Randomized Controlled Trial of Ultrasonic Propulsion-Facilitated Clearance of Residual Kidney Stone Fragments vs Observation.

PURPOSE: Ultrasonic propulsion is an investigational procedure for awake patients. Our purpose was to evaluate whether ultrasonic propulsion to facilitate residual kidney stone fragment clearance reduced relapse. MATERIALS AND METHODS: This multicenter, prospective, open-label, randomized, controlled trial used single block randomization (1:1) without masking. Adults with residual fragments (individually ≤5 mm) were enrolled. Primary outcome was relapse as measured by stone growth, a stone-related urgent medical visit, or surgery by 5 years or study end. Secondary outcomes were fragment passage within 3 weeks and adverse events within 90 days. Cumulative incidence of relapse was estimated using the Kaplan-Meier method. Log-rank test was used to compare the treatment (ultrasonic propulsion) and control (observation) groups. RESULTS: The trial was conducted from May 9, 2015, through April 6, 2024. Median follow-up (interquartile range) was 3.0 (1.8-3.2) years. The treatment group (n = 40) had longer time to relapse than the control group (n = 42; P < .003). The restricted mean time-to-relapse was 52% longer in the treatment group than in the control group (1530 ± 92 days vs 1009 ± 118 days), and the risk of relapse was lower (hazard ratio 0.30, 95% CI 0.13-0.68) with 8 of 40 and 21 of 42 participants, respectively, experiencing relapse. Omitting 3 participants not asked about passage, 24 treatment (63%) and 2 control (5%) participants passed fragments within 3 weeks of treatment. adverse events were mild, transient, and self-resolving, and were reported in 25 treated participants (63%) and 17 controls (40%). CONCLUSIONS: Ultrasonic propulsion reduced relapse and added minimal risk. CLINICAL TRIAL REGISTRATION NO.: NCT02028559.

The Prostate Cancer Active Lifestyle Study (PALS): A randomized controlled trial of diet and exercise in overweight and obese men on active surveillance.

BACKGROUND: Active surveillance (AS) is increasingly used to monitor patients with lower risk prostate cancer (PCa). The Prostate Cancer Active Lifestyle Study (PALS) was a randomized controlled trial to determine whether weight loss improves obesity biomarkers on the causal pathway to progression in patients with PCa on AS. METHODS: Overweight/obese men (body mass index >25 kg/m2) diagnosed with PCa who elected AS were recruited. The intervention was a 6-month, individually delivered, structured diet and exercise program adapted from the Diabetes Prevention Program with a 7% weight loss goal from baseline. Control participants attended one session reviewing the US Dietary and Physical Activity Guidelines. The primary outcome was change in glucose regulation from baseline to the end of the 6-month intervention, which was measured by fasting plasma glucose, C-peptide, insulin, insulin-like growth factor 1, insulin-like growth factor binding protein-3, adiponectin, and homeostatic model assessment for insulin resistance. RESULTS: Among 117 men who were randomized, 100 completed the trial. The mean percentage weight loss was 7.1% and 1.8% in the intervention and control arms, respectively (adjusted between-group mean difference, -6.0 kg; 95% confidence interval, -8.0, -4.0). Mean percentage changes from baseline for insulin, C-peptide, and homeostatic model assessment for insulin resistance in the intervention arm were -23%, -16%, and -25%, respectively, compared with +6.9%, +7.5%, and +6.4%, respectively, in the control arm (all p for intervention effects ≤ .003). No significant between-arm differences were detected for the other biomarkers. CONCLUSIONS: Overweight/obese men with PCa undergoing AS who participated in a lifestyle-based weight loss intervention successfully met weight loss goals with this reproducible lifestyle intervention and experienced improvements in glucose-regulation biomarkers associated with PCa progression.

A Phase 1/2 Study of Rapamycin and Cisplatin/Gemcitabine for Treatment of Patients With Muscle-Invasive Bladder Cancer.

