The impact of the social construct of race on outcomes among bacille Calmette-Guérin-treated patients with high-risk non-muscle-invasive bladder cancer in an equal-access setting.

BACKGROUND: The objective of this study was to describe bladder cancer outcomes as a function of race among patients with high-risk non-muscle-invasive bladder cancer (NMIBC) in an equal-access setting. METHODS: A total of 412 patients with high-risk NMIBC who received bacille Calmette-Guérin (BCG) from January 1, 2010, to December 31, 2015, were assessed. The authors used the Kaplan-Meier method to estimate event-free survival and Cox regression to determine the association between race and recurrence, progression, disease-specific, and overall survival outcomes. RESULTS: A total of 372 patients who had complete data were included in the analysis; 48 (13%) and 324 (87%) were Black and White, respectively. There was no difference in age, sex, smoking status, or Charlson Comorbidity Index by race. White patients had a higher socioeconomic status with a greater percentage of patients living above the poverty level in comparison with Black patients (median, 85% vs 77%; P < .001). A total of 360 patients (97%) received adequate induction BCG, and 145 patients (39%) received adequate maintenance BCG therapy. There was no significant difference in rates of adequate induction or maintenance BCG therapy according to race. There was no significant difference in recurrence (hazard ratio [HR], 1.53; 95% confidence interval [CI], 0.64-3.63), progression (HR, 0.77; 95% CI, 0.33-1.82), bladder cancer-specific survival (HR, 1.01; 95% CI, 0.30-3.46), or overall survival (HR, 0.97; 95% CI, 0.56-1.66) according to Black race versus White race. CONCLUSIONS: In this small study from an equal-access setting, there was no difference in the receipt of BCG or any differences in bladder cancer outcomes according to race.

Increasing use of positron emission tomography among medicare beneficiaries undergoing radical cystectomy.

OBJECTIVE: To examine factors associated with PET scan use in the pre-operative evaluation of patients diagnosed with bladder cancer. METHODS: Using SEER-Medicare data, we identified bladder cancer patients who underwent radical cystectomy from 2006 to 2011 (n = 4,138). The primary outcome was PET scan use within 6 months before surgery. To examine predictors of PET scan use, we fit a mixed logit model with health service area as a random effect to account for patients nested within health service areas. We also calculated the adjusted probability of use over time and examined variation among the highest volume surgeons. RESULTS: Among the 4,138 patients, 406 (10%) received a pre-operative PET scan. The adjusted probability of a patient undergoing a PET scan increased from 0.04 in 2004 to 0.10 in 2011 (p < .001). Among the 78 highest volume surgeons, there was significant variation in PET scan use (p < .001). Patients with non-urothelial histology, measurement of alkaline phosphatase levels, and receipt of neoadjuvant chemotherapy were more likely to receive PET scan (all p < .05). CONCLUSION: Use of PET prior to radical cystectomy doubled over a 5-year period, suggesting its increased use in patients with muscle-invasive bladder cancer, particularly those with high-risk disease. Whether its use is warranted and improves patient outcomes is not clear and requires further studies.

E-cadherin is downregulated in benign prostatic hyperplasia and required for tight junction formation and permeability barrier in the prostatic epithelial cell monolayer.

BACKGROUND: We previously reported the presence of prostate-specific antigen (PSA) in the stromal compartment of benign prostatic hyperplasia (BPH). Since PSA is expressed exclusively by prostatic luminal epithelial cells, PSA in the BPH stroma suggests increased tissue permeability and the compromise of epithelial barrier integrity. E-cadherin, an important adherens junction component and tight junction regulator, is known to exhibit downregulation in BPH. These observations suggest that the prostate epithelial barrier is disrupted in BPH and E-cadherin downregulation may increase epithelial barrier permeability. METHODS: The ultra-structure of cellular junctions in BPH specimens was observed using transmission electron microscopy (TEM) and E-cadherin immunostaining analysis was performed on BPH and normal adjacent specimens from BPH patients. In vitro cell line studies using benign prostatic epithelial cell lines were performed to determine the impact of small interfering RNA knockdown of E-cadherin on transepithelial electrical resistance and diffusion of fluorescein isothiocyanate (FITC)-dextran in transwell assays. RESULTS: The number of kiss points in tight junctions was reduced in BPH epithelial cells as compared with the normal adjacent prostate. Immunostaining confirmed E-cadherin downregulation and revealed a discontinuous E-cadherin staining pattern in BPH specimens. E-cadherin knockdown increased monolayer permeability and disrupted tight junction formation without affecting cell density. CONCLUSIONS: Our results indicate that tight junctions are compromised in BPH and loss of E-cadherin is potentially an important underlying mechanism, suggesting targeting E-cadherin loss could be a potential approach to prevent or treat BPH.

