Publications by authors named "Misop Han"

147 Publications

Obesity is Associated with Shorter Telomere Length in Prostate Stromal Cells in Men with Aggressive Prostate Cancer.

Cancer Prev Res (Phila) 2021 Apr 22;14(4):463-470. Epub 2020 Dec 22.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

In our prior studies, obesity was associated with shorter telomeres in prostate cancer-associated stromal (CAS) cells, and shorter CAS telomeres were associated with an increased risk of prostate cancer death. To determine whether the association between obesity and shorter CAS telomeres is replicable, we conducted a pooled analysis of 790 men who were surgically treated for prostate cancer, whose tissue samples were arrayed on five tissue microarray (TMA) sets. Telomere signal was measured using a quantitative telomere-specific FISH assay and normalized to 4',6-diamidino-2-phenylindole for 351 CAS cells (mean) per man; men were assigned their median value. Weight and height at surgery, collected via questionnaire or medical record, were used to calculate body mass index (BMI; kg/m) and categorize men as normal (<25), overweight (25 ≤ BMI < 30), or obese (≥30). Analyses were stratified by grade and stage. Men were divided into tertiles of TMA- (overall) or TMA- and disease aggressiveness- (stratified) specific distributions; short CAS telomere status was defined by the bottom two tertiles. We used generalized linear mixed models to estimate the association between obesity and short CAS telomeres, adjusting for age, race, TMA set, pathologic stage, and grade. Obesity was not associated with short CAS telomeres overall, or among men with nonaggressive disease. Among men with aggressive disease (Gleason≥4+3 and stage>T2), obese men had a 3-fold increased odds of short CAS telomeres (OR: 3.06; 95% confidence interval: 1.07-8.75; = 0.045) when compared with normal weight men. Telomere shortening in prostate stromal cells may be one mechanism through which lifestyle influences lethal prostate carcinogenesis. PREVENTION RELEVANCE: This study investigates a potential mechanism underlying the association between obesity and prostate cancer death. Among men with aggressive prostate cancer, obesity was associated with shorter telomeres prostate cancer associated stromal cells, and shorter CAS telomeres have been associated with an increased risk of prostate cancer death.
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http://dx.doi.org/10.1158/1940-6207.CAPR-20-0250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026488PMC
April 2021

Comparison of Perioperative and Pathologic Outcomes Between Single-port and Standard Robot-assisted Radical Prostatectomy: An Analysis of a High-volume Center and the Pooled World Experience.

Urology 2021 Jan 5;147:223-229. Epub 2020 Sep 5.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD.

Objective: To perform an early comparative study of outcomes between single-port and robot-assisted laparoscopic radical prostatectomy (SP-RALRP) and standard RALRP at our institution and pooled analysis of series to date.

Patients And Methods: Patients with organ-confined prostate cancer undergoing SP-RALRP at a high-volume institution were identified retrospectively along with reported SP-RALRP series to date. Data were compared to a contemporary prospective cohort of men undergoing standard RALRP. Patient demographics, perioperative and postoperative data, and complications categorized by the Clavien-Dindo system were compared for the institutional and pooled SP-RALRP cohorts to standard RALRP.

Results: A total of 208 SP-RALRP cases were identified (26 from our institution) and compared to 376 standard RALRP cases. In the institutional analysis, there was no difference in operative time, length of stay, overall complications (15.4% vs 17.3%, P= 1.0), major (Clavien ≥III) complications (3.8% vs 3.7%, P = .6), inpatient opioid use, or patient-reported pain scores; median estimated blood loss (100 mL vs 150 mL, P = .02) and number of lymph nodes removed (5.5 vs 9, P = .002) were lower for SP-RALRP. In the pooled analysis, 208 patients receiving SP-RALRP had similar estimated blood loss and complication rates but fewer lymph nodes removed (P = .02) and marginally longer operating time (+16 minutes, P = .01) compared to standard RALRP. The difference in rate of positive surgical margins was not statistically significant (31.3% vs 24.5%, P = .08).

Conclusion: Based on an early experience with SP-RALRP at a high-volume center and a pooled analysis of SP series to date, perioperative and pathologic outcomes appear nearly equivalent compared to standard RALRP.
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http://dx.doi.org/10.1016/j.urology.2020.08.046DOI Listing
January 2021

Clinical stage provides useful prognostic information even after pathological stage is known for prostate cancer in the PSA era.

PLoS One 2020 11;15(6):e0234391. Epub 2020 Jun 11.

Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States of America.

Background: Pathological and clinical stage are associated with prostate cancer-specific survival after prostatectomy. With PSA screening, the post-surgery prognostic utility of clinical stage is debatable in studies seeking to identify new biomarkers. Few studies have investigated clinical stage and lethal prostate cancer association after accounting for pathological stage. We hypothesize that clinical stage provides prognostic information beyond pathological stage in the PSA era.

Methods: Cox regression models tested associations between clinical and pathological stage and lethal prostate cancer among 3,064 participants from the Health Professionals Follow-Up Study and Physicians' Health Study (HPFS/PHS) who underwent prostatectomy. Likelihood ratio tests and c-statistics were used to assess the models' prognostic utility. Equivalent analyses were performed in 16,134 men who underwent prostatectomy at Johns Hopkins.

Results: Independently, clinical and pathological stage were associated (p<0.0001 for both) with rate of lethal prostate cancer in HPFS/PHS. The model with clinical and pathological stage fit significantly better than the model with only pathological stage in all men (p = 0.01) and in men diagnosed during the PSA era (p = 0.04). The mutually adjusted model also improved discriminatory ability. In the Johns Hopkins cohort, the model with clinical and pathological stage improved discriminatory ability and fit significantly better overall (p<0.0001) and in the PSA era (p<0.0001).

