Geriatric assessment-derived deficit accumulation and patient-reported treatment burden in older adults with bladder cancer.

BACKGROUND: When a person's workload of healthcare exceeds their resources, they experience treatment burden. At the intersection of cancer and aging, little is known about treatment burden. We evaluated the association between a geriatric assessment-derived Deficit Accumulation Index (DAI) and patient-reported treatment burden in older adults with early-stage, non-muscle-invasive bladder cancer (NMIBC). METHODS: We conducted a cross-sectional survey of older adults with NMIBC (≥65 years). We calculated DAI using the Cancer and Aging Research Group's geriatric assessment and measured urinary symptoms using the Urogenital Distress Inventory-6 (UDI-6). The primary outcome was Treatment Burden Questionnaire (TBQ) score. A negative binomial regression with LASSO penalty was used to model TBQ. We further conducted qualitative thematic content analysis of responses to an open-ended survey question ("What has been your Greatest Challenge in managing medical care for your bladder cancer") and created a joint display with illustrative quotes by DAI category. RESULTS: Among 119 patients, mean age was 78.9 years (SD 7) of whom 56.3% were robust, 30.3% pre-frail, and 13.4% frail. In the multivariable model, DAI and UDI-6 were significantly associated with TBQ. Individuals with DAI above the median (>0.18) had TBQ scores 1.94 times greater than those below (adjusted IRR 1.94, 95% CI 1.33-2.82). Individuals with UDI-6 greater than the median (25) had TBQ scores 1.7 times greater than those below (adjusted IRR 1.70, 95% CI 1.16-2.49). The top 5 themes in the Greatest Challenge question responses were cancer treatments (22.2%), cancer worry (19.2%), urination bother (18.2%), self-management (18.2%), and appointment time (11.1%). CONCLUSIONS: DAI and worsening urinary symptoms were associated with higher treatment burden in older adults with NMIBC. These data highlight the need for a holistic approach that reconciles the burden from aging-related conditions with that resulting from cancer treatment.

Preventing Prostate Biopsy Complications: to Augment or to Swab?

OBJECTIVE: To use data from a large, prospectively- acquired regional collaborative database to compare the risk of infectious complications associated with three American Urologic Association- recommended antibiotic prophylaxis pathways, including culture-directed or augmented antibiotics, following prostate biopsy. METHODS: Data on prostate biopsies and outcomes were collected from the Pennsylvania Urologic Regional Collaborative, a regional quality collaborative working to improve the diagnosis and treatment of prostate cancer. Patients were categorized as receiving one of three prophylaxis pathways: culture-directed, augmented, or provider-discretion. Infectious complications included fever, urinary tract infections or sepsis within one month of biopsy. Odds ratios of infectious complication by pathway were determined, and univariate and multivariate analyses of patient and biopsy characteristics were performed. RESULTS: 11,940 biopsies were included, 120 of which resulted in infectious outcomes. Of the total biopsies, 3246 used "culture-directed", 1446 used "augmented" and 7207 used "provider-discretion" prophylaxis. Compared to provider-discretion, the culture-directed pathway had 84% less chance of any infectious outcome (OR= 0.159, 95% CI = [0.074, 0.344], P < 0.001). There was no difference in infectious complications between augmented and provider-discretion pathways. CONCLUSIONS: The culture-directed pathway for transrectal prostate biopsy resulted in significantly fewer infectious complications compared to other prophylaxis strategies. Tailoring antibiotics addresses antibiotic-resistant bacteria and reduces future risk of resistance. These findings make a strong case for incorporating culture-directed antibiotic prophylaxis into clinical practice guidelines to reduce infection following prostate biopsies.

Validation of an mRNA-based Urine Test for the Detection of Bladder Cancer in Patients with Haematuria.