Small cell bladder cancer: should we consider prophylactic cranial irradiation?

PURPOSE: To describe the clinical characteristics, treatment patterns, and outcomes in patients with small cell bladder cancer at our institution, including those who received prophylactic cranial irradiation (PCI) for the prevention of intracranial recurrence. MATERIALS AND METHODS: Patients with small cell bladder cancer treated at a single institution between January 1990 and August 2015 were identified and analyzed retrospectively for demographics, tumor stage, treatment, and overall survival. RESULTS: Of 44 patients diagnosed with small cell bladder cancer, 11 (25%) had metastatic disease at the time of presentation. Treatment included systemic chemotherapy (70%), radical surgery (59%), and local radiation (39%). Six patients (14%) received PCI. Median overall survival was 10 months (IQR 4 - 41). Patients with extensive disease had worse overall survival than those with organ confined disease (8 months vs. 36 months, respectively, p = 0.04). Among those who received PCI, 33% achieved 5 - year survival. CONCLUSION: Outcomes for patients with small cell bladder cancer remain poor. Further research is indicated to determine if PCI increases overall survival in small call bladder cancer patients, especially those with extensive disease who respond to chemotherapy.

The comparative effectiveness of quadratus lumborum blocks and paravertebral blocks in radical cystectomy patients.

INTRODUCTION: Multimodal analgesia is an effective way to control pain and limit opioid use after surgery. The quadratus lumborum block and paravertebral block are two regional anesthesia techniques that leverage multimodal analgesia to improve postoperative pain control. We sought to compare the efficacy of these blocks for pain management following radical cystectomy. MATERIALS AND METHODS: We performed a retrospective review of radical cystectomy patients who received bilateral continuous paravertebral blocks (n = 125) or bilateral single shot quadratus lumborum blocks (n = 50) between 2014-2016. The primary outcome was postoperative opiate consumption on day 0. Secondary outcomes included self-reported pain scores and hospital length of stay. RESULTS: Quadratus lumborum block patients had similar opioid use on postoperative day 0 compared with paravertebral block patients (29 mg versus 30 mg, p = 0.90). Pain scores on postoperative day 0 were similar between quadratus lumborum block and paravertebral block groups (4.0 versus 3.8, p = 0.72); however, the paravertebral block group had lower pain scores on days 1-3 compared with the quadratus lumborum block group (all p < 0.05). Hospital length of stay was similar between groups (6.6 days versus 6.2 days, p = 0.41). CONCLUSIONS: There were no differences in opioid consumption among patients receiving bilateral single shot quadratus lumborum blocks and bilateral continuous paravertebral blocks after radical cystectomy. These data suggest that the quadratus lumborum block is a viable alternative for delivering multimodal analgesia in cystectomy patients.

Preoperative immunonutrition prior to radical cystectomy: a pilot study.

