Faculty Bibliography

PURPOSE: Lymphopenia as a likely index of poor systemic immunity is an independent predictor of inferior outcome in patients with clear cell renal cell carcinoma (RCC). We sought to evaluate the prognostic relevance of preoperative absolute lymphocyte count (ALC) in a cohort of patients with papillary RCC (PRCC). MATERIALS AND METHODS: A prospectively maintained, renal cancer database was analyzed. Patients with preoperative ALC, within 3 months before surgery, were eligible for the study. Those with multifocal or bilateral renal tumors were excluded. Correlations between ALC and age, gender, smoking, Charlson comorbidity index, pathologic T category, PRCC subtype, and TNM stage were evaluated. Differences in overall survival (OS) and cancer-specific survival by ALC status were assessed using the log-rank test and cumulative incident estimators, respectively. Cox proportional hazards model was used for multivariable analyses. RESULTS: A total of 192 patients met the inclusion criteria. As a continuous variable, preoperative ALC was associated with higher TNM stage (P = 0.001) and older age (P = 0.01). As a dichotomous variable, lymphopenia (<1,300 cells/microl) was associated with higher TNM stage (P = 0.003). On multivariable analyses, controlling for covariates, after a median follow-up of 37.3 months, lymphopenia was associated with inferior OS (hazard ratio = 2.3 [95% CI: 1.2-4.3], P = 0.011) and trended to significance for cancer-specific survival (P = 0.071). Among patients with nonmetastatic disease and lymphopenia, OS at 37.5 months was shorter compared with those with normal ALC (83% vs. 93%, P = 0.0006). CONCLUSIONS: In patients with PRCC, lymphopenia is associated with lower survival independent of TNM stage, age, and histology. ALC may provide an additional preoperative prognostic factor.

PURPOSE/OBJECTIVE:Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management. MATERIALS AND METHODS/METHODS:Members of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes. RESULTS:The Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes. CONCLUSIONS:The definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening.

OBJECTIVE:To evaluate whether poor nutrition is associated with mortality in patients undergoing cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS/METHODS:A multi-institutional review of prospective databases identified 246 patients meeting inclusion criteria who underwent CN for mRCC from 1993 to 2012. Nutritional markers evaluated were: body mass index <18.5 kg/m(2) , serum albumin <3.5 g/dL, or preoperative weight loss of ≥5% of body weight. Primary outcomes were overall (OS) and disease-specific survival (DSS). Secondary outcome was 'early mortality' defined as death at ≤6 months of surgery. Survival curves were estimated using the Kaplan-Meier product-limit method and multivariate analysis using logistic regression was used to test associations between nutritional markers and survival outcomes. RESULTS:In all, 119 patients (median follow-up 17 months) were categorised as having any abnormal nutrition parameter (48%). Hypoalbuminaemia was the only independent predictor of OS and DSS (OS: median 8 vs 23 months, P < 0.001; DSS: 11 vs 33 months, P < 0.001). On multivariate analysis, hypoalbuminaemia remained a significant predictor of death for both overall [hazard ratio (HR) 2, 95% confidence interval (CI) 1.4-2.8; P < 0.001) and disease-specific mortality (HR 2.2, 95% CI 1.4-3.3; P < 0.001). Hypoalbuminaemia was also associated with early mortality (overall: P < 0.001 and disease specific: P = 0.002). CONCLUSION/CONCLUSIONS:Patients with mRCC and hypoalbuminaemia undergoing CN have decreased OS and CSS, and increased risk of all-cause and disease-specific early mortality. As such, serum albumin may help risk stratify patients selected as candidates for CN. Furthermore, future work should evaluate whether nutritional depletion is a modifiable risk factor.

