Sustained IL-6 and sTNF-αR1 levels after hip fracture predict 5-year mortality: A prospective cohort study from the Baltimore Hip Studies.

BACKGROUND: Persistent inflammation is associated with adverse health outcomes, but its impact on mortality has not been investigated previously among hip fracture patients. This article aims to investigate the influence of changes in levels of cytokines in the 2 months after a hip fracture repair on 5-year mortality. METHODS: This is a prospective cohort study from the Baltimore Hip Studies (BHS) with 191 community-dwelling older men and women (≥65 years) who had recently undergone surgical repair of an acute hip fracture, with recruitment from May 2006 to June 2011. Plasma interleukin-6 (IL-6), soluble tumor necrosis factor alpha receptor1 (sTNFα-R1), and interleukin-1 receptor agonist (IL-1RA) were obtained within 22 days of admission and at 2 months. All-cause mortality over 5 years was determined. Logistic regression analysis tested the associations between the cytokines' trajectories and mortality over 5 years, adjusted for covariates (age, sex, education, body mass index, lower extremity physical activities of daily living, and Charlson comorbidity index). RESULTS: High levels of IL-6 and sTNFα-R1 at baseline with small or no decline at 2 months were associated with higher odds of 5-year mortality compared with those with lower levels at baseline and greater decline at 2 months after adjustment for age, and other potential confounders (OR = 4.71, p = 0.01 for IL-6; OR = 15.03, p = 0.002 for sTNFα-R1). Similar results that failed to reach significance were found for IL-1RA (OR = 2.40, p = 0.18). Those with higher levels of cytokines at baseline with greater decline did not have significantly greater mortality than the reference group, those with lower levels at baseline and greater decline. CONCLUSION: Persistent elevation of plasma IL-6 and sTNFα-R1 levels within the first 2 months after hospital admission in patients with hip fracture is associated with higher 5-year mortality. These patients may benefit from enhanced care and earlier intensive interventions to reduce the risk of death.

Associations between living alone, social interactions, and physical performance differ by sex: Results from the Baltimore Hip Studies.

BACKGROUND: There is mixed evidence on whether living arrangements and social interactions are associated with poorer health outcomes after hip fracture repair. Distinct social profiles among male and female older adults may explain some of the differences. However, prior studies did not evaluate these differences by sex. This article aims to assess if the associations between living alone, social interaction, and physical performance differ by sex among hip fracture survivors. METHODS: This prospective cohort study is part of the Baltimore Hip Studies seventh cohort, with 168 male and 171 female hip fracture patients assessed at baseline (≤22 days after hospitalization) and at 2, 6, and 12 months post admission. Living arrangements and interaction with children or siblings and others in the past 2 weeks were collected at all visits. Physical performance was measured in the follow-up visits with the Short Physical Performance Battery (SPPB). Linear mixed models tested associations of living alone and social interaction with SPPB over time adjusted for age, education, comorbidities, physical functioning pre-fracture, cognitive function, self-rated health, and time. RESULTS: For men only, living alone was associated with worse performance (0.7 points lower SPPB scores, p = 0.05). Higher social interaction was associated with 0.8 and 1.2 point higher SPPB scores for men and women, respectively (p < 0.05). Visiting with friends was significantly associated with better function among males, while visiting with children or siblings was associated with worse SPPB among females. CONCLUSIONS: Living arrangements and types of social interaction are differentially associated with physical function for older men and women. Screening for social isolation/integration and including interventions that promote social interaction and participation should be considered in healthcare programs for hip fracture survivors.

Outcomes after endoscopic local excision of early-stage gastric adenocarcinoma in the United States.