INTRODUCTION: To investigate the use of a high-arginine immunonutrient supplement prior to radical cystectomy for bladder cancer. MATERIALS AND METHODS: We recruited 40 patients to consume a total of four high-arginine immunonutrient shakes per day for 5 days prior to radical cystectomy. The primary outcome measures were safety, tolerability and adherence to the supplementation regimen. Ninety-day postoperative outcomes were also compared between supplemented patients and a cohort of 104 prospectively identified non-supplemented radical cystectomy patients. Multivariable logistic regression models were used to compare overall complications, infectious complications, and readmission rates between groups. RESULTS: There were no serious adverse events during supplementation. Four patients (10%) stopped supplementation due to nausea (n = 2) and bloating (n = 2). Thirty-three patients (83%) consumed all prescribed shakes. Immunonutrient supplementation was not significantly associated with overall complications (adjusted odds ratio [OR] 1.08; 95% confidence interval [CI] 0.50-2.33), infectious complications (OR 1.23; 95% CI 0.49-3.07), or readmissions (OR 1.48; 95% CI 0.62-3.51) on multivariable analyses. CONCLUSIONS: Preoperative supplementation with a high-arginine immunonutrient shake was safe and well tolerated prior to radical cystectomy. Contrary to prior reports, immunonutrient supplementation was not associated with lower postoperative infectious complications in this cohort, perhaps owing to the 5 day supplementation period. Further study is needed to identify the optimal immunonutrient supplement regimen for radical cystectomy patients.

Influence of E. coli-induced prostatic inflammation on expression of androgen-responsive genes and transforming growth factor beta 1 cascade genes in rats.

BACKGROUND: Prostatic inflammation is reportedly associated with the development of prostatic hyperplasia. We investigated the effects of prostatic inflammation on expression levels of androgen-responsive genes and growth factors in the rat prostate. METHODS: Prostatic inflammation was induced by Escherichia coli (strain 1677) injection (0.2 ml of 1 × 10(8) CFU/ml) into the prostatic urethra of male Sprague-Dawley rats, and ventral lobes of the prostate were harvested on day 84. Rats were given 10 mg/kg celecoxib during the last month in the COX-2 inhibitor treated group. Histopathology and multiplex enzyme-linked immunosorbent assay (ELISA) for inflammation-related proteins were performed. Glandular epithelial cells and stromal regions were separately isolated using laser-capture microdissection (LCM). Real-time RT-PCR was performed to examine mRNA levels of androgen-responsive genes in the epithelium and tumor growth factor-ß1 (TGF-ß1) cascade genes in the stroma. RESULTS: Hematoxylin and eosin staining showed that mild inflammation was distributed diffusely throughout the prostate. Polymorphonuclear cells infiltrated the slightly edematous stroma, but no morphological changes were observed in the epithelium. Immunohistochemically, expression of androgen receptor and TGF-ß1 in addition to IL-6 and cyclooxigenase-2 (COX-2) were enhanced in the E. coli inoculated rats. All of these factors were suppressed in the celecoxib-treated rats. Upregulation of IL-1α, IL-1ß, IL-6, and RANTES in the E. coli-inoculated rats was normalized by celecoxib treatment. Significant upregulation of androgen receptor and androgen-responsive genes such as Eaf2, ELL2, FKBP5, calreticulin, and ornithine decarboxylase was observed in the LCM-dissected epithelium. Also TGF-ß1 and its downstream cascade genes such as Hic-5, collagen 1, and fibronectin were upregulated significantly in the LCM-dissected stroma. The COX-2 inhibitor treatment suppressed upregulation of these genes. CONCLUSIONS: Prostatic inflammation changed the expression of androgen-responsive genes in the epithelium and TGF-ß1 cascade genes in the stroma. Activation of TGF-ß1 cascade genes in the inflamed stroma, as well as altered androgen-responsive gene expression in the epithelium, might be involved in the development of BPH. Prostate 75:381-389, 2015. © 2014 Wiley Periodicals, Inc.

Radical prostatectomy versus observation for localized prostate cancer.

