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.

Assessing the role of race in pathological upstaging of renal cell carcinoma: Results from the National Cancer Database.

PURPOSE: Pathologic upstaging in renal cell carcinoma (RCC) is common and confers a significant risk of poor surgical and survival outcomes. Preoperative predictors of upstaging are of great clinical relevance but empirical evidence specific to racial minorities remains scarce. METHODS: National Cancer Database (NCDB) analysis of T3a-specific upstaging among White, African-American, Hispanic and Asian Pacific Islander (API) patients with AJCC cT1N0M0 RCC who underwent partial or radical nephrectomy between 2010 and 2015. Independent preoperative predictors of tumour upstaging were identified using multivariate logistic regression analyses. RESULTS: A total of 81 002 patients met the criteria for inclusion (5.6% T3a-specific upstaging). Increased age, increased Charlson-Deyo comorbidity index, clinical stages cT1b and unspecified cT1, and increased Fuhrman nuclear grade were identified as independent risk factors for upstaging. Independent protective factors for upstaging were younger age, female sex, African-American race and papillary, chromophobe, and unspecified RCC histologic subtypes. Significant risk factors and protective factors within individual racial subgroups were highly consistent with those observed in the overall study sample. All independent factors identified on race-specific subgroup analyses were significant in the same direction relative to the overall study sample. Variables found to be non-significant in the overall study sample remained non-significant across all racial subgroup analyses. CONCLUSION: The present study of nationally representative data found no clinically significant differences in upstaging risk across individual racial subgroups relative to the overall study sample. Preoperative factors that can be used to predict pT3a-specific tumour upstaging in CT1N0M0 RCC likely persist across different racial groups.

Racial Differences in Incident Genitourinary Cancer Cases Captured in the National Cancer Database.

Background and Objectives: The National Cancer Database (NCDB) captures nearly 70% of all new cancer diagnoses in the United States, but there exists significant variation in this capture rate based on primary tumor location and other patient demographic factors. Prostate cancer has the lowest coverage rate of all major cancers, and other genitourinary malignancies likewise fall below the average NCDB case coverage rate. We aimed to explore NCDB coverage rates for patients with genitourinary cancers as a function of race. Materials and Methods: We compared the incidence of cancer cases in the NCDB with contemporary United States Cancer Statistics data. Results: Across all malignancies, American Indian/Alaskan Natives subjects demonstrated the lowest capture rates, and Asian/Pacific Islander subjects exhibited the second-lowest capture rates. Between White and Black subjects, capture rates were significantly higher for White subjects overall and for prostate cancer and kidney cancer in White males, but significantly higher for bladder cancer in Black versus White females. No significant differences were observed in coverage rates for kidney cancer in females, bladder cancer in males, penile cancer, or testicular cancer in White versus Black patients. Conclusions: Differential access to Commission on Cancer-accredited treatment facilities for racial minorities with genitourinary cancer constitutes a unique avenue for health equity research.

Treatment delays from transfers of care and their impact on breast cancer quality measures.

PURPOSE: Despite delays between diagnosis and surgery adversely affecting survival, patients frequently transfer their breast cancer care between institutions. This study was performed to assess the prevalence and effect of such transfers of care (TsOC) on the time to surgery, and its impact on current time-dependent breast cancer quality metrics at Commission on Cancer (CoC) and National Accreditation Program for Breast Centers (NAPBC)-accredited institutions. METHODS: Patients having non-metastatic invasive breast cancer diagnosed between 2006 and 2015 at CoC and NAPBC centers ("reporting facilities") in the National Cancer Database were reviewed. TsOC refer to transferring into or out of a reporting facility between diagnosis and surgery. RESULTS: Among 622,793 patients, 36.6% of patients transferred care. TsOC add 7.3, 7.8, 8.7, and 9.8 days in time to surgery, chemotherapy, radiotherapy, and endocrine therapy, respectively (p's < 0.0001). On multivariable analysis, the odds of surgery occurring > 90 days from diagnosis were greatest for patients undergoing unilateral or bilateral mastectomy, Black or Hispanic patients, and those having TsOC (ORs > 1.73, p's < 0.0001). TsOC increase the odds of non-compliance, per patient, for chemotherapy, radiotherapy and endocrine therapy time-dependent measures by 65.4%, 25.6%, and 56.5%, respectively (p < 0.0001). CONCLUSIONS: TsOC for newly diagnosed breast cancers to or from an accredited facility result in delays in time to surgery which can affect compliance with time-dependent quality measures. Facilities frequently receiving transferred patients may be most adversely affected. Although non-compliance with these quality measures is low, institutions and accrediting bodies should be aware of these associations in order to comply with time-dependent standards.

