Bladder Cancer Survivors Who Do Not Smoke Have Better Longitudinal Health-Related Quality of Life Measures: An Assessment of the Comparative Effectiveness and Survivorship Health in Bladder Cancer (CEASE-BC) Study.

PURPOSE: Cigarette smoking is the most common risk factor for the development of bladder cancer (BC), yet there is a paucity of data characterizing the relationship between smoking status and longitudinal health-related quality of life (HRQoL) outcomes in patients with BC. We examined the association between smoking status and HRQoL among patients with BC. MATERIALS AND METHODS: Data were sourced from a prospective, longitudinal study open between 2014 and 2017, which examined HRQoL in patients aged ≥ 18 years old diagnosed with BC across North Carolina. The QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core instrument) was administered at 3, 12, and 24 months after BC diagnosis. Our primary exposure of interest was current smoking status. Linear regression using generalized estimating equations was used to analyze the relationship between smoking status and various domains of the QLQ-C30. RESULTS: A total of 154 patients enrolled in the study. Eighteen percent were classified as smoking at 3 months from diagnosis, and packs per day ranged from < 0.5 to 2. When controlling for time from diagnosis, demographic covariates, cancer stage, and treatment type, mean differences for physical function (7.4), emotional function (5.6), and fatigue measures (-8.2) were significantly better for patients with BC who did not smoke. CONCLUSIONS: Patients with BC who do not smoke have significantly better HRQoL scores in the domains of physical function, emotional function, and fatigue. These results underscore the need to treat smoking as an essential component of BC care.

Primary Retroperitoneal Lymph Node Dissection for Seminoma Metastatic to the Retroperitoneum.

PURPOSE: Primary surgical treatment with retroperitoneal lymph node dissection aims to accurately stage and treat patients with node-positive pure seminoma while avoiding long-term risks of chemotherapy or radiation, traditional standard-of-care treatments. MATERIALS AND METHODS: We reported the pathologic and oncologic outcomes of patients with pure seminoma treated with primary retroperitoneal lymph node dissection in a retrospective, single-institution case series over 10 years. The primary outcome was 2-year recurrence-free survival stratified by adjuvant management strategy (surveillance vs adjuvant chemotherapy). RESULTS: Forty-five patients treated with primary retroperitoneal lymph node dissection for pure testicular seminoma metastatic to the retroperitoneum were identified. Median size of largest lymph node before surgery was 1.8 cm. Viable germ cell tumor, all of which was pure seminoma, was found in 96% (n=43) of patients. The median number of positive nodes and nodes removed was 2 and 54, respectively. Median positive pathologic node size was 2 cm (IQR 1.4-2.5 cm, range 0.1-5 cm). Four of 29 patients managed with postoperative surveillance experienced relapse; 2-year recurrence-free survival was 81%. Median follow-up for those managed with surveillance who did not relapse was 18.5 months. There were no relapses in the retroperitoneum, visceral recurrences, or deaths. Among the 16 patients who received adjuvant treatment, 1 patient experienced relapse in the pelvis at 19 months. CONCLUSIONS: Primary retroperitoneal lymph node dissection for pure seminoma with low-volume metastases to the retroperitoneum is safe and effective, allowing most patients to avoid long-term toxicities from chemotherapy or radiation.

Smoking characteristics and years since quitting smoking of US adults diagnosed with lung and bladder cancer: A national health and nutrition examination survey analysis.

PURPOSE: Smoking is a recognized risk factor for bladder BC and lung cancer LC. We investigated the enduring risk of BC after smoking cessation using U.S. national survey data. Our analysis focused on comparing characteristics of LC and BC patients, emphasizing smoking status and the latency period from smoking cessation to cancer diagnosis in former smokers. MATERIALS AND METHODS: We analyzed data from the National Health and Examination Survey (2003-2016), identifying adults with LC or BC history. Smoking status (never, active, former) and the interval between quitting smoking and cancer diagnosis for former smokers were assessed. We reported descriptive statistics using frequencies and percentages for categorical variables and median with interquartile ranges (IQR) for continuous variables. RESULTS: Among LC patients, 8.9% never smoked, 18.9% active smokers, and 72.2% former smokers. Former smokers had a median interval of 8 years (IQR 2-12) between quitting and LC diagnosis, with 88.3% quitting within 0-19 years before diagnosis. For BC patients, 26.8% never smoked, 22.4% were active smokers, and 50.8% former smokers. Former smokers had a median interval of 21 years (IQR 14-33) between quitting and BC diagnosis, with 49.3% quitting within 0-19 years before diagnosis. CONCLUSIONS: BC patients exhibit a prolonged latency period between smoking cessation and cancer diagnosis compared to LC patients. Despite smoking status evaluation in microhematuria, current risk stratification models for urothelial cancer do not incorporate it. Our findings emphasize the significance of long-term post-smoking cessation surveillance and advocate for integrating smoking history into future risk stratification guidelines.