BACKGROUND: The effectiveness of surgery versus observation for men with localized prostate cancer detected by means of prostate-specific antigen (PSA) testing is not known. METHODS: From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer (mean age, 67 years; median PSA value, 7.8 ng per milliliter) to radical prostatectomy or observation and followed them through January 2010. The primary outcome was all-cause mortality; the secondary outcome was prostate-cancer mortality. RESULTS: During the median follow-up of 10.0 years, 171 of 364 men (47.0%) assigned to radical prostatectomy died, as compared with 183 of 367 (49.9%) assigned to observation (hazard ratio, 0.88; 95% confidence interval [CI], 0.71 to 1.08; P=0.22; absolute risk reduction, 2.9 percentage points). Among men assigned to radical prostatectomy, 21 (5.8%) died from prostate cancer or treatment, as compared with 31 men (8.4%) assigned to observation (hazard ratio, 0.63; 95% CI, 0.36 to 1.09; P=0.09; absolute risk reduction, 2.6 percentage points). The effect of treatment on all-cause and prostate-cancer mortality did not differ according to age, race, coexisting conditions, self-reported performance status, or histologic features of the tumor. Radical prostatectomy was associated with reduced all-cause mortality among men with a PSA value greater than 10 ng per milliliter (P=0.04 for interaction) and possibly among those with intermediate-risk or high-risk tumors (P=0.07 for interaction). Adverse events within 30 days after surgery occurred in 21.4% of men, including one death. CONCLUSIONS: Among men with localized prostate cancer detected during the early era of PSA testing, radical prostatectomy did not significantly reduce all-cause or prostate-cancer mortality, as compared with observation, through at least 12 years of follow-up. Absolute differences were less than 3 percentage points. (Funded by the Department of Veterans Affairs Cooperative Studies Program and others; PIVOT ClinicalTrials.gov number, NCT00007644.).

5α-Reductase inhibition coupled with short off cycles increases survival in the LNCaP xenograft prostate tumor model on intermittent androgen deprivation therapy.

PURPOSE: Intermittent androgen deprivation therapy in patients with prostate specific antigen progression after localized prostate cancer treatment is an alternative to standard continuous androgen deprivation therapy. Intermittent androgen deprivation therapy allows for testosterone recovery during off cycles. This stimulates regrowth and differentiation of the regressed prostate tumor, lessens the side effects of continuous androgen deprivation therapy and potentially prolongs survival. Previously intermittent androgen deprivation therapy coupled with finasteride was shown to prolong survival in animals bearing androgen sensitive prostate tumors when the off cycle duration was not prolonged but rather fixed at 10 to 14 days. Regressed prostate tumor xenografts with testosterone replacement were initially responsive to 5α-reductase inhibition but growth resumed after several days. In shorter off cycles of testosterone recovery 5α-reductase inhibition might maximize tumor growth inhibition during intermittent androgen deprivation therapy and perhaps increase survival. MATERIALS AND METHODS: We used the LNCaP xenograft tumor model to evaluate the effectiveness of short off cycles of 4 days coupled with 5α-reductase inhibition on survival and tumor regrowth while on intermittent androgen deprivation therapy. RESULTS: Dutasteride inhibited initial testosterone induced tumor regrowth off cycles 1 and 2, and significantly increased survival. CONCLUSIONS: These results further support the potential for intermittent androgen deprivation therapy combined with 5α-reductase inhibition to improve survival in patients with prostate cancer when off cycle duration is short or very short.

Genomic classifiers and prognosis of localized prostate cancer: a systematic review.

BACKGROUND: Refinement of the risk classification for localized prostate cancer is warranted to aid in clinical decision making. A systematic analysis was undertaken to evaluate the prognostic ability of three genomic classifiers, Decipher, GPS, and Prolaris, for biochemical recurrence, development of metastases and prostate cancer-specific mortality in patients with localized prostate cancer. METHODS: Data sources: MEDLINE, Embase, and Web of Science were queried for reports published from January 2010 to April 2022. STUDY SELECTION: prospective or retrospective studies reporting prognosis for patients with localized prostate cancer. DATA EXTRACTION: relevant data were extracted into a customized database by one researcher with a second overreading. Risk of bias was assessed using a validated tool for prognostic studies, Quality in Prognosis Studies (QUIPS). Disagreements were resolved by consensus or by input from a third reviewer. We assessed the certainty of evidence by GRADE incorporating adaptation for prognostic studies. RESULTS: Data synthesis: a total of 39 studies (37 retrospective) involving over 10,000 patients were identified. Twenty-two assessed Decipher, 5 GPS, and 14 Prolaris. Thirty-four studies included patients who underwent prostatectomy. Based on very low to low certainty of evidence, each of the three genomic classifiers modestly improved upon the prognostic ability for biochemical recurrence, development of metastases, and prostate cancer-specific mortality compared to standard clinical risk-classification schemes. LIMITATIONS: downgrading of confidence in the evidence stemmed largely from bias due to the retrospective nature of the studies, heterogeneity in treatment received, and era in which patients were treated (i.e., prior to the 2000s). CONCLUSIONS: Genomic classifiers provide a small but consistent improvement upon the prognostic ability of clinical classification schemes, which may be helpful when treatment decisions are uncertain. However, evidence from current management-era data and of the predictive ability of these tests is needed.