Comparison of nocturia etiology in black and white male patients.

INTRODUCTION: Much of what is known about the etiology of nocturia (i.e., nocturnal polyuria [NP], small bladder capacity [SBC], etc.) at the population level stems from the Krimpen study, which enrolled aging males from a homogenous municipality in the Netherlands. Given the higher prevalence of benign prostatic hyperplasia and overactive bladder in black versus white males in population research, we aim to test the hypothesis that black males seeking treatment for lower urinary tract symptoms (LUTS) are more likely to have nocturia owing to SBC. MATERIALS AND METHODS: We retrospectively analyzed 24 hour frequency-volume charts (FVCs) completed by males seeking treatment for LUTS at a Veterans Affairs urology clinic from 2008-2016. Patients were included if they were ≥ 18 years, identified as either Caucasian or African American, and had a complete baseline FVC showing ≥ 1 nocturnal void. Patients were stratified by race and classified as having nocturia owing to SBC (defined by a maximum voided volume < 200 mL or a nocturnal bladder capacity index > 1.3); NP (defined by a nocturnal polyuria index > 0.33); 'mixed' (SBC + NP); or 'other' (neither SBC nor NP). RESULTS: Between white and black patients, 28 (24%) versus 28 (26%) had NP, 32 (27%) versus 33 (30%) had SBC, and 35 (30%) versus 30 (28%) had mixed nocturia. Overall, there was no difference in distribution of underlying etiology by race (p = 0.51). CONCLUSIONS: Our results demonstrate no difference in the etiology of nocturia between black and white males. Accordingly, race should not play a role in the evaluation of patients seeking treatment for nocturia.

Axillary Surgery for Early-Stage, Node-Positive Mastectomy Patients and the Use of Postmastectomy Chest Wall Radiation Therapy.

BACKGROUND: We examined axillary surgery in mastectomy patients with tumor-positive nodes and how the type of axillary surgery impacted use of postmastectomy chest wall radiation therapy (PMRT). METHODS: Using the National Cancer Data Base, we selected patients with AJCC cT1/T2c N0 breast cancer with one to three tumor-positive lymph nodes treated between 2013 and 2014. Type of axillary surgery was analyzed using the FORDS scope of regional lymph node surgery variable. Multivariable logistic regression modeling was used to identify independent predictors associated with SNB alone and the use of PMRT. RESULTS: Of 8089 patients, 2482 (30.7%) underwent SNB alone, 1339 (16.6%) underwent axillary dissection (ALND) alone, and 4268 (52.7%) underwent SNB followed by ALND. Fifty-seven percent of patients with micrometastases underwent SNB alone compared with 22.6% of patients with macrometastases. Independent predictors of SNB alone for patients with micrometastases were African American race, number of nodes positive, and PMRT. For patients with macrometastases, age, facility type and location, and PMRT were independent predictors for SNB alone. Of 2449 patients who underwent SNB alone, 1538 (62.8%) had no PMRT, 261 (10.7%) had PMRT alone, and 650 (26.5%) had PMRT with regional nodal irradiation. Patients undergoing SNB alone were 1.70 times [96% confidence interval (CI) 1.45-2.00] more likely to undergo PMRT than upfront ALND and 1.51 times (96% CI 1.34-1.71) more likely than SNB followed by ALND. CONCLUSIONS: Surgeons are omitting completion ALND in a third of early-stage, node-positive mastectomy patients. SNB alone patients are more likely to undergo PMRT than patients undergoing ALND.

Minimally Invasive Adrenalectomy for Adrenocortical Carcinoma: Five-Year Trends and Predictors of Conversion.

BACKGROUND: Adrenocortical carcinoma (ACC) is rare but often fatal. Surgery offers the only chance of cure. As minimally invasive (MI) procedures for cancer become common, their role for ACC is still debated. We reviewed usage of MI approaches for ACC over time and risk factors for conversion using a large national database. METHODS: ACC patients with localized disease were identified in the National Cancer Data Base from 2010 to 2014. A retrospective review examined trends in the surgical approach over time. Patient demographics, surgical approach, and tumor characteristics between MI, open, and converted procedures were compared. RESULTS: 588 patients underwent adrenalectomy for ACC, of which 200 were minimally invasive. From 2010 to 2014, MI operations increased from 26 to 44% with robotic procedures increasing from 5 to 16%. The use of MI operations compared to open was not different based on facility type (p = 0.40) or location (p = 0.63). MI tumors were more likely to be confined to the adrenal (p < 0.001) but final margin status was not different (p = 0.56). Conversion was performed in 38/200 (19%). Average tumor size was 10.2 cm in the converted group compared to 8.6 cm in the MI group (p = 0.09). There was no difference in extent of disease (p = 0.33), margin status (p = 0.12), or lymphovascular invasion (p = 0.59) between MI and converted procedures. Tumor size > 5 cm was the only significant predictor of conversion (p = 0.04). No patients with pathologic stage I disease required conversion (0/19). CONCLUSIONS: The frequency of MI approaches for ACC is increasing. In the final year of the study, 44% of adrenalectomies were MI. Size > 5 cm was the only significant predictor of conversion.

