I-Chun Thomas

Utilization of cytoreductive nephrectomy and patient survival in the targeted therapy era

We sought to analyze utilization and survival outcomes of cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (RCC) before and after introduction of targeted therapy. We identified patients with metastatic RCC between 1993 and 2010 in the SEER registry and examined temporal trends in utilization. We performed a joinpoint regression to determine when changes in utilization of CN occurred. We fitted multivariable proportional hazard models in full and propensity score‐matched cohorts. We performed a difference‐in‐difference analysis to compare survival outcomes before and after introduction of targeted therapy. The proportion of patients undergoing CN increased from 1993 to 2004, from 29% to 39%. We identified a primary joinpoint of 2004, just prior to the introduction of targeted therapy. Beginning in 2005, there was a modest decrease in utilization of CN. CN was associated with a lower adjusted relative hazard (0.41, 95% confidence interval 0.34–0.43). Median survival among patients receiving CN increased in the targeted therapy era (19 vs. 13 months), while median survival among patients not receiving CN increased only slightly (4 vs. 3 months). Difference‐in‐difference analysis showed a significant decrease in hazard of death among patients who received CN in the targeted therapy era. Despite decreased utilization in the targeted therapy era, CN remains associated with improved survival. Prospective randomized trials are needed to confirm the benefit of CN among patients with metastatic RCC treated with novel targeted therapies.

Biologic differences between peripheral and transition zone prostate cancer

Prostate cancer arises in the transition zone (TZ) in approximately 20–25% of cases. Modern biopsy and surveillance protocols, and advances in prostate cancer imaging, have renewed interest in TZ prostate cancers. We compared TZ and PZ prostate cancer to determine if cancer location is independently associated with better outcomes.

Prevalence and correlates of functional dependence among maintenance dialysis patients

Functional dependence is an important determinant of longevity and quality of life. The purpose of the current study was to determine the prevalence and correlates of functional dependence among patients with end‐stage renal disease (ESRD) receiving maintenance dialysis. We enrolled 148 participants with ESRD from five clinics. Functional status, as measured by basic and instrumental activities of daily living (ADL, IADL), was ascertained by validated questionnaires. Functional dependence was defined as needing assistance in at least one of seven IADLs or at least one of four ADLs. Demographic characteristics, chronic health conditions, anthropometric measurements, and laboratories were assessed by a combination of self‐report and chart review. Cognitive function was assessed with a neurocognitive battery, and depressive symptoms were assessed by questionnaire. Mean age of the sample was 56.2 ± 14.6 years. Eighty‐seven participants (58.8%) demonstrated dependence in ADLs or IADLs, 70 (47.2%) exhibited IADL dependence alone, and 17 (11.5%) exhibited combined IADL and ADL dependence. In a multivariable‐adjusted model, stroke, cognitive impairment, and higher systolic blood pressure were independent correlates of functional dependence. We found no significant association between demographic characteristics, chronic health conditions, depressive symptoms or laboratory measurements, and functional dependence. Impairment in executive function was more strongly associated with functional dependence than memory impairment. Functional dependence is common among ESRD patients and independently associated with stroke, systolic blood pressure, and executive function impairment.

Overall Survival in Patients with Localized Prostate Cancer in the US Veterans Health Administration: Is PIVOT Generalizable?

UNLABELLED A better understanding of overall survival among patients with clinically localized prostate cancer (PCa) in the US Veterans Health Administration (VHA) is critical to inform PCa treatment decisions, especially in light of data from the Prostate Intervention Versus Observation Trial (PIVOT). We sought to describe patterns of survival for all patients with clinically localized PCa treated by the VHA. We created an analytic cohort of 35 954 patients with clinically localized PCa diagnosed from 1995 to 2001, approximating the PIVOT inclusion criteria (age of diagnosis ≤75 yr and clinical stage T2 or lower). Mean patient age was 65.9 yr, and median follow-up was 161 mo. Overall, 22.5% of patients were treated with surgery, 16.6% were treated with radiotherapy, and 23.1% were treated with androgen deprivation. Median survival of the entire cohort was 14 yr (25th, 75th percentiles, range: 7.9-20 yr). Among patients who received treatment with curative intent, median survival was 17.9 yr following surgery and 12.9 yr following radiotherapy. One-third of patients died within 10 yr of diagnosis compared with nearly half of the participants in PIVOT. This finding sounds a note of caution when generalizing the mortality data from PIVOT to VHA patients and those in the community. PATIENT SUMMARY More than one-third of patients diagnosed with clinically localized prostate cancer treated through the US Veterans Health Administration from 1995 to 2001 died within 10 yr of their diagnosis. Caution should be used when generalizing the estimates of competing mortality data from PIVOT.

Contemporary Use of Partial Nephrectomy: Are Older Patients With Impaired Kidney Function Being Left Behind?