INTRODUCTION: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy is the standard for muscle-invasive bladder cancer (MIBC), however, NAC confers only a small survival benefit and new strategies are needed to increase its efficacy. Pre-clinical data suggest that in response to DNA damage the tumor microenvironment (TME) adopts a paracrine secretory phenotype dependent on mTOR signaling which may provide an escape mechanism for tumor resistance, thus offering an opportunity to increase NAC effectiveness with mTOR blockade. PATIENTS & METHODS: We conducted a phase I/II clinical trial to assess the safety and efficacy of gemcitabine-cisplatin-rapamycin combination. Grapefruit juice was administered to enhance rapamycin pharmacokinetics by inhibiting intestinal enzymatic degradation. Phase I was a dose determination/safety study followed by a single arm Phase II study of NAC prior to radical cystectomy evaluating pathologic response with a 26% pCR rate target. RESULTS: In phase I, 6 patients enrolled, and the phase 2 dose of 35 mg rapamycin established. Fifteen patients enrolled in phase II; 13 were evaluable. Rapamycin was tolerated without serious adverse events. At the preplanned analysis, the complete response rate (23%) did not meet the prespecified level for continuing and the study was stopped due to futility. With immunohistochemistry, successful suppression of the mTOR signaling pathway in the tumor was achieved while limited mTOR activity was seen in the TME. CONCLUSION: Adding rapamycin to gemcitabine-cisplatin therapy for patients with MIBC was well tolerated but failed to improve therapeutic efficacy despite evidence of mTOR blockade in tumor cells. Further efforts to understand the role of the tumor microenvironment in chemotherapy resistance is needed.

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.

Improving risk stratification among veterans diagnosed with prostate cancer: impact of the 17-gene prostate score assay.

BACKGROUND: Active surveillance (AS) has been widely implemented within Veterans Affairs' medical centers (VAMCs) as a standard of care for low-risk prostate cancer (PCa). Patient characteristics such as age, race, and Agent Orange (AO) exposure may influence advisability of AS in veterans. The 17-gene assay may improve risk stratification and management selection. OBJECTIVES: To compare management strategies for PCa at 6 VAMCs before and after introduction of the Oncotype DX Genomic Prostate Score (GPS) assay. STUDY DESIGN: We reviewed records of patients diagnosed with PCa between 2013 and 2014 to identify management patterns in an untested cohort. From 2015 to 2016, these patients received GPS testing in a prospective study. Charts from 6 months post biopsy were reviewed for both cohorts to compare management received in the untested and tested cohorts. SUBJECTS: Men who just received their diagnosis and have National Comprehensive Cancer Network (NCCN) very low-, low-, and select cases of intermediate-risk PCa. RESULTS: Patient characteristics were generally similar in the untested and tested cohorts. AS utilization was 12% higher in the tested cohort compared with the untested cohort. In men younger than 60 years, utilization of AS in tested men was 33% higher than in untested men. AS in tested men was higher across all NCCN risk groups and races, particular in low-risk men (72% vs 90% for untested vs tested, respectively). Tested veterans exposed to AO received less AS than untested veterans. Tested nonexposed veterans received 19% more AS than untested veterans. Median GPS results did not significantly differ as a factor of race or AO exposure. CONCLUSIONS: Men who receive GPS testing are more likely to utilize AS within the year post diagnosis, regardless of age, race, and NCCN risk group. Median GPS was similar across racial groups and AO exposure groups, suggesting similar biology across these groups. The GPS assay may be a useful tool to refine risk assessment of PCa and increase rates of AS among clinically and biologically low-risk patients, which is in line with guideline-based care.

Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The complete version of the NCCN Guidelines for Bladder Cancer addresses additional aspects of the management of bladder cancer, including non-muscle-invasive urothelial bladder cancer and nonurothelial histologies, as well as staging, evaluation, and follow-up.

NCCN Guidelines Insights: Bladder Cancer, Version 2.2016.

These NCCN Guidelines Insights discuss the major recent updates to the NCCN Guidelines for Bladder Cancer based on the review of the evidence in conjunction with the expert opinion of the panel. Recent updates include (1) refining the recommendation of intravesical bacillus Calmette-Guérin, (2) strengthening the recommendations for perioperative systemic chemotherapy, and (3) incorporating immunotherapy into second-line therapy for locally advanced or metastatic disease. These NCCN Guidelines Insights further discuss factors that affect integration of these recommendations into clinical practice.

Evaluating disparities in inpatient surgical cancer care among American Indian/Alaska Native patients.