Conclusions: Despite stage migration resulting from widespread PSA screening, clinical stage remains associated with progression to lethal prostate cancer independent of pathological stage. Future studies evaluating associations between new factors and poor outcome following prostatectomy should consider including both clinical and pathological stages since the data is already available.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0234391PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289430PMC
August 2020

Effect of Pharmacologic Prophylaxis on Venous Thromboembolism After Radical Prostatectomy: The PREVENTER Randomized Clinical Trial.

Eur Urol 2020 09 19;78(3):360-368. Epub 2020 May 19.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Background: Direct high-quality evidence is lacking evaluating perioperative pharmacologic prophylaxis (PP) after radical prostatectomy (RP) to prevent venous thromboembolism (VTE) leading to significant practice variation.

Objective: To study the impact of in-hospital PP on symptomatic VTE incidence and adverse events after RP at 30 d, with the secondary objective of evaluating overall VTE in a screening subcohort.

Design, Setting, And Participants: A prospective, phase 4, single-center, randomized trial of men with prostate cancer undergoing open or robotic-assisted laparoscopic RP was conducted (July 2017-November 2018).

Intervention: PP (subcutaneous heparin) plus routine care versus routine care alone. The screening subcohort was offered lower extremity duplex ultrasound at 30 d.

Outcomes Measurements And Statistical Analysis: The primary efficacy outcome was symptomatic VTE incidence (pulmonary embolism [PE] or deep venous thrombosis [DVT]). Primary safety outcomes included the incidence of symptomatic lymphocele, hematoma, or bleeding after surgery. Secondary outcomes were overall VTE, estimated blood loss, total surgical drain output, complications, and surveillance imaging bias. Fisher's exact test and modified Poisson regression were performed.

Results And Limitations: A total of 501 patients (75% robotic) were randomized and >99% (500/501) completed follow-up. At second interim analysis (N = 445), the symptomatic VTE rate was 2.3% (four PE + DVT and one DVT) for routine care versus 0.9% (one PE + DVT and one DVT) for PP (relative risk 0.40 [95% confidence interval 0.08-2.03], p = 0.3) meeting a futility threshold for early stopping. In the screening subcohort, the overall VTE rate was 3.3% versus 2.4% (p = 0.7). Results were similar at the final analysis (symptomatic VTE: 2.0% vs 0.8%, p = 0.3; overall VTE: 2.9% vs 2.8%, p = 1). No differences were observed in safety or secondary outcomes. All VTE events (seven symptomatic and three asymptomatic) occurred in patients undergoing pelvic lymph node dissection.

Conclusions: This study was not able to demonstrate a statistically significant reduction in symptomatic VTE associated with PP. There was no increase in the development of symptomatic lymphoceles, bleeding, or other adverse events. Given that the event rate was lower than powered for, further research is needed among high-risk patients (Caprini score ≥8) or patients receiving pelvic lymph node dissection.

Patient Summary: In this report, we randomized patients undergoing radical prostatectomy to perioperative pharmacologic prophylaxis or routine care alone. We found that pharmacologic prophylaxis did not reduce postoperative symptomatic venous thromboembolism significantly for men at routine risk. Importantly, pharmacologic prophylaxis did not increase adverse events, such as formation of lymphoceles or bleeding, and can safely be implemented when indicated for patients with risk factors undergoing radical prostatectomy.
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http://dx.doi.org/10.1016/j.eururo.2020.05.001DOI Listing
September 2020

Reducing preoperative blood orders and costs for radical prostatectomy.

J Comp Eff Res 2020 02 11;9(3):219-226. Epub 2020 Feb 11.

The James Buchanan Brady Urological Institute & Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.

A maximum surgical blood order schedule (MSBOS) was implemented at our institution to optimize preoperative blood ordering and reduce unnecessary blood preparation for patients undergoing radical prostatectomy (RP), a common urologic procedure. We conducted a retrospective review of patients who underwent RP from 2010 to 2016 and categorized patients by date of RP (pre- or post-MSBOS) and compared preoperative blood-ordering practices. After MSBOS implementation, preoperative blood orders changed from predominantly type and cross-match 2 units (53%) to no sample (56%) for robot-assisted laparoscopic RP, and from mostly type and cross-match 2 units (62%) to type and screen (75%) for open RP with resultant cost savings. MSBOS implementation and compliance decreases unnecessary preoperative blood orders.
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http://dx.doi.org/10.2217/cer-2019-0126DOI Listing
February 2020

Effect of a prospective opioid reduction intervention on opioid prescribing and use after radical prostatectomy: results of the Opioid Reduction Intervention for Open, Laparoscopic, and Endoscopic Surgery (ORIOLES) Initiative.

BJU Int 2020 03 15;125(3):426-432. Epub 2019 Nov 15.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objectives: To evaluate the effect of a prospective opioid reduction intervention after radical prostatectomy (RP; based on a surgery-specific guideline and education) on post-discharge opioid prescribing, use, disposal, and need for additional opioid medication.

Patients And Methods: A prospective, non-randomised, pre-post interventional trial of patients undergoing RP for prostate cancer (August 2017-November 2018) was conducted as part of the Opioid Reduction Intervention for Open, Laparoscopic, and Endoscopic Surgery (ORIOLES) Initiative. An evidence-based intervention including: a discharge sheet, nursing education, and standardised prescribing guideline, was applied with the primary outcome of total oral morphine equivalents (OMEQ) used after RP. Secondary outcomes included opioid prescribing, opioid disposal, need for additional opioid medication, and presence of incisional/post-surgical abdominal pain at 30 days after RP.