BACKGROUND AND OBJECTIVES: Local excision (LE) for early-stage gastric cancer has expanded in the United States over recent years, however, national outcomes are unknown. The objective of the study was to evaluate national survival outcomes following LE for early-stage gastric cancer. METHODS: Patients with resectable gastric adenocarcinoma between 2010 and 2016 were identified from the National Cancer Database then classified by LE curability into eCuraA (high) and eCuraC (low) according to Japanese Gastric Cancer Association guidelines. Demographics, clinical/provider descriptors, and perioperative/survival outcomes were extracted. Propensity-weighted cox proportional hazards regression assessed factors associated with overall survival. RESULTS: Patients were stratified into eCuraA (N = 1167) and eCuraC (N = 13,905) subgroups. Postoperative 30-day mortality (0% vs 2.8%, p < 0.001) and readmission (2.3% vs 7.8%, p = 0.005) favored LE. Local excision was not associated with survival on propensity-weighted analyses. However, among eCuraC patients, LE was associated with higher likelihood of positive margins (27.1% vs 7.0%, p < 0.001), which was the strongest predictor of poor survival (HR 2.0, p < 0.001). CONCLUSIONS: Although early morbidity is low, oncologic outcomes following LE are compromised for eCuraC patients. These findings support careful patient selection and treatment centralization in the early adoption phase of LE for gastric cancer.

Artificial intelligence CAD tools in trauma imaging: a scoping review from the American Society of Emergency Radiology (ASER) AI/ML Expert Panel.

BACKGROUND: AI/ML CAD tools can potentially improve outcomes in the high-stakes, high-volume model of trauma radiology. No prior scoping review has been undertaken to comprehensively assess tools in this subspecialty. PURPOSE: To map the evolution and current state of trauma radiology CAD tools along key dimensions of technology readiness. METHODS: Following a search of databases, abstract screening, and full-text document review, CAD tool maturity was charted using elements of data curation, performance validation, outcomes research, explainability, user acceptance, and funding patterns. Descriptive statistics were used to illustrate key trends. RESULTS: A total of 4052 records were screened, and 233 full-text articles were selected for content analysis. Twenty-one papers described FDA-approved commercial tools, and 212 reported algorithm prototypes. Works ranged from foundational research to multi-reader multi-case trials with heterogeneous external data. Scalable convolutional neural network-based implementations increased steeply after 2016 and were used in all commercial products; however, options for explainability were narrow. Of FDA-approved tools, 9/10 performed detection tasks. Dataset sizes ranged from < 100 to > 500,000 patients, and commercialization coincided with public dataset availability. Cross-sectional torso datasets were uniformly small. Data curation methods with ground truth labeling by independent readers were uncommon. No papers assessed user acceptance, and no method included human-computer interaction. The USA and China had the highest research output and frequency of research funding. CONCLUSIONS: Trauma imaging CAD tools are likely to improve patient care but are currently in an early stage of maturity, with few FDA-approved products for a limited number of uses. The scarcity of high-quality annotated data remains a major barrier.

Examining transitions of care among nursing home residents with and without antipsychotic medication use.

OBJECTIVES: This study examines the association between antipsychotic (AP) medication use and care transitions in the nursing home (NH) population. METHODS: This cross-sectional study used data from a 5% random sample of Medicare beneficiaries between 2011 and 2015. Propensity score adjusted negative binomial regression was performed and conditional probabilities of having a first transition from the NH to specific locations were calculated. RESULTS: Among 150,284 eligible beneficiaries, the majority were female (67%), white (84%), and >75 years old (63%). Controlling for resident characteristics, the odds of having any transition was 5% lower among those with AP use [IRR (95% confidence interval (CI))=0.95(0.94-0.96)] relative to those with no AP use. Residents with AP use had higher proportions of transitions to hospital (22.7% vs. 19.5%, p < 0.01), emergency department (19.6% vs. 10.7%, p < 0.01), and different NH (1.5% vs. 0.4%, p < 0.01), and lower proportions of transition to non-healthcare locations compared to those without AP use. CONCLUSIONS: Findings demonstrate that residents with AP use had higher probabilities of transitions to more costly care settings such as the emergency department and hospital compared to those without AP use. Future longitudinal studies will help to inform clinical interventions aimed at improving the quality of care for this population.

Increasing utilization of endoscopic local excision for early-stage gastric cancers in the United States.