BACKGROUND: American Indian/Alaska Native (AI/AN) patients with cancer have the lowest survival rates of all racial and ethnic groups, possibly because they are less likely to receive "best practice" surgical care than patients of other races. METHODS: Prospective cohort study comparing adherence with generic and cancer-specific guidelines on processes of surgical care between AI/AN and non-Hispanic white (NHW) patients in Washington State (2010 to 2014) was conducted. RESULTS: A total of 156 AI/AN and 6,030 NHW patients underwent operations for 10 different cancers, and had similar mean adherence to generic surgical guidelines (91.5% vs 91.9%, P = .57). AI/AN patients with breast cancer less frequently received preoperative diagnostic core needle biopsy (81% vs 94%, P = .004). AI/AN patients also less frequently received care adherent to prostate cancer-specific guidelines (74% vs 92%, P = .001). CONCLUSION: Although AI/ANs undergoing cancer operations in Washington receive similar overall best practice surgical cancer care to NHW patients, there remain important, modifiable disparities that may contribute to their lower survival.

Root Causes and Modifiability of 30-Day Hospital Readmissions after Radical Cystectomy for Bladder Cancer.

PURPOSE: Radical cystectomy is associated with high complication and rehospitalization rates. An understanding of the root causes of hospital readmissions and the modifiability of factors contributing to readmissions may decrease the morbidity associated with radical cystectomy. We characterize the indications for rehospitalization following radical cystectomy, and determine whether these indications represent immutable patient disease and procedure factors or whether they are modifiable. MATERIALS AND METHODS: From MarketScan® databases we identified patients younger than 65 years with a diagnosis of bladder cancer who underwent radical cystectomy between 2008 and 2011 and were readmitted to the hospital within 30 days of radical cystectomy. All associated ICD-9 codes in the index admission, subsequent outpatient claims and readmission claims were independently reviewed by 3 surgeons to determine a root cause of rehospitalization. Causes were broadly categorized as medical, surgical or infectious, and reviewers determined whether the readmission was modifiable. Multivariate logistical regression models were used to identify factors associated with rehospitalization. RESULTS: A total of 1,163 patients were included in the study and 242 (21%) were readmitted to the hospital within 30 days. Of these readmissions 26% were considered modifiable (kappa=0.71). Of the nonmodifiable readmissions an infectious cause accounted for 52% and a medical cause accounted for 48%, whereas of the modifiable readmissions 62% were due to surgical causes, 30% to medical and 8% to infectious causes. On multivariate analysis only discharge to a skilled nursing facility was associated with modifiable (OR 6.12, 95% CI 2.32-16.14) or nonmodifiable (OR 3.27, 95% CI 1.63-6.53) hospital readmissions. CONCLUSIONS: The majority of rehospitalizations after radical cystectomy are attributable its inherent morbidity. However, optimization of aspects of peri-cystectomy care could minimize the morbidity of radical cystectomy.

Preliminary Comparative Effectiveness of Robotic Versus Open Radical Cystectomy in Elderly Patients.

INTRODUCTION: Treatment for muscle-invasive bladder cancer (MIBC) remains highly morbid despite improving surgical techniques. As the median age of diagnosis is 73, many patients are elderly at the time of cystectomy. We compare perioperative surgical outcomes in elderly patients undergoing robotic vs open radical cystectomy (RC). MATERIALS AND METHODS: Patients >75 years at time of RC were identified. Demographic, clinicopathologic, and perioperative variables were examined. Estimated blood loss (EBL) and length of stay (LOS) data were collected with multivariate linear regression analysis performed to assess whether technique was independently associated with outcomes. RESULTS: Eighty-seven patients >75 years of age underwent cystectomy for MIBC (58 open, 29 robotic). Mean age was 79.6 (±3.2) and 79.2 (±3.5) for open and robotic groups, respectively (p = 0.64). There were no significant differences in baseline comorbidities, clinical or pathologic stage, or use of neoadjuvant chemotherapy. The mean number of lymph nodes removed was similar (p = 0.08). Robotic cystectomy had significantly longer mean OR times (p < 0.001). On multivariate analyses, robotic surgery was associated with -389cc less EBL (95% CI -547 to -230, p < 0.001) and a -1.5-day-shortened LOS (95%CI -2.9 to -0.2, p = 0.02) compared with open surgery. There were no significant differences in surgical complications or 90-day readmission rates between the two groups. CONCLUSIONS: Robotic cystectomy is safe and feasible in an elderly population. We observed longer OR times with robotic surgery, but with decreased EBL, shorter hospital stays, and comparable complication and readmission rates with open RC. Larger prospective studies are required to confirm these findings.

