Assessment of MYC/PTEN Status by Gene-Protein Assay in Grade Group 2 Prostate Biopsies.

This study leveraged a gene-protein assay to assess MYC and PTEN status at prostate cancer biopsy and examined the association with adverse outcomes after surgery. MYC gain and PTEN loss were simultaneously assessed by chromogenic in situ hybridization and immunohistochemistry, respectively, using 277 Grade Group 2 needle biopsies that were followed by prostatectomy. The maximal size of cribriform Gleason pattern 4 carcinoma (CRIB), the presence of intraductal carcinoma (IDC), and percentage of Gleason pattern 4 carcinoma at biopsy were also annotated. MYC gain or PTEN loss was present in 19% and 18% of biopsies, respectively, whereas both alterations were present in 9% of biopsies. Tumors with one or both alterations were significantly more likely to have non-organ-confined disease (NOCD) at radical prostatectomy. In logistic regression models, including clinical stage, tumor volume on biopsy, and presence of CRIB/IDC, cases with MYC gain and PTEN loss remained at higher risk for NOCD (odds ratio, 6.23; 95% CI, 1.74-24.55; P = 0.005). The area under the curve for a baseline model using CAPRA variables (age, prostate-specific antigen, percentage of core involvement, clinical stage) was increased from 0.68 to 0.69 with inclusion of CRIB/IDC status and to 0.75 with MYC/PTEN status. Dual MYC/PTEN status can be assessed in a single slide and is independently associated with increased risk of NOCD for Grade Group 2 biopsies.

PTEN status assessment in the Johns Hopkins active surveillance cohort.

BACKGROUND: Up to half of men with Gleason score 6 (GS6) prostate cancers initially managed with active surveillance (AS) will eventually require definitive therapy, usually due to tumor grade reclassification during follow-up. We examined the association between PTEN status on biopsy and subsequent clinicopathologic outcomes in men with GS6 cancers who enrolled in AS. METHODS: We performed a case-control study of men enrolled in the Johns Hopkins AS cohort with diagnostic biopsy tissue available for immunohistochemical (IHC) staining. IHC was performed for PTEN using genetically validated protocols for all patients. Cases included men who underwent grade reclassification to GS ≥ 3 + 4 = 7 on biopsy within 2 years of follow-up (i.e., early reclassification) or reclassification to GS ≥ 4 + 3 = 7 on biopsy or radical prostatectomy during follow-up (i.e., extreme reclassification). Control patients were diagnosed with GS6 cancer and monitored on AS for at least 8 years without undergoing biopsy reclassification. RESULTS: Among 67 cases with adequate tissue, 31 men underwent early reclassification and 36 men underwent extreme reclassification. Cases were compared to 65 control patients with adequate tissue for assessment. On initial prostate biopsy, cases were older (median age 67 vs. 65, p = 0.024) and were less likely to meet very-low-risk criteria (64 vs 79%, p = 0.042) as compared to controls. Although not statistically significant, PTEN loss was observed in only 1 (1.5%) of 65 controls as compared to 6 (9%) of 67 cases (p = 0.062). CONCLUSIONS: PTEN loss was rare among men with GS6 prostate cancer enrolled in AS at Johns Hopkins. Despite this, PTEN loss was more frequent among men who underwent early or extreme reclassification to higher-grade cancer as compared to controls. Additional studies in larger low-risk cohorts may better elucidate a potential role for PTEN in selecting patients for AS.

The effect of socioeconomic status, race, and insurance type on newly diagnosed metastatic prostate cancer in the United States (2004-2013).

BACKGROUND: Understanding the characteristics of men who initially present with metastatic prostate cancer (mPCa) can better enable directed improvement initiatives. The objective of this study was to assess the relationship between socioeconomic status (SES) and newly diagnosed mPCa. MATERIALS METHODS: All men diagnosed with PCa in the National Cancer Data Base from 2004 to 2013 were identified. Characteristics of men presenting with and without metastatic disease were compared. A 4-level composite metric of SES was created using Census-based income and education data. Multivariable logistic regression was used to evaluate the association between SES, race/ethnicity, and insurance and the risk of presenting with mPCa at the time of diagnosis. RESULTS: Of 1,034,754 patients diagnosed with PCa, 4% had mPCa at initial presentation. Lower SES (first vs. fourth quartile; odds ratio [OR] = 1.39, 95% CI: 1.35-1.44), black and Hispanic race/ethnicity (vs. white; OR = 1.47, 95% CI: 1.43-1.51 and OR = 1.22, 95% CI: 1.17-1.28, respectively), and having Medicaid or no insurance (vs. Medicare or private; OR = 3.91, 95% CI: 3.78-4.05) were each independently associated with higher odds of presenting with mPCa after adjusting for all other covariates. CONCLUSIONS: Lower SES, race/ethnicity, and having Medicaid or no insurance were each independently associated with higher odds of presenting with metastases at the time of PCa diagnosis. Our findings may partially explain current PCa outcomes disparities and inform future efforts to reduce disparities.