BACKGROUND: The Japanese Gastric Cancer Association provided updated criteria for endoscopic local excision of early-stage gastric cancer in 2018. The purpose of this study was to evaluate utilization patterns for endoscopic local excision in the United States for resectable gastric adenocarcinoma. METHODS: Patients with resectable gastric adenocarcinoma were identified from the National Cancer Database between 2010 and 2017. Patients were classified into strict appropriate criteria, expanded criteria, and inappropriate based on the Japanese Gastric Cancer Association guidelines. Factors associated with endoscopic local excision were identified using univariate and logistic multivariate regression. RESULTS: Within the National Cancer Database, 46,334 patients were stratified into strict appropriate criteria (n = 1,405), expanded criteria (n = 727), and inappropriate (n = 43,675). Annual cases of local excision increased by 76.9% over the study period, from 273 in 2010 to 483 in 2017. Among patients who underwent local excision, 10.1% were classified as strict appropriate criteria, 1.6% were classified as expanded criteria, and 84.5% were classified as inappropriate. Among inappropriate patients, factors associated with endoscopic local excision were: more recent year of diagnosis, increasing age, female sex, tumor located in the cardia, smaller size, low-grade, absence of lymphovascular invasion, and treatment at an academic facility. CONCLUSION: The use of endoscopic local excision for gastric cancer has nearly doubled since 2010. However, most patients do not satisfy consensus criteria for endoscopic therapy.

Reducing Inpatient Hypoglycemia in the General Wards Using Real-time Continuous Glucose Monitoring: The Glucose Telemetry System, a Randomized Clinical Trial.

OBJECTIVE: Use of real-time continuous glucose monitoring (RT-CGM) systems in the inpatient setting is considered investigational. The objective of this study was to evaluate whether RT-CGM, using the glucose telemetry system (GTS), can prevent hypoglycemia in the general wards. RESEARCH DESIGN AND METHODS: In a randomized clinical trial, insulin-treated patients with type 2 diabetes at high risk for hypoglycemia were recruited. Participants were randomized to RT-CGM/GTS or point-of-care (POC) blood glucose testing. The primary outcome was difference in inpatient hypoglycemia. RESULTS: Seventy-two participants were included in this interim analysis, 36 in the RT-CGM/GTS group and 36 in the POC group. The RT-CGM/GTS group experienced fewer hypoglycemic events (<70 mg/dL) per patient (0.67 [95% CI 0.34-1.30] vs. 1.69 [1.11-2.58], P = 0.024), fewer clinically significant hypoglycemic events (<54 mg/dL) per patient (0.08 [0.03-0.26] vs. 0.75 [0.51-1.09], P = 0.003), and a lower percentage of time spent below range <70 mg/dL (0.40% [0.18-0.92%] vs. 1.88% [1.26-2.81%], P = 0.002) and <54 mg/dL (0.05% [0.01-0.43%] vs. 0.82% [0.47-1.43%], P = 0.017) compared with the POC group. No differences in nocturnal hypoglycemia, time in range 70-180 mg/dL, and time above range >180-250 mg/dL and >250 mg/dL were found between the groups. The RT-CGM/GTS group had no prolonged hypoglycemia compared with 0.20 episodes <54 mg/dL and 0.40 episodes <70 mg/dL per patient in the POC group. CONCLUSIONS: RT-CGM/GTS can decrease hypoglycemia among hospitalized high-risk insulin-treated patients with type 2 diabetes.

PSA Doubling Time and Absolute PSA Predict Metastasis-free Survival in Men With Biochemically Recurrent Prostate Cancer After Radical Prostatectomy.

INTRODUCTION: The aim of this study was to investigate the association of prostate-specific antigen (PSA) values on metastasis-free survival (MFS) in men with biochemically recurrent prostate cancer (BRPC) and PSA doubling time (PSADT) < 12 months. This dataset also reflects an update with longer follow-up of our prior publications on the natural history of BRPC in the absence of treatment. MATERIALS AND METHODS: In this report, we combined databases from the Center for Prostate Disease Research and Johns Hopkins University (CPDR/JHU). In the CPDR/JHU radical prostatectomy database (30,936 total patients), 656 men with BRPC (> 0.2 ng/mL) after prostatectomy and PSADT < 12 months, who received no adjuvant/salvage androgen deprivation and/or radiation therapy, were prospectively followed until radiologic evidence of metastasis and are included in this analysis. RESULTS: Metastasis occurred in 250 of 656 patients with BRPC (median follow-up, 5 years). PSADT < 7.5 months and Gleason score were independent risk factors for distant metastasis in multivariable analysis. Risk of metastasis increased for PSADT 6.01 to 7.50, 4.51 to 6.0, 3.01 to 4.50, and ≤ 3.0 months, after adjusting for Gleason score. A PSA value ≥ 0.5 ng/mL significantly and independently increased risk of metastasis in patients with PSADT < 12 months (hazard ratio, 2.79; 95% confidence interval, 1.47-5.29; P = .001). CONCLUSIONS: In men with PSADT < 12 months, PSADT ≤ 7.5 months, PSA ≥ 0.5 ng/mL, and Gleason score are independent predictors of MFS on multivariable analysis.

