Immunotherapy in Bacillus Calmette-Guerin (BCG) unresponsive nonmuscle invasive bladder cancer.

PURPOSE OF REVIEW: A number of promising therapies for Bacillus Calmette-Guerin (BCG) unresponsive nonmuscle invasive bladder cancer (NMIBC) are in the pipeline. In this review, we discuss the history of immunotherapy for the treatment of NMIBC and future developments, focusing on novel intravesical treatments. RECENT FINDINGS: The term BCG unresponsive NMIBC encompasses patients with both BCG refractory and BCG relapsing disease. This definition was adopted to standardize inclusion criteria for patients enrolling in clinical trials in this setting. A host of intravesical immuno-oncologic therapies that include gene therapies, oncolytic viruses, cell surface molecule delivered immunotoxins, and cytokine driven agonism of cellular immunity, are in various phases of the drug development pipeline. In addition, pembrolizumab, an immune-checkpoint inhibitor, has recently been approved as a treatment option for BCG unresponsive NMIBC. SUMMARY: Patients with BCG unresponsive disease face many difficulties. Although radical cystectomy is the most effective treatment option for these patients, it is associated with significant morbidity, difficult recovery challenges, and refusal by many patients. Cancer immunotherapies may provide bladder sparing options for some patients who develop BCG unresponsive disease.

Palliative care use amongst patients with bladder cancer.

OBJECTIVES: To describe the rate and determinants of palliative care use amongst Medicare beneficiaries with bladder cancer and encourage a national dialogue on improving coordinated urological, oncological, and palliative care in patients with genitourinary malignancies. PATIENTS AND METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified patients diagnosed with muscle-invasive bladder cancer (MIBC) between 2008 and 2013. Our primary outcome was receipt of palliative care, defined as the presence of a claim submitted by a Hospice and Palliative Medicine subspecialist. We examined determinants of palliative care use using logistic regression analysis. RESULTS: Over the study period, 7303 patients were diagnosed with MIBC and 262 (3.6%) received palliative care. Of 2185 patients with advanced bladder cancer, defined as either T4, N+ , or M+ disease, 90 (4.1%) received palliative care. Most patients that received palliative care (>80%, >210/262) did so within 24 months of diagnosis. On multivariable analysis, patients receiving palliative care were more likely to be younger, female, have greater comorbidity, live in the central USA, and have undergone radical cystectomy as opposed to a bladder-sparing approach. The adjusted probability of receiving palliative care did not significantly change over time. CONCLUSIONS: Palliative care provides a host of benefits for patients with cancer, including improved spirituality, decrease in disease-specific symptoms, and better functional status. However, despite strong evidence for incorporating palliative care into standard oncological care, use in patients with bladder cancer is low at 4%. This study provides a conservative baseline estimate of current palliative care use and should serve as a foundation to further investigate physician-, patient-, and system-level barriers to this care.

Trends in renal calculus composition and 24-hour urine analyses in patients with neurologically derived musculoskeletal deficiencies.

PURPOSE: To better characterize metabolic stone risk in patients with neurologically derived musculoskeletal deficiencies (NDMD) by determining how patient characteristics relate to renal calculus composition and 24-hour urine parameters. MATERIALS AND METHODS: We performed a retrospective cohort study of adult patients with neurologically derived musculoskeletal deficiencies presenting to our multidisciplinary Kidney Stone Clinic. Patients with a diagnosis of NDMD, at least one 24-hour urine collection, and one chemical stone analysis were included in the analysis. Calculi were classified as primarily metabolic or elevated pH. We assessed in clinical factors, demographics, and urine metabolites for differences between patients who formed primarily metabolic or elevated pH stones. RESULTS: Over a 16-year period, 100 patients with NDMD and nephrolithiasis were identified and 41 met inclusion criteria. Thirty percent (12 / 41) of patients had purely metabolic calculi. Patients with metabolic calculi were significantly more likely to be obese (median body mass index 30.3kg / m2 versus 25.9kg / m2), void spontaneously (75% vs. 6.9%), and have low urine volumes (100% vs. 69%). Patients who formed elevated pH stones were more likely to have positive preoperative urine cultures with urease splitting organisms (58.6% vs. 16.7%) and be hyperoxaluric and hypocitraturic on 24-hour urine analysis (37mg / day and 265mg / day versus 29mg / day and 523mg / day). CONCLUSIONS: Among patients with NDMD, metabolic factors may play a more significant role in renal calculus formation than previously believed. There is still a high incidence of carbonate apatite calculi, which could be attributed to bacteriuria. However, obesity, low urine volumes, hypocitraturia, and hyperoxaluria suggest an underrecognized metabolic contribution to stone formation in this population.