Erectile Dysfunction Treatment Following Radical Cystoprostatectomy: Analysis of a Nationwide Insurance Claims Database.

INTRODUCTION: To improve care for patients after radical cystoprostatectomy (RCP), focus on survivorship issues such as sexual function needs to increase. Previous studies have demonstrated the burden of erectile dysfunction (ED) after RCP to be as high as 89%. AIM: To determine the rates of ED treatment use (phosphodiesterase type 5 inhibitors, injectable therapies, urethral suppositories, vacuum erection devices, and penile prosthetics) in patients with bladder cancer before and after RCP to better understand current patterns of care. METHODS: Men with bladder cancer undergoing RCP were identified in the MarketScan database (2010-2014). ED treatment use was assessed at baseline (during the 1 year before RCP) and at 6-month intervals (0-6, 7-12, 13-18, 19-24 months) after RCP. Multivariable logistic regression models were used to identify predictors of ED treatment use at 6-month intervals after RCP. OUTCOMES: ED treatment rates and predictors of ED treatment at 0-6, 7-12, 13-18, 19-24 month follow-up after RCP. RESULTS: At baseline, 6.5% of patients (77 of 1,176) used ED treatments. The rates of ED treatment use at 0 to 6, 7 to 12, 13 to 18, and 19 to 24 months after RCP were 15.2%, 12.7%, 8.1%, and 10.1% respectively. Phosphodiesterase type 5 inhibitors were the most commonly used treatment at all time points. In the multivariable model, predictors of ED treatment use at 0 to 6 months after RCP were age younger than 50 years (odds ratio [OR] = 3.17, 95% CI = 1.68-6.01), baseline ED treatment use (OR = 5.75, 95% CI = 3.08-10.72), neoadjuvant chemotherapy (OR = 1.72, 95% CI = 1.13-2.61), and neobladder diversion (OR = 2.40, 95% CI = 1.56-3.70). Baseline ED treatment use continued to be associated with ED treatment use at 6 to 12 months (OR = 5.63, 95% CI = 2.42-13.10) and 13 to 18 months (OR = 8.99, 95% CI = 3.05-26.51) after RCP. CLINICAL IMPLICATIONS: While the burden of ED following RCP is known to be high, overall ED treatment rates are low. These findings suggest either ED treatment is low priority for RCP patients or education about potential ED therapies may not be commonly discussed with patients following RCP. Urologists should consider discussing sexual function more frequently with their RCP patients. STRENGTHS & LIMITATIONS: Strengths include the use of a national claims database, which allows for longitudinal follow-up and detailed information on prescription medications and devices. Limitations include the lack of pathologic and oncologic outcomes data. CONCLUSION: ED treatment use after RCP is quite low. The strongest predictor of ED treatment use after RCP was baseline treatment use. These findings suggest ED treatment is a low priority for patients with RCP or education about potential ED therapies might not be commonly discussed with patients after RCP. Urologists should consider discussing sexual function more frequently with their patients undergoing RCP. Chappadi MR, Kates M, Sopko NA, et al. Erectile Dysfunction Treatment Following Radical Cystoprostatectomy: Analysis of a Nationwide Insurance Claims Database. J Sex Med 2017;14:810-817.

Evaluation of gender-based disparities in time from initial haematuria presentation to upper tract urothelial carcinoma diagnosis: analysis of a nationwide insurance claims database.