Genetic Alterations Detected in Cell-Free DNA Are Associated With Enzalutamide and Abiraterone Resistance in Castration-Resistant Prostate Cancer.

PURPOSE: Androgen receptor (AR) gene alterations, including ligand-binding domain mutations and copy number (CN) gain, have yet to be fully established as predictive markers of resistance to enzalutamide and abiraterone in men with metastatic castration-resistant prostate cancer (mCRPC). The goal of this study was to validate AR gene alterations detected in cell-free DNA (cfDNA) as markers of enzalutamide and abiraterone resistance in patients with mCRPC. METHODS: Patients with mCRPC (N = 62) were prospectively enrolled between 2014 and 2018. Blood was collected before therapies-enzalutamide (n = 25), abiraterone (n = 35), or enzalutamide and abiraterone (n = 2)-and at disease progression. We used deep next-generation sequencing to analyze cfDNA for sequence variants and CN status in AR and 45 additional cancer-associated genes. Primary end points were prostate-specific antigen response, progression-free survival (PFS), and overall survival (OS). RESULTS: Elevated tumor-specific cfDNA (circulating tumor DNA) was associated with a worse prostate-specific antigen response (hazard ratio [HR], 3.17; 95% CI, 1.11 to 9.05; P = .031), PFS (HR, 1.76; 95% CI, 1.03 to 3.01; P = .039), and OS (HR, 2.92; 95% CI, 1.40 to 6.11; P = .004). AR ligand-binding domain missense mutations (HR, 2.51; 95% CI, 1.15 to 5.72; P = .020) were associated with a shorter PFS in multivariable models. AR CN gain was associated with a shorter PFS; however, significance was lost in multivariable modeling. Genetic alterations in tumor protein p53 (HR, 2.70; 95% CI, 1.27 to 5.72; P = .009) and phosphoinositide 3-kinase pathway defects (HR, 2.62; 95% CI, 1.12 to 6.10; P = .026) were associated with a worse OS in multivariable models. CONCLUSION: These findings support the conclusion that high circulating tumor DNA burden is associated with worse outcomes to enzalutamide and abiraterone in men with mCRPC. Tumor protein p53 loss and phosphoinositide 3-kinase pathway defects were associated with worse OS in men with mCRPC. AR status associations with outcomes were not robust, and additional validation is needed.

Predictors of a successful primary bladder closure in cloacal exstrophy: A multivariable analysis.

PURPOSE: To investigate the factors affecting primary bladder closure in cloacal exstrophy (CE). A successful primary closure is important for optimizing reconstructive outcomes, and it is a critical first-step in the reconstruction of CE. The authors' hypothesize that a smaller diastasis and use of an osteotomy are independent predictors of a successful closure. METHODS: A prospectively maintained database of 1332 exstrophy-epispadias complex (EEC) patients was reviewed for CE patients closed between 1975 and 2015. Univariate and multivariable analyses were performed to identify significant factors associated with CE primary bladder closure. RESULTS: Of 143 CE patients identified, 99 patients met inclusion criteria. Median follow-up time was 8.82 [IQR 5.43-14.26] years. In the multivariable model, the odds of having a successful closure are about 4 times greater for the staged cloacal approach compared to the 1-stage approach (OR, 3.7; 95% CI 1.2-11.5; p-value = 0.023). Also, having an osteotomy increases the chance of a successful closure by almost six-fold (OR, 5.8; 95% CI 1.7-19.6; p-value = 0.004). CONCLUSIONS: Using the staged approach with a pelvic osteotomy is paramount to a successful primary closure in CE. The authors strongly recommend using the staged approach and osteotomy as these factors independently increase the chance for a successful primary bladder closure. STUDY TYPE: Therapeutic study. LEVEL OF EVIDENCE: Level III, Retrospective comparative study.

Clinical utility of assessing PTEN and ERG protein expression in prostate cancer patients: a proposed method for risk stratification.