Results: A total of 214 (Pre-Intervention arm) and 229 (Post-Intervention arm) adult patients were enrolled (100% follow-up). The intervention reduced post-discharge opioid prescribing (from 224.3 to 120.3 mg; -46.4%, P = 0.01), reduced opioid use (from 52.1 to 38.3 mg; -26.5%, P < 0.01), and increased opioid disposal (+13.5%, P < 0.01). Greater prescribing of opioids at discharge, higher body mass index, and use of opioid medication prior to surgery, were independently associated with greater post-discharge opioid use, while history of a chronic pain diagnosis was not statistically significant. In the Post-Intervention cohort, 2.2% of patients needed additional medication for post-surgical pain (0.9% obtained a prescription) and 1.3% initiated long-term use.

Conclusions: A prospective, evidence-based intervention reduced post-discharge opioid prescribing and use, while increasing disposal after RP. Risk factors for increased opioid use were identified. The results support expanding the use of evidence-based opioid reduction interventions to other surgical specialties.
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http://dx.doi.org/10.1111/bju.14932DOI Listing
March 2020

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

Clin Genitourin Cancer 2019 12 21;17(6):470-475.e1. Epub 2019 Aug 21.

Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.

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.
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http://dx.doi.org/10.1016/j.clgc.2019.08.002DOI Listing
December 2019

Robotic Transrectal Ultrasound Guided Prostate Biopsy.

IEEE Trans Biomed Eng 2019 09 7;66(9):2527-2537. Epub 2019 Jan 7.

We present a robot-assisted approach for transrectal ultrasound (TRUS) guided prostate biopsy. The robot is a hands-free probe manipulator that moves the probe with the same 4 DoF that are used manually. Software was developed for three-dimensional (3-D) imaging, biopsy planning, robot control, and navigation. Methods to minimize the deformation of the prostate caused by the probe at 3-D imaging and needle targeting were developed to reduce biopsy targeting errors. We also present a prostate coordinate system (PCS). The PCS helps defining a systematic biopsy plan without the need for prostate segmentation. Comprehensive tests were performed, including two bench tests, one imaging test, two in vitro targeting tests, and an IRB-approved clinical trial on five patients. Preclinical tests showed that image-based needle targeting can be accomplished with accuracy on the order of 1 mm. Prostate biopsy can be accomplished with minimal TRUS pressure on the gland and submillimetric prostate deformations. All five clinical cases were successful with an average procedure time of 13 min and millimeter targeting accuracy. Hands-free TRUS operation, transrectal TRUS guided prostate biopsy with minimal prostate deformations, and the PCS-based biopsy plan are novel methods. Robot-assisted prostate biopsy is safe and feasible. Accurate needle targeting has the potential to increase the detection of clinically significant prostate cancer.
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http://dx.doi.org/10.1109/TBME.2019.2891240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726124PMC
September 2019

Evaluating the impact of length of time from diagnosis to surgery in patients with unfavourable intermediate-risk to very-high-risk clinically localised prostate cancer.

BJU Int 2019 08 27;124(2):268-274. Epub 2019 Jan 27.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Objective: To evaluate the impact of length of time from diagnostic biopsy to radical prostatectomy (RP) on oncological outcomes amongst men diagnosed with unfavourable intermediate- to very-high-risk clinically localised prostate cancer.

Patients And Methods: We performed a retrospective review of men with a diagnosis of grade group (GG) ≥3 prostate cancer on biopsy, who underwent RP within 6 months of diagnosis, at our institution between 2005 and 2018. We assessed patient demographics, pre-biopsy disease characteristics, and receipt of neoadjuvant therapy. We categorised time between biopsy and RP into two intervals: <3 and 3-6 months. For each GG, we compared receipt of adjuvant therapy, pathological outcomes at RP (positive surgical margin [PSM], extraprostatic extension [EPE], seminal vesicle invasion [SVI], and lymph node involvement [LNI]), risk of 2- and 5-year biochemical recurrence-free survival (BCRFS), and 2-, 5-, and 10-year metastasis-free survival (MFS) between patients who underwent RP at <3 vs 3-6 months after diagnosis.

Results: Amongst 2303 men who met the study inclusion criteria, 1244 (54%) had GG 3, 608 (26%) had GG 4, and 451 (20%) had GG 5 disease. In all, 72% underwent RP at <3 months after diagnosis. For each diagnostic GG, there was no significant difference in rates of adjuvant therapy, PSM, EPE, SVI, or LNI in men who had RP at <3 vs 3-6 months after diagnosis. In all, 1568 men had follow-up after RP of >1 year. For each diagnostic GG, there was no significant difference in 2- and 5-year BCRFS between patients who had RP at <3 vs 3-6 months after diagnosis (GG 3: 78% vs 83% and 69% vs 66%, respectively, P = 0.6; GG 4: 68% vs 74% and 51% vs 57%, respectively, P = 0.4; GG 5: 58% vs 74% and 48% vs 54%, respectively, P = 0.2). Similarly, for each diagnostic GG, there was no significant difference in 2-, 5-, and 10-year MFS between patients who had RP at <3 vs 3-6 months after diagnosis, although we were not able to calculate 10-year MFS for patients with GG 5 disease due to limited follow-up in that group (GG 3: 98%, 92%, and 84% vs 97%, 95%, and 91%, respectively, P = 0.4; GG 4: 97%, 90%, and 72% vs 94%, 91%, and 81%, respectively, P = 0.8; GG 5: 89% and 81% vs 91% and 71%, respectively, P = 0.9).