Untargeted Metabolomics to Characterize the Urinary Chemical Landscape of E-Cigarette Users.

The health and safety of using e-cigarette products (vaping) have been challenging to assess and further regulate due to their complexity. Inhaled e-cigarette aerosols contain chemicals with under-recognized toxicological profiles, which could influence endogenous processes once inhaled. We urgently need more understanding on the metabolic effects of e-cigarette exposure and how they compare to combustible cigarettes. To date, the metabolic landscape of inhaled e-cigarette aerosols, including chemicals originated from vaping and perturbed endogenous metabolites in vapers, is poorly characterized. To better understand the metabolic landscape and potential health consequences of vaping, we applied liquid chromatography-mass spectrometry (LC-MS) based nontargeted metabolomics to analyze compounds in the urine of vapers, cigarette smokers, and nonusers. Urine from vapers (n = 34), smokers (n = 38), and nonusers (n = 45) was collected for verified LC-HRMS nontargeted chemical analysis. The altered features (839, 396, and 426 when compared smoker and control, vaper and control, and smoker and vaper, respectively) among exposure groups were deciphered for their structural identities, chemical similarities, and biochemical relationships. Chemicals originating from e-cigarettes and altered endogenous metabolites were characterized. There were similar levels of nicotine biomarkers of exposure among vapers and smokers. Vapers had higher urinary levels of diethyl phthalate and flavoring agents (e.g., delta-decalactone). The metabolic profiles featured clusters of acylcarnitines and fatty acid derivatives. More consistent trends of elevated acylcarnitines and acylglycines in vapers were observed, which may suggest higher lipid peroxidation. Our approach in monitoring shifts of the urinary chemical landscape captured distinctive alterations resulting from vaping. Our results suggest similar nicotine metabolites in vapers and cigarette smokers. Acylcarnitines are biomarkers of inflammatory status and fatty acid oxidation, which were dysregulated in vapers. With higher lipid peroxidation, radical-forming flavoring, and higher level of specific nitrosamine, we observed a trend of elevated cancer-related biomarkers in vapers as well. Together, these data present a comprehensive profiling of urinary biochemicals that were dysregulated due to vaping.

Using a multilevel implementation strategy to facilitate the screening and treatment of tobacco use in the outpatient urology clinic: A prospective hybrid type I study.

BACKGROUND: Urologists frequently treat patients for tobacco-related conditions but infrequently engage in evidence-based practices (EBPs) that screen for and treat tobacco use. Improving the use of EBPs will help to identify smokers, promote cessation, and improve patients' health outcomes. METHODS: A prospective type I hybrid effectiveness-implementation study was performed to test the feasibility and effectiveness of using a multilevel implementation strategy to improve the use of tobacco EBPs. All urology providers at outpatient urology clinics within the Veterans Health Administration Greater Los Angeles and all patients presenting for a new urology consultation were included. The primary outcome was whether a patient was screened for tobacco use at the time of consultation. Secondary outcomes included a patient's willingness to quit, chosen quit strategy, and subsequent engagement in quit attempts. RESULTS: In total, 5706 consecutive veterans were seen for a new consultation during the 30-month study period. Thirty-six percent of all visits were for a tobacco-related urologic diagnosis. The percentage of visits that included tobacco use screening increased from 18% (before implementation) to 57% in the implementation phase and to 60% during the maintenance phase. There was significant provider-level variation in adherence to screening. Of all screened patients, 38% were willing to quit, and most patients chose a "cold turkey" method; 22% of the patients elected referral to a formal smoking cessation clinic, and 24% chose telephone counseling. Among those willing to quit, 39% and 49% made a formal quit attempt by 3 and 6 months, respectively. CONCLUSIONS: A strategy that includes provider education and a customized clinical decision support tool can facilitate provider use of tobacco EBPs in a surgery subspecialty clinic.