Metformin effects on biochemical recurrence and metabolic signaling in the prostate.

BACKGROUND: Metformin has received considerable attention as a potential anti-cancer agent. Animal and in-vitro prostate cancer (PCa) models have demonstrated decreased tumor growth with metformin, however the precise mechanisms are unknown. We examine the effects of metformin on PCa biochemical recurrence (BCR) in a large clinical database followed by evaluating metabolic signaling changes in a cohort of men undergoing prostate needle biopsy (PNB). METHODS: Men treated for localized PCa were identified in a comprehensive clinical database between 2001 and 2010. Cox regression was performed to determine association with BCR relative to metformin use. We next identified a separate case-control cohort of men undergoing prostate needle biopsy (PNB) stratified by metformin use. Differences in mean IHC scores were compared with linear regression for phosphorylated IR, IGF-IR, AKT, and AMPK. RESULTS: One thousand seven hundred and thirty four men were evaluated for BCR with mean follow up of 41 months (range 1-121 months). "Ever" metformin use was not associated with BCR (HR 1.12, 0.77-1.65), however men reporting both pre/post-treatment metformin use had a 45% reduction in BCR (HR = 0.55 (0.31-0.96)). For the tissue-based study, 48 metformin users and 42 controls underwent PNB. Significantly greater staining in phosphorylated nuclear (p-IR, p-AKT) and cytoplasmic (p-IR, p-IGF-1R) insulin signaling proteins were seen in patients with PCa detected compared to those with negative PNB (P-values all <0.006). When stratified by metformin use, IGF-1R remained significantly elevated (P = 0.01) in men with PCa detected whereas p-AMPK (P = 0.05) was elevated only in those without PCa. CONCLUSION: Metformin use is associated with reduced BCR after treatment of localized PCa when considering pre-diagnostic and cumulative dosing. In men with cancer detected on PNB, insulin signaling markers were significantly elevated compared to negative PNB patients. The finding of IGF-1R elevation in positive PNBs versus p-AMPK elevation in negative PNBs suggests altered metabolic pathway activation precipitated by metformin use.

Burden and timing of venothrombolic events in patients younger than 65 years undergoing radical cystectomy for bladder cancer.

INTRODUCTION AND OBJECTIVES: Venothrombolic events (VTEs) following radical cystectomy (RC) are a significant contributor to postoperative morbidity. A better understanding of the incidence and timing of VTE would clarify chemoprophylaxis strategies among RC patients. We sought to characterize the burden of VTE after RC by defining their timing and effect utilizing the MarketScan commercial databases. METHODS: From MarketScan databases, we identified patients younger than 65 years undergoing RC for a primary diagnosis of bladder cancer between 2008 and 2011 with International Classification of Diseases, 9th Edition diagnosis and procedure codes. MarketScan includes inpatient and outpatient health insurance claims of 34 million enrollees annually with data from 150 employers and 13 commercial health plans. We identified the occurrence of VTE, including both pulmonary embolism and deep vein thrombosis, in patients undergoing RC by searching MarketScan for relevant International Classification of Diseases, 9th Edition codes for these diagnoses. Our primary outcome of interest was the timing of VTEs. Multivariate logistical regression models were used to identify patient factors that were associated with VTEs. RESULTS: A total of 1,581 patients were included in our analysis. Overall, 10% of patients experienced VTEs within 90 days of RC. The incidence of postoperative VTEs during the index admission, after discharge and within 30 days of surgery, and between 31 and 90 days postoperatively was 2.9%, 3.8%, and 3.3%, respectively. Prolonged index hospitalization, discharge to a skilled nursing facility, and orthotopic neobladder urinary diversion were significantly associated with VTE within 30 days of RC. CONCLUSION: Most VTEs occur after discharge from the index RC hospitalization. Consideration should be given to extended chemoprophylaxis in this high-risk group of patients.