Aberrant methylation and loss of CADM2 tumor suppressor expression is associated with human renal cell carcinoma tumor progression.

Cell adhesion molecules (CADMs) comprise a protein family whose functions include maintenance of cell polarity and tumor suppression. In this report, we show that the CADM2 gene is repressed in human clear renal cell carcinoma by DNA promoter hypermethylation and/or loss of heterozygosity. Moreover, the loss of CADM2 expression is associated with a higher tumor pathology stage (p<0.05). The re-expression of CADM2 in the renal cancer cell line 786-O significantly suppressed tumor cell growth in vitro and in mouse xenografts by a G1 phase cell cycle arrest and the induction of apoptosis. Lentivirus-mediated CADM2 expression also significantly suppressed cancer cell anchorage-independent growth and invasion. Furthermore, the inhibition of endogenous CADM2 expression using siRNAs induced a tumorigenic phenotype in polarized non-tumorigenic MDCK cells. Thus, we conclude that CADM2 functions as a novel tumor suppressor and may serve as a potential therapeutic target for human renal cell carcinoma.

Impact of Race on Outcomes of High-Risk Patients With Prostate Cancer Treated With Moderately Hypofractionated Radiotherapy in an Equal Access Setting.

Background: Moderately hypofractionated radiotherapy (MHRT) is an accepted treatment for localized prostate cancer; however, limited MHRT data address high-risk prostate cancer (HRPC) and/or African American patients. We report clinical outcomes and toxicity profiles for individuals with HRPC treated in an equal access system. Methods: We identified patients with HRPC treated with MHRT at a US Department of Veterans Affairs referral center. Exclusion criteria included < 12 months follow-up and elective nodal irradiation. MHRT included 70 Gy over 28 fractions or 60 Gy over 20 fractions. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicities were graded using Common Terminology Criteria for Adverse Events, version 5.0. Clinical endpoints, including biochemical recurrence-free survival (BRFS), distant metastases-free survival (DMFS), overall survival (OS), and prostate cancer-specific survival (PCSS) were estimated using Kaplan-Meier methods. Clinical outcomes, acute toxicity, and late toxicity-free survival were compared between African American and White patients with logistic regression and log-rank testing. Results: Between November 2008 and August 2018, 143 patients with HRPC were treated with MHRT and followed for a median of 38.5 months; 82 (57%) were African American and 61 were White patients. Concurrent androgen deprivation therapy (ADT) was provided for 138 (97%) patients for a median duration of 24 months. No significant differences between African American and White patients were observed for 5-year OS (73% [95% CI, 58%-83%] vs 77% [95% CI, 60%-97%]; P = .55), PCSS (90% [95% CI, 79%-95%] vs 87% [95 % CI, 70%-95%]; P = .57), DMFS (91% [95% CI, 80%-96%] vs 81% [95% CI, 62%-91%]; P = .55), or BRFS (83% [95% CI, 70%-91%] vs 71% [95% CI, 53%-82%]; P = .57), respectively. Rates of acute grade 3+ GU and GI were low overall (4% and 1%, respectively). Late toxicities were similarly favorable with no significant differences by race. Conclusions: Individuals with HRPC treated with MHRT in an equal access setting demonstrated favorable clinical outcomes that did not differ by race, alongside acceptable rates of acute and late toxicities.

Investigation of phosphoprotein signatures of archived prostate cancer tissue specimens via proteomic analysis.