Association of Biochemically Verified Post-Diagnosis Smoking and Nonmuscle-Invasive Bladder Cancer Recurrence Risk.

PURPOSE: Our goal was to determine the association between biochemically verified post-diagnosis smoking exposure and nonmuscle-invasive bladder cancer (NMIBC) recurrence risk. MATERIALS AND METHODS: We conducted a prospective study of 354 NMIBC patients with a smoking history undergoing care between 2015 and 2018. Patients contributed at least 2 biospecimens during followup which were tested for cotinine to determine biochemically verified post-diagnosis smoking exposure (yes/no). Our primary endpoint was time to first recurrence after study start date. We examined whether post-diagnosis smoking exposure was associated with recurrence risk in multivariable Cox proportional hazards models that accounted for demographics, clinicopathological variables, time since diagnosis and pack-years. RESULTS: Patients were predominantly White, male and had a median age of 68 years. Most patients had Ta disease (62%) and tumors of high grade (68%). Intravesical bacillus Calmette-Guérin was given to 63% of the cohort. Patients were followed for a median of 3.6 years since study start. Post-diagnosis smoking exposure was detected in 22% of patients, and 38.7% (137) of patients experienced a recurrence during followup. In multivariable models, only bacillus Calmette-Guérin treatment and prior recurrence rate were significantly associated with recurrence. There was no association between post-diagnosis smoking exposure and recurrence risk (HR: 0.73, 95% CI: 0.45-1.20). CONCLUSIONS: In a cohort of patients with predominantly high risk NMIBC, post-diagnosis smoking exposure was not associated with NMIBC recurrence. However, smoking cessation support remains a critical component of cancer care given that the benefits of quitting extend far beyond NMIBC recurrence.

A Systematic Review and Scoping Analysis of Smoking Cessation after a Urological Cancer Diagnosis.

PURPOSE: Smoking cessation after a urological cancer diagnosis significantly benefits patients. It is not well known how often patients quit after diagnosis or how urologists intervene to support patients' smoking cessation efforts. We examined rates of smoking cessation after diagnosis among patients with urological cancers, and assessed how often patients are given advice and support to quit smoking in the urology setting. MATERIALS AND METHODS: Following PRISMA guidelines, a systematic review was conducted of the available studies on smoking cessation after a urological cancer diagnosis during April 2020 by a trained medical librarian using the MEDLINE®, PsycInfo®, Embase® and Cochrane Central databases. Studies were included based on 3 independent reviews and if they met a priori inclusion/exclusion criteria. In total, 2,568 records were identified, 31 of which were included for final analysis. RESULTS: Four studies (587 patients) reported outcomes related to the prospective implementation of a smoking cessation program with patient-level quit rates ranging from 3.2% to 47.3%. A total of 21 studies (3,669 patients) reported outcomes of passive (no directed, active intervention) smoking cessation after the diagnosis of a urological cancer with widely varying quit rates. In general, the quality of included studies was poor. There was no standardization of the measurement or timing of outcomes, and few studies included validated survey instruments or biochemical confirmation of cessation. A total of 17 studies included data on whether patients received advice to quit smoking after diagnosis. The proportion of patients in each study who were told to quit ranged from 2.8% to 78.3%. CONCLUSIONS: There are few smoking cessation interventions that have been prospectively implemented and reported in the urology literature, and studies on quit rates after diagnosis are limited. The paucity of quality data and lack of smoking cessation interventions being used in routine urological oncology care underscores the need for more rigorous study and implementation of evidence-based practices in this area.

Patterns of Current Cigarette Smoking, Quit Attempts and Cessation Counseling among Survivors of Smoking-Related and Nonsmoking-Related Urological Malignancies: A Nationally Representative Cross-Sectional Analysis.

