Determinants of neoadjuvant chemotherapy for urothelial muscle-invasive bladder cancer: Does location matter?

INTRODUCTION: Bladder cancer care has been increasingly concentrated in high-volume metropolitan medical centres (ie, "regionalisation" of care). We aimed to assess the potential role of geographic factors, including facility region and distance to treatment centre, as determinants of neoadjuvant chemotherapy (NAC) delivery in patients with non-metastatic urothelial muscle-invasive bladder cancer (MIBC) using nationally representative data from the United States. METHODS: We queried the National Cancer Database to identify patients with cT2-cT4a, N0M0 urothelial MIBC who underwent radical cystectomy (RC) from 2006 to 2015. Patients who received radiation therapy, single-agent chemotherapy, adjuvant chemotherapy or systemic therapies other than multi-agent chemotherapy were excluded. Multivariate logistic regression analysis was performed to identify independent predictors of receiving NAC. RESULTS: A total of 5986 patients met the criteria for inclusion, of whom 1788 (29.9%) received NAC and 4108 received RC alone. Younger age, increased Charlson-Deyo score, increased cT stage, increased annual income, increased distance from cancer treatment centre, treatment at an Academic Research Program or Integrated Network Cancer Program and a later year of diagnosis were independently predictive of NAC receipt. Older age, Medicare insurance and treatment in the East South Central or West South Central regions were independently associated with decreased odds of NAC receipt. CONCLUSIONS: Distance to treatment centre and United States geographic region were found to affect the likelihood of NAC receipt independently of other established predictors of success in this quality-of-care metric. Access to transportation and related resources merits consideration as additional pertinent social determinants of health in bladder cancer care.

Primary Small Cell Carcinoma of the Kidney: Disease Characteristics and Treatment Outcomes.

Background: Primary small cell carcinoma of the kidney (PSCCK) is exceedingly rare and data on disease characteristics and outcomes are sparse. This study examines a nationally-representative cancer registry to better characterize PSCCK. Methods: We queried the National Cancer Database to identify patients with histology-confirmed PSCCK from 2004 to 2015. Adjusted Cox proportional hazards regression and Kaplan-Meier analyses were employed to assess predictors of mortality and estimate median survival time, respectively. Results: A total of 110 patients were included (47:53% female:male, 77% ≥60 years of age, 86% Caucasian). Significant predictors of mortality included female sex, age 60-69 years, treatment at an Integrated Network Cancer Program, stage cM1, and lack of surgical and chemoradiotherapy treatment. Independent protective factors were high socioeconomic status and treatment at an Academic Research Program. The estimated median overall survival time was 9.31 (95% CI 7.28-10.98) months for all patients. No differences in estimated survival time were observed across individual treatment modalities among those patients who underwent treatment (p = 0.214). Conclusions: PSCCK is an aggressive malignancy with a median survival time of less than one year. Future studies that correlate clinical tumor staging with specific treatment modalities are needed to optimize and individualize management.

Phenotyping the Association between Nocturia and Hypertension: A Systematic Review and Meta-Analysis.

PURPOSE: The association between nocturia and hypertension has been widely reported yet remains poorly characterized, precluding a more refined understanding of blood pressure as it relates to the clinical urology setting. We synthesized current evidence on the relationship between nocturia and hypertension as a function of nocturia severity, age, gender, race, body mass index and diuretic use. MATERIALS AND METHODS: We searched PubMed®, EMBASE® and Cochrane databases for studies published up to May 2020. Random effects meta-analyses were performed to identify pooled odds ratios for nocturia given the presence of hypertension. Meta-regression and subgroup analyses were performed to identify differences across study samples. RESULTS: Of 1,193 identified studies, 25 met the criteria for inclusion. The overall pooled OR for the association of nocturia with hypertension was 1.25 (95% CI 1.21-1.28, p <0.001). Pooled estimates were 1.20 (1.16-1.25, p <0.001) and 1.30 (1.25-1.36, p <0.001) using a 1-void and 2-void cutoff for nocturia, respectively (p <0.001 between cutoffs). The association was more robust in patient-based (1.74 [1.54-1.98], p <0.001) vs community-based (1.24 [1.24-1.29], p <0.001) study samples (p <0.001). The association was stronger in females compared to males (1.45 [1.32-1.58] vs 1.28 [1.22-1.35], p <0.001), and Black (1.56 [1.25-1.94]) and Asian (1.28 [1.23-1.33]) vs White subgroups (1.16 [1.08-1.24]; p <0.05 for both). No effect was observed for age or body mass index. Evidence on diuretics was limited. CONCLUSIONS: Hypertension is associated with a 1.2-fold to 1.3-fold higher risk of nocturia. This association is more robust at a higher nocturia cutoff, in patient-based study samples, among females and in Black and Asian patients, but unrelated to age or body mass index.

