Is it time to say goodbye to culture and sensitivity? The case for culture-independent urology

Next-generation sequencing has highlighted the limitations of conventional culture methods in the role of urology while discovering the intricate details of the role of microbiota in urologic health and disease. This review article explores: the utility and limitations of conventional culture methods; how culture-independent technologies are revolutionizing medicine; and how the implementation of these technologies may lead to improved patient outcomes. Finally, this article discusses the barriers to widespread adoption of culture-independent technologies, with suggestions for how these hurdles may be overcome

Characteristics of radiation-associated bladder cancer compared to primary bladder cancer

582 Background: Radiation-associated muscle-invasive bladder cancer (RA-MIBC) has been suggested to represent a more aggressive disease variant compared to primary (non-radiation associated) MIBC. We sought to characterize the presentation, patterns of care, and outcomes of RA-MIBC compared to primary MIBC. Methods: We identified 60,117 patients diagnosed with non-metastatic or metastatic MIBC between 1988 and 2015 using the Surveillance, Epidemiology, and End Results (SEER) database and stratified patients based on whether radiation had been administered to a pelvic primary prior to the development of bladder cancer. We used logistic regression to compare rates of chemotherapy, surgery, or radiation for patients with RA-MIBC compared to primary MIBC. We used Fine-Gray competing risks regression to compare adjusted bladder cancer-specific mortality (BCSM) for RA-MIBC and primary MIBC. Results: There were 1,093 patients with RA-MIBC and 59,024 patients with primary MIBC. Patients with RA-MIBC were older compared to patients with primary MIBC (mean age 77.4 years vs 72.4 years, p < 0.001) and more likely to be male (86.8% vs 73.3%, p<0.001). RA-MIBCs were more likely to be high-grade (57.5% vs 47.6%, p<0.001), more likely to have T4 disease at diagnosis (21.0% vs 17.3%, p<0.001), and less likely to be node-positive (4.2% vs 8.1%, p < 0.001). In terms of treatment, non-metastatic primary MIBC patients were more likely to undergo radiation (14.0% vs 3.1%, p<0.001) as well as radiation with cystectomy (1.9% vs 0.8%, p<0.001) compared to those with RA-MIBC. Median survival was significantly shorter for patients with RA-MIBC (13 mo. vs 19 mo.; p<0.001). Conclusions: RA-MIBCs tend to present with higher grade and higher stage disease and are less likely to receive curative treatment. Even when adjusting for stage, grade, and receipt of treatment, patients with RA-MIBC have worse survival compared to those with primary MIBC. These findings raise the possibility that RA-MIBC represents a biologically more aggressive disease compared to primary MIBC. Future research is needed to better understand biological differences between RA-MIBC and primary MIBC and develop improved therapeutics for radiation-associated cancers

Trends, Quality, and Readability of Online Health Resources on Proton Radiation Therapy

Many patients weighing cancer treatment options may consider relatively novel options including proton radiation therapy (PRT) and turn to the Internet for online health resources (OHR). However, quality and readability of OHR for radiation oncology therapies has been shown to need improvement. Because the OHR that patients access can influence their treatment decisions, our study sought to understand the patterns of use, quality, and readability of OHR on PRT. To validate the need to assess OHR on PRT, we assessed search patterns in the United States for the search phrase “proton therapy” using Google Trends. The Google search engine was then queried for websites with PRT information using 10 search phrases. The subsequent websites were analyzed for readability by the Flesch-Kincaid Grade Level and a Composite Grade Level (CGL) metric comprised of 5 readability metrics. Quality was analyzed using the DISCERN instrument. Search volume index for “proton therapy” increased by an average of 2.0% each year for the last 15 years (January 1, 2005 to June 1, 2019, P < .001). States that had a greater number of proton centers tended to have a greater relative search volume in Google (P < .001). Of the 45 unique websites identified, the mean Flesch-Kincaid Grade Level was 12.0 (range, 7.3-18.6) and the mean CGL was 12.4 (range, 7-18). In addition, 80% of PRT pages required greater than 11th grade CGL. The mean DISCERN score of all websites was 39.8 out of 75, which corresponds to “fair” quality OHR. Despite increasing interest in PRT OHR, in general, PRT websites require reading levels much higher than currently recommended, making PRT OHR less accessible to the average patient. Provision of high-quality PRT OHR at the appropriate reading level may increase comprehension of PRT, improve patient autonomy, and facilitate informed decision-making among radiation oncology patients

General and Health-Related Internet Use Among Cancer Survivors in the United States: A 2013-2018 Cross-Sectional Analysis