OBJECTIVE: To investigate the length of time from initial haematuria presentation to upper tract urothelial carcinoma (UTUC) diagnosis and the effect of gender on this duration. PATIENTS AND METHODS: Patients with haematuria claims in the year prior to UTUC diagnosis were identified from the MarketScan database (2010-2014). Delayed diagnosis was defined as >90 days from haematuria presentation to UTUC diagnosis. Multivariable Poisson regression models were used to determine factors associated with delayed UTUC diagnosis. RESULTS: Among 1 326 patients with UTUC, 469 (35.4%) experienced delayed diagnosis. Men (n = 866) had a longer median interval from haematuria to diagnosis than women (60 vs 49 days; P = 0.04). In the multivariable model, male gender (relative risk [RR] 1.13, 95% confidence interval [CI] 0.95-1.34) was not associated with delayed diagnosis, while urinary tract infection (UTI; RR 1.52, 95% CI 1.32-1.76), nephrolithiasis (RR 1.23, 95% CI 1.06-1.44), new (RR 1.37, 95% CI 1.12-1.66) and recurrent prostate-related diagnoses (RR 1.61, 95% CI 1.23-2.10) were. For men presenting to non-urologists, UTI (RR 1.44, 95% CI 1.22-1.71), nephrolithiasis (RR 1.25 95% CI 1.05-1.49), new (RR 1.41, 95% CI 1.12-1.78) and recurrent prostate-related diagnoses (RR 1.94, 95% CI 1.45-2.58) were associated with delayed diagnosis; however, for men presenting to urologists, nephrolithiasis (RR 1.08 95% CI 0.78-1.49), new (RR 1.15, 95% CI 0.79-1.68) and recurrent prostate-related diagnoses (RR 1.17, 95% CI 0.69-1.97) were not associated with delayed diagnosis, while UTI diagnosis (RR 1.74, 95% CI 1.31-2.31) was still associated with delayed diagnosis. CONCLUSION: A UTUC diagnosis was made >90 days after haematuria presentation in approximately one-third of patients. Men experienced a longer median interval from haematuria to UTUC diagnosis compared with women, but male gender was not an independent predictor of delayed diagnosis. Benign diagnoses during haematuria evaluation were strongly associated with delayed diagnosis, especially among patients initially seen by non-urologists. Future interventions should focus on development of non-invasive techniques to improve clinical risk stratification of patients presenting with haematuria and to educate practitioners, especially non-urologists, with regard to the importance of a thoughtful haematuria evaluation and the common mimickers of UTUC, to help reduce delays in diagnosis.

Prostate Health Index density improves detection of clinically significant prostate cancer.

OBJECTIVES: To explore the utility of Prostate Health Index (PHI) density for the detection of clinically significant prostate cancer (PCa) in a contemporary cohort of men presenting for diagnostic evaluation of PCa. PATIENTS AND METHODS: The study cohort included patients with elevated prostate-specific antigen (PSA; >2 ng/mL) and negative digital rectal examination who underwent PHI testing and prostate biopsy at our institution in 2015. Serum markers were prospectively measured per standard clinical pathway. PHI was calculated as ([{-2}proPSA/free PSA] × [PSA]½ ), and density calculations were performed using prostate volume as determined by transrectal ultrasonography. Logistic regression was used to assess the ability of serum markers to predict clinically significant PCa, defined as any Gleason score ≥7 cancer or Gleason score 6 cancer in >2 cores or >50% of any positive core. RESULTS: Of 118 men with PHI testing who underwent biopsy, 47 (39.8%) were found to have clinically significant PCa on biopsy. The median (interquartile range [IQR]) PHI density was 0.70 (0.43-1.21), and was 0.53 (0.36-0.75) in men with negative biopsy or clinically insignificant PCa and 1.21 (0.74-1.88) in men with clinically significant PCa (P < 0.001). Clinically significant PCa was detected in 3.6% of men in the first quartile of PHI density (<0.43), 36.7% of men in the IQR of PHI density (0.43-1.21), and 80.0% of men with PHI density >1.21 (P < 0.001). Using a threshold of 0.43, PHI density was 97.9% sensitive and 38.0% specific for clinically significant PCa, and 100% sensitive for Gleason score ≥7 disease. Compared with PSA (area under the curve [AUC] 0.52), PSA density (AUC 0.70), %free PSA (AUC 0.75), the product of %free PSA and prostate volume (AUC 0.79), and PHI (AUC 0.76), PHI density had the highest discriminative ability for clinically significant PCa (AUC 0.84). CONCLUSIONS: Based on the present prospective single-centre experience, PHI density could be used to avoid 38% of unnecessary biopsies, while failing to detect only 2% of clinically significant cancers.

Tracking early readmission after pancreatectomy to index and nonindex institutions: a more accurate assessment of readmission.

IMPORTANCE: Readmission after pancreatectomy is common, but few data compare patterns of readmission to index and nonindex hospitals. OBJECTIVES: To evaluate the rate of readmission to index and nonindex institutions following pancreatectomy at a tertiary high-volume institution and to identify patient-level factors predictive of those readmissions. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of a prospectively collected institutional database linked to statewide data of patients who underwent pancreatectomy at a tertiary care referral center between January 1, 2005, and December 2, 2010. EXPOSURE: Pancreatectomy. MAIN OUTCOMES AND MEASURES: The primary outcome was unplanned 30-day readmission to index or nonindex hospitals. Risk factors and reasons for readmission were measured and compared by site using univariable and multivariable analyses. RESULTS: Among all 623 patients who underwent pancreatectomy during the study period, 134 (21.5%) were readmitted to our institution (105 [78.4%]) or to an outside institution (29 [21.6%]). Fifty-six patients (41.8%) were readmitted because of a gastrointestinal or nutritional problem related to surgery and 42 patients (31.3%) because of a postoperative infection. On multivariable analysis, factors independently associated with readmission included age 65 years or older (odds ratio [OR], 1.80; 95% CI, 1.19-2.71), preexisting liver disease (OR, 2.28; 95% CI, 1.23-4.24), distal pancreatectomy (OR, 1.77; 95% CI, 1.11-2.84), and postoperative drain placement (OR, 2.81; 95% CI, 1.00-7.14). CONCLUSIONS AND RELEVANCE: In total, 21.5% of patients required early readmission after pancreatectomy. Even in the setting of a tertiary care referral center, 21.6% of these readmissions were to nonindex institutions. Specific patient-level factors were associated with an increased risk of readmission.