OBJECTIVE To assess whether patient factors, such as age and preoperative kidney function, were associated with receipt of partial nephrectomy in a national integrated healthcare system. MATERIALS AND METHODS We identified patients treated with a radical or partial nephrectomy from 2002 to 2014 in the Veterans Health Administration. We examined associations among patient age, sex, race or ethnicity, multimorbidity, baseline kidney function, tumor characteristics, and receipt of partial nephrectomy. We estimated the odds of receiving a partial nephrectomy and assessed interactions between covariates and the year of surgery to explore whether patient factors associated with partial nephrectomy changed over time. RESULTS In our cohort of 14,186 patients, 4508 (31.2%) received a partial nephrectomy. Use of partial nephrectomy increased from 17% in 2002 to 32% in 2008 and to 38% in 2014. Patient race or ethnicity, age, tumor stage, and year of surgery were independently associated with receipt of partial nephrectomy. Black veterans had significantly increased odds of receipt of partial nephrectomy, whereas older patients had significantly reduced odds. Partial nephrectomy utilization increased for all groups over time, but older patients and patients with worse baseline kidney function showed the least increase in odds of partial nephrectomy. CONCLUSION Although the utilization of partial nephrectomy increased for all groups, the greatest increase occurred in the youngest patients and those with the highest baseline kidney function. These trends warrant further investigation to ensure that patients at the highest risk of impaired kidney function are considered for partial nephrectomy whenever possible.

Incident CKD after Radical or Partial Nephrectomy

The comparative effectiveness of partial nephrectomy versus radical nephrectomy to preserve kidney function has not been well established. We determined the risk of clinically significant (stage 4 and higher) CKD after radical or partial nephrectomy among veterans treated for kidney cancer in the Veterans Health Administration (2001-2013). Among patients with preoperative eGFR≥30 ml/min per 1.73 m2, the incidence of CKD stage 4 or higher after radical (n=9759) or partial nephrectomy (n=4370) was 7.9% overall. The median time to stage 4 or higher CKD after surgery was 5 months, after which few patients progressed. In propensity score-matched cohorts, partial nephrectomy associated with a significantly lower relative risk of incident CKD stage 4 or higher (hazard ratio, 0.34; 95% confidence interval [95% CI], 0.26 to 0.43, versus radical nephrectomy). In a parallel analysis of patients with normal or near-normal preoperative kidney function (eGFR≥60 ml/min per 1.73 m2), partial nephrectomy was also associated with a significantly lower relative risk of incident CKD stage 3b or higher (hazard ratio, 0.15; 95% CI, 0.11 to 0.19, versus radical nephrectomy) in propensity score-matched cohorts. Competing risk regression models produced consistent results. Finally, patients treated with a partial nephrectomy had reduced risk of mortality (hazard ratio, 0.55; 95% CI, 0.49 to 0.62). In conclusion, compared with radical nephrectomy, partial nephrectomy was associated with a marked reduction in the incidence of clinically significant CKD and with enhanced survival. Postoperative decline in kidney function occurred mainly in the first year after surgery and appeared stable over time.

The Research Implications of Prostate Specific Antigen Registry Errors: Data from the Veterans Health Administration

Purpose: We sought to characterize the effects of prostate specific antigen registry errors on clinical research by comparing cohorts based on cancer registry prostate specific antigen values with those based directly on results in the electronic health record. Materials and Methods: We defined sample cohorts of men with prostate cancer using data from the Veterans Health Administration, including those with a prostate specific antigen value less than 4.0, 4.0 to 10.0, 10.0 to 20.0 and 20.0 to 98.0 ng/ml, respectively. We compared the composition of each cohort and overall patient survival when using prostate specific antigen values from the Veteran Affairs Central Cancer Registry vs the gold standard electronic health record laboratory file results. Results: There was limited agreement among cohorts when defined by cancer registry prostate specific antigen values vs the laboratory file of the electronic health record. The least agreement of 58% was seen in patients with prostate specific antigen less than 4.0 ng/ml and greatest agreement of 89% was noted among patients with prostate specific antigen between 4.0 and 10.0 ng/ml. In each cohort patients assigned to a cohort based only on the cancer registry prostate specific antigen value had significantly different overall survival when compared with patients assigned based on registry and laboratory file prostate specific antigen values. Conclusions: Cohorts based exclusively on cancer registry prostate specific antigen values may have high rates of misclassification that can introduce concerning differences in key characteristics and result in measurable differences in clinical outcomes.