CONCORDANCE OF PRE-OPERATIVE CLINICAL STAGE WITH PATHOLOGIC STAGE IN PATIENTS ≥45 YEARS OLD WITH WELL-DIFFERENTIATED THYROID CANCER.

OBJECTIVE: Clinical stage (cStage) in thyroid cancer determines extent of surgical therapy and completeness of resection. Pathologic stage (pStage) is an important determinant of outcome. The rate of discordance between clinical and pathologic stage in thyroid cancer is unknown. METHODS: The National Cancer Data Base was queried to identify 27,473 patients ≥45 years old with cStage I through IV differentiated thyroid cancer undergoing surgery from 2008-2012. RESULTS: There were 16,286 (59.3%) cStage I patients; 4,825 (17.6%) cStage II; 4,329 (15.8%) cStage III; and 2,013 (7.3%) cStage IV patients. The upstage rate was 15.1%, and the downstage rate was 4.6%. For cStage II, there was a 25.5% upstage rate. The change in cStage was a result of inaccurate T-category in 40.8%, N-category in 36.3%, and both in 22.9%. On multivariate analysis, the patients more likely to be upstaged had papillary histology, tumors 2.1 to 4 cm, total thyroidectomy, nodal surgery, positive margins, or multifocal disease. Upstaged patients received radioiodine more frequently (75.3% vs. 48.1%; P<.001). CONCLUSION: Approximately 20% of cStage is discordant to pStage. Certain populations are at risk for inaccurate staging, including cT2 and cN0 patients. Upstaged patients are more likely to receive radioactive iodine therapy. ABBREVIATIONS: CI = confidence interval; cStage = clinical stage; DTC = differentiated thyroid cancer; NCDB = National Cancer Data Base; OR = odds ratio; pStage = pathologic stage; RAI = radioactive iodine.

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.

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.

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.

Overnight Urge Perception in Nocturia Is Independent of Depression, PTSD, or Anxiety in a Male Veterans Administration Population.

STUDY OBJECTIVES: The goal of this study was to compare the urge perception associated with nocturnal voiding at the time of voiding in individuals with and without depression, posttraumatic stress disorder (PTSD), or anxiety diagnoses to test the hypothesis that patients with such diagnoses are more likely to experience insomnia-driven convenience voiding during the sleep period. METHODS: A database of voiding diaries with urge perception grades (UPGs) from 429 adult males seeking treatment for nocturia at a Veterans Affairs-based urology clinic was analyzed. The UPG categorizes perception for urinating from 0 (out of convenience) to 4 (desperate urge). Diaries completed by males age 18 years and older showing ≥ 2 nocturnal voids were included. Those included (n = 178) were divided into two cohorts based on the presence (n = 62) or absence (n = 116) of one or more previously established mental health diagnoses (depression, PTSD, or anxiety). The chi-square test was used to determine significance between groups. RESULTS: Patients with a mental health diagnosis were more likely to report convenience voiding compared to those without depression, PTSD, or anxiety (14.5% versus 0.8%, P < .01). However, most voids in both groups were associated with the perception of urinary urgency. There were no differences in urinary volumes or hourly rates of urine production between the groups. CONCLUSIONS: A relatively small subset of urology patients experience nocturnal voiding because they are awake for reasons other than the urge to void. Mental health factors had a substantial, albeit minimal, effect. Most nocturia reflects urgency to urinate rather than voiding by convenience.

Liver transplant offers a survival benefit over margin negative resection in patients with small unifocal hepatocellular carcinoma and preserved liver function.