Conclusions: Waiting for RP up to 6 months after diagnosis is not associated with adverse outcomes amongst patients with unfavourable intermediate- to very-high-risk prostate cancer.
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http://dx.doi.org/10.1111/bju.14659DOI Listing
August 2019

Aspirin and Non-Aspirin NSAID Use and Prostate Cancer Incidence, Mortality, and Case Fatality in the Atherosclerosis Risk in Communities Study.

Cancer Epidemiol Biomarkers Prev 2019 03 28;28(3):563-569. Epub 2018 Nov 28.

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Background: NSAIDs appear to moderately reduce prostate cancer risk. However, evidence is limited on whether NSAIDs protect against prostate cancer mortality (death from prostate cancer among men without a cancer history) and case fatality (death from prostate cancer among men with prostate cancer), and whether benefits are consistent in white and black men. This study investigated associations of aspirin and non-aspirin (NA) NSAID use with prostate cancer incidence, mortality, and case fatality in a population-based cohort of white and black men.

Methods: We included 6,594 men (5,060 white and 1,534 black) from the Atherosclerosis Risk in Communities study without a cancer history at enrollment from 1987 to 1989. NSAID use was assessed at four study visits (1987-1998). Cancer outcomes were ascertained through 2012. Cox proportional hazards regression was used to estimate adjusted HRs, overall and by race.

Results: Aspirin use was not associated with prostate cancer incidence. However, aspirin use was inversely associated with prostate cancer mortality [HR, 0.59; 95% confidence interval (CI), 0.36-0.96]. This association was consistent among white and black men and appeared restricted to men using aspirin daily and/or for cardiovascular disease prevention. Aspirin use was inversely associated with case fatality (HR, 0.45; 95% CI, 0.22-0.94). NA-NSAID use was not associated with these endpoints.

Conclusions: Aspirin use was inversely associated with prostate cancer mortality and case fatality among white and black men.

Impact: If confirmed by additional studies, benefits of aspirin for preventing prostate cancer mortality may need to be factored into risk-benefit calculations of men considering an aspirin regimen.
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http://dx.doi.org/10.1158/1055-9965.EPI-18-0965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401240PMC
March 2019

Outcomes of very high-risk prostate cancer after radical prostatectomy: Validation study from 3 centers.

Cancer 2019 02 13;125(3):391-397. Epub 2018 Nov 13.

Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Among men with localized high-risk prostate cancer (PCa), patients who meet very high-risk (VHR) criteria have been shown to experience worse outcomes after radical prostatectomy (RP) in a previous study. Variations of VHR criteria have been suggested to be prognostic in other single-center cohorts, but multicenter outcomes validating VHR criteria have not been described. This study was designed to validate VHR criteria for identifying which PCa patients are at greatest risk for cancer progression.

Methods: Patients with high-risk PCa undergoing RP (2005-2015) at 3 tertiary centers were pooled. The outcomes of men with VHR PCa were compared with the outcomes of those who did not meet VHR criteria. The high-risk criteria were a clinical stage of T3 to T4, a prostate-specific antigen level > 20 ng/mL, or a biopsy Gleason grade sum of 8 to 10. The VHR criteria were multiple high-risk features, >4 biopsy cores with a Gleason grade sum of 8 to 10, or primary Gleason grade pattern 5. Biochemical recurrence, metastasis (METS), and cancer-specific mortality (CSM) were assessed with competing risks regressions. Overall mortality was assessed with Cox survival models.

Results: Among 1981 patients with high-risk PCa, men with VHR PCa (n = 602) had adverse pathologic outcomes: 37% versus 25% for positive margins and 37% versus 15% for positive lymph nodes (P <  .001 for both comparisons). Patients with VHR PCa also had higher adjusted hazard ratios for METS (2.78; 95% confidence interval [CI], 2.08-3.72), CSM (6.77; 95% CI, 2.91-15.7), and overall mortality (2.44; 95% CI, 1.56-3.80; P <  .001 for all comparisons).

Conclusions: In a validation study of patients who underwent treatment for high-risk PCa, VHR criteria were strongly associated with adverse pathologic and oncologic outcomes.
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http://dx.doi.org/10.1002/cncr.31833DOI Listing
February 2019

Clinical, Pathological and Oncologic Findings of Radical Prostatectomy with Extraprostatic Extension Diagnosed on Preoperative Prostate Biopsy.

J Urol 2019 05;201(5):937-942

Brady Urological Institute, The Johns Hopkins University School of Medicine , Baltimore , Maryland.

Purpose: Prostatic adenocarcinoma with extraprostatic extension detected on prostate needle biopsy is an uncommon finding. We describe clinical and pathological findings in a large cohort of patients with prostatic adenocarcinoma who were treated with radical prostatectomy and in whom extraprostatic extension was identified on prostate needle biopsy.

Materials And Methods: Using our institutional pathology database we identified 83 patients with prostatic adenocarcinoma and with extraprostatic extension on prostate needle biopsy between 2000 to 2018 who underwent radical prostatectomy and had clinical followup information. Clinical and pathological outcomes were examined.