A significant proportion of cancer survivors endorse ongoing health information needs and may use the internet to access information. We assessed patterns and predictors of general and health-specific internet use among cancer survivors. Using data from the National Health Interview Survey (NHIS), which was administered in 2013 through 2018, for adults reporting a cancer diagnosis, sample weight-adjusted estimates defined prevalence and multivariable logistic regressions defined adjusted odds ratios (aORs) of general and health-specific internet use, adjusting for relevant sociodemographic covariates, including healthcare satisfaction as the primary independent variable. The analysis for health-specific internet use was also repeated including a sex (female vs male)*healthcare satisfaction (very satisfied/somewhat satisfied vs somewhat dissatisfied/very dissatisfied) interaction term. Among 12,970 survivors of cancer, general and health-specific internet use increased from 2013 to 2018 (from 63.2% to 70.8% and from 46.8% to 52.2%, respectively; P<.05 for both). Survivors who were very dissatisfied with healthcare were more likely to use the internet for health information compared with those who were very satisfied (59.5% vs 48.0%; aOR, 1.78; 95% CI, 1.20-2.64; P=.004). Younger age, female sex, higher educational attainment, and higher socioeconomic status were all associated with increased reported use of the internet for both general and health-specific purposes (P<.001 for all). There was a significant sex*healthcare satisfaction interaction (P=.009) such that for female survivors, healthcare dissatisfaction was associated with higher odds of health-specific internet use (61.4% vs 52.5%; P<.001; men, P=.97). No association was found between healthcare satisfaction and general internet use (P=.42). The increasing proportion of survivors of cancer using the internet for health-specific information may be associated with self-reported dissatisfaction with healthcare. Efforts are needed to improve both access to the internet and the quality of cancer-relevant online health information, and to enhance patients' online health literacy

Association Between Travel Distance and Use of Postoperative Radiation Therapy Among Men With Organ-Confined Prostate Cancer: Does Geography Influence Treatment Decisions?

After radical prostatectomy, men with adverse pathologic features or a persistent postoperative detectable prostate-specific antigen (PSA) are candidates for postoperative radiation therapy (PORT). Previous data have suggested disparities in receipt of adjuvant radiation therapy for adverse pathologic features according to travel distance. Among patients without adverse pathologic features (pT2 disease and negative margins), the main indication for PORT is a persistent postoperative detectable PSA. However, it remains unknown whether the rate of receipt of PORT in this cohort of men with persistently detectable PSA is related to travel distance from the treating facility. Using the National Cancer Database, we identified 170,379 men with prostate cancer diagnosed from 2004 to 2015 managed with upfront surgery who were found to have pT2 disease with negative surgical margins. Multivariable logistic regression defined adjusted odds ratios (AORs) with 95% confidence intervals (CIs) of receiving PORT as the primary dependent variable and distance (<5, 5-10, 10-20, ≥20 miles from the treatment facility) as the primary independent variable. Within our cohort, progressively farther distance from the treatment facility was associated with lower rates of PORT. In patients living 20 miles from the treating facility, rates of PORT of were 1.37% (referent), 1.16% (AOR, 0.90; 95% CI, 0.79-1.04; P = .158), 0.98% (AOR, 0.80; 95% CI, 0.70-0.93; P = .003), and 0.64% (AOR, 0.47; 95% CI, 0.41-0.54; P < .001), respectively. For men with localized prostate cancer without adverse pathologic features managed with surgery, increasing distance from treatment facility was associated with lower receipt of PORT. Given that the rate of a persistent postoperative detectable PSA is unlikely to depend on the distance to the treatment facility, these findings raise the possibility that the geographic availability of radiation treatment facilities influences the decision to undergo PORT for patients with persistent postoperative detectable PSA

Validation of a subclassification for high-risk prostate cancer in a prospective cohort