Guideline-concordant cancer care and survival among American Indian/Alaskan Native patients.

BACKGROUND: American Indians/Alaskan Natives (AI/ANs) have the worst 5-year cancer survival of all racial/ethnic groups in the United States. Causes for this disparity are unknown. The authors of this report examined the receipt of cancer treatment among AI/AN patients compared with white patients. METHODS: This was a retrospective cohort study of 338,204 patients who were diagnosed at age ≥65 years with breast, colon, lung, or prostate cancer between 1996 and 2005 in the Surveillance, Epidemiology, and End Results-Medicare database. Nationally accepted guidelines for surgical and adjuvant therapy and surveillance were selected as metrics of optimal, guideline-concordant care. Treatment analyses compared AI/ANs with matched whites. RESULTS: Across cancer types, AI/ANs were less likely to receive optimal cancer treatment and were less likely to undergo surgery (P ≤ .025 for all cancers). Adjuvant therapy rates were significantly lower for AI/AN patients with breast cancer (P < .001) and colon cancer (P = .001). Rates of post-treatment surveillance also were lower among AI/ANs and were statistically significantly lower for AI/AN patients with breast cancer (P = .002) and prostate cancer (P < .001). Nonreceipt of optimal cancer treatment was associated with significantly worse survival across cancer types. Disease-specific survival for those who did not undergo surgery was significantly lower for patients with breast cancer (hazard ratio [HR], 0.62), colon cancer (HR, 0.74), prostate cancer (HR, 0.52), and lung cancer (HR, 0.36). Survival rates also were significantly lower for those patients who did not receive adjuvant therapy for breast cancer (HR, 0.56), colon cancer (HR, 0.59), or prostate cancer (HR, 0.81; all 95% confidence intervals were <1.0). CONCLUSIONS: Fewer AI/AN patients than white patients received guideline-concordant cancer treatment across the 4 most common cancers. Efforts to explain these differences are critical to improving cancer care and survival for AI/AN patients.

Use and outcomes of extended antibiotic prophylaxis in urological cancer surgery.

PURPOSE: Although perioperative antibiotic prophylaxis prevents postoperative infectious complications, national guidelines recommend cessation of antibiotics within 24 hours after the procedure. Extended antibiotic prophylaxis beyond 24 hours may contribute to hospital acquired infections such as Clostridium difficile colitis. We evaluated practice patterns of antibiotic prophylaxis in genitourinary cancer surgery and assessed the impact of antibiotic prophylaxis on hospital acquired C. difficile infections. MATERIALS AND METHODS: We identified 59,184 patients treated with radical prostatectomy, 27,921 who underwent partial or radical nephrectomy, and 5,425 treated with radical cystectomy for prostate, kidney and bladder cancers, respectively, from the Premier Perspective Database (Premier Inc., Charlotte, North Carolina) from 2007 to 2012. We constructed hierarchical linear regression models to identify patient and hospital factors associated with extended antibiotic prophylaxis. We evaluated the association between extended antibiotic prophylaxis and C. difficile infections for patients who underwent partial or radical nephrectomy and radical cystectomy with multivariate logistic regression. RESULTS: Surgery specific models demonstrated that hospital identity was associated with a substantial proportion of the variation in extended antibiotic prophylaxis (20% to 35% for radical prostatectomy, partial or radical nephrectomy, and radical cystectomy). Postoperative C. difficile colitis occurred in 0.02% of patients treated with radical prostatectomy, 0.23% of those treated with partial or radical nephrectomy and 1.7% of those treated with radical cystectomy. On multivariate analysis extended antibiotic prophylaxis was associated with higher odds of C. difficile infection after partial or radical nephrectomy (OR 3.79, 95% CI 2.46-5.84) and radical cystectomy (OR 1.64, 95% CI 1.12-2.39). CONCLUSIONS: Antibiotics may be overused after genitourinary cancer surgery and this overuse is associated with hospital acquired C. difficile colitis. Efforts are needed to encourage greater compliance with evidence-based approaches to postoperative care.

Role of maximal endoscopic resection before cystectomy for invasive urothelial bladder cancer.

