Patrick Karabon

The Impact of Local Treatment on Overall Survival in Patients with Metastatic Prostate Cancer on Diagnosis: A National Cancer Data Base Analysis.

BACKGROUND The role of local treatment (LT) in patients with metastatic prostate cancer (mPCa) at diagnosis is controversial. OBJECTIVE We set to evaluate the potential impact of LT on overall mortality (OM) in men with mPCa, and how this impact is influenced by tumor and patient characteristics. DESIGN, SETTINGS, AND PARTICIPANTS A total of 15 501 patients with mPCa were identified in the National Cancer Data Base (2004-2012) and categorized in LT (radical prostatectomy or radiation therapy targeted to prostate) versus nonlocal treatment (NLT; all other patients). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The two arms (LT vs NLT) were matched using propensity scores to minimize selection bias. To evaluate LT impact on OM in relation to baseline characteristics, first multivariable Cox regression analysis was used to predict OM in patients treated with NLT, then interaction between predicted OM risk and LT status was tested. RESULTS AND LIMITATIONS Overall, 9.5% (n=1470) of patients received LT. In the postpropensity matched cohorts, 3-yr OM-free survival was higher in the LT group versus the NLT group (69% vs 54%; p<0.001). In multivariable Cox regression, the NLT group, age, and Charlson comorbidity index were predictors of OM (all p≤0.03). This model was used to predict the 3-yr OM risk. The interaction between predicted OM and LT status was significant (p<0.001). The benefit of LT on OM decreased progressively as predicted OM risk increased. Specifically, the 3-yr absolute improvement in OM-free survival was 15.7%, for patients with predicted OM risk ≤20% versus 0% for those with predicted OM risk ≥72%. CONCLUSIONS Men with mPCa at diagnosis benefit from LT in terms of OM. This is largely affected by baseline characteristics. Specifically, patients with a relatively low tumor risk and good general health status appear to benefit the most. PATIENT SUMMARY We used a large hospital-based database to evaluate which patients might benefit from local therapy when metastasized prostate cancer was present at diagnosis. Local therapy is associated with a survival benefit in men with less aggressive tumors and good general health.

A Pragmatic Randomized Controlled Trial Examining the Impact of the Retzius-sparing Approach on Early Urinary Continence Recovery After Robot-assisted Radical Prostatectomy

BACKGROUND Retzius-sparing (posterior) robot-assisted radical prostatectomy (RARP) may expedite postoperative urinary continence recovery. OBJECTIVE To compare the short-term (≤3 mo) urinary continence (UC), urinary function (UF), and UF-related bother outcomes of posterior RARP compared with standard anterior approach RARP. DESIGN, SETTING, AND PARTICIPANTS A total of 120 patients aged 40-75 yr with low-intermediate-risk prostate cancer (per the National Comprehensive Cancer Network guidelines) underwent primary RARP at a tertiary care institution. INTERVENTION Eligible men were randomized to receive either posterior (n=60) or anterior (n=60) RARP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES Primary outcome was UC (defined as 0 pads/one security liner per day) 1 week after catheter removal. Secondary outcomes were short-term (≤3 mo) UC recovery, and UF and UF-related bother scores (measured by the International Prostate Symptom Score [IPSS] and IPSS quality-of-life scores, respectively) assessed at 1 and 2 wk, and 1 and 3 mo following catheter removal. Continence outcomes were objectively verified using 24-hr pad weights. UC recovery was analyzed using Kaplan-Meier method and Cox proportional hazards regression; UF and UF-related bother outcomes were compared using linear generalized estimating equations (GEEs). Perioperative complications, positive surgical margin, and biochemical recurrence-free survival (BCRFS) represent secondary outcomes reported in the study. RESULTS AND LIMITATIONS Compared with 48% in the anterior arm, 71% men undergoing posterior RARP were continent 1 wk after catheter removal (p=0.01); corresponding median 24-h pad weights were 25 and 5g (p=0.001). Median time to continence in posterior versus anterior RARP was 2 and 8 d postcatheter removal, respectively (log-rank p=0.02); results were confirmed on multivariable regression analyses. GEE analyses showed that UF-related bother (but not UF) scores were significantly lower in the posterior versus anterior RARP group at 1 wk, 2 wk, and 1 mo on GEE analyses. Incidence of postoperative complications (12% anterior vs 18% posterior) and probability of BCRFS (0.91 vs 0.91) were comparable in the two arms. CONCLUSIONS In this single-center randomized study, the Retzius-sparing approach of RARP resulted in earlier recovery of UC and lower UF-related bother compared with standard RARP. These results require long-term validation and reproduction by other centers, as well as studies on men with high-risk localized disease. PATIENT SUMMARY In our hands, men with low-intermediate-risk prostate cancer undergoing Retzius-sparing robot-assisted radical prostatectomy (RARP) had earlier recovery of urinary continence and lower urinary function-related bother than those undergoing standard RARP.