Results: Of the 83 patients 54 (65%) presented with clinical stage T2 or greater disease. On biopsy 50 of the 83 patients (60%) had Grade Group 4-5 and 66 (81%) had perineural invasion. Extraprostatic extension was confirmed in the radical prostatectomy specimen in 81 of 83 cases (98%). At radical prostatectomy 49 of 83 patients (59%) had positive surgical margins, 37 (45%) had seminal vesicle invasion and 30 (37%) had lymph node involvement. Median followup after radical prostatectomy was 2 years. Overall 34 of 76 men (45%) received postoperative radiation a median of 1 year after radical prostatectomy and 8 (11%) received chemotherapy a median of 2 years after radical prostatectomy. The 3-year biochemical recurrence-free survival rate was 48.4% (95% CI 0.345-0.610) and the 3-year metastasis-free survival rate was 75.2% (95% CI 0.603-0.851).

Conclusions: Patients in whom extraprostatic extension is detected on prostate needle biopsy almost always have extraprostatic disease and markedly adverse pathology findings at radical prostatectomy. Many of them experience biochemical recurrence and most will require multimodal therapy. These data can be useful to counsel such patients in regard to the treatment approach and the expected outcomes after surgery.
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http://dx.doi.org/10.1016/j.juro.2018.10.023DOI Listing
May 2019

A Prospective Cohort Study of Postdischarge Opioid Practices After Radical Prostatectomy: The ORIOLES Initiative.

Eur Urol 2019 02 21;75(2):215-218. Epub 2018 Oct 21.

The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Opioid pain medications are overprescribed, but few data are available to help in appropriate tailoring of postdischarge opioid prescriptions after surgery. Prior studies are retrospective and based on incomplete responses (<50%) to questionnaires, with small sample sizes for any particular surgery. The ORIOLES initiative was a prospective cohort study (2017-2018) designed to measure postdischarge opioid prescribing and use and clinical predictors of use for consecutive patients after radical prostatectomy. The objectives were to establish a postdischarge opioid reference value to meet the needs of >80% of patients and compare open and robotic surgery. A total of 205 adult patients were enrolled, with 100% completing follow-up. In units of oral morphine equivalents (OMEQ), a median of 225mg was prescribed and 22.5mg used. There was no difference by surgical approach or among patients with a history of pain-related diagnoses. Overall, 77% of postdischarge opioid medication was unused, with 84% of patients requiring ≤112.5mg OMEQ. Only 9% of patients appropriately disposed of leftover medication. Approximately 5% reported continued incisional pain due to surgery at 30d, but none required continued opioid medication use. Prescribing more opioids was independently associated with greater opioid use in adjusted models. PATIENT SUMMARY: In this report, we looked at opioid medication use following discharge after radical prostatectomy. We found that 77% of opioid pain medication prescribed was unused, with 84% of patients using less than half of their prescription. Prescribing more opioids was associated with greater use; only 9% of patients appropriately disposed of leftover medication.
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http://dx.doi.org/10.1016/j.eururo.2018.10.013DOI Listing
February 2019

PTEN status assessment in the Johns Hopkins active surveillance cohort.

Prostate Cancer Prostatic Dis 2019 03 2;22(1):176-181. Epub 2018 Oct 2.

Department of Urology, Johns Hopkins School of Medicine, Baltimore, MD, USA.

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.
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http://dx.doi.org/10.1038/s41391-018-0093-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372343PMC
March 2019

MEIS1 and MEIS2 Expression and Prostate Cancer Progression: A Role For HOXB13 Binding Partners in Metastatic Disease.

Clin Cancer Res 2018 08 1;24(15):3668-3680. Epub 2018 May 1.

The Committee on Cancer Biology, The University of Chicago, Chicago, Illinois.

Germline mutations within the MEIS-interaction domain of HOXB13 have implicated a critical function for MEIS-HOX interactions in prostate cancer etiology and progression. The functional and predictive role of changes in MEIS expression within prostate tumor progression, however, remain largely unexplored. Here we utilize RNA expression datasets, annotated tissue microarrays, and cell-based functional assays to investigate the role of MEIS1 and MEIS2 in prostate cancer and metastatic progression. These analyses demonstrate a stepwise decrease in the expression of both MEIS1 and MEIS2 from benign epithelia, to primary tumor, to metastatic tissues. Positive expression of MEIS proteins in primary tumors, however, is associated with a lower hazard of clinical metastasis (HR = 0.28) after multivariable analysis. Pathway and gene set enrichment analyses identified MEIS-associated networks involved in cMYC signaling, cellular proliferation, motility, and local tumor environment. Depletion of MEIS1 and MEIS2 resulted in increased tumor growth over time , and decreased MEIS expression in both patient-derived tumors and MEIS-depleted cell lines was associated with increased expression of the protumorigenic genes cMYC and CD142, and decreased expression of AXIN2, FN1, ROCK1, SERPINE2, SNAI2, and TGFβ2. These data implicate a functional role for MEIS proteins in regulating cancer progression, and support a hypothesis whereby tumor expression of MEIS1 and MEIS2 expression confers a more indolent prostate cancer phenotype, with a decreased propensity for metastatic progression. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-3673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082699PMC
August 2018

Targeted antimicrobial prophylaxis for transrectal ultrasound-guided prostate biopsy during active surveillance: Effect on hospitalization.

Urol Oncol 2018 04 26;36(4):158.e7-158.e12. Epub 2017 Dec 26.

The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD.

Objectives: We investigated the effect of targeted antibiotic prophylaxis using rectal swab cultures on hospitalization for infectious complications after transrectal ultrasound-guided prostate biopsy (TRUSP).

Materials And Methods: A cohort of men (1995-2016) with prostate cancer on active surveillance receiving annual TRUSP biopsies was surveyed to determine the incidence of hospitalization for suspected postbiopsy sepsis. We compared biopsy events (i.e., unique biopsies) in the era of empiric prophylaxis to those in the era of targeted prophylaxis based on culture. The effect of fluoroquinolone resistant organisms (FQ-R), and other demographic and clinical factors, on hospitalization was assessed using logistic regression.