OBJECTIVES: To assess the prognostic value of ERG and PTEN protein expression as two of the most common genetic aberration in men with prostate cancer managed non-surgically by androgen deprivation therapy (ADT). MATERIALS AND METHODS: 463 tumor samples were assessed by double immunohistochemistry stains for ERG and PTEN and data correlated with clinical pathological features including, Gleason score, patients' outcome and ADT. RESULTS: ERG expression and PTEN protein loss were present in 28.2% and 38% of total patients respectively. There was a significant interplay between ERG and PTEN expression with 21.8% PTEN negative tumors being ERG positive (p < 0.001). Both ERG and PTEN showed significant association with lethal disease in all patients and those treated with prior ADT representing castrate-resistant disease. However, only PTEN remained significant in multivariable proportional hazards regression analysis, when including Gleason score and patients' age. Depending on patient's subgroup, intact positive PTEN intensity showed better cancer-specific survival with HR ranging from 0.25 to 0.4 compared to tumors with loss of PTEN expression. Assessing combined marker status, patients with decreased PTEN intensity without ERG positivity showed the worst clinical outcome compared to those with no PTEN loss and no ERG expression, where they had best clinical outcome. Patients with ERG expression with or without PTEN loss showed intermediate risk in relation to lethal disease. CONCLUSION: This study confirms a significant prognostic role for assessing ERG and PTEN in men with prostate cancer. It supports a role for utilizing combined ERG/PTEN status clinically and prospectively for stratifying PCa patients into different prognostic groups.

Prostate Specific Antigen Testing after Radical Prostatectomy-Can We Stop at 20 Years?

PURPOSE: We examined the clinical features and outcomes associated with delayed biochemical recurrence after radical prostatectomy, specifically among men with more than 20 years of followup. MATERIALS AND METHODS: A total of 16,720 men underwent radical prostatectomy and 2,699 experienced biochemical recurrence. We determined predictors of delayed biochemical recurrence as well as metastasis-free and cancer specific survival rates for recurrence at various time points after radical prostatectomy. We performed subset analysis of the 732 men with 20 or more years of recurrence-free followup. Cumulative incidence curves for metastasis and prostate cancer death were calculated and stratified by biochemical recurrence time points. RESULTS: Predictors of delayed biochemical recurrence included elevated prostate specific antigen at radical prostatectomy, higher clinical and pathological stage, and positive surgical margins. Delayed biochemical recurrence was associated with favorable cumulative incidence curves for metastasis and prostate cancer death compared to early biochemical recurrence. Among the 732 men with undetectable prostate specific antigen at 20 years biochemical recurrence developed in 17 (2.3%), metastatic disease developed in a single patient and none died of prostate cancer. The actuarial probability of biochemical recurrence among men with undetectable prostate specific antigen at 20 years increased with adverse pathological features. CONCLUSIONS: Men with delayed biochemical recurrence have favorable clinical features and improved survival. Men with undetectable prostate specific antigen 20 years after radical prostatectomy had a low rate of recurrence and no deaths from prostate cancer. This suggests that 20 years is a reasonable time to discontinue prostate specific antigen testing.

Prostate MRI prior to radical prostatectomy: effects on nerve sparing and pathological margin status.

OBJECTIVES: The aim of this study was to assess the positive surgical margin (PSM) and nerve sparing (NS) rates in patients who underwent prostate MRI (pMRI) prior to radical prostatectomy (RP) and compare them with matched, nonimaged control RP patients. METHODS: We identified 204 men who underwent preoperative pelvic MRI (pelMRI), of whom 176 (86.3%) underwent pMRIs, within 60 days of RP, and compared them (1:1) with a nonim-aged control group matched by surgeon, age, race, body mass index (BMI), prostate-specific antigen (PSA), pathological Gleason score, prostate specimen weight, and RP year. RESULTS: The rates of nonfocal extracapsular extension (nfECE) on RP pathology in the MRI and control groups were similar. PSM rates were lower in the MRI group (13.7% vs 19.3%; P=0.14), but the difference did not meet statistical significance; this was also the case in patients with nfECE on RP pathology (27.7% vs 39.5%; P=0.3). NS rates were similar between groups. In the MRI group, 54 (26.5%) patients had an MRI suspicious for nfECE; their PSM rate (20.4%) was higher than that of patients with an MRI not suspicious for nfECE (11.3%; P=0.11), but the difference lacked statistical significance; the former group had significantly lower rates of NS. Limitations of the study include sample power and nonuniform heeding of MRI results by each surgeon. CONCLUSION: MRI did not significantly decrease the rates of PSM, including in the subset of patients with nfECE on final pathology. Even wider resection may be necessary in patients with MRIs suggesting locally-advanced disease. Studies with greater power are needed.