Early detection of prostate cancer and determination of its aggressiveness are critical factors that influence treatment outcomes. To aid in the clinical decision making, novel biomarkers are being sought. Direct, global-scale examination of primary human specimens provides the most relevant picture of the tumor machinery and its perturbations, and this information is highly significant in the context of biomarker discovery. In the pilot study reported here, we focused on mapping of the phosphoproteome in human prostate cancer specimens obtained from a tissue repository. A gel-free proteomic strategy included whole proteome digestion, phosphopeptide enrichment with immobilized metal ion affinity chromatography (IMAC), and phosphoprotein identification via LC-MS/MS and database searches. We applied this strategy to obtain phosphoprotein signatures from a set of five specimens. Phosphoproteins were characterized from each specimen. The phosphoprotein panels included 16-23 phosphoproteins that encompassed 18-30 phosphorylation sites. Some of proteins/sites were characterized in multiple specimens, whereas the majority of sites were found in single specimens. The characterized panels include caldesmone, desmin, HSP ß-1, synaptopodin-2, filamin-C, tensin-1, and others. In summary, the study showed that cancer-relevant phosphoproteins can be characterized directly from archived prostate tumor specimens, establishing the groundwork for further biomarker discovery.

Associations Between Female Sex and Treatment Patterns and Outcomes for Muscle-invasive Bladder Cancer.

OBJECTIVE: To investigate the association of female sex with the selected treatment for patients with nonmetastatic muscle-invasive bladder cancer. Sex is a known independent predictor of death from bladder cancer. A potential explanation for this survival disparity is difference in treatment pattern and stage presentation among males and females. MATERIALS AND METHODS: Using the surveillance, epidemiology, and end results-medicare data set, we identified 6809 patients initially diagnosed with nonmetastatic muscle-invasive bladder cancer between 2004 and 2014. We fit multivariable logistic regression and Cox models to assess the relationship of sex with treatment modality and survival adjusting for differences in patient characteristics. RESULTS: Of the 6809 patients with nonmetastatic muscle invasive bladder cancer, 2528 (37%) received a radical cystectomy while 4281 (63%) received an alternative bladder sparing intervention. Women were significantly more likely to receive a cystectomy (odds ratios [OR] 1.39; 95% confidence intervals [CI] 1.20-1.61), present at an older age with less comorbidities compared to men (P <.001). Women were also found to have worse bladder cancer-specific survival (CSS) than men (hazard ratio [HR] 1.18; 95% CI 1.05-1.32), no difference in overall survival (OS) (female HR 0.93; 0.86-1.01) and lower mortality from other causes (HR 0.78; 95% CI 0.70-0.86). There were no differences in OS and CSS by sex in patients with stage pT4a. CONCLUSION: Female sex predicted more aggressive treatment with radical cystectomy yet worse cancer-specific survival than males. This sex disparity in CSS reduced the known OS advantage observed in women.

Enhanced oncolytic activity of vesicular stomatitis virus encoding SV5-F protein against prostate cancer.

PURPOSE: Vesicular stomatitis virus has been investigated as an oncolytic agent for cancer therapy because it preferentially replicates in tumor but not in normal cells due to the lack of a robust interferon antiviral system in transformed cells. However, wild-type vesicular stomatitis virus can induce a strong systemic immunological response and replicate in the central nervous system, potentially limiting its clinical usefulness. We report the construction of the recombinant, replication restricted vesicular stomatitis virus encoding SV5-F, which can induce syncytial formation with enhanced oncolytic properties against TRAMP-C2 tumors in an immunocompetent mouse model of prostate cancer. MATERIALS AND METHODS: We constructed the SV5-F recombinant restricted virus vector by replacing the vesicular stomatitis virus G gene with that of the SV5-F transgene to generate rVSV-DeltaG-SV5-F. Morphological changes and DNA fragmentation induced by rVSV-DeltaG-GFP or rVSV-DeltaG-SV5-F were determined by phase contrast microscopy and gel electrophoresis. In vitro cytotoxicity by recombinant vesicular stomatitis virus was done by MTT assay. In vivo study of rVSV treatment was done in immunocompetent mice by subcutaneous administration of TRAMP-C2 cells. RESULTS: In vitro characterization of the recombinant fusogenic VSV-DeltaG vector on TRAMP-C2 cells showed significantly enhanced apoptotic and cytotoxic effects relative to a similar virus encoding green fluorescent protein, that is rVSV-DeltaG-GFP. Regardless of initial tumor size intratumor rVSV-DeltaG-SV5-F administration in mice bearing subcutaneous TRAMP-C2 tumors resulted in a significantly reduced tumor load over that of the nonfusogenic green fluorescent control virus and of heat inactivated recombinant vesicular stomatitis virus in treated animals (p <0.01). CONCLUSIONS: Results show that G complemented recombinant VSV-DeltaG vectors, especially rVSV-DeltaG-SV5-F, are an effective oncolytic agent against mouse prostate cancer cells in vitro and in an in vivo immunocompetent mouse model system.