BACKGROUND: In patients with haematuria, a fast, noninvasive test with high sensitivity (SN) and negative predictive value (NPV), which is able to detect or exclude bladder cancer (BC), is needed. A newly developed urine assay, Xpert Bladder Cancer Detection (Xpert), measures five mRNA targets (ABL1, CRH, IGF2, UPK1B, and ANXA10) that are frequently overexpressed in BC. OBJECTIVE: To validate the performance of Xpert in patients with haematuria. DESIGN, SETTING, AND PARTICIPANTS: Voided precystoscopy urine specimens were prospectively collected at 22 sites from patients without prior BC undergoing cystoscopy for haematuria. Xpert, cytology, and UroVysion procedures were performed. Technical validation was performed and specificity (SP) was determined in patients without BC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Test characteristics were calculated based on cystoscopy and histology results, and compared between Xpert, cytology, and UroVysion. RESULTS AND LIMITATIONS: We included 828 patients (mean age 64.5 yr, 467 males, 401 never smoked). Xpert had an SN of 78% (95% confidence interval [CI]: 66-87) overall and 90% (95% CI: 76-96) for high-grade (HG) tumours. The NPV was 98% (95% CI: 97-99) overall. The SP was 84% (95% CI: 81-86). In patients with microhaematuria, only one HG patient was missed (NPV 99%). Xpert had higher SN and NPV than cytology and UroVysion. Cytology had the highest SP (97%). In a separate SP study, Xpert had an SP of 89% in patients with benign prostate hypertrophy and 92% in prostate cancer patients. CONCLUSIONS: Xpert is an easy-to-use, noninvasive test with improved SN and NPV compared with cytology and UroVysion, representing a promising tool for identifying haematuric patients with a low likelihood of BC who might not need to undergo cystoscopy. PATIENT SUMMARY: Xpert is an easy-to-perform urine test with good performance compared with standard urine tests. It should help identify (micro)haematuria patients with a very low likelihood to have bladder cancer.

Prospective Validation of an mRNA-based Urine Test for Surveillance of Patients with Bladder Cancer.

BACKGROUND: A fast, noninvasive test with high sensitivity (SN) and a negative predictive value (NPV), which is able to detect recurrences in bladder cancer (BC) patients, is needed. A newly developed urine assay, Xpert Bladder Cancer Monitor (Xpert), measures five mRNA targets (ABL1, CRH, IGF2, UPK1B, and ANXA10) that are frequently overexpressed in BC. OBJECTIVE: To validate Xpert characteristics in patients previously diagnosed with non-muscle-invasive BC. DESIGN, SETTING, AND PARTICIPANTS: Voided precystoscopy urine samples were prospectively collected at 22 sites. Xpert, cytology, and UroVysion were performed. If cystoscopy was suspicious for BC, a histologic examination was performed. Additionally, technical validation was performed and specificity was determined in patients without a history or clinical evidence of BC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Test characteristics were calculated based on cystoscopy and histology results, and compared between Xpert, cytology, and UroVysion. RESULTS AND LIMITATIONS: Of the eligible patients, 239 with a history of BC had results for all assays. The mean age was 71 yr; 190 patients were male, 53 never smoked, and 64% had previous intravesical immunotherapy (35%) or chemotherapy (29%). Forty-three cases of recurrences occurred. Xpert had overall SN of 74% (95% confidence interval [CI]: 60-85) and 83% (95% CI: 64-93) for high-grade (HG) tumors. The NPV was 93% (95% CI: 89-96) overall and 98% (95% CI: 94-99) for HG tumors. Specificity was 80% (95% CI: 73-85). Xpert SN and NPV were superior to those of cytology and UroVysion. Specificity in non-BC individuals (n=508) was 95% (95% CI: 93-97). CONCLUSIONS: Xpert has an improved NPV compared with UroVysion and cytology in patients under follow-up for BC. It represents a promising tool for excluding BC in these patients, reducing the need for cystoscopy. PATIENT SUMMARY: Xpert is an easy-to-perform urine test with good performance compared with standard urine tests. It should help optimize the follow-up of recurrent bladder cancer patients.

Burden of Multiple Chronic Conditions among Patients with Urological Cancer.