Patterns of Pelvic Lymph Node Dissection at the Time of Radical Prostatectomy for Low-risk Men.

OBJECTIVE: To examine nationwide patterns of lymph node dissection (LND) in men with D'Amico low-risk prostate cancer, including the rate of detected lymph node metastasis and factors associated with the decision to perform LND. Existing guidelines recommend against LND at the time of radical prostatectomy (RP) in low-risk men, yet this is still a common practice. MATERIALS AND METHODS: The 2013 National Cancer Database includes 1,208,180 cases of prostate cancer diagnosed between 2004 and 2013. Of these, 50,245 met D'Amico low-risk criteria, had complete clinicopathologic data, and underwent RP. Mixed effects multivariable logistic regression models were used to identify hospital and treatment characteristics independently associated with LND, extended LND, and the detection of lymph node metastasis. RESULTS: A total of 20,556 men (40.9%) underwent LND and 4360 (8.7%) had extended LND. Lymph node metastasis was present in 76 cases (0.37%). On multivariable analysis, robotic vs open RP had odds ratio (OR) = 0.16 (0.14-0.17), P < .0001, for LND, and surgery at an academic center had OR = 1.76 (1.33-2.33), P < .0001, for LND. Men on Medicaid were less likely than the privately insured to undergo LND, and the highest earners were most likely to undergo LND. In multivariable analysis, race was significantly associated with lymph node metastasis, with black men having the highest rates (P < .0001). CONCLUSION: LND is performed in nearly half of low-risk men, more commonly during open surgery at academic centers, yet metastasis is discovered less than 1% of the time. Guidelines suggest that percentage core involvement should be considered, but if the overall risk of metastasis is low, LND should not be performed.

Prediction of pathological stage based on clinical stage, serum prostate-specific antigen, and biopsy Gleason score: Partin Tables in the contemporary era.

OBJECTIVE: To update the Partin Tables for prediction of pathological stage in the contemporary setting and examine trends in patients treated with radical prostatectomy (RP) over the past three decades. PATIENTS AND METHODS: From January 2010 to October 2015, 4459 men meeting inclusion criteria underwent RP and pelvic lymphadenectomy for histologically confirmed prostate cancer at the Johns Hopkins Hospital. Preoperative clinical stage, serum prostate-specific antigen (PSA) level, and biopsy Gleason score (i.e. prognostic Grade Group) were used in a polychotomous logistic regression model to predict the probability of pathological outcomes categorised as: organ-confined (OC), extraprostatic extension (EPE), seminal vesicle involvement (SV+), or lymph node involvement (LN+). Preoperative characteristics and pathological findings in men treated with RP since 1983 were collected and clinical-pathological trends were described. RESULTS: The median (range) age at surgery was 60 (34-77) years and the median (range) PSA level was 4.9 (0.1-125.0) ng/mL. The observed probabilities of pathological outcomes were: OC disease in 74%, EPE in 20%, SV+ in 4%, and LN+ in 2%. The probability of EPE increased substantially when biopsy Gleason score increased from 6 (Grade Group 1, GG1) to 3 + 4 (GG2), with smaller increases for higher grades. The probability of LN+ was substantially higher for biopsy Gleason score 9-10 (GG5) as compared to lower Gleason scores. Area under the receiver operating characteristic curves for binary logistic models predicting EPE, SV+, and LN+ vs OC were 0.724, 0.856, and 0.918, respectively. The proportion of men treated with biopsy Gleason score ≤6 cancer (GG1) was 47%, representing a substantial decrease from 63% in the previous cohort and 77% in 2000-2005. The proportion of men with OC cancer has remained similar during that time, equalling 73-74% overall. The proportions of men with SV+ (4.1% from 3.4%) and LN+ (2.3% from 1.4%) increased relative to the preceding era for the first time since the Partin Tables were introduced in 1993. CONCLUSIONS: The Partin Tables remain a straightforward and accurate approach for projecting pathological outcomes based on readily available clinical data. Acknowledging these data are derived from a tertiary care referral centre, the proportion of men with OC disease has remained stable since 2000, despite a substantial decline in the proportion of men with biopsy Gleason score 6 (GG1). This is consistent with the notion that many men with Gleason score 6 (GG1) disease were over treated in previous eras.

