Faculty Bibliography

OBJECTIVES: * To develop a '2010 Partin Nomogram' with total prostate-specific antigen (tPSA) as a continuous biomarker, in light of the fact that the current 2007 Partin Tables restrict the application of tPSA as a non-continuous biomarker by creating 'groups' for risk stratification with tPSA levels (ng/mL) of 0-2.5, 2.6-4.0, 4.1-6.0, 6.1-10.0 and >10.0. * To use a 'predictiveness curve' to calculate the percentile risk of a patient among the cohort. PATIENTS AND METHODS: * In all, 5730 and 1646 patients were treated with radical prostatectomy (without neoadjuvant therapy) between 2000 and 2005 at the Johns Hopkins Hospital (JHH) and University Clinic Hamburg-Eppendorf (UCHE), respectively. * Multinomial logistic regression analysis was performed to create a model for predicting the risk of the four non-ordered pathological stages, i.e. organ-confined disease (OC), extraprostatic extension (EPE), and seminal vesicle (SV+) and lymph node (LN+) involvement. * Patient-specific risk was modelled as a function of the B-spline basis of tPSA (with knots at the first, second and third quartiles), clinical stage (T1c, T2a, and T2b/T2c) and biopsy Gleason score (5-6, 3 + 4 = 7, 4 + 3 = 7, 8-10). RESULTS: * The '2010 Partin Nomogram' calculates patient-specific absolute risk for all four pathological outcomes (OC, EPE, SV+, LN+) given a patient's preoperative clinical stage, tPSA and biopsy Gleason score. * While having similar performance in terms of calibration and discriminatory power, this new model provides a more accurate prediction of patients' pathological stage than the 2007 Partin Tables model. * The use of 'predictiveness curves' has also made it possible to obtain the percentile risk of a patient among the cohort and to gauge the impact of risk thresholds for making decisions regarding radical prostatectomy. CONCLUSION: * The '2010 Partin Nomogram' using tPSA as a continuous biomarker together with the corresponding 'predictiveness curve' will help clinicians and patients to make improved treatment decisions

BACKGROUND: Despite its expense and controversy surrounding its benefit, the surgical robot has been widely adopted for the treatment of prostate cancer. OBJECTIVES: To determine the relationship between surgical robot acquisition and changes in volume of radical prostatectomy (RP) at the regional and hospital levels. RESEARCH DESIGN: Retrospective cohort study. SUBJECTS: Men undergoing RP for prostate cancer at nonfederal, community hospitals located in the states of Arizona, Florida, Maryland, North Carolina, New York, New Jersey, and Washington. MEASURES: Change in number of RPs at the regional and hospital levels before (2001) and after (2005) dissemination of the surgical robot. RESULTS: Combining data from the Healthcare Cost and Utilization Project State Inpatient Databases 2001 and 2005 with the 2005 American Hospital Association Survey and publicly available data on robot acquisition, we identified 554 hospitals in 71 hospital referral regions (HRR). The total RPs decreased from 14,801 to 14,420 during the study period. Thirty six (51%) HRRs had at least 1 hospital with a surgical robot by 2005; 67 (12%) hospitals acquired at least 1 surgical robot. Adjusted, clustered generalized estimating equations analysis demonstrated that HRRs with greater numbers of hospitals acquiring robots had higher increases in RPs than HRRs acquiring none (mean changes in RPs for HRRs with 9, 4, 3, 2, 1, and 0 are 414.9, 189.6, 106.6, 14.7, -11.3, and -41.2; P<0.0001). Hospitals acquiring surgical robots increased RPs by a mean of 29.1 per year, while those without robots experienced a mean change of -4.8, P<0.0001. CONCLUSIONS: Surgical robot acquisition is associated with increased numbers of RPs at the regional and hospital levels. Policy makers must recognize the intimate association between technology diffusion and procedure utilization when approving costly new medical devices with unproven benefit