BACKGROUND: Studies comparing orthotopic liver transplantation to margin negative resection for patients with small unifocal hepatocellular carcinoma have not controlled for degree of cirrhosis. METHODS: The National Cancer Database was used to identify patients with preserved liver function (Model for End-stage Liver Disease score ≤12) who underwent orthotopic liver transplantation or margin negative resection for American Joint Committee on Cancer stage I hepatocellular carcinoma lesions <3 cm between 2010 and 2013. Multivariable and Cox regression adjusting for age, demographics, comorbid disease burden, Model for End-stage Liver Disease score, tumor size, and operation were used to compare overall survival between cohorts. RESULTS: In the study, 241 (53%) patients underwent orthotopic liver transplantation. In addition, 219 (47%) underwent margin negative resection. On multivariable regression, patients having a Charlson comorbidity score ≥2 were more likely to undergo orthotopic liver transplantation, (odds ratio 1.94, P=.03). African American patients (odds ratio 0.44, P=.02), and patients of advanced age (odds ratio 0.92, P<.001) were more likely to undergo margin negative resection. Patients undergoing orthotopic liver transplantation had longer overall survival than those undergoing margin negative resection (median OS not reached versus 67.6 months, P<.001). Multivariable Cox regression identified surgical procedure as the only independent determinant of survival with margin negative resection conferring a nearly 3-fold increased risk of death (hazard ratio 2.86, P<.001). CONCLUSION: Orthotopic liver transplantation offers a survival advantage relative to margin negative resection for patients with small unifocal hepatocellular carcinoma and preserved liver function.

Does adjuvant radiation provide any survival benefit after an R1 resections for pancreatic cancer?

BACKGROUND: The benefit of adding external beam radiation to adjuvant chemotherapy in patients that have undergone a margin positive resection for early stage, pancreatic ductal adenocarcinoma has not been determined definitively. METHODS: The National Cancer Data Base was queried to evaluate the utility of adjuvant radiation in patients with pathologic stage I-II pancreatic ductal adenocarcinoma who underwent upfront pancreatoduodenectomy with a positive margin (margin positive resection) between 2004 and 2013. RESULTS: In the study, 1,392 patients met inclusion criteria, of whom 263 (18.9%) were lymph node-negative (pathologic stages IA, IB, IIA) and 1,129 (81.1%) were node-positive (pathologic stage IIB); 938 (67.4%) patients received adjuvant radiation and chemotherapy, while 454 (32.6%) received adjuvant chemotherapy alone. Cox modeling stratified by nodal status demonstrated the benefit of radiation to be statistically significant only in node positive patients (hazard ratio 0.81, 95% confidence interval, 0.71-0.93). Node-positive patients receiving adjuvant radiation and chemotherapy had an adjusted median survival of 17.5 months vs 15.2 months for those receiving adjuvant chemotherapy alone (P=.003). In patients who had negative nodes, there was no difference in overall survival with radiation (22.5 vs 23.6 months, P=.511). CONCLUSION: Addition of radiation to adjuvant chemotherapy after a margin positive resection confers a survival benefit albeit limited (about 2 months) in patients with node-positive pancreatic head cancer. (Surgery 2017;160:XXX-XXX.).

Orthotopic liver transplantation provides a survival advantage compared with resection in patients with hepatocellular carcinoma and preserved liver function.

BACKGROUND: Prior studies comparing the efficacy of orthotopic liver transplantation to resection in patients with hepatocellular carcinoma have not controlled for underlying severity of liver disease. METHODS: Patients with stage I to III hepatocellular carcinoma and preserved liver function (model for end-stage liver disease <12) who underwent resection or orthotopic liver transplantation between 2010 and 2013 were identified from the National Cancer Database. Short-term (30- and 90-day) and overall survival were assessed from 1:1 propensity score-matched cohorts based on patient and tumor characteristics. RESULTS: During the period studied, 689 (28%) underwent orthotopic liver transplantation, and 1,774 (72%) patients underwent resection. Propensity score matching yielded 374 undergoing orthotopic liver transplantation matched to 374 patients undergoing resection. Rates of 30-day mortality (01.9% vs 0.8%, respectively; P = .34) and 90-day mortality (3.5% vs 2.1%, P = .38) were not different between matched cohorts. Orthotopic liver transplantation did, however, result in a greater overall survival compared with resection (median overall survival not reached versus 4.5 years; P = .01). On multivariable Cox regression, resection was associated with a 67% greater likelihood of overall mortality compared with orthotopic liver transplantation (hazard ratio 1.67; 95% confidence interval, 1.15-2.43). CONCLUSION: For patients diagnosed with hepatocellular carcinoma in the context of preserved liver function, orthotopic liver transplantation was associated with a significant improvement in overall survival relative to resection.