INTRODUCTION/BACKGROUND: The aim of this study was to examine whether TUR of all visible endophytic tumors performed before RC, with or without NC, affects final pathologic staging. PATIENTS AND METHODS: We retrospectively reviewed data from patients with clinical T2-T4N0-1 urothelial carcinoma of the bladder who underwent RC at our institution between July 2005 and November 2011. Degree of TUR was derived from review of operative reports. We used multivariate logistic regression to assess the association of maximal TUR on pT0 status at time of RC. RESULTS: Of 165 eligible RC patients, 81 received NC. Reported TUR of all visible tumors was performed in 38% of patients who did not receive NC and 48% of NC patients (P = .19). Nine percent of patients who underwent maximal TUR and did not receive NC were pT0, whereas among NC patients, pT0 was seen in 39% and 19% of those with and without maximal TUR, respectively (P = .05). On multivariate analysis in all patients, maximal TUR was associated with a nonsignificant increased likelihood of pT0 status (odds ratio [OR], 2.03; 95% confidence interval [CI], 0.84-4.94), which was significant when we restricted the analysis to NC patients (OR, 3.17; 95% CI, 1.02-9.83). CONCLUSION: Maximal TUR of all endophytic tumors before NC is associated with complete pathologic tumor response at RC. Candidates for NC before RC should undergo resection of all endophytic tumors when feasible. Larger series are warranted to see if maximal TUR leads to improved overall and disease-specific survival.

Identification of underserved areas for urologic cancer care.

BACKGROUND: The delivery of urologic oncology care is susceptible to regional variation. In the current study, the authors sought to define patterns of care for patients undergoing genitourinary cancer surgery to identify underserved areas for urologic cancer care in Washington State. METHODS: The authors accessed the Washington State Comprehensive Hospital Abstract Reporting System from 2003 through 2007. They identified patients undergoing radical prostatectomy, radical cystectomy (RC), partial nephrectomy (PN), radical nephrectomy, and transurethral resection of the prostate (TURP). TURP was included for comparison as a reference procedure indicative of access to urologic care. Hospital service areas (HSAs) are where the majority of local patients are hospitalized; hospital referral regions (HRR) are where most patients receive tertiary care. The authors created multivariate hierarchical logistic regression models to examine patient and HSA characteristics associated with the receipt of urologic oncology care out of the HRR for each procedure. RESULTS: Greater than one-half of patients went out of their HRR in 7 HSAs (11%) for radical prostatectomy, 3 HSAs (5%) for radical nephrectomy, 10 HSAs (15%) for PN, and 14 HSAs (22%) for RC. No HSAs had high export rates for TURP. Few patient factors were found to be associated with surgical care out of the HRR. High-export HSAs for PN and RC exhibited lower socioeconomic characteristics than low-export HSAs, adjusting for HSA population, race, and HSA procedure rates for PN and RC. CONCLUSIONS: Patients living in areas with lower socioeconomic status have a greater need to travel for complex urologic surgery. Consideration of geographic delineation in the delivery of urologic oncology care may aid in regional quality improvement initiatives.

Nonresponse to neoadjuvant chemotherapy for muscle-invasive urothelial cell carcinoma of the bladder.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NC) is commonly used in the treatment of muscle-invasive urothelial cell carcinoma of the bladder (UC) and has been shown to improve survival. However, not all patients respond to NC, thus delaying the interval to potentially curative surgical therapy, risking disease progression and subjecting patients to potential morbidity from NC. In this study, we perform a retrospective analysis of patients who received NC prior to cystectomy to identify factors associated with nonresponse. PATIENTS AND METHODS: We identified 80 patients with clinical T2 to T4, N0 to N1 UC of the bladder who received NC and underwent radical cystectomy. Nonresponse was defined as patients with higher pathologic T stage than clinical stage or patients with nodal involvement identified on final pathology. RESULTS: Overall, 20% of patients were considered nonresponders. In multivariate analysis, age was predictive of nonresponse (P(trend) < .05). Compared with those < 60 years of age, those aged 60 to 69 years (odds ratio [OR], 2.9; 95% CI, 0.7-12) and those aged ≥ 70 (OR, 5.0; 95% CI, 0.9-28) had higher odds of nonresponse. Patients who received gemcitabine-carboplatin had higher odds of nonresponse compared with those who received gemcitabine-cisplatin (OR, 4.4; 95% CI, 0.8-21). CONCLUSION: A subset of patients receiving NC prior to cystectomy will experience disease progression. Future study will need to better identify methods to distinguish individuals more likely to benefit from NC and those that should receive upfront cystectomy.