Trauma capacity in the central plateau department of Haiti.

BACKGROUND: Surgical burden is a large and neglected global health problem in low- and middle-income countries. With the increasing trauma burden, the goal of this study was to evaluate the trauma capacity of hospitals in the central plateau of Haiti. MATERIALS AND METHODS: The World Health Organization Emergency and Essential Surgical Care survey was adapted with a focus on trauma capacity. Interviewers along with translators administered the survey to key hospital staff. RESULTS: Seven hospitals in the region were surveyed. Of the hospitals surveyed, 3/7 had functioning surgical facilities. None of the hospitals had trauma registries. 71% of the hospitals had no formal trauma guidelines. 2/7 hospitals had a general surgeon available 100% of the time. All surgical facilities had oxygen cylinders available 100% of the time, but three of the primary level hospitals only had it available 51%-90% of the time. Intubation equipment was available at 57% of the facilities. Ventilators were only available in the operating room. Only the largest hospital had a computed tomography scanner. Other hospitals (66%) had a functioning x-ray machine 76%-90% of the time. Hospitals (57%) had an ultrasound machine. The most common reasons for referral were lack of appropriate facilities and supplies at the primary level care centers or lack of trained personnel at higher-level facilities. CONCLUSIONS: Trauma capacity in the central plateau of Haiti is limited. There is a great need for more personnel, trauma training at all staff levels, emergency care guidelines, trauma registries, and imaging equipment and training, specifically in ultrasonography. To accomplish this, coordination is needed between the Haitian government and local and international nongovernmental organizations.

Incidence and clinical characteristics of lower urinary tract symptoms as a presenting symptom for patients with newly diagnosed bladder cancer.

PURPOSE: The incidence of lower urinary tract symptoms (LUTS) as the sole presenting symptom for bladder cancer has traditionally been reported to be low. The objective of this study was to evaluate the prevalence and clinical characteristics of newly diagnosed bladder cancer patients who presented with LUTS in the absence of gross or microscopic hematuria. MATERIALS AND METHODS: We queried our database of bladder cancer patients at the Atlanta Veteran's Affairs Medical Center (AVAMC) to identify patients who presented solely with LUTS and were subsequently diagnosed with bladder cancer. Demographic, clinical, and pathologic variables were examined. RESULTS: 4.1% (14/340) of bladder cancer patients in our series presented solely with LUTS. Mean age and Charlson Co-morbidity Index of these patients was 66.4 years (range = 52-83) and 3 (range = 0-7), respectively. Of the 14 patients in our cohort presenting with LUTS, 9 (64.3%), 4 (28.6%), and 1 (7.1%) patients presented with clinical stage Ta, carcinoma in Situ (CIS), and T2 disease. At a median follow-up of 3.79 years, recurrence occurred in 7 (50.0%) patients with progression occurring in 1 (7.1%) patient. 11 (78.6%) patients were alive and currently disease free, and 3 (21.4%) patients had died, with only one (7.1%) death attributable to bladder cancer. CONCLUSIONS: Our database shows a 4.1% incidence of LUTS as the sole presenting symptom in patients with newly diagnosed bladder cancer. This study suggests that urologists should have a low threshold for evaluating patients with unexplained LUTS for underlying bladder cancer.

Predictors of high-intensity care at the end of life among older adults with solid tumors: A population-based study.