Results: Of 1,167 men on active surveillance, 825 responded for a total of 3,361 biopsy events; 7 (0.79%) of 886 biopsies preceded by rectal swab culture resulted in hospitalization compared to 24 (0.97%) of 2,475 biopsies without culture (OR = 0.81, 95% CI: 0.35-1.89, P = 0.63). Among 886 cultures performed, FQ-R organisms were identified in 194 (21.9%); 6 out of 194 (3.1%) biopsies with swabs positive for FQ-R resulted in admission compared to 1 out of 692 (0.14%) biopsies with fluoroquinolone sensitive swabs (OR = 22.1, 95% CI: 2.6-184.3, P<0.01). Smaller prostate volume at diagnosis was significantly associated with hospitalization (OR = 2.57, 95% CI: 1.04-6.31) for<45 g vs. ≥45 g, P = 0.039).

Conclusion: Targeted antibiotic prophylaxis is not associated with a significant reduction in hospitalization for suspected post-TRUSP biopsy sepsis. FQ-R and prostate volume exhibited strong associations with risk of hospitalization and could be included in a risk-adapted approach to prophylaxis, but better prophylactic strategies are needed for patients identified to be at high risk of subsequent hospitalization.
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http://dx.doi.org/10.1016/j.urolonc.2017.12.005DOI Listing
April 2018

Absorbable Hydrogel Spacer Use in Prostate Radiotherapy: A Comprehensive Review of Phase 3 Clinical Trial Published Data.

Urology 2018 May 23;115:39-44. Epub 2017 Nov 23.

Carolina Urologic Research Center, Myrtle Beach, SC. Electronic address:

Objective: To provide an update on SpaceOAR System, a Food and Drug Administration-approved hydrogel indicated to create distance between the prostate and the rectum which has been studied in phase 2 and 3 clinical trials. Here, we review and summarize these clinical results including the safety of prostate-rectum spacer application technique, the implant quality and resulting rectal dose reduction, acute and long-term rectal, urinary, and sexual toxicity, as well as patient-reported outcomes.

Materials And Methods: A prospective, randomized patient-blinded clinical study was performed comparing image-guided intensity modulated prostate radiotherapy (79.2 Gy in 44 fractions) in men with or without prostate-rectum hydrogel spacer. Patients were followed up for 3 years, allowing assessment of long-term safety and efficacy.

Results: Spacer application was well tolerated with a 99% technical success rate. The mean additional space created between the prostate and the rectum was just over 1 cm, which allowed significant rectum and penile bulb radiation dose reduction, resulting in less acute pain, lower rates of late rectal toxicity, and improved bowel and urinary quality of life (QOL) scores from 6 months onward. Improvements in sexual QOL were also observed at 37 months in baseline-potent men, with 37.5% of control and 66.7% of spacer men capable of "erections sufficient for intercourse."

Conclusion: Prostate-rectum hydrogel spacer application is a relatively safe technical procedure that is well tolerated and has a high technical success rate. Spacer application significantly reduces rectal radiation dose and results in long-term reductions in rectal toxicity, as well as improvements in bowel, urinary, and sexual QOL.
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http://dx.doi.org/10.1016/j.urology.2017.11.016DOI Listing
May 2018

Incidence of Extraprostatic Extension at Radical Prostatectomy with Pure Gleason Score 3 + 3 = 6 (Grade Group 1) Cancer: Implications for Whether Gleason Score 6 Prostate Cancer Should be Renamed "Not Cancer" and for Selection Criteria for Active Surveillance.

J Urol 2018 06 15;199(6):1482-1487. Epub 2017 Nov 15.

Johns Hopkins Medical Institutions, Baltimore, Maryland. Electronic address:

Purpose: We assessed the risk of locally aggressive behavior in pure Gleason score 6 (Grade Group 1) prostate cancer using contemporary grading criteria. To our knowledge this has been studied in only 1 prior cohort.

Materials And Methods: We evaluated consecutive radical prostatectomy specimens from an academic institution, including those from 3,291 men with Gleason score 6 and 4,202 with Gleason score 3 + 4 = 7 (Grade Group 2) disease between 2005 and 2016. For dichotomous variables the Pearson chi-square test was used.

Results: Of the 3,288 Gleason score 6 cancer cases 128 (3.9%) showed focal extraprostatic extension compared to 593 of the 4,202 (14.1%) with Gleason score 3 + 4 = 7 (p <0.0001). Of the 3,288 Gleason score 6 cancer cases 79 (2.4%) showed nonfocal extraprostatic extension compared to 639 of the 4,202 (15.2%) with Gleason score 3 + 4 = 7 (p <0.0001). The incidence of focal extraprostatic extension with Gleason score 3 + 4 = 7 with less than 5% Gleason pattern 4 was 129 of 1,147 cases (11.2%), which was between Gleason scores 6 and 3 + 4 = 7 with greater than 5% Gleason pattern 4. The incidence of nonfocal extraprostatic extension in Gleason score 3 + 4 = 7 with less than 5% Gleason pattern 4 was 96 of 1,147 cases (8.4%), which was between Gleason scores 6 and 3 + 4 = 7 with greater than 5% Gleason pattern 4. One of the 3,290 Gleason score 6 cases (0.03%) showed seminal vesicle invasion compared to 93 of the 4,202 (2.2%) of Gleason score 3 + 4 = 7 (p <0.0001). A limitation of our study was its retrospective design.