Determinants of adequate lymph node dissection following neoadjuvant chemotherapy in patients with urothelial muscle-invasive bladder cancer: results from the National Cancer Database.

PURPOSE: Recent literature has separately identified multiple determinants of the use of neoadjuvant chemotherapy (NAC) and adherence to pelvic lymph node dissection (PLND) guidelines in the management of non-metastatic bladder cancer. However, such NAC/PLND analyses tend not to account for the other modality, despite the fact that NAC may impact the extent of dissectible lymph nodes. We aimed to determine the predictors of adequate PLND in patients with non-metastatic urothelial muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC) following receipt of NAC. METHODS: We queried the National Cancer Database to identify patients from 2006-2015 with cT2-cT4a/N0M0 urothelial MIBC who underwent RC and were pre-treated with NAC. Multivariate logistic regression analysis was used to identify independent predictors of undergoing an adequate PLND (defined as > 8 nodes). RESULTS: A total of 1518 patients met the criteria for inclusion (74.4% underwent adequate PLND). Adequate PLND was associated with treatment at an academic research facility (OR 2.762 [95% CI 2.119-3.599], p < 0.001). The likelihood of adequate PLND was significantly decreased in patients of older age (0.607 [0.441-0.835], p = 0.002 for age 70-79 years; 0.459 [0.245-0.860], p = 0.015 for age ≥ 80 years), a Charlson-Deyo score of 1 (0.722 [0.537-0.971], p = 0.031), and those who were uninsured (0.530 [0.292-0.964], p = 0.038). CONCLUSIONS: Established predictors of PLND may not necessarily be generalizable to all patients undergoing treatment for bladder cancer. The interplay between PLND and NAC merits further study, particularly in view of recent literature calling into question the survival benefit of PLND in patients pre-treated with NAC.

Impact of neuraxial analgesia on outcomes following radical cystectomy: A systematic review.

Radical cystectomy (RC) is associated with significant morbidity. Neuraxial analgesia is recommended by enhanced recovery after surgery guidelines, but largely supported by evidence extrapolated from colorectal surgery outcomes. We synthesized current evidence regarding short- and long-term outcomes associated with neuraxial analgesia versus patient controlled non-neuraxial analgesia following RC. PubMed, Embase, and Cochrane databases were searched for relevant studies published up to May 2020. Studies reporting complications, length of stay (LOS), pain score, opioid usage within 72 hours, overall survival, cancer-specific survival, and recurrence rate were included. Of 550 identified studies, 9 met criteria for inclusion. Four studies demonstrated a higher percentage of 90-day complications in the neuraxial analgesia cohort. Out of 6 studies reporting information regarding LOS, 4 demonstrated no improvement in LOS in the neuraxial cohort. A reduction in 72 hours post-RC opioid usage was observed in 2 out of 3 studies with available data. Information regarding post-RC pain scores were variable up to 3 days post-RC. One out of 2 studies with available data reported a significant association between neuraxial analgesia and an earlier time to recurrence. No significant associations were seen with respect to overall survival or cancer-specific survival. A majority of low-to-moderate quality evidence demonstrates neuraxial analgesia is associated with a higher rate of complications, variable information regarding pain control, no improvements in LOS, and no significant association with long-term oncological outcomes. Further research regarding the incorporation of nonopiate-based analgesic modalities into RC ERAS protocols is warranted.

Sodium restriction improves nocturia in patients at a cardiology clinic.

This study aims to determine whether dietary sodium restriction counseling decreases nocturnal voiding frequency in cardiology patients with concomitant nocturia. Patients who had established care at a cardiology clinic from 2015 to 2018 reporting ≥1 average nocturnal void(s) underwent a comprehensive sodium intake interview by their cardiologist, who provided them with individualized strategies for dietary sodium reduction and assessed adherence at follow-up. Average nocturnal voiding frequency and dietary adherence were documented in the medical record. A nocturia database was compiled for retrospective analysis. A total of 74 patients were included. Patients considered to be adherent with dietary sodium restriction at follow-up (n = 56) demonstrated a decrease in median nocturia frequency (2.5 [2.3-3.0] vs 1.0 [1.0-2.0] voids, P < .001). Among nonadherent patients (n = 18), median nocturia frequency did not significantly change from baseline to follow-up (2.0 [1.5-3.8] vs 2.0 [1.5-4.8] voids, P = .423). Median changes were significantly different between the adherent and nonadherent groups (P < .001). Examination of second follow-up available from 37 patients showed a continued effect. In conclusion, adherence with dietary sodium counseling appears to improve nocturia. Accordingly, dietary modification may represent an important adjunct therapy to lifestyle and pharmacologic interventions for decreasing nocturia frequency. Reduction in nocturnal voiding frequency may also reflect an additional benefit of dietary sodium restriction in accordance with best practice standards for cardiovascular disease.