Comparison of Neoadjuvant and Adjuvant Chemotherapy in Muscle-invasive Bladder Cancer.

BACKGROUND: We use observational methods to compare impact of perioperative chemotherapy timing (ie, neoadjuvant and adjuvant) on overall survival (OS) in muscle-invasive bladder cancer because there is no head-to-head randomized trial, and patient factors may influence decision-making. PATIENTS AND METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified patients receiving cystectomy for muscle-invasive bladder cancer diagnosed between 2004 and 2013. Patients were classified as receiving neoadjuvant or adjuvant chemotherapy. Propensity of receiving neoadjuvant chemotherapy was determined using gradient boosted models. Inverse probability of treatment weighted survival curves were adjusted for 13 demographic, socioeconomic, temporal, and oncologic covariates. RESULTS: We identified 1342 patients who received neoadjuvant (n = 676) or adjuvant chemotherapy (n = 666) with a median follow-up of 23 months (interquartile range, 9-55 months). Inverse probability of treatment weighted adjustment allows comparison of the groups head-to-head as well as counterfactual scenarios (eg, effect if those getting one treatment were to receive the other). The average treatment effect (ie, "head-to-head" comparison) of adjuvant compared with neoadjuvant on OS was not significant (hazard ratio, 1.14; 95% confidence interval, 0.99-1.31). However, the average treatment effect of the treated (ie, the effect if the neoadjuvant patients were to receive adjuvant instead) was associated with a 33% increase in risk of mortality if they were given adjuvant therapy instead (hazard ratio, 1.33; 95% confidence interval, 1.12-1.57). CONCLUSION: Significant treatment selection bias was noted in peri-cystectomy timing, which limits the ability to discriminate differential efficacy of these 2 approaches with observational data. However, patients with higher propensity to receive neoadjuvant therapy were predicted to have increased OS with approach, in keeping with existing paradigms from trial data.

Self-Management in Long-Term Prostate Cancer Survivors: A Randomized, Controlled Trial.

PURPOSE: This randomized clinical trial compared a personally tailored, automated telephone symptom management intervention to improve self-management among long-term survivors of prostate cancer with usual care enhanced with a nontailored newsletter about symptom management. We hypothesized that intervention-group participants would have more confident symptom self-management and reduced symptom burden. METHODS: A total of 556 prostate cancer survivors who, more than 1 year after treatment, were experiencing symptom burden were recruited from April 2015 to February 2017 across four Veterans Affairs sites. Participants were randomly assigned to intervention (n = 278) or usual care (n = 278) groups. We compared differences in the primary (symptom burden according to Expanded Prostate Cancer Index Composite-26 [EPIC], confidence in self-management) and secondary outcomes between groups using intent-to-treat analyses. We compared domain-specific changes in symptom burden from baseline to 5 and 12 months among the intervention group according to the primary symptom focus area (urinary, bowel, sexual, general) of participants. RESULTS: Most of the prostate cancer survivors in this study were married (54.3%), were white (69.2%), were retired (62.4%), and underwent radiation therapy (56.7% v 46.2% who underwent surgery), and the mean age was 67 years. There were no baseline differences in urinary, bowel, sexual, or hormonal domain EPIC scores across groups. We observed higher EPIC scores in the intervention arm in all domain areas at 5 months, though differences were not statistically significant. No differences were found in secondary outcomes; however, coping appraisal was higher (2.8 v 2.6; P = .02) in intervention-arm patients at 5 months. In subgroup analyses, intervention participants reported improvement from baseline at 5 and 12 months in their symptom focus area domains. CONCLUSION: This intervention was well received among veterans who were long-term survivors of prostate cancer. Although overall outcome differences were not observed across groups, the intervention tailored to symptom area of choice may hold promise to improve associated burden.