Dialysis versus Medical Management at Different Ages and Levels of Kidney Function in Veterans with Advanced CKD

Background Appropriate patient selection and optimal timing of dialysis initiation among older adults with advanced CKD are uncertain. We determined the association between dialysis versus medical management and survival at different ages and levels of kidney function.Methods We assembled a nationally representative 20% sample of United States veterans with eGFR<30 ml/min per 1.73 m2 between 2005 and 2010 (n=73,349), with follow-up through 2012. We used an extended Cox model to determine associations among the time-varying exposures, age (<65, 65-74, 75-84, and ≥85 years), eGFR (<6, 6-<9, 9-<12, 12-<15, and 15-<29 ml/min per 1.73 m2), and provision of dialysis, and survival.Result Over the mean±SEM follow-up of 3.4±2.2 years, 15% of patients started dialysis and 52% died. The eGFR at which dialysis, compared with medical management, associated with lower mortality varied by age (P<0.001). For patients aged <65, 65-74, 75-84, and ≥85 years, dialysis associated with lower mortality for those with eGFR not exceeding 6-<9, <6, 9-<12, and 9-<12 ml/min per 1.73 m2, respectively. Dialysis initiation at eGFR<6 ml/min per 1.73 m2 associated with a higher median life expectancy of 26, 25, and 19 months for patients aged 65, 75, and 85 years, respectively. When dialysis was initiated at eGFR 9-<12 ml/min per 1.73 m2, the estimated difference in median life expectancy was <1 year for these patients.Conclusions Provision of dialysis at higher levels of kidney function may extend survival for some older patients.

A Temporal Examination of Platelet Counts as a Predictor of Prognosis in Lung, Prostate, and Colon Cancer Patients

Platelets, components of hemostasis, when present in excess (>400 K/μL, thrombocytosis) have also been associated with worse outcomes in lung, ovarian, breast, renal, and colorectal cancer patients. Associations between thrombocytosis and cancer outcomes have been made mostly from single-time-point studies, often at the time of diagnosis. Using laboratory data from the Department of Veterans Affairs (VA), we examined the potential benefits of using longitudinal platelet counts in improving patient prognosis predictions. Ten features (summary statistics and engineered features) were derived to describe the platelet counts of 10,000+ VA lung, prostate, and colon cancer patients and incorporated into an age-adjusted LASSO regression analysis to determine feature importance, and predict overall or relapse-free survival, which was compared to the previously used approach of monitoring for thrombocytosis near diagnosis (Postdiag AG400 model). Temporal features describing acute platelet count increases/decreases were found to be important in cancer survival and relapse-survival that helped stratify good and bad outcomes of cancer patient groups. Predictions of overall and relapse-free survival were improved by up to 30% compared to the Postdiag AG400 model. Our study indicates the association of temporally derived platelet count features with a patients’ prognosis predictions.

PD03-05 EXTERNAL VALIDATION OF THE AGE-ADJUSTED PROSTATE CANCER-SPECIFIC COMORBIDITY INDEX (PCCI), A CLAIMS-BASED TOOL FOR PREDICTION OF LIFE EXPECTANCY IN MEN WITH PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: Accurate assessment of life expectancy (LE) is critical to appropriate case selection for men with prostate cancer. We previously reported the age-adjusted Prostate Cancer Comorbidity Index (PCCI), a LE prediction tool that uses a weighted score incorporating age and comorbidities to estimate 2, 5, and 10-year mortality in men with prostate cancer. We sought to operationalize the PCCI for clinical application using claims data and externally validate it across a nationally representative sample. We then compared its ability to identify patients at risk for overtreatment with the age-adjusted Charlson comorbidity index. METHODS: We sampled 181,209 men with prostate cancer diagnosed from 2000 to 2011 in the Veterans Affairs healthcare system. We used claims data within 12 months of biopsy to determine comorbidities at diagnosis. We used Kaplan-Meier analysis to plot overall survival and multivariable Cox proportional hazards analysis to assess risk discrimination between PCCI and Charlson score subgroups. We then compared the number of men with <10year LE who were treated with surgery or radiation between the two indices. RESULTS: Kaplan-Meier analysis showed a stepwise increase in risk of overall mortality with increasing PCCI score (Figure). Ten-year mortality among men with PCCI scores of 1-2, 3-4, 5-6, 7-9, and 10þ was 26%, 36%, 41%, 52%, and 69%, respectively. Multivariable models showed excellent risk discrimination with hazard ratios of 1.22 (95%CI 1.18-1.27), 1.69 (95%CI 1.61-1.76), 2.08 (95%CI 2.00-2.17), 2.88 (95%CI 2.76-3.00), 4.50 (95%CI 4.32-4.69) for PCCI scores of 1-2, 3-4, 5-6, 7-9, and 10þ, respectively. The PCCI identified 30,610 men with LE <10 years (<50% median survival at 10 years) vs. 25,455 men in the Charlson index. Furthermore, the PCCI identified significantly more men with <10-year LE who were overtreated with surgery or radiation compared with the Charlson index: 12,531 (41%) vs. 7,098 (28%) (p<0.0001). CONCLUSIONS: The age-adjusted Prostate Cancer Specific Comorbidity Index (PCCI) showed excellent prognostic utility across a nationally representative sample of men with prostate cancer. It was superior to the Charlson index in identifying men at risk for overtreatment due to limited LE. Source of Funding: None