INTRODUCTION: High-intensity end-of-life (EoL) care can be burdensome for patients, caregivers, and health systems and does not confer any meaningful clinical benefit. Yet, there are significant knowledge gaps regarding the predictors of high-intensity EoL care. In this study, we identify risk factors associated with high-intensity EoL care among older adults with the four most common malignancies, including breast, prostate, lung, and colorectal cancer. MATERIALS AND METHODS: Using SEER-Medicare data, we conducted a retrospective analysis of Medicare beneficiaries aged 65 and older who died of breast, prostate, lung, or colorectal cancer between 2011 and 2015. We used multivariable logistic regression to identify clinical, demographic, socioeconomic, and geographic predictors of high-intensity EoL care, which we defined as death in an acute care hospital, receipt of any oral or parenteral chemotherapy within 14 days of death, one or more admissions to the intensive care unit within 30 days of death, two or more emergency department visits within 30 days of death, or two or more inpatient admissions within 30 days of death. RESULTS: Among 59,355 decedents, factors associated with increased likelihood of receiving high-intensity EoL care were increased comorbidity burden (odds ratio [OR]:1.29; 95% confidence interval [CI]:1.28-1.30), female sex (OR:1.05; 95% CI:1.01-1.09), Black race (OR:1.14; 95% CI:1.07-1.23), Other race/ethnicity (OR:1.20; 95% CI:1.10-1.30), stage III disease (OR:1.11; 95% CI:1.05-1.18), living in a county with >1,000,000 people (OR:1.23; 95% CI:1.16-1.31), living in a census tract with 10%-<20% poverty (OR:1.09; 95% CI:1.03-1.16) or 20%-100% poverty (OR:1.12; 95% CI:1.04-1.19), and having state-subsidized Medicare premiums (OR:1.18; 95% CI:1.12-1.24). The risk of high-intensity EoL care was lower among patients who were older (OR:0.98; 95% CI:0.98-0.99), lived in the Midwest (OR:0.69; 95% CI:0.65-0.75), South (OR:0.70; 95% CI:0.65-0.74), or West (OR:0.81; 95% CI:0.77-0.86), lived in mostly rural areas (OR:0.92; 95% CI:0.86-1.00), and had poor performance status (OR:0.26; 95% CI:0.25-0.28). Results were largely consistent across cancer types. DISCUSSION: The risk factors identified in our study can inform the development of new interventions for patients with cancer who are likely to receive high-intensity EoL care. Health systems should consider incorporating these risk factors into decision-support tools to assist clinicians in identifying which patients should be referred to hospice and palliative care.

High levels of IL-7 cause dysregulation of thymocyte development.

IL-7 signaling is required for thymocyte development and its loss has a severe deleterious effect on thymus function. Thymocyte-stromal cell interactions and other mechanisms tightly regulate IL-7 expression. We show that disruption of that regulation by over-expression of IL-7 inhibits T-cell development and promotes extensive B-cell lymphopoiesis in the thymus. Our data reveal that high levels of IL-7 negate Notch-1 function in thymocytes found in IL-7 transgenic mice and in co-culture with OP9-DL1 cells. While high levels of IL-7R are present on thymocytes, increased suppressor of cytokine signaling-1 expression blunts IL-7 downstream signaling, resulting in hypo-phosphorylation of proteins in the PI3K-Akt pathway. Consequently, GSK3ß remains active and inhibits Notch-1 signaling as observed by decreased Hes-1 and Deltex expression in thymic progenitors. This is the first demonstration that high levels of IL-7 antagonize Notch-1 signaling and suggest that IL-7 may affect T- versus B-lineage choice in the thymus.

Palliative care knowledge, attitudes, and experiences amongst patients with bladder cancer and their caregivers.

OBJECTIVES: Palliative care is underutilized amongst patients with bladder cancer despite guideline recommendations and known benefits. In order to uncover potential access barriers, we sought to describe patient and caregiver knowledge, attitudes and experiences surrounding palliative care. METHODS: We surveyed 272 patients with bladder cancer and their caregivers through the Bladder Cancer Advocacy Network Patient Survey Network. In addition to collecting demographic, socioeconomic, and clinical characteristics, previously studied and validated questionnaires on palliative care knowledge and beliefs were administered. Patients and caregivers were also queried regarding their experiences with palliative care consultation. RESULTS: Survey respondents demonstrated highly accurate knowledge of palliative care services. Attitudes and beliefs surrounding palliative care were overall positive. Caregivers demonstrated better knowledge and more positive beliefs of palliative care compared to patients. Despite an overall positive sentiment toward palliative care, only 9% of the cohort had palliative care consultation as part of their cancer treatment plan. Most patients with muscle-invasive or metastatic bladder cancer wished that palliative care had been discussed by their providers. CONCLUSIONS: A subset of bladder cancer patients possess accurate knowledge and positive beliefs of palliative care. Palliative care is infrequently discussed during the treatment of bladder cancer, with patients and their caregivers expressing desire for palliative care to be discussed more often. Provider education surrounding palliative care services is imperative to improving access for bladder cancer patients and caregivers.