The Impact of Downgrading from Biopsy Gleason 7 to Prostatectomy Gleason 6 on Biochemical Recurrence and Prostate Cancer Specific Mortality.

PURPOSE: Gleason score is one of the most important prognostic indicators for prostate cancer. Downgrading from biopsy Gleason score 7 to radical prostatectomy Gleason score 6 occurs commonly and yet to our knowledge the impact on survival outcomes is unknown. We examined biochemical recurrence and prostate cancer specific mortality risk in a large cohort evaluated by a single group of expert urological pathologists. MATERIALS AND METHODS: Of 23,918 men who underwent radical prostatectomy at our institution between 1984 and 2014, 10,236 with biopsy and radical prostatectomy Gleason score 6 or 7 without upgrading were included in analysis. The cohort was divided into 3 groups, including group 1-biopsy and radical prostatectomy Gleason score 6 in 6,923 patients (67.6%), group 2-Gleason score 7 downgraded to radical prostatectomy Gleason score 6 in 648 (6.3%) and group 3-biopsy and radical prostatectomy Gleason score 7 in 2,665 (26.0%). Biochemical recurrence and prostate cancer specific mortality risks were compared using Cox regression and competing risk analyses adjusting for clinicopathological variables. RESULTS: At a median followup of 5 years (range 1 to 29), 992 men experienced biochemical recurrence and 95 had died of prostate cancer. Biochemical recurrence-free survival in downgraded cases (group 2) was better than in group 3 cases, which had Gleason score 7 on biopsy and radical prostatectomy (p <0.001), but worse than group 1 cases, which had Gleason score 6 on biopsy and radical prostatectomy (p <0.001). Downgrading was independently associated with biochemical recurrence (adjusted HR 1.87, p <0.0001) but not with prostate cancer specific mortality (adjusted HR 1.65, p = 0.636). CONCLUSIONS: Downgrading from biopsy Gleason score 7 to radical prostatectomy Gleason score 6 was an independent predictor of biochemical recurrence but not prostate cancer specific mortality, likely due to the presence of minor amounts of Gleason pattern 4.

New Prostate Cancer Grading System Predicts Long-term Survival Following Surgery for Gleason Score 8-10 Prostate Cancer.

BACKGROUND: The newly proposed five-tiered prostate cancer grading system (PCGS) divides Gleason score (GS) 8-10 disease into GS 8 and GS 9-10 on the basis of biochemical recurrence (BCR) following radical prostatectomy (RP) as an outcome. However, BCR does not necessarily portend worse survival outcomes. OBJECTIVE: To assess the significance of distinguishing GS 8 versus 9-10 disease in terms of long-term survival outcomes for both the preoperative setting using biopsy (Bx) GS and the postoperative setting with RP GS. DESIGN, SETTING, AND PARTICIPANTS: Of 23918 men who underwent RP between 1984 and 2014, there were 721 men with biopsy GS 8-10, and 1047 men with RP GS 8-10. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Clinicopathologic characteristics were compared between men with GS 8 and those with GS 9-10. We compared all-cause mortality (ACM) and prostate cancer-specific mortality (PCSM) risk between the groups using Cox regression and competing-risks analyses, adjusting for other perioperative variables and death from other causes as the competing event. RESULTS AND LIMITATIONS: Compared to men with GS 8, men with GS 9-10 had later RP year and higher pathologic stage. Among men with Bx GS 8-10, 115 died (82 due to PC) with median follow-up of 3 yr (interquartile range [IQR] 1-7) for both overall and cancer-specific survival. Of men with RP GS 8-10, 221 died (151 due to PC) with median follow-up of 4 yr (IQR 2-8) and 4 yr (IQR 2-9) for overall and cancer-specific survival, respectively. PC-specific survival rates were significantly lower for men with GS 9-10 compared to men with GS 8 for both Bx (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.37-3.30; p<0.01) and RP GS (HR 2.38, 95% CI 1.74-3.28; p<0.01). This association persisted in multivariable models after adjusting for perioperative variables. CONCLUSIONS: Men with GS 9-10 had higher ACM and PCSM rates compared to those with GS 8. GS 8 and GS 9-10 PC should be considered separately in both the preoperative and postoperative setting as suggested by the new PCGS. PATIENT SUMMARY: The prostate cancer grading system can predict mortality risk after radical prostatectomy (RP) for men with Gleason score 8-10 disease based on both biopsy and RP Gleason scores. There are significant differences in all-cause mortality and prostate cancer-specific mortality following surgery between men with Gleason score 8 and those with Gleason score 9-10 disease.