Impact of travel distance to the treatment facility on overall mortality in US patients with prostate cancer

The objective of this study was to investigate the impact of travel distance to the treating facility on the risk of overall mortality (OM) among US patients with prostate cancer (PCa).

Racial differences in prostate-specific antigen–based prostate cancer screening: State-by-state and region-by-region analyses☆

OBJECTIVE Black men are more prone to harbor prostate cancer. They are more likely to succumb to this tumor than their White counterparts and may benefit from early detection and treatment. In this study, we assess the nationwide and regional disparity in prostate-specific antigen (PSA) screening for prostate cancer between Black men and non-Hispanic Whites (NHWs). METHODS A total of 247,079 (weighted 55,185,102) men, aged 40 to 99 years, who responded to the 2012 and 2014 behavioral risk factor surveillance system surveys were used for our analysis. End points consisted of self-reported PSA screening and self-reported nonrecommended PSA screening within 12 months of the interview. The latter was defined as screening in men with <10-year life expectancy. Available sociodemographic variables were used to predict these end points. The independent predictors from multivariate models were used to calculate the adjusted prevalence of PSA screening and nonrecommended PSA screening on a nationwide and regional level. These numbers were calculated for Blacks and NHWs separately and were compared between the 2 groups. RESULTS Prevalence of PSA screening was 30.7% in NHWs vs. 28.1% in Blacks (P<0.001). On a region-based analysis, New England, Middle Atlantic, South Atlantic, East North Central, East South Central, West South Central, and Mountain showed a significantly higher rate of PSA screening in NHWs as compared to Blacks (all P<0.001). Middle Atlantic had a significantly higher prevalence of nonrecommended screening in NHWs as compared to Blacks, whereas South Atlantic, West South Central, and Pacific had a significantly higher prevalence of nonrecommended screening in Blacks as compared to NHWs (all P<0.001). Overall, 43 states performed screening more frequently to NHWs, whereas only 8 states performed it more frequently to Black men. The nonrecommended screening was performed more frequently to NHWs in 19 states, whereas 24 states performed it more frequently to Black men. CONCLUSION Our study demonstrates that on a regional-level (and state-level), there are significant racial differences in overall and nonrecommended PSA screening across the United States. Further research is necessary to identify the reasons for the differences and help overcoming it.

Contemporary Trends in the Incidence of Metastatic Prostate Cancer Among US Men: Results from Nationwide Analyses

Studies have noted contrasting findings with regard to the contemporary incidence of metastatic prostate cancer (PCa) in the USA, especially in light of the United States Preventive Services Task Force (USPSTF) recommendations against prostate-specific antigen (PSA) screening in recent years. We used data from the 18 population- based tumor registries of the Surveillance, Epidemiology and End Results (SEER) 2004-2013 database to study trends in the incidence of metastatic PCa among men stratified by age and race. Joinpoint regression analyses were performed to identify time points associated with any statistically significant change in incidence. Overall, there was a significant increase in incidence between 2009 and 2013 (annual percentage change [APC] 3.10%; p<0.05). In age-stratified analyses, there was a continuous increase in the incidence of metastatic PCa from 2004 to 2013 among men aged 45-54 yr and 55-64 yr (APC 1.77% and 1.43% respectively; both p<0.05). For men aged ≥75 yr there was a significant decline in the incidence of metastatic PCa from 2004 to 2011 (APC -2.07%; p<0.05) and a nonsignificant increase from 2011 onwards (APC 6.09%). Distinct incidence trends were noted for white and black men. While it is too early to presume that the recent decline in PSA screening secondary to the USPSTF statement is causally associated with our findings, our results highlight a concerning trend of increasing metastatic disease. Our results thus warrant validation in future longer-term studies on the contemporary incidence and mortality of metastatic PCa. PATIENT SUMMARY: We noted increasing incidence of metastatic prostate cancer from 2009 onwards among US men (especially those aged 45-74 yr) in a population-based tumor registry. Pending validation in longer-term studies, our results suggest the need for close surveillance of trends for metastatic prostate cancer incidence and mortality.