PURPOSE: Cigarette smoking is the leading modifiable risk factor for several genitourinary malignancies. Although smoking cessation after genitourinary cancer diagnosis is a critical component of survivorship, factors related to continued smoking are under studied. MATERIALS AND METHODS: A cross-sectional analysis was conducted using data from the National Health Interview Survey (2014-2018). Our primary study outcome was the prevalence and correlates of cigarette smoking among adults with a history of smoking-related (kidney or bladder) urological cancer compared to a nonsmoking-related control (prostate cancer). We used regression analyses to assess the association of having a smoking-related genitourinary cancer history with continued cigarette smoking after diagnosis. Secondary outcomes were yearly smoking trends, quit attempts and reported receipt of smoking cessation counseling. RESULTS: A total of 2,664 respondents reported a history of genitourinary cancer, representing weighted estimates of 990,820 (smoking-related genitourinary cancer) and 2,616,596 (prostate cancer) adults. Survivors of smoking-related genitourinary cancers had a significantly higher overall prevalence of current cigarette use (14.8% vs 8.6%, p <0.001) and also reported more frequent receipt of counseling (79.8% vs 66.2%, p=0.02) but did not attempt to quit any more often than those with prostate cancer (52.4% vs 47.2%, p=0.44). Time trends demonstrated stable and persistent cigarette use among survivors of all genitourinary cancers. After adjustment for sociodemographic confounders, cancer type was not associated with current cigarette smoking (OR 1.23, 95% CI 0.86-1.77). However, older age and more advanced educational attainment were associated with lower odds of current cigarette smoking, while single marital status was associated with higher odds. CONCLUSIONS: In this population-based cross-sectional study of survivors of genitourinary cancers, those with a reported smoking-related genitourinary cancer had a higher prevalence of current cigarette smoking compared to those with prostate cancer, our nonsmoking-related control. Those with smoking-related genitourinary cancers reported more frequent receipt of smoking cessation counseling.

Tobacco Screening and Treatment during Outpatient Urology Office Visits in the United States.

PURPOSE: Tobacco use is a causative or exacerbating risk factor for benign and malignant urological disease. However, it is not well known how often urologists screen for tobacco use and provide tobacco cessation treatment at the population level. We sought to evaluate how often urologists see patients for tobacco-related diagnoses in the outpatient setting and how often these visits include tobacco use screening and treatment. MATERIALS AND METHODS: We used the National Ambulatory Medical Care Survey public use files for the years 2014-2016 to identify all outpatient urology visits with adults 18 years old or older. Clinic visit reasons were categorized according to diagnoses associated with the encounter: all urological diagnoses, a tobacco-related urological condition or a urological cancer. Our primary outcome was the percentage of visits during which tobacco screening was reported. Secondary outcomes included reported delivery of cessation counseling and provision of cessation pharmacotherapy. RESULTS: We identified 4,625 unique urological outpatient encounters, representing a population-weighted estimate of 63.9 million visits over 3 years. Approximately a third of all urology visits were for a tobacco-related urological diagnosis and 15% were for urological cancers. An estimated 1.1 million visits over 3 years were with patients who identified as current tobacco users. Of all visits, 70% included tobacco screening. However, only 7% of visits with current smokers included counseling and only 3% of patients were prescribed medications. No differences in screening and treatment were observed between visit types. CONCLUSIONS: Urologists regularly see patients for tobacco-related conditions and frequently, although not universally, screen patients for tobacco. However, urologists rarely offer counseling or cessation treatment. These findings may represent missed opportunities to decrease the morbidity associated with tobacco use.

The emerging role of homologous recombination repair and PARP inhibitors in genitourinary malignancies.