OBJECTIVE:To examine relative contributions of functional parenchymal preservation and renal ischemia following nephron-sparing surgery (NSS). While residual functional parenchymal volume (FPV) is proposed as the key factor in predicting functional outcomes following NSS, efforts to curtail ischemia time continue to add technical complexity to partial nephrectomy. METHODS:Our kidney cancer database was queried for patients who underwent NSS with warm ischemia time (WIT). Patients with cross-sectional imaging for FPV calculation were included. Cylindrical volume approximation methodology was used to calculate FPV, accounting for the volume of tumor's endophytic component. Percent estimated glomerular filtration rate (eGFR) preservation, perioperatively and at 6 months, was the outcome metric. Spearman correlation and linear regression analyses were used to evaluate associations of WIT and %FPV preservation with renal function preservation. RESULTS:Of the 179 patients included, median preoperative eGFR was 88.4 (9.5% chronic kidney disease III or IV), tumor size was 2.7 cm (interquartile range [IQR] 2.0-3.6 cm), and R.E.N.A.L. nephrometry was low in 34%, intermediate in 57%, and high in 9%. Median WIT was 30 minutes (IQR 24-36), resulting in 97.4% FPV preservation. Median postoperative eGFR at 6.4 months was 80.5 (19.1% chronic kidney disease III or IV), a median of 93.1% eGFR preservation (IQR 85.1-101.7). At discharge, WIT (P <.001), not %FPV (P = .112), was associated with %eGFR preservation. However, 6 months following surgery, on multivariable analysis, both preoperative eGFR (linear regression coefficient = -0.208, P = .006) and %FPV preservation (linear regression coefficient = 0.491, P = .001), but not WIT (P = .946), demonstrated statistically significant association with %eGFR preservation. CONCLUSION/CONCLUSIONS:Residual FPV, and not WIT, appears to be the main predictor of ultimate renal function following NSS.

PURPOSE/OBJECTIVE:We evaluated temporal trends in systemic therapy use in patients undergoing cytoreductive nephrectomy for metastatic renal cell carcinoma. We used data from a large national cancer registry and assessed characteristics associated with the receipt of systemic treatment. MATERIALS AND METHODS/METHODS:We reviewed the NCDB to identify patients with stage IV renal cell carcinoma who underwent cytoreductive nephrectomy between 1998 and 2010. Systemic therapy was defined as immunotherapy and/or chemotherapy, including targeted agents. We evaluated associations between clinicopathological features and receipt of systemic therapy using multivariable logistic regression with generalized estimating equations. RESULTS:Of 22,409 patients with metastatic renal cell carcinoma treated with cytoreductive nephrectomy 8,830 (39%) received systemic therapy. Use of systemic therapy increased from 32% of cases in 1998 to 49% in 2010 (p < 0.001). After adjustment older patient age (71 years or greater OR 0.36, CI 0.31-0.43), increasing comorbidity count (Charlson comorbidity index 2 or greater OR 0.79, 95% CI 0.68-0.92), papillary histology (OR 0.81, 95% CI 0.71-0.93), sarcomatoid histology (OR 0.88, 95% CI 0.80-0.98), Medicaid (OR 0.61, 95% CI 0.5-0.74), Medicare (OR 0.70, 95% CI 0.62-0.79) and no insurance (OR 0.75, 95% CI 0.63-0.91) were associated with significantly decreased systemic therapy use. Male gender (OR 1.05, 95% CI 1.02-1.08) predicted an increased likelihood of systemic therapy. CONCLUSIONS:Systemic therapy in patients undergoing cytoreductive nephrectomy has increased with time, coinciding with the introduction of targeted therapies. Nevertheless, still less than half of such patients receive systemic treatment. While the etiology of the lack of treatment is likely multifactorial, the potential health policy implications of disparities in care warrant further investigation.