Blood Transfusion is Associated with Increased Perioperative Morbidity and Adverse Oncologic Outcomes in Bladder Cancer Patients Receiving Neoadjuvant Chemotherapy and Radical Cystectomy.

PURPOSE: Perioperative blood transfusion (PBT) has been inconsistently associated with adverse outcomes. Bladder cancer patients are unique as they frequently undergo neoadjuvant chemotherapy (NAC) with resulting immunosuppression, which may be exacerbated by transfusion-related immunomodulation. We examined the effect of leukoreduced PBT on oncologic outcomes and perioperative morbidity in radical cystectomy (RC) patients who received NAC, quantifying exposure with a novel dose-index variable. METHODS: The Johns Hopkins Radical Cystectomy database was queried for patients who had undergone NAC followed by RC from 2010 to 2013. Overall, 119 patients had available PBT and survival data. A multivariable Cox model evaluated risk factors, including pathologic stage, Charlson Comorbidity Index, age, race, year of surgery, surgical margin status, PBT, and preoperative hemoglobin for bladder cancer-specific survival (CSS) and overall survival (OS). Logistic regression models determined factors that were independently associated with perioperative morbidity. RESULTS: Median follow-up was 7.8 months (range 0.2-41.8), and during follow-up there were 25 deaths and 21 cancer deaths. PBT significantly predicted OS (hazard ratio [HR] 1.26, 95 % confidence interval [CI] 1.07-1.49; p = 0.005), CSS (HR 1.32, 95 % CI 1.11-1.57; p = 0.002), and morbidity (odds ratio [OR] 1.67, 95 % CI 1.26-2.21; p = 0.004) in univariate analyses. In multivariable models, PBT was significantly associated with morbidity (OR 1.77, 95 % CI 1.30-2.39; p = 0.0002), but not OS or CSS. Intraoperative transfusion was associated with decreased OS and CSS, and increased morbidity, whereas postoperative transfusion was only associated with increased morbidity. CONCLUSIONS: Intraoperative blood transfusion was associated with increased perioperative morbidity and worsened OS and CSS in patients undergoing RC who had NAC. Although PBT may be life-saving in certain patients, a restrictive transfusion strategy may improve outcomes.

Predictors of Adverse Pathology in Men Undergoing Radical Prostatectomy Following Initial Active Surveillance.

OBJECTIVE: To report pathologic outcomes and predictors of adverse pathology in men undergoing radical prostatectomy (RP) after an initial period of active surveillance (AS). METHODS: We studied pathologic outcomes in men who underwent RP after some time on AS. Pathologic outcomes were compared between men with and without evidence of disease reclassification on AS. Rates of adverse pathology (defined as pathologic stage ≥ pT3a, RP Gleason ≥ 4+3, or lymph node involvement) were determined and were compared depending on the variable that defined disease reclassification. RESULTS: Of 1086 men enrolled in AS, 130 (12.0%) underwent RP after a median time of 1.96 years (range, 0.55-12.26 years) on AS. Ninety-seven (74.6%) of these men had evidence of disease reclassification on AS. Rates of adverse pathology were greater in men with evidence of reclassification compared to those without (P = .05). Among men with disease reclassification, rates of adverse pathology ranged from 23.8% to 44.7% depending on the variable used to define reclassification. Longer time on AS was not associated with adverse pathology (P = .68). CONCLUSION: Adverse pathology after RP is more common in men with evidence of disease reclassification on AS compared to those undergoing RP for other reasons. However, we identified varying outcomes among these patients depending on the criterion that defined reclassification. These data may enable identification of men who can safely continue on AS despite evidence of disease reclassification.