Exploring knowledge, perspectives, and misperceptions of palliative care: A mixed methods analysis.

OBJECTIVES: To better understand palliative care knowledge and beliefs of patients with stage II or greater bladder cancer and their caregivers. SUBJECTS AND METHODS: Participants were primarily patients diagnosed with muscle-invasive or locally advanced bladder cancer. All were encouraged to enroll with a caregiver (defined as the individual who most closely assists with a patient's care). Participants completed a survey and semistructured interview. Applied thematic analysis techniques were used to analyze the interview data. In total, we recruited 16 dyads, 11 patients who participated alone, and 1 caregiver who participated alone. RESULTS: Patients and caregivers had high levels of palliative care knowledge and there was no difference in baseline knowledge. Palliative care receptivity was also high, with most participants stating that they would be "very likely" to consider palliative care for themselves or a loved one. However, based on the analysis of multiple-choice palliative care questions and interview transcripts, many participants lacked a nuanced understanding of palliative care and harbored many common misconceptions of the basic tenants. Five main themes emerged related to palliative care: (1) Participants have a general lack of awareness of it, (2) Participants associate it with hospice and death, (3) Participants view it as primarily emotional or psychological support, (4) Participants believe it is for patients without a strong support system, and (5) Participants believe it is for people who have "given up." CONCLUSIONS: High educational attainment and baseline palliative care knowledge did not preclude the most common misperceptions related to palliative care. These study results indicate that patients need clearer counseling regarding the definition, goals, benefits, and availability of palliative care.

Predicting Limited Survival Following Inguinal Lymph Node Dissection in Penile Cancer: Should We Revisit the Goals of Care?

OBJECTIVE: Patients with advanced penile squamous cell cancer have a poor prognosis and can benefit from early palliative care consultation. We built a model to identify those patients most likely to benefit. METHODS: Patients with penile squamous cell cancer undergoing inguinal lymph node dissection were identified from the National Cancer Database (NCDB) and a multi-institutional international dataset (INT). A multivariable Cox proportional hazards model for overall survival (OS) was developed using the NCDB and applied to the INT dataset. Parameters were used to make receiver operating characteristic (ROC) curves. ROC-related criteria were optimized to identify a predictive probability cut point and dichotomize patients from INT into risk groups for limited OS of <6 and <12 months. RESULTS: NCDB had 860 deaths; 105 (5%) at 6 months and 296 (15%) at 12 months. INT had 257 deaths; 56 (8%) at 6 months and 124 (18%) at 12 months. Limited OS was associated with older age, greater T and N stage, and fewer lymph nodes removed. Optimized ROC criteria using the OS <6 months curve best dichotomized INT patients into high-risk group with median OS of 24 months (95% CI 18-34) and low-risk group with median OS of 174 months (95% CI 120-NE). CONCLUSION: We developed a simple model that could be used as a screening tool for early palliative care referral.

Is There a Role for Palliative Services and Supportive Care in Managing Advanced Penile Cancer?

OBJECTIVES: We aim to review the benefits of palliative care, describe why a palliative approach to care is needed for patients with advanced penile squamous cell carcinoma and propose ways in which oncology nurses can improve access to and provision of palliative care. DATA SOURCES: A review of the literature was performed and identified a range of randomized trials and systematic reviews regarding the benefits of palliative care in this patient group. Cohort studies of patients with penile cancer were used to describe the psychosocial and physical disease burden of penile cancer. CONCLUSION: Throughout each phase of penile cancer and its treatment, oncology nurses can engage in care that goes beyond cancer-directed treatments to address the whole person, thereby improving quality of life by delivering person-centered palliative care in line with individual needs. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses are in key positions to explore many concerns that patients with penile cancer have for themselves or their caregivers. Through speaking directly with patients and caregivers, oncology nurses can uncover sources of distress, assess for unmet needs, and advocate for improved primary palliative care or early referral to specialty palliative care teams.