OBJECTIVES: To assess a novel application of the Prostate Health Index (phi) and biopsy tissue DNA content in benign-adjacent and cancer areas to predict which patients would eventually require treatment of prostate cancer in the Proactive Surveillance cohort. METHODS: We identified 71 men who had had serum and biopsy tissue from their diagnosis banked and available for the present study. Of the 71 patients, 39 had developed unfavorable biopsy findings and 32 had maintained favorable biopsy status during surveillance. The serum total prostate-specific antigen (tPSA), free PSA (fPSA) and [-2]proPSA were measured using the Beckman Coulter immunoassay. The DNA content measurements of Feulgen-stained biopsy sections were performed using the AutoCyte imaging system. RESULTS: The ratio of phi was significantly greater (37.23 +/- 15.76 vs 30.60 +/- 12.28; P = .03) in men who ultimately had unfavorable biopsy findings. The serum phi ratio (P = .003), [-2]proPSA/%fPSA (P = .004), biopsy tissue DNA content (ie, benign-adjacent excess of optical density, P = .019; and cancer area standard deviation of optical density, P = .002) were significant predictors of unfavorable biopsy conversion on Cox regression analysis. However, phi and [-2]proPSA/%fPSA showed a highly significant correlation (rho = 0.927, P < .0001) and no difference in accuracy (c-index, 0.6247 vs 0.6158; P = .704) for unfavorable biopsy conversion prediction. Furthermore, phi and [-2]proPSA/%fPSA remained significant (P = .047 and P = .036, respectively) in the multivariate models and, combined with the biopsy tissue DNA content, showed improvement in the predictive accuracy (c-index, 0.6908 and 0.6884, respectively) for unfavorable biopsy conversion. CONCLUSIONS: The Prostate Health Index to proPSA/%fPSA, combined with biopsy tissue DNA content, improved the accuracy to about 70% to predict unfavorable biopsy conversion at the annual surveillance biopsy examination among men enrolled in an Active Surveillance program

OBJECTIVES: A PSA velocity (PSAV) >0.35 ng/ml/year approximately 10-15 years prior to diagnosis is associated with a greater risk of lethal prostate cancer. Some have recommended that a PSAV >0.35 ng/ml/year should prompt a prostate biopsy in men with a low serum PSA (<4 ng/ml) and benign DRE. However, less is known about the utility of this PSAV cutpoint for the prediction of treatment outcomes among men undergoing radical prostatectomy (RP). METHODS: Between 1992 and 2007, 339 men underwent RP at our institution with a preoperative PSA <4 ng/ml, benign DRE, and multiple preoperative PSA measurements. PSAV was calculated by linear regression analysis using all PSA values within 18 months prior to diagnosis. Kaplan-Meier survival analysis was performed, and biochemical progression rates were compared between PSAV strata using the log-rank test. RESULTS: The preoperative PSAV was >0.35 ng/ml/year in 124 (36.6%) of 339 men. Although there were no significant differences in clinico-pathological characteristics based upon PSAV, men with a PSAV >0.35 ng/ml/year were significantly more likely to experience biochemical progression after RP at a median follow-up of 4 years (P = 0.022). CONCLUSIONS: In this low-risk population with a preoperative PSA <4 ng/ml and benign DRE, approximately 1/3 had a preoperative PSAV >0.35 ng/ml/year. Physicians should carefully monitor men with a preoperative PSA >0.35 ng/ml/year as they are at increased risk of biochemical progression following RP

BACKGROUND: In adult inpatients with acute kidney injury (AKI), clinicians routinely order a renal ultrasonography (RUS) study. It is unclear how often this test provides clinically useful information. METHODS: Cross-sectional study, including derivation and validation samples, of 997 US adults admitted to Yale-New Haven Hospital from January 2005 to May 2009, who were diagnosed as having AKI and who underwent RUS to evaluate elevated creatinine level. Pregnant women, renal transplant recipients, and patients with recently diagnosed hydronephrosis (HN) were excluded. Demographic and clinical characteristics were abstracted from the medical records. A multivariable logistic regression model was developed to create risk strata for HN and HN requiring an intervention (HNRI); a separate sample was used for validation. The frequency of incidental findings on RUS was assessed for each stratum. RESULTS: In a derivation sample of 200 patients, 7 factors were found to be associated with HN: history of HN; recurrent urinary tract infections; diagnosis consistent with obstruction; nonblack race; and absence of the following: exposure to nephrotoxic medications, congestive heart failure, or prerenal AKI. Among 797 patients in the validation sample (mean age, 65.6 years), 10.6% had HN and 3.3% had HNRI. Of 223 patients in the low-risk group, 7 (3.1%) had HN and 1 (0.4%) had HNRI (223 patients needed to be screened to find 1 case of HNRI). In this group, there were 0 incidental findings on RUS unknown to the clinical team. In the higher-risk group, 15.7% had HN and 4.7% had HNRI. CONCLUSION: In adult inpatients with AKI, specific factors can identify patients unlikely to have HN or HNRI on RUS