A subgroup of men with favorable high-risk prostate cancer (T1c with either a Gleason score of 4 + 4 = 8 and a prostate-specific antigen [PSA] level 20 ng/mL) has been associated with improved outcomes in comparison with other standard high-risk patients. This study was designed to validate the prognostic utility of a subclassification for high-risk disease with a prospectively collected data set. This study identified 3033 men from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had been diagnosed from 1993 to 2001 with clinically localized prostate cancer-either intermediate-risk disease (clinical stage T2b-c, a Gleason score of 7, or a PSA level of 10 to 20 ng/mL) or high-risk disease (clinical stage T3-T4, a Gleason score of 8-10, or a PSA level >20 ng/mL)-that was managed with radical prostatectomy or radiation therapy. Multivariable logistic regression was used to calculate adjusted odds ratios (aORs) for pathological T3 to T4 or N1 (pT3-T4/pN1) disease. Fine and Gray competing risks regression was used to determine adjusted hazard ratios (aHRs) of prostate cancer-specific mortality (PCSM). The median follow-up was 5.7 years. Patients with favorable high-risk disease had lower 8-year PCSM in comparison with patients with standard high-risk disease (2.2% vs 10.8%; aHR, 0.26; 95% confidence interval [CI], 0.09-0.73; P = .01) but similar PCSM in comparison with patients with intermediate-risk disease (2.2% vs 2.2%; aHR, 0.90; 95% CI, 0.32-2.54; P = .84). Among those who underwent surgery, those with favorable high-risk disease had lower odds of pT3-T4/pN1 disease than those with standard high-risk disease (46.2% vs 63.3%; aOR, 0.50; 95% CI, 0.27-0.94; P = .03). This study validates the prognostic utility of a subclassification for high-risk disease in a prospectively collected patient cohort. Patients with favorable high-risk disease have PCSM similar to that of patients with intermediate-risk disease and significantly better than that of patients with standard high-risk disease. Future trials are needed to assess possible de-intensification of therapy for favorable high-risk disease

Surgical management versus combination radiotherapy in Gleason score 9-10 prostate cancer

135 Background: For men with Gleason score 9-10 prostate cancer, studies have demonstrated conflicting results on the outcomes from combination radiation therapy (ComboRT) with external beam radiation therapy plus brachytherapy boost versus radical prostatectomy (RP), with or without adjuvant radiation therapy (ART). Differences in patient selection and management may explain some of the disparate outcomes of prior reports. Methods: The Surveillance, Epidemiology, and End Results database identified 10,396 men managed with ComboRT versus RP (+/-ART). Competing-risks regression analysis with treatment propensity adjustment defined hazard ratios (aHR) for prostate cancer-specific mortality (PCSM), controlling for patient-specific demographic factors. To explore the possible effect of patient selection, analyses were conducted before and after excluding men from analysis if they had evidence-based indications for ART (adverse pathology, i.e. pT3-T4 or positive margins) but did not receive it. Results: Median age was 64 years; median follow-up was 69 months. Five-year PCSM was similar between patients treated with RP (with or without ART, regardless of pathologic features, N=8,934) and ComboRT (N=1,462) (6.9% vs 8.1%, aHR=0.94, 95% confidence interval [CI] 0.78–1.13, P=0.51). After excluding RP-treated men with adverse pathology who did not receive ART (N=4,527 excluded), patients treated with RP+/-ART (N=4,407) had improved 5-year PCSM compared with those treated with ComboRT (5.3% vs 8.1%, aHR=0.74, 95% CI 0.60–0.91, P=0.004). Conclusions: For Gleason 9-10 prostate cancer, ComboRT was associated with similar PCSM compared to RP, but risk-tailored surgical management may be associated with superior PCSM

Clinical characterization of radiation-associated muscle-invasive bladder cancer

To characterize the presentation, patterns of care, and outcomes of radiation-associated muscle-invasive bladder cancer (RA-MIBC) compared to primary (non-radiation associated) MIBC. RA-MIBC has been suggested to represent a more aggressive disease variant and be more difficult to treat compared to primary (non-radiation associated) MIBC. We identified 60,090 patients diagnosed with MIBC between 1988-2015 using the Surveillance, Epidemiology, and End Results database and stratified patients based on whether radiation had been administered to a prior pelvic primary cancer. We used Fine-Gray competing risks regression to compare adjusted bladder cancer-specific mortality (BCSM) for RA-MIBC compared to primary MIBC. There were 1,093 patients with RA-MIBC and 58,997 patients with primary MIBC. RA-MIBCs were more likely to be T4 at diagnosis (21.0% vs 17.3%, P < .001), and less likely to be node-positive (10.3% vs 17.1%, P < .001). The rate of 5-year BCSM was significantly higher for patients with RA-MIBC vs primary MIBC (56.1% vs 35.3%, AHR 1.24, P < .001), even after stratification by other tumor, treatment and patient-specific factors. RA-MIBCs tended to present with higher grade and T stage disease and were less likely to receive curative treatment. Even when accounting for stage, grade, and receipt of treatment, patients with RA-MIBC had worse survival compared to those with primary MIBC. These findings suggest that RA-MIBC present unique clinical challenges and may also represent a biologically more aggressive disease compared to primary MIBC. Future research is needed to better understand the biology of RA-MIBC and develop improved treatment approaches