As cells age and are exposed to genotoxic stress, preservation of the genomic code requires multiple DNA repair pathways to remove single-strand or double-strand breaks. Loss of function somatic genomic aberrations or germline deficiency in genes involved in DNA repair can result in acute cell death or, after a latency period, cellular transformation. Therapeutic exploitation of DNA repair by inhibition of poly (adenosine diphosphate [ADP]) ribose polymerases (PARP), a family of enzymes involved in the repair of single-strand and in some cases double-strand breaks, has become a novel cancer treatment. Although the application of PARP inhibitors (PARPis) initially focused on tumors with BRCA1 or BRCA2 deficiencies, synthetic susceptibilities to PARPis have been expanded due to the identification of tumors with mutations pathways involved in DNA damage repair, in particular those that repair double-strand breaks using homologous recombination (HR). There is an increasing appreciation that genitourinary (GU) malignancies, including bladder cancer and especially prostate cancer, contain subsets of patients with germline and somatic alterations in HR genes that may reflect an increased response to PARPis. In this review, the authors describe the mechanisms and rationale of the use of PARPis in patients with GU cancers, summarize previously reported preclinical and clinical trials, and identify ongoing trials to determine how PARPis and strategies targeted at HR repair can have widespread application in patients with GU cancers. Cancer 2017;123:1912-1924. © 2017 American Cancer Society.

Implementation of a Surgeon-Level Comparative Quality Performance Review to Improve Positive Surgical Margin Rates during Radical Prostatectomy.

PURPOSE: Success in the era of value-based payment will depend on the capacity of health systems to improve quality while controlling costs. Comparative quality performance review can be used to drive improvements in surgical outcomes and thereby reduce costs. We sought to determine the efficacy of a comparative quality performance review to improve a surgeon-level measure of surgical oncologic quality, that is the positive surgical margin rate at the time of radical prostatectomy. MATERIALS AND METHODS: Eight surgeons who performed consecutive radical prostatectomies at a single high volume institution between January 1, 2015 and December 31, 2015 were included in analysis. Individual surgeons were provided with confidential report cards every 6 months detailing their case mix, case volume and pT2 radical prostatectomy positive surgical margin rate relative to 1) their own self-matched data, 2) the de-identified data of their colleagues and 3) institutional aggregate data during the study period. Positive surgical margin rates were compared before and after intervention. Hierarchal logistic regression analysis was used to examine the association of study period on the odds of positive surgical margins, adjusted for prostate specific antigen level and National Comprehensive Cancer Network® risk group. RESULTS: Overall, 1,822 (1,392 before and 430 after intervention) radical prostatectomies were performed that met study inclusion criteria. The aggregate departmental unadjusted positive surgical margin rates were 10.6% and 7.4% in the pre-intervention and post-intervention groups, respectively. After adjusting for higher risk cancer in the post-intervention group, there was a significant protective association of post-intervention status on positive margins (OR 0.64, 95% CI 0.43-0.97, p = 0.03). All 5 surgeons with positive surgical margin rates higher than the aggregate department rate in the pre-intervention period showed improvement after intervention. CONCLUSIONS: Comparative quality performance review can be implemented at the surgeon level and can promote improvement in an objective measure of surgical oncology quality.

Venous thromboembolism after nephrectomy: incidence, timing and associated risk factors from a national multi-institutional database.

PURPOSE: To evaluate the rate of venous thromboembolism (VTE) after nephrectomy with specific focus on event timing and location (before or after hospital discharge) in order to identify modifiable risk factors and establish benchmarks for preventive interventions. METHODS: Using the ACS-NSQIP database, we identified patients undergoing nephrectomy from 2006 to 2012. Patients were analyzed in two cohorts: collectively and by surgical approach [open vs. lap/robotic (MIS)]. Rates of deep vein thrombosis (DVT) and pulmonary embolus (PE) were assessed and time to each event was established in relation to discharge status. Logistic regression analysis was performed to assess association between preoperative risk factors, surgical variables, and VTE. RESULTS: In total, 13,208 patients met inclusion criteria. The overall rate of VTE was 1.2% (PE = 0.5% and DVT = 0.8, 0.1% DVT and PE). Using regression analysis, diabetes, dependent functional status, and longer operative time were associated with higher odds of DVT. For PE, dyspnea, disseminated cancer, and longer operative time were significant associations. The rate of VTE was higher in open surgery compared to MIS (2 vs. 0.8%, p < 0.001). Median times to DVT and PE were 8.5 and 6 days, respectively, with 53.3% of DVTs and 63.1% of PEs occurring prior to discharge. CONCLUSIONS: The overall rate of VTE after nephrectomy is low, occurs roughly one week after surgery, and is associated with longer hospital stays. Certain patient factors, open surgical approach, and longer operative times were associated with higher odds of post-operative VTE; these patients may benefit from more aggressive prophylaxis.