PURPOSE: We describe age, multiple chronic condition profiles and health system contact in patients with urological cancer. MATERIALS AND METHODS: Using Geisinger Health System electronic health records we identified adult primary care patients and a subset with at least 1 urology encounter between 2001 and 2015. The Agency for Health Care Research and Quality Chronic Condition Indicator and Clinical Classifications Software tools were applied to ICD-9 codes to identify chronic conditions. Multiple chronic conditions were defined as 2 or more chronic conditions. Patients with urological cancer were identified using ICD-9 codes for prostate, bladder, kidney, testis and penile cancer. Inpatient and outpatient visits in the year prior to the most recent encounter were counted to document health system contact. RESULTS: We identified 357,100 primary care and 33,079 urology patients, of whom 4,023 had urological cancer. Patients with urological cancer were older than primary care patients (71 vs 46 years) and they had more median chronic conditions (7 vs 4). Kidney and bladder cancer were the most common chronic conditions (median 8 patients each). Coronary artery disease and chronic kidney disease were common in urological cancer cases compared to mental health conditions in primary care cases. Patients with urological cancer who had multiple chronic conditions had the most health system contact, including 32% with at least 1 hospitalization and 68% with more than 5 outpatient visits during 1 year. CONCLUSIONS: Urology patients are older and more medically complex, especially those with urological cancer than primary care patients. These data may inform care redesign to reduce the treatment burden and improve care coordination in urological cancer cases.

Patient-reported quality of life recovery curves after robotic prostatectomy are similar across body mass index categories.

PURPOSE: To assess the impact of body mass index (BMI) on postoperative recovery curve of urinary and sexual function after robotic-assisted laparoscopic prostatectomy (RALP). We hypothesized that overweight and obese men have different recovery curves than normal weight men. MATERIALS AND METHODS: We reviewed preoperative and postoperative surveys from 691 men who underwent RALP from 2004-2014 in an integrated healthcare delivery system. Survey instruments included: sexual health inventory for men (SHIM), urinary behavior, leakage, and incontinence impact questionnaire (IIQ). A repeated measures analysis with autoregressive covariance structure was employed with linear splines with 2 knots for the time factor. We fit unadjusted and adjusted models and stratified by BMI (under/normal weight, overweight, and obese). Adjusted models included age, race/ethnicity, smoking status, diabetes, operation length, prostate-specific antigen, pathologic stage, nerve-sparing status, and surgery year. RESULTS: Mean age was 59 years. Most men were overweight (43%) and obese (42%). There were no significant differences in mean baseline SHIM, urinary behavior, leakage, and IIQ scores by BMI category. All groups had initial steep declines in urinary and sexual function in the first 3 months after RALP. There were no significant differences in postoperative urinary and sexual function score curves by BMI category. CONCLUSIONS: The pattern of urinary and sexual function recovery was similar across all BMI categories. Overweight and obese men may be counseled that urinary and sexual function recovery curves after surgery is similar to that of normal weight men.

Combined inhibition of heat shock proteins 90 and 70 leads to simultaneous degradation of the oncogenic signaling proteins involved in muscle invasive bladder cancer.

Heat shock protein 90 (HSP90) plays a critical role in the survival of cancer cells including muscle invasive bladder cancer (MIBC). The addiction of tumor cells to HSP90 has promoted the development of numerous HSP90 inhibitors and their use in clinical trials. This study evaluated the role of inhibiting HSP90 using STA9090 (STA) alone or in combination with the HSP70 inhibitor VER155008 (VER) in several human MIBC cell lines. While both STA and VER inhibited MIBC cell growth and migration and promoted apoptosis, combination therapy was more effective. Therefore, the signaling pathways involved in MIBC were systematically interrogated following STA and/or VER treatments. STA and not VER reduced the expression of proteins in the p53/Rb, PI3K and SWI/SWF pathways. Interestingly, STA was not as effective as VER or combination therapy in degrading proteins involved in the histone modification pathway such as KDM6A (demethylase) and EP300 (acetyltransferase) as predicted by The Cancer Genome Atlas (TCGA) data. This data suggests that dual HSP90 and HSP70 inhibition can simultaneously disrupt the key signaling pathways in MIBC.