: Data were extracted from the National Cancer Data Base on black and white adults with muscle-invasive bladder cancer from 2004 to 2015. The impact of tumor, access, and treatment variables on differences in survival was inferred by the performance of sequential propensity score-weighted analyses in which black and white patients were balanced with respect to demographics and health status (comorbidities) tumor characteristics, treatment, and access-related variables. The propensity score-weighted hazard of death (black vs white) was calculated after each iteration. RESULTS: This study identified 44,577 patients with a median follow-up of 77 months. After demographics and health status were balanced, black race was associated with 18% worse mortality (hazard ratio, 1.18; 95% confidence interval [CI], 1.12-1.25; P < .001). Balancing by tumor characteristics reduced this to 16%, balancing by treatment reduced this to 10%, and balancing by access-related variables resulted in no difference. Access-related variables explained 40% (95% CI, 22.9%-57.0%) of the excess risk of death in blacks, whereas treatment factors explained 35% (95% CI, 22.2%-46.9%). The contribution of tumor characteristics was not significant. CONCLUSIONS: In the models, differences in survival for black and white patients with bladder cancer are best explained by disparities in access and treatment, not tumor characteristics. Access to care is likely a key factor in racial disparities in cancer.

Active Surveillance of Prostate Cancer is a Viable Option for Men Younger than 60 Years.

PURPOSE: At most centers strict age criteria are lacking for eligibility for active surveillance of prostate cancer. Younger men are often counseled to undergo definitive treatment despite limited data on the outcomes of active surveillance in younger men. We compared clinical characteristics and outcomes in men who enrolled in active surveillance at age less than 60 vs 60 years old or older. MATERIALS AND METHODS: We retrospectively reviewed the records of 2 institutional cohorts of a total of 2,084 men in whom prostate cancer was managed by active surveillance between 1995 and 2016. We compared outcomes in men who began active surveillance at age 60 vs 60 years or older using the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: We identified 417 and 1,667 men who began active surveillance at younger than 60 and 60 years old or older, respectively, who met study inclusion criteria. At a median followup of 6.2 years we found no significant difference between men younger than 60 and 60 years old or older in the 5-year rates of biopsy progression-free survival (83% vs 83%), treatment-free survival (74% vs 71%), metastasis-free survival (99.7% vs 99.0%) or prostate cancer specific survival (100% vs 99.7%). Of the younger men 131 (31%) ultimately underwent treatment, including for pathological progression in 67% and prostate specific antigen progression in 18%. On multivariate analysis significant predictors of biopsy progression and progression to treatment among younger men were 20% or greater involvement of any core on diagnostic biopsy (HR 2.21, p = 0.003) and prostate specific antigen density 0.15 ng/ml/ml or greater (HR 1.93, p = 0.01). CONCLUSIONS: Active surveillance is a viable option in select men younger than 60 years with low volume, low risk prostate cancer. However, patients must be surveyed closely and understand the significant likelihood of ultimately requiring treatment.

Examining the relationship between complications and perioperative mortality following radical cystectomy: a population-based analysis.

OBJECTIVE: To examine the incidence of perioperative complications after radical cystectomy (RC) and assess their impact on 90-day postoperative mortality during the index stay and upon readmission. PATIENTS AND METHODS: A total of 57 553 patients with bladder cancer (unweighted cohort: 9137 patients) treated with RC, at 360 hospitals in the USA between 2005 and 2013 within the Premier Healthcare Database, were used for analysis. The 90-day perioperative mortality was the primary outcome. Multivariable regression was used to predict the probability of mortality; models were adjusted for patient, hospital, and surgical characteristics. RESULTS: An increase in the number of complications resulted in an increasing predicted probability of mortality, with a precipitous increase if patients had four or more complications compared to one complication during hospitalisation following RC (index stay; 1.0-9.7%, P < 0.001) and during readmission (2.0-13.1%, P < 0.001). A readmission complication nearly doubled the predicted probability of postoperative mortality as compared to an initial complication (3.9% vs 7.4%, P < 0.001). During the initial hospitalisation cardiac- (odds ratio [OR] 3.1, 95% confidence interval [CI] 1.9-5.1), pulmonary- (OR 4.8, 95% CI 2.8-8.4), and renal-related (OR 3.6, 95% CI 2-6.7) complications had the most significant impact on the odds of mortality across categories examined. CONCLUSIONS: The number and nature of complications have a distinct impact on mortality after RC. As complications increase there is an associated increase in perioperative mortality.

Evaluating the cost of surveillance for non-muscle-invasive bladder cancer: an analysis based on risk categories.