PURPOSE: Few groups have examined satisfaction after prostate cancer treatment. We determined 1) predictors of satisfaction between 3 months and 2 years after open radical retropubic prostatectomy, and 2) whether these factors are time dependent. MATERIALS AND METHODS: This prospective cohort study included 1,542 men who underwent radical retropubic prostatectomy from October 2000 to July 2008. The primary outcome was satisfaction self-assessed at 3, 6, 12 and 24 months. We used multivariate logistic regression and repeated measures analysis to determine predictors of satisfaction, adjusting for demographic and clinical characteristics. RESULTS: Median followup was 24 months. About 93% of the men were satisfied. On multivariate analysis men were significantly less satisfied at 3 months when the urinary catheter was indwelling for 3 weeks or greater (OR 0.23, 95% CI 0.10-0.54), or they required intervention for anastomotic stricture (OR 0.23, 95% CI 0.11-0.49) or experienced 4-point or greater worsening in American Urological Association symptom score (OR 0.26, 95% CI 0.13-0.49). At 6 months worsening urinary function (OR 0.34, 95% CI 0.13-0.88) and biochemical failure (OR 0.15, 95% CI 0.05-0.43) were significantly associated with satisfaction. Worsening sexual function became significant at 12 and 24 months. These associations were confirmed on repeated measures analysis. CONCLUSIONS: Most men were satisfied after radical retropubic prostatectomy. Satisfaction determinants showed a nonsignificant trend toward time dependence. Postoperative factors, such as the duration of indwelling Foley catheterization, were associated with short-term satisfaction while sexual and urinary function, and biochemical failure were associated with long-term satisfaction. Based on high satisfaction rates open radical retropubic prostatectomy is an excellent treatment for prostate cancer

PURPOSE: Among men with biochemical progression after radical prostatectomy little is known about prostate specific antigen at the time of metastasis to bone in hormone naive patients. This information would be useful in determining when to initiate androgen deprivation therapy. MATERIALS AND METHODS: From a large radical prostatectomy series we identified 193 hormone naive men in whom bone metastases developed at a mean of 6 years postoperatively. We examined the prostate specific antigen distribution at bone scan conversion by time from radical prostatectomy to metastasis. ANOVA and linear regression were also used to examine the association of clinicopathological tumor features with prostate specific antigen at bone metastasis. RESULTS: Median prostate specific antigen was 31.9 ng/ml at the initial diagnosis of metastatic disease. Bone scan conversion occurred at a prostate specific antigen of less than 10, 10 to 100 and greater than 100 ng/ml in 50 (25.9%), 98 (50.8%) and 45 (23.3%) men, respectively. Lower prostate specific antigen at diagnosis, higher prostatectomy Gleason scores and shorter time to metastasis were associated with lower prostate specific antigen at bone metastasis, whereas prostate specific antigen at metastasis was not significantly associated with other clinicopathological features. CONCLUSIONS: Prostate specific antigen at the time of bone scan detected metastasis is highly variable. Unlike the pretreatment setting when metastases are rare at a prostate specific antigen of less than 10 ng/ml, 25.9% of bone metastases after radical prostatectomy occurred at a prostate specific antigen of less than 10 ng/ml. Because metastasis may occur at a low prostate specific antigen, patients with biochemical progression managed expectantly need regular bone scans even if prostate specific antigen is low to detect metastasis before symptoms