The effect of repair costs on the profitability of a ureteroscopy program.

BACKGROUND AND PURPOSE: Ureteroscopy (URS) is a common treatment for patients with stone disease. One of the disadvantages of this approach is the great capital expense associated with the purchase and repair of endoscopic equipment. In some cases, these costs can outpace revenues and lead to an unprofitable and unsustainable enterprise. We sought to characterize the profitability of our URS program when accounting for endoscope maintenance and repair costs. MATERIALS AND METHODS: We identified all URS cases performed at a single hospital during fiscal year 2013 (FY2013). Charges, collection rates, and fixed and variable costs including annual equipment repair costs were obtained. The net margin and break-even point of URS were derived on a per-case basis. RESULTS: For 190 cases performed in FY2013, total endoscope repair costs totaled $115,000, resulting in an average repair cost of $605 per case. The vast majority of cases (94.2%) were conducted in the outpatient setting, which generated a net margin of $659 per case, while inpatient cases yielded a net loss of $455. URS was ultimately associated with a net positive margin approaching $600 per case. On break-even analysis, URS remained profitable until repair costs reached $1200 per case. CONCLUSIONS: Based on these findings, an established URS program can sustain profitability even with large equipment repair costs. Nonetheless, our findings serve to emphasize the importance of controlling costs, particularly in the current setting of decreasing reimbursement. A multifaceted approach, based on improving endoscope durability and exploring digital and disposable platforms, will be critical in maintaining the sustainability of URS.

Readmissions after complex aneurysm repair are frequent, costly, and primarily at nonindex hospitals.

OBJECTIVE: Readmissions after complex vascular surgery are not well studied. We sought to determine the rate of readmission after thoracic and thoracoabdominal aortic aneurysm repair (TAA/TAAAR) at our institution and to identify risk factors for and costs of readmission. METHODS: Using a prospectively collected institutional database in conjunction with a Maryland statewide database, we reviewed index admissions and early readmissions for all patients who underwent TAA/TAAAR between 2002 and 2013 at the Johns Hopkins Hospital. Only Maryland residents were included to capture readmissions to any Maryland hospital. RESULTS: We identified 115 Maryland residents (58% men; mean age, 65 ± 1.2 years) undergoing TAA/TAAAR (57% open repair). Early readmissions were frequent and occurred in 29% of patients. Of the readmitted patients, 79% (P < .001) were not readmitted to the index hospital where their operation was performed. Readmitted patients were not significantly different from nonreadmitted patients in age, gender, race, aneurysm type, and index length of stay. They were not different in preoperative comorbidities (including coronary artery disease, diabetes mellitus, smoking, renal insufficiency, and pulmonary disease), postoperative neurologic, renal, and cardiovascular complications, or 30-day or 5-year mortality. Multivariable analysis showed that significant risk factors for readmission were open repair (odds ratio, 3.12; 95% confidence interval, 1.12-9.54; P = .03) and postoperative pneumonia (odds ratio, 4.31; 95% confidence interval, 1.28-15.4; P = .02). Readmitted patients had significantly lower average income compared with the nonreadmitted cohort (U.S. $62,000 ± $4000 vs $73,000 ± $3000; P = .04). Striking differences were seen between patients readmitted to the index hospital where the operation was performed, and those who were readmitted to a nonindex hospital: patients readmitted to the index hospital were readmitted mainly for aneurysm-related surgical issues, whereas patients readmitted to the nonindex hospital were readmitted for medical morbidities. An aneurysm-related intervention was required in 75% of patients readmitted to the index hospital vs in 9% of patients readmitted to the nonindex hospital. Readmissions to a nonindex hospital cost significantly less than to the index hospital (U.S. $20,000 ± $4400 vs $42,000 ± $8800; P = .03) and were not associated with increased overall mortality. CONCLUSIONS: Early readmissions after TAA/TAAA repair are frequent and often occur at hospitals other than the index institution. Risk factors for readmission include open repair and postoperative pneumonia but not pre-existing patient comorbidities. Readmissions to nonindex hospitals were related to medical morbidities that were associated with fewer interventions and lower costs compared with the index hospital. Focusing on preoperative risk factors in this group of patients may not lead to reduction in readmissions. Minimizing nonsurgical complications may reduce post-TAA/TAAAR readmissions and the high costs associated with repeat care.