BACKGROUND:Prostate and thyroid cancers represent two of the most overdiagnosed tumors in the US. Hypothesizing that patients diagnosed with one of these malignancies were more likely to be diagnosed with the other, we examined the coupling of diagnoses of prostate and thyroid cancer in a large US administrative dataset. METHODS:The surveillance, epidemiology, and end results (SEER) database was used to identify men diagnosed with clinically localized prostate cancer (CaP) or thyroid cancer between 1995 and 2010. SEER*stat software was used to estimate multivariable-adjusted standardized incidence ratios (SIRs) and investigate the rates of subsequent malignancy diagnosis. Additional non-urologic cancer sites were added as control groups. RESULTS:Patients with thyroid cancer were much more likely to be diagnosed with CaP than patients in the SEER control group (SIR 1.28 [95% CI 1.1-1.5]; p < 0.05). Similarly, the observed incidence of thyroid cancer was significantly higher in patients with CaP when compared with SEER controls (SIR 1.30 [95% CI 1.2-1.4]; p < 0.05). When stratified by follow-up interval, the observed thyroid cancer diagnosis rate among men with CaP was significantly higher than expected at 2-11 (SIR 1.83 [95% CI 1.4-2.4]), 12-59 (SIR 1.24 [95% CI 1.0-1.5]), and 60-119 (SIR 1.25 [95% CI 1.0-1.5]) months of follow-up. There was no increased risk of CaP or thyroid cancer diagnosis among patients with non-urologic malignancies. CONCLUSIONS:There is a significant association of diagnoses with prostate and thyroid cancer in the US. In the absence of a known biological link between these tumors, these data suggest that diagnosis patterns for prostate and thyroid malignancies are linked.

OBJECTIVE:To test the association between hospital type and performance of candidate quality measures for treatment of muscle-invasive bladder cancer (MIBC) using a large national tumour registry. Proposed quality measures include receipt of neoadjuvant chemotherapy, timely treatment, adequate lymph node dissection, and continent urinary diversion. PATIENTS AND METHODS/METHODS:Using the National Cancer Database, patients with stage ≥II urothelial carcinoma treated with radical cystectomy (RC) from 2003 to 2010 were identified. Hospitals were grouped by type and annual RC volume: community, comprehensive low volume (CLV), comprehensive high volume (CHV), academic low volume (ALV), and academic high volume (AHV) groups. Logistic regression models were used to test the association between hospital group and performance of quality measures, adjusting for year, demographic, and clinical/pathological characteristics; generalised estimating equations were fitted to the models to adjust for clustering at the hospital level. RESULTS:In all, 23 279 patients underwent RC at community (12.4%), comprehensive (CLV 38%, CHV 5%), and academic (ALV 17%, AHV 28%) hospitals. While only 0.8% (175) of patients met all four quality criteria, 61% of patients treated at AHV hospitals met two or more quality metric indicators compared with ALV (45%), CHV (44%), CLV (38%), and community (37%) hospitals (P < 0.001). After adjustment, patients were more likely to receive two or more quality measures when treated at AHV (odds ratio [OR] 2.4, confidence interval [CI] 2.0-2.9), ALV (OR 1.3, CI 1.1-1.6), and CHV (OR 1.3, CI 1.03-1.7) hospitals compared with community hospitals. CONCLUSIONS:Patients undergoing RC at AHV hospitals were more likely to meet quality criteria. However, performance remains low across hospital types, highlighting the opportunity to improve quality of care for MIBC.

PURPOSE/OBJECTIVE:Hypothesizing that changing hospitals between diagnosis and definitive therapy (care transition) may delay timely treatment, we identified the association between care transitions and a treatment delay of 3 months or greater in patients with muscle invasive bladder cancer. MATERIALS AND METHODS/METHODS:Using the National Cancer Database we identified all patients with stage II or greater urothelial carcinoma treated from 2003 to 2010. Care transition was defined as a change in hospital from diagnosis to definitive treatment course, that is diagnosis to radical cystectomy or the start of neoadjuvant chemotherapy. Logistic regression models were used to test the association between care transition and treatment delay. RESULTS:Of 22,251 patients 14.2% experienced a treatment delay of 3 months or greater and this proportion increased with time (13.5% in 2003 to 2006 vs 14.8% in 2007 to 2010, p = 0.01). Of patients who underwent a care transition 19.4% experienced a delay to definitive treatment compared to 10.7% diagnosed and treated at the same hospital (p <0.001). The proportion of patients with a care transition increased during the study period (37.4% in 2003 to 2006 vs 42.3% in 2007 to 2010, p <0.001). After adjustment patients were more likely to experience a treatment delay when undergoing a care transition (OR 2.0, 95% CI 1.8-2.2). CONCLUSIONS:Patients with muscle invasive bladder cancer who underwent a care transition were more likely to experience a treatment delay of 3 months or greater. Strategies to expedite care transitions at the time of hospital referral may improve quality of care.