INTRODUCTION: Non-muscle-invasive bladder cancer (NMIBC) is a biologically heterogeneous disease and is one of the most expensive malignancies to treat on a per patient basis. In part, this high cost is attributed to the need for long-term surveillance. We sought to perform an economic analysis of surveillance strategies to elucidate cumulative costs for the management of NMIBC. METHODS: A Markov model was constructed to determine the average 5-year costs for the surveillance of patients with NMIBC. Patients were stratified into low, intermediate, and high-risk groups based on the EORTC risk calculator to determine recurrence and progression rates according to each category. The index patient was a compliant 65-year-old male. A total of four health states were utilized in the Markov model: no evidence of disease, recurrence, progression and cystectomy, and death. RESULTS: Cumulative costs of care over a 5-year period were $52,125 for low-risk, $146,250 for intermediate-risk, and $366,143 for high-risk NMIBC. The primary driver of cost was progression to muscle-invasive disease requiring definitive therapy, contributing to 81% and 92% of overall cost for intermediate- and high-risk disease. Although low-risk tumors have a high likelihood of 5-year recurrence, the overall cost contribution of recurrence was 8%, whereas disease progression accounted for 71%. CONCLUSION: Although protracted surveillance cystoscopy contributes to the expenditures associated with NMIBC, progression increases the overall cost of care across all three patient risk groups and most notably for intermediate- and high-risk disease patients.

Associations of specific postoperative complications with costs after radical cystectomy.

OBJECTIVE: To quantify the financial impact of complications after radical cystectomy (RC) and their associations with respective 90-day costs, as RC is a morbid surgery plagued by complications and the expenditure attributed to specific complications after RC is not well characterised. PATIENTS AND METHODS: We used the Premier Hospital Database (Premier Inc., Charlotte, NC, USA) to identify 9 137 RC patients (weighted population of 57 553) from 360 hospitals between 2003 and 2013. Complications were categorised according to Agency for Healthcare Research and Quality Clinical Classifications. Patients with and without complications were compared, and multivariable analysis was performed. RESULTS: An index complication increased costs by $9 262 (95% confidence interval [CI] 8 300-10 223) and a readmission complication increased costs by $20 697 (95% CI 18 735-22 660). The four most costly index complications (descending order) were venous thromboembolism (VTE), infection, wound and soft tissue complications, and pulmonary complications (P < 0.001, vs no complication). A complication increased length of stay by 4 days (95% CI 3.6-4.3). One in five patients were readmitted in 90 days and the four costliest readmission complications (descending order) were pulmonary, bleeding, VTE, and gastrointestinal complications (P < 0.001, vs no complication). Readmitted patients had multiple complications upon readmission (median of 3, interquartile range 2-4). On multivariable analysis, more comorbidities, longer surgery (>6 h), transfusions of >3 units, and teaching hospitals were associated with higher costs (P < 0.05), whilst high-volume surgeons and shorter surgeries (<4 h) were associated with lower costs (P < 0.05). CONCLUSIONS: Complications after RC increase index and readmission costs for hospitals, and can be categorised based on magnitude. Future initiatives in RC may also consider costs of complications when establishing quality improvement priorities for patients, providers, or policymakers.

NCCN Guidelines Insights: Bladder Cancer, Version 5.2018.

The NCCN Clinical Practice Guidelines in Oncology for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer. These NCCN Guidelines Insights discuss important updates to the 2018 version of the guidelines, including implications of the 8th edition of the AJCC Cancer Staging Manual on treatment of muscle-invasive bladder cancer and incorporating newly approved immune checkpoint inhibitor therapies into treatment options for patients with locally advanced or metastatic disease.

Characterizing trends in treatment modalities for localized muscle-invasive bladder cancer in the pre-immunotherapy era.

INTRODUCTION: Muscle-invasive bladder cancer (MIBC) is an aggressive disease for which treatment strategies are continuously evolving. We characterized trends in treatment modalities for MIBC from 2004 to 2013 (the "pre-immunotherapy era") and identified predictors of receiving the current standard of care treatment: neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC). METHODS: We used the National Cancer Database to identify individuals diagnosed with clinically localized MIBC from 2004 to 2013. We calculated the yearly prevalence of NAC followed by RC, RC as first treatment, trimodal therapy, chemotherapy and/or radiation alone, and no treatment. We then identified factors associated with receiving NAC prior to RC. RESULTS: There was a notable increase in the use of NAC followed by RC over the study period, from 3.68% in 2004 to 14.83% in 2013 (P < 0.001). Factors associated with decreased odds of receiving this regimen included being older, Black, uninsured, less educated, and more burdened by comorbidities. Rates of trimodal therapy and chemotherapy and/or radiation alone remained relatively constant (approximately 5 and 17%, respectively). There was a consistent decline in the proportion of patients who did not receive any treatment, down to 34.20% in 2013. CONCLUSION: Trends in localized MIBC treatment have evolved substantially since the early 2000s, and certain patient characteristics are associated with lower odds of receiving the current standard of care. This serves as a foundation from which to judge the impact of the upcoming immunotherapy era on the treatment landscape for this disease.