Incorporating palliative care principles to improve patient care and quality of life in urologic oncology.

Palliative care - specialized healthcare focused on improving quality of life for patients with serious illnesses - can help urologists to care for patients with unmet symptom, coping and communication needs. Society guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend incorporating palliative care into standard oncological care, based on multiple randomized trials demonstrating that it significantly improves physical well-being, patient satisfaction and goal concordant care. Misconceptions regarding the objective and ideal timing of palliative care are common; a key concept is that palliative care and treatments seeking to cure or prolong life are not mutually exclusive. Urologists are well positioned to champion the integration of palliative care into surgical urologic oncology and should be aware of palliative care guidelines, indications for palliative care use and how the field of urologic oncology can adopt best practices.

High-intensity end-of-life care among Medicare beneficiaries with bladder cancer.

OBJECTIVES: To quantify the proportion of patients receiving high-intensity end-of-life care, identify associated risk factors, and assess how receipt of palliative care impact end-of-life care; as the delivery of such care, and how it relates to palliative care, has not been reported in bladder cancer SUBJECTS AND METHODS: We conducted a retrospective cohort study of patients with bladder cancer who died within 1 year of diagnosis using Surveillance, Epidemiology, and End Results linked Medicare data. The primary outcome was a composite measure of high-intensity end-of-life care (>1 hospital admission, >1 ED visit, or ≥1 ICU admission within the last month of life; receipt of chemotherapy within the last 2 weeks of life; or acute care in-hospital death). Secondary outcomes included the use of such care over time and any association with the use of palliative care. A generalized linear mixed model assessed for independent determinants. RESULTS: Overall, 45% of patients received high-intensity end-of-life care. This proportion decreased over time. Patients receiving high-intensity care had higher rates of comorbidities, advanced bladder cancer, and nonbladder cancer cause of death. These patients more often received palliative care but, compared to those not receiving high-intensity care, this occurred farther removed from bladder cancer diagnosis and closer to death. CONCLUSIONS: Nearly half of Medicare beneficiaries with bladder cancer who die within 1 year of diagnosis receive high-intensity care at the end of life. Palliative care was seldom used and only very near the time of death.

Resurrecting immortal-time bias in the study of readmissions.

OBJECTIVE: To compare readmission rates as measured by the Centers for Medicare and Medicaid Services and the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) methods. DATA SOURCES: 20 percent sample of national Medicare data for patients undergoing cystectomy, colectomy, abdominal aortic aneurysm (AAA) repair, and total knee arthroplasty (TKA) between 2010 and 2014. STUDY DESIGN: Retrospective cohort study comparing 30-day readmission rates. DATA COLLECTION/EXTRACTION METHODS: Patients undergoing cystectomy, colectomy, abdominal aortic aneurysm repair, and total knee arthroplasty between 2010 and 2014 were identified. PRINCIPAL FINDINGS: Cystectomy had the highest and total knee arthroplasty had the lowest readmission rate. The NSQIP measure reported significantly lower rates for all procedures compared to the CMS measure, which reflects an immortal-time bias. CONCLUSIONS: We found significantly different readmission rates across all surgical procedures when comparing CMS and NSQIP measures. Longer length of stay exacerbated these differences. Uniform outcome measures are needed to eliminate ambiguity and synergize research and policy efforts.

Rate and Determinants of Completing Neoadjuvant Chemotherapy in Medicare Beneficiaries With Bladder Cancer: A SEER-Medicare Analysis.