Conclusions: It is not rare for pure Gleason score 6 prostate cancer to locally extend out of the prostate 3.9% focally and 2.4% nonfocally. In extremely rare cases Gleason score 6 can be associated with seminal vesicle invasion and yet not lymph node metastases. Our overall findings support the argument for continuing to use the term cancer for these tumors.
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http://dx.doi.org/10.1016/j.juro.2017.11.067DOI Listing
June 2018

The effect of limited (tertiary) Gleason pattern 5 on the new prostate cancer grade groups.

Hum Pathol 2017 05 16;63:27-32. Epub 2016 Dec 16.

The Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. Electronic address:

The risk of recurrence for prostatic adenocarcinoma after prostatectomy, as detected by prostate-specific antigen or other modalities, is based primarily on Gleason score along with pathologic tumor stage and surgical margin status. Recent large multi-institutional data spanning the last decade have supported modification of risk of recurrence stratification based on grade groups: grade group 1 (3+3=6), grade group 2 (3+4=7), grade group 3 (4+3=7), grade group 4 (4+4=8), and grade group 5 (Gleason scores 9 and 10). Using currently accepted grading definitions of grade patterns and grading rules, this study examines how the introduction of a limited, less than 5%, Gleason pattern 5 component at prostatectomy affects prognosis and fits into the grade group schema and reporting. The aggregate data from 2 independent major academic medical centers comprising 7606 patient records were analyzed with respect to biochemical recurrence-free survival. The presence of a limited (tertiary) Gleason pattern 5 component in the context of Gleason scores 3+4=7 (grade group 2) and 4+3=7 (grade group 3) imparts an intermediate prognosis relative to the next highest grade group. As such, we suggest that an additional comment and designation to the grade groups be provided reflecting the increased risk of recurrence in such cases (such as grade group 2+ or 3+). In contrast, the presence of limited (<5%) Gleason pattern 5 in the context of Gleason score 4+4=8 imparts a poor prognosis equivalent to grade group 5 and therefore should be reported as grade group 5.
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http://dx.doi.org/10.1016/j.humpath.2016.12.008DOI Listing
May 2017

Germline Mutations in ATM and BRCA1/2 Distinguish Risk for Lethal and Indolent Prostate Cancer and are Associated with Early Age at Death.

Eur Urol 2017 05 15;71(5):740-747. Epub 2016 Dec 15.

Department of Urology and the James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA. Electronic address:

Background: Germline mutations in BRCA1/2 and ATM have been associated with prostate cancer (PCa) risk.

Objective: To directly assess whether germline mutations in these three genes distinguish lethal from indolent PCa and whether they confer any effect on age at death.

Design, Setting, And Participants: A retrospective case-case study of 313 patients who died of PCa and 486 patients with low-risk localized PCa of European, African, and Chinese descent. Germline DNA of each of the 799 patients was sequenced for these three genes.

Outcome Measurements And Statistical Analysis: Mutation carrier rates and their effect on lethal PCa were analyzed using the Fisher's exact test and Cox regression analysis, respectively.

Results And Limitations: The combined BRCA1/2 and ATM mutation carrier rate was significantly higher in lethal PCa patients (6.07%) than localized PCa patients (1.44%), p=0.0007. The rate also differed significantly among lethal PCa patients as a function of age at death (10.00%, 9.08%, 8.33%, 4.94%, and 2.97% in patients who died ≤ 60 yr, 61-65 yr, 66-70 yr, 71-75 yr, and over 75 yr, respectively, p=0.046) and time to death after diagnosis (12.26%, 4.76%, and 0.98% in patients who died ≤ 5 yr, 6-10 yr, and>10 yr after a PCa diagnosis, respectively, p=0.0006). Survival analysis in the entire cohort revealed mutation carriers remained an independent predictor of lethal PCa after adjusting for race and age, prostate-specific antigen, and Gleason score at the time of diagnosis (hazard ratio=2.13, 95% confidence interval: 1.24-3.66, p=0.004). A limitation of this study is that other DNA repair genes were not analyzed.

Conclusions: Mutation status of BRCA1/2 and ATM distinguishes risk for lethal and indolent PCa and is associated with earlier age at death and shorter survival time.

Patient Summary: Prostate cancer patients with inherited mutations in BRCA1/2 and ATM are more likely to die of prostate cancer and do so at an earlier age.
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http://dx.doi.org/10.1016/j.eururo.2016.11.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535082PMC
May 2017

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

Eur Urol 2017 06 19;71(6):907-912. Epub 2016 Nov 19.

Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.eururo.2016.11.006DOI Listing
June 2017

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

J Urol 2017 04 12;197(4):1060-1067. Epub 2016 Nov 12.

Department of Urology, The James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland. Electronic address:

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.
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http://dx.doi.org/10.1016/j.juro.2016.11.079DOI Listing
April 2017

Call Schedule and Sleep Patterns of Urology Residents Following the 2011 ACGME Reforms.

Urol Pract 2016 Mar;3(2):147-152

The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins School of Medicine.

Introduction: In response to the 2011 Accreditation Council for Graduate Medical Education duty hour restrictions, many residency programs adopted a night float system. Due to concerns regarding the effects of night float on sleep and subsequently on patient care, we examined sleep patterns of residents on different call schedules.

Methods: Urology residents assigned to day shift (Monday-Friday, 6am-6pm), night float (Sunday-Friday, 6pm-6am) or 24-hour home call and attending physicians were monitored for two-week periods using actigraphy bands. Total sleep time, light versus deep sleep time, sleep latency and number of sleep disruptions were measured. Comparative statistics and logistic regression were used to compare call systems and to determine predictors of sleep metrics.