Differential Nocturnal Diuresis Rates Among Patients with and Without Nocturnal Polyuria Syndrome.

BACKGROUND: The mechanism of nocturnal polyuria (NP), a leading cause of nocturia, is poorly understood. OBJECTIVE: To characterize NP in terms of diuresis rate changes before and after the first nocturnal awakening. DESIGN, SETTING, AND PARTICIPANTS: A frequency-volume chart (FVC) database of 773 entries from 440 veterans treated at a Veterans Affairs urology clinic was analyzed. The first FVCs completed by male patients aged ≥18 years with two or more nocturnal voids were included. Patients were excluded if they were taking diuretics or had sleep apnea, heart failure, edema, kidney disease, or diabetes insipidus. The 130 included individuals were divided into two cohorts: patients with NP and patients below this threshold. Analyses were performed using two different cutoffs for NP: nocturnal urine production (NUP) >90ml/h and nocturnal polyuria index (NPi) >0.33. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We compared "early nocturnal diuresis rate" (ENDR; first nocturnal voided volume/length of first uninterrupted sleep period), "late nocturnal diuresis rate" (LNDR; remaining nocturnal urine volume/remaining hours of sleep), and diurnal diuresis rate (daytime urine volume/hours awake) in patients with the nocturnal polyuria syndrome (NPS). RESULTS AND LIMITATIONS: Within groups, there were significant differences between ENDR and LNDR for NPS patients at NUP >90ml/h (152 vs 120ml/h, p=0.02) and NPi >0.33 (120 vs 91ml/h, p=0.02) but not for those without NPS at NUP ≤90ml/h (60 vs 59ml/h, p=0.29) or NPi ≤0.33 (75 vs 75ml/h, p=0.25). Limitations include retrospective design, single institution participation, and small sample size. CONCLUSIONS: There exists a significant drop-off in nocturnal diuresis rate after the time of first awakening that is unique to patients with NPS. The large volume of urine produced in the early hours of sleep may provide the specific substrate for short-acting antidiuretics approved for use in patients with nocturia owing to NPS. PATIENT SUMMARY: We analyzed adult males diagnosed with nocturnal polyuria syndrome to determine how their rate of urine production changed throughout the night. Our finding that these individuals produce urine at the highest rate in the early hours of sleep suggests that they may benefit from pharmaceuticals specifically designed to reduce urine production during this period.

Current guidelines and treatment paradigms for nocturnal polyuria: A "NEW" disease state for US physicians, patients and payers.

Nocturia is one of the most bothersome symptoms encountered in urology, and its prevalence rises with age. Causes include both urological and non-urological aetiologies, often in combination. The effects of nocturia on a patient's quality of life can be detrimental. The initial approach to managing this condition includes appropriately classifying nocturia based on the results of a 24-hour bladder diary. Broadly, the categories under which nocturia can be classified include: low nocturnal or global bladder capacity, nocturnal polyuria, global polyuria and mixed.Based on the type of nocturia and possible underlying causes, clinicians can appropriately discuss with patients the treatment plans that may include a combination of behavioural, pharmacologic, and invasive therapy. The available literature on the management of nocturia was reviewed. Findings were incorporated into a practice-based approach for its workup and treatment.

Deflate-gate: Conservative Management of a Large Ruptured Hydrocele.

A hydrocele is a common cause of intrascrotal swelling that results when fluid accumulates between the parietal and visceral layers of the tunica vaginalis. Over time, fluid may collect to form a massive hydrocele and result in significant discomfort for the patient. In this case report, we present a rare event of a 28-year-old gentleman with a documented massive hydrocele measuring 14.1 × 8.9 cm who ruptured his hydrocele during sexual intercourse. We expectantly managed the patient's ruptured hydrocele and encountered no complications throughout the course of his recovery.