OBJECTIVE: To determine the rate and determinants of neoadjuvant chemotherapy noncompletion in patients with muscle-invasive bladder cancer. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified all patients who underwent cystectomy between 2008-2013 and received chemotherapy within 6 months. Of these, 594 patients received neoadjuvant chemotherapy, defined as the presence of a claim for chemotherapy within the 180 days preceding cystectomy. Our primary outcome was noncompletion of neoadjuvant chemotherapy. We determined regimen-specific cut points for noncompletion based on clinical trials and national guidelines. RESULTS: Over the study period, 174 of 594 patients (29%) did not complete neoadjuvant chemotherapy. Noncompleters and completers received a median interquartile range of 4.4 (3.0-8.0) and 10.0 (7.7-11.2) weeks of chemotherapy, respectively. A total of 391 (66%) patients received a cisplatin-based regimen and 203 (34%) patients received an alternative regimen, with 27% and 33% not completing chemotherapy, respectively. After adjusting for covariates, age and geographic region were independently associated with failing to complete chemotherapy. CONCLUSION: Nearly 30% of patients who received neoadjuvant chemotherapy did not complete their regimen. Advanced age and nonclinical factors, such as practice patterns in certain geographic regions, may influence a patient's likelihood of successfully completing chemotherapy.

Effect of multimodal analgesia with paravertebral blocks on biochemical recurrence in men undergoing open radical prostatectomy.

BACKGROUND: Recent studies suggest that anesthetic technique during radical prostatectomy for prostate cancer may affect recurrence or progression. This association has previously been investigated in series that employ epidural analgesia. The objective of this study is to determine the association between the use of a multimodal analgesic approach incorporating paravertebral blocks and risk of biochemical recurrence following open radical prostatectomy. PATIENTS AND METHODS: Using a prospective database of 3,029 men undergoing open radical prostatectomy by a single surgeon, we identified 2,909 men who received no neoadjuvant androgen deprivation and had at least 1 year of follow up. We retrospectively compared patients who received general analgesia with opioid analgesia (1999-2003, n = 662) to those who received general analgesia with multimodal analgesia incorporating paravertebral blocks (2003-2014, n = 2,247). The primary outcome was time to biochemical recurrence. Biochemical recurrence-free interval was assessed using the Kaplan-Meier technique and compared using a multivariate Cox-proportional hazards regression model. RESULTS: In total, 395 patients (14%) experienced biochemical recurrence following radical prostatectomy, including 265 (12%) who received multimodal analgesia and 130 (20%) who did not (adjusted P = 0.27). After adjusting for age, race, body mass index, preoperative prostate specific antigen, grade, stage, perineural invasion, margin status, percent of tumor in the gland, and diameter of the dominant nodule, there was no difference in recurrence-free interval between groups (HR = 0.92, 95% CI: 0.73-1.17). CONCLUSION: Use of a multimodal analgesic approach incorporating paravertebral blocks is not associated with a reduced risk of biochemical recurrence following radical prostatectomy.

Urologic Phenotype and Patterns of Care in Patients With Megacystis Microcolon Intestinal Hypoperistalsis Syndrome Presenting to a Major Pediatric Transplantation Center.

OBJECTIVE: To describe the phenotype, referral pattern, and trends of urologic management for children with megacystis microcolon intestinal hypoperistalsis syndrome. MATERIALS AND METHODS: We performed a retrospective review of all patients with megacystis microcolon intestinal hypoperistalsis syndrome treated at a large tertiary children's medical center over a 14-year period. Our primary outcomes included the rate of urology referral, urodynamic characteristics of bladder function, and the proportion of patients managed with clean intermittent catheterization. RESULTS: Twenty-six patients were evaluated at our institution with a median age at presentation of 1.3 years (73% female, 19 of 26). Most patients presented for intestinal transplantation evaluation and were dependent on parenteral nutrition. Megacystis was diagnosed prenatally in 15 patients and postnatally in 11 patients. Twenty patients (77%, 20 of 26) were evaluated by a pediatric urologist. Six patients (23%, 6 of 26) had varying degrees of vesicoureteral reflux. Early bladder management consisted of clean intermittent catheterization in 13 patients and vesicostomy in 8 patients. CONCLUSION: Megacystis microcolon intestinal hypoperistalsis syndrome is a severe form of intestinal failure and bladder atony with substantial urologic morbidity. Parents should be counseled accordingly and prompt urologic consultation should be included in the multidisciplinary approach to these complex patients.