Trends and appropriateness of perioperative chemotherapy for muscle-invasive bladder cancer.

INTRODUCTION: Contemporary guidelines recommend cystectomy with neoadjuvant or adjuvant cisplatin-based chemotherapy given with curative intent for patients with resectable muscle-invasive bladder cancer (MIBC). However, rates and appropriateness of perioperative chemotherapy utilization remain unclear. We therefore sought to characterize use of perioperative chemotherapy in older radical cystectomy MIBC patients and examine factors associated with use. METHODS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified patients with MIBC diagnosed between 2004 and 2013 and treated with radical cystectomy. We classified patients into 3 treatment groups: cystectomy alone, neoadjuvant, or adjuvant chemotherapy. Chemotherapy was classified by regimen. We then fit a multinomial multivariable logistic regression model to assess association between patient factors with the receipt of each treatment. RESULTS: We identified 3,826 eligible patients. The majority (484; 65%) received cystectomy alone. Neoadjuvant (676; 18% overall, 69% cisplatin-based), and adjuvant chemotherapy (666, 17% overall, 55% cisplatin-based) were used in similar proportions of cystectomy patients. Over the study period, the odds of receiving adjuvant chemotherapy decreased by 7.5%, whereas neoadjuvant therapy increased by 27.5% (both P < 0.001). There was an increase in use of cisplatin-based regimens in the neoadjuvant setting (35 to 72%, P < 0.001), but not the adjuvant setting. Female gender, lower comorbidity, married status, and lower stage disease were associated with greater odds of receiving neoadjuvant chemotherapy (all P < 0.05). CONCLUSION: From 2004 to 2013 use of neoadjuvant chemotherapy for MIBC increased while use of adjuvant chemotherapy decreased. Future studies examining barriers to appropriate chemotherapy use, and the comparative effectiveness of neoadjuvant versus adjuvant chemotherapy are warranted.

Implications of Cystectomy Travel Distance for Hospital Readmission and Survival.

BACKGROUND: Regionalization of complex surgical care results in increasing need for patients to travel for complex oncologic procedures such as cystectomy in bladder cancer. We examined the association between travel distance to a cystectomy center, readmission, and survival. PATIENTS AND METHODS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified bladder cancer patients undergoing radical cystectomy during 2004-2011. Patients were grouped into quartiles of distance to cystectomy center in miles (< 6 [close], 6-16.9 [moderately close], 17-47.9 [moderately far], ≥ 48 [far]). Multivariable logistic regression, accounting for clustering within hospitals, was used to assess the association between travel distance and readmission. A secondary analysis examined the association between travel distance and survival using multivariable proportional hazard regression. RESULTS: Among 4556 patients who underwent cystectomy, 1857 (41%) were readmitted, and 1251 (67%) of readmissions were to the index hospital. With increasing travel distance there was no significant difference in the overall rate of 90-day readmission. However, the farther a patient traveled, the lower the odds of being readmitted to the index hospital (adjusted odds ratio [95% confidence interval] as follows: moderately close, 0.43 miles [0.29-0.63]; moderately far, 0.14 miles [0.10-0.19]; and far, 0.07 [0.05-0.11]). Increasing travel distance was associated with improved survival. CONCLUSION: With greater distance traveled to a cystectomy center, rates of readmission to nonindex centers increased. Survival differences may be explained by the impact of travel burden on processes of care and case mix. Future efforts should focus on improving care coordination between index and nonindex hospitals and ensuring equitable access to cystectomy and other critical cancer services.

Aggressive surgical management of adenocarcinoma of the rete testis.

Adenocarcinoma of the rete testis is a rare and aggressive malignancy arising from the epididymal epithelium. We present a case of a 66-year-old male who presented with left testis mass. Histopathological analysis of orchiectomy specimen was consistent with adenocarcinoma of the rete testis. Subsequent retroperitoneal lymph node dissection revealed metastatic disease not detected on preoperative PET-CT. Prior reports have suggested poor response rates to both systemic chemotherapy and radiation therapy. Aggressive surgical management of the retroperitoneum should be considered even in clinically node-negative patients given the paucity of other effective treatment regimens.