Efficacy of Systemic Chemotherapy Plus Radical Nephroureterectomy for Metastatic Upper Tract Urothelial Carcinoma

Given the growing body of evidence supporting the benefit of primary tumor control for a wide range of metastatic malignancies, we hypothesized that chemotherapy plus radical nephroureterectomy (RNU) is associated with an overall survival (OS) benefit compared to chemotherapy alone for metastatic upper tract urothelial carcinoma (mUTUC). Within the National Cancer Data Base (2004-2012), we identified 398 (38.4%) and 637 (61.6%) patients who received chemotherapy plus RNU and chemotherapy alone, respectively. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves showed that 3-yr OS was 16.2% (95% confidence interval [CI] 12.1-20.3) for chemotherapy plus RNU and 6.4% (95%CI 4.1-8.7) for chemotherapy alone (p<0.001). In IPTW-adjusted Cox regression analysis, chemotherapy plus RNU was associated with a significant OS benefit (hazard ratio 0.70, 95% CI 0.61-0.80; p<0.001). Despite the usual biases related to the observational study design, our findings show a net OS benefit for fit patients who received chemotherapy plus RNU for mUTUC relative to their counterparts treated with chemotherapy alone. PATIENT SUMMARY We examined the role of radical nephroureterectomy in addition to systemic chemotherapy for metastatic upper tract urothelial carcinoma. We found that such treatment may be associated with an overall survival benefit compared to chemotherapy alone in fit patients.

The Association between Mortality and Distance to Treatment Facility in Patients with Muscle Invasive Bladder Cancer

Purpose: Regionalization of bladder cancer treatment is suggested to improve quality of care. As an unintended consequence some patients travel farther for care with unknown implications on outcomes. We characterized the relationship between distance and overall mortality in patients with invasive bladder cancer and those who underwent radical cystectomy. Materials and Methods: We performed a retrospective cohort study using NCDB (National Cancer Database) from 2004 to 2012 to identify patients with muscle invasive bladder cancer (cT2a‐T4 N0 M0). We also extracted a subgroup of patients who underwent radical cystectomy. Multivariate Cox proportional hazards and multinomial logistic regression analyses were performed in each group, controlling for demographic, clinical, hospital and geographic factors. Results: For 34,729 patients with muscle invasive bladder cancer traveling farther for treatment was associated with a lower probability of overall mortality (referent less than 12.5 miles, 12.5 to 49.9 miles HR 0.96, 95% CI 0.92–0.99 and 50 to 249.9 miles HR 0.91, 95% CI 0.86–0.96). This was significant for patients with cT2 disease and those treated at academic centers (p ≤0.05). For 11,059 patients who underwent radical cystectomy this trend did not reach significance. However, longer distance was associated with surgery at a high volume institution and receipt of neoadjuvant chemotherapy (each p <0.001). Conclusions: Patients who traveled farther for bladder cancer treatment did not experience inferior survival outcomes and traveling to academic institutions was associated with reduced mortality. For patients who undergo cystectomy this relationship was equivocal, although longer distance was associated with receiving neoadjuvant chemotherapy or surgery at a high volume facility. These findings may reflect a complex association of regionalization of bladder cancer care with patient individual health and health care seeking behavior.