Persistence of urothelial carcinoma of the bladder risk among former smokers: results from a contemporary, prospective cohort study.

OBJECTIVES: Cigarette smoking is a known risk factor for urothelial carcinoma (UC) of the bladder. However, the persistence of an increased risk for UC following smoking cessation is not well established. We assessed the risk of UC among former smokers using a recent, prospective cohort with a high proportion of former smokers. MATERIALS AND METHODS: Study participants were members of the VITamins And Lifestyle cohort (VITAL), a group of 77,719 men and women between the ages of 50 and 76 years from western Washington State. Smoking history and other risk factors were obtained at the time of recruitment. The primary outcome was a new diagnosis of UC (n =385), as determined through linkage to a population-based cancer registry. RESULTS AND LIMITATIONS: The cohort included 8% current and 44% former smokers, and among the UC cases, 15% were current and 60% former smokers. Both the current and former smoker had an increased risk of UC compared with never smokers (hazard ratio [HRs]: 3.81; 95% confidence intervals [CI] 2.71-5.35 and 2.0; 95% CI 1.55-2.58, respectively). Among former smokers, the risk of UC increased with the pack-years smoked and decreased with the years since quitting. When both the measures of smoking were considered together, the risk of UC was similar for long-term quitters and recent quitters for a given level of pack-years. For example, for those with pack-years of 22.5-37.5, the HR of UC was 1.91 (95% CI 1.17-3.11) for the distant quitters (≥ 23.5 y before baseline) and HR = 1.92 (95% CI 1.26-2.94) among the recent quitters. Limitations include the small number of cases at the extremes of smoking history and errors in self-reported smoking history. CONCLUSIONS: The risk of bladder cancer in former smokers remains elevated>32 years after quitting, even among those with moderate smoking histories. This argues that a history of smoking confers a lifelong increased risk of UC.

Treatment of early-stage prostate cancer among rural and urban patients.

BACKGROUND: Geographic barriers and limited availability of cancer specialists may influence early prostate cancer treatment options for rural men. This study compares receipt of different early prostate cancer treatments between rural and urban patients. METHODS: Using 2004-2006 SEER Limited-Use Data, 51,982 early prostate cancer patients were identified (T1c, T2a, T2b, T2c, T2NOS; no metastases) who were most likely to benefit from definitive treatment (< 75 years old, Gleason score < 8, PSA ≤ 20). Definitive treatment included radical prostatectomy, daily external beam radiation for 5 to 8 weeks, brachytherapy, or combination external beam radiation/brachytherapy. Adjusted definitive treatment rates were calculated by rural-urban residence overall, and for different sociodemographic and cancer characteristics, and different states based on logistic regression analyses, using general estimating equation methods to account for clustering by county. RESULTS: Adjusted definitive treatment rates were lower for rural (83.7%) than urban (87.1%) patients with early-stage prostate cancer (P ≤ .01). Rural men were more likely than urban men to receive non-definitive surgical treatment and no initial treatment. The lowest definitive treatment rates were among rural subgroups: 70 to 74 years (73.9%), African Americans (75.6%), American Indians/Alaska Natives (77.8%), single/separated/divorced (76.8%), living in New Mexico (69.3%), and living in counties with persistent poverty (79.6%). CONCLUSIONS: Between 2004 and 2006, this adjusted analysis found that men who were living in rural areas were less likely to receive definitive treatment for their early-stage prostate cancer than those living in urban areas. Certain rural patient groups with prostate cancer need particular attention to ensure their access to appropriate treatment. Rural providers, rural health care systems, and cancer advocacy and support organizations should ensure resources are in place so that the most vulnerable rural groups (men between 60 and 74 years of age; African American men; men who are single, separated, or divorced; and men living in rural New Mexico) can make informed prostate cancer treatment choices based on their preferences.