Efficacy of Local Treatment in Prostate Cancer Patients with Clinically Pelvic Lymph Node-positive Disease at Initial Diagnosis

BACKGROUND There is limited evidence supporting the use of local treatment (LT) for prostate cancer (PCa) patients with clinically pelvic lymph node-positive (cN1) disease. OBJECTIVE To examine the efficacy of any form of LT±androgen deprivation therapy (ADT) in treating these individuals. DESIGN, SETTING, AND PARTICIPANTS Using the National Cancer Database (2003-2011), we retrospectively identified 2967 individuals who received LT±ADT versus ADT alone for cN1 PCa. Only radical prostatectomy (RP) and radiation therapy (RT) were considered as definitive LT. INTERVENTION LT±ADT versus ADT alone. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Instrumental variable analyses (IVA) were performed using a two-stage residual inclusion approach to compare overall mortality (OM)-free survival between patients who received LT±ADT versus ADT alone. The same methodology was used to further compare OM-free survival between patients who received RP±ADT versus RT±ADT. RESULTS AND LIMITATIONS Overall, 1987 (67%) and 980 (33%) patients received LT±ADT and ADT alone, respectively. In the LT±ADT group, 751 (37.8%) and 1236 (62.2%) patients received RP±ADT and RT±ADT, respectively. In IVA, LT±ADT was associated with a significant OM-free survival benefit (hazard ratio=0.31, 95% confidence interval [CI]=0.13-0.74, p=0.007), when compared with ADT alone. At 5 yr, OM-free survival was 78.8% (95% CI: 74.1-83.9%) versus 49.2% (95% CI: 33.9-71.4%) in the LT±ADT versus ADT alone groups. When comparing RP±ADT versus RT±ADT, IVA showed no significant difference in OM-free survival between the two treatment modalities (hazard ratio=0.54, 95% CI=0.19-1.52, p=0.2). Despite the use of an IVA, our study may be limited by residual unmeasured confounding. CONCLUSIONS Our findings show that PCa patients with clinically pelvic lymph node-positive disease may benefit from any form of LT±ADT over ADT alone. While not necessarily curative by itself, the use of RP or RT could be the first step in a multi-modality approach aiming at providing the best cancer control outcomes for these individuals. PATIENTS SUMMARY We examined the role of local treatment for clinically pelvic lymph node-positive prostate cancer. We found that the delivery of radical prostatectomy or radiation therapy may be associated with an overall mortality-free survival benefit compared with androgen deprivation therapy alone.

Prostate Cancer Screening in Early Medicaid Expansion States

Purpose The PPACA (Patient Protection and Affordable Care Act) of 2010 included a provision to expand Medicaid by 2014. Six states and jurisdictions elected to expand Medicaid early before 2012. This provided a natural experiment to test the association between expanded insurance coverage and preventive service utilization, including prostate cancer screening. Materials and Methods Using the 2012 and 2014 BRFSS (Behavioral Risk Factor Surveillance System) surveys we identified men 40 to 64 years old who reported prostate specific antigen testing in the preceding 12 months. Sociodemographic and access to care variables were extracted. Income was stratified by the relationship to Medicaid eligibility and the federal poverty level (less than 138%, 138% to 400% and greater than 400%). The weighted prevalence of prostate specific antigen was estimated. Multivariable logistic regression models were used to evaluate factors associated with prostate specific antigen screening. Interaction analysis for Medicaid expansion was performed. Results Among 158,103 respondents individuals in nonexpansion states had the highest incidence of prostate specific antigen screening. Nationally screening decreased between 2011 and 2013 (OR 0.87, 95% CI 0.83–0.91). In only early expansion states there was a 3% absolute increase in screening among men in the less than 138% federal poverty level, which was associated with expansion status (pinteraction = 0.04). Increased screening in early expansion states was also seen in men who were 55 to 59 years old, nonHispanic African American, Hispanic, previously married, not high school graduates and current smokers. Conclusions Between 2011 and 2013 there were national declines in prostate cancer screening. However, there was significant narrowing of the gap in prostate specific antigen screening between higher and low income men in Medicaid early expansion states. This may reflect improved access to preventive services among populations with historic barriers to care.

Trends in Prostate-Specific Antigen Screening Since the Implementation of the 2012 US Preventive Services Task Force Recommendations

In 2012, the US Preventive Services Task Force recommended against prostate-specific antigen (PSA) screening. Following the initial decrease in PSA screening rate, there appears to be no further decrease in screening rate from 2013 to 2015. In addition, the screening rate did not differ by age or race.