Results: When comparing day shift, night float, and 24-hour home call, the only significant difference was in sleep latency. All sleep variables except sleep latency were significantly different among residents of various levels (junior, senior, research year). Compared to residents, attendings had shorter sleep latency and were woken less frequently. Being a research year resident was the only significant univariate predictor of total sleep. Age and being a research year resident were significant univariate predictors of sleep latency.

Conclusions: This pilot study demonstrates the feasibility of actigraphy in measuring sleep patterns of urology house officers. It also suggests that night float does not significantly impact total sleep or quality of sleep. Further research is needed to confirm these findings and to determine the effects of night float rotations on resident quality of life and patient safety.
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http://dx.doi.org/10.1016/j.urpr.2015.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5102057PMC
March 2016

Geometric systematic prostate biopsy.

Minim Invasive Ther Allied Technol 2017 Apr 11;26(2):78-85. Epub 2016 Nov 11.

a Robotics Laboratory, Urology Department, School of Medicine , Johns Hopkins University , Baltimore , MD , USA.

Objective: The common sextant prostate biopsy schema lacks a three-dimensional (3D) geometric definition. The study objective was to determine the influence of the geometric distribution of the cores on the detection probability of prostate cancer (PCa).

Methods: The detection probability of significant (>0.5 cm) and insignificant (<0.2 cm) tumors was quantified based on a novel 3D capsule model of the biopsy sample. The geometric distribution of the cores was optimized to maximize the probability of detecting significant cancer for various prostate sizes (20-100cm), number of biopsy cores (6-40 cores) and biopsy core lengths (14-40 mm) for transrectal and transperineal biopsies.

Results: The detection of significant cancer can be improved by geometric optimization. With the current sextant biopsy, up to 20% of tumors may be missed at biopsy in a 20 cm prostate due to the schema. Higher number and longer biopsy cores are required to sample with an equal detection probability in larger prostates. Higher number of cores increases both significant and insignificant tumor detection probability, but predominantly increases the detection of insignificant tumors.

Conclusion: The study demonstrates mathematically that the geometric biopsy schema plays an important clinical role, and that increasing the number of biopsy cores is not necessarily helpful.
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http://dx.doi.org/10.1080/13645706.2016.1249890DOI Listing
April 2017

SPINK1 Defines a Molecular Subtype of Prostate Cancer in Men with More Rapid Progression in an at Risk, Natural History Radical Prostatectomy Cohort.

J Urol 2016 11 27;196(5):1436-1444. Epub 2016 May 27.

Northwestern University Feinberg School of Medicine, Chicago, Illinois. Electronic address:

Purpose: Prostate cancer is clinically and molecularly heterogeneous. We determined the prognosis of men with ERG-ETS fusions and SPINK1 over expression.

Materials And Methods: Men were identified with intermediate or high risk localized prostate cancer treated with radical prostatectomy and no therapy before metastasis. A case-cohort design sampled a cohort (262) enriched with metastasis from the entire cohort and a cohort (213) enriched with metastasis from patients with biochemical recurrence. We analyzed transcriptomic profiles and subtyped tumors as m-ERG, m-ETS, m-SPINK1 or Triple Negative (m-ERG/m-ETS/m-SPINK1), and multivariable logistic regression analyses, Kaplan-Meier and multivariable Cox models were used to evaluate subtypes as predictors of clinical outcomes.

Results: Overall 36%, 13%, 11% and 40% of prostate cancer was classified as m-ERG, m-ETS, m-SPINK1 and Triple Negative, respectively. Univariable analysis demonstrated that m-SPINK1 tumors were more common in African-American men (OR 5, 95% CI 1.6-16) but less commonly associated with positive surgical margins (OR 0.16, 95% CI 0.03-0.69) compared to the m-ERG group. Compared to the Triple Negative group, m-SPINK1 showed similar associations with race and surgical margins in univariable and multivariable analyses across the entire cohort. Survival analyses did not show significant differences among m-ERG, m-ETS and Triple Negative cases. m-SPINK1 independently predicted prostate cancer specific mortality after metastasis (HR 2.48, 95% CI 0.96-6.4) and biochemical recurrence (HR 3, 95% CI 1.1-8).

Conclusions: SPINK1 over expression is associated with prostate cancer specific mortality in at risk men with biochemical and clinical recurrence after prostatectomy. ERG-ETS alterations are not prognostic for outcome.
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http://dx.doi.org/10.1016/j.juro.2016.05.092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615051PMC
November 2016

Pathological analysis of the prostatic anterior fat pad at radical prostatectomy: insights from a prospective series.

BJU Int 2017 03 30;119(3):444-448. Epub 2016 Sep 30.

Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.

Objective: To assess factors associated with lymphatic drainage and lymph node (LN) metastasis to the prostatic anterior fat pad (PAFP) in men with prostate cancer and the utility of routine PAFP analysis at the time of radical prostatectomy (RP).

Patients And Methods: Our institution began to prospectively collect PAFP tissue in 2010. The PAFP was removed at the time of RP and sent as a pathological specimen separate from the pelvic LNs and prostate. Consecutive RPs performed at our institution in which the PAFP was removed were reviewed to determine the rate of LNs in the PAFP, the rate of metastatic LNs in the PAFP, and the association of metastatic PAFP LN with clinical and pathological features. The impact on biochemical recurrence (BCR) was assessed with a Cox's proportional hazard model.

Results: In all, 2 413 PAFP specimens were available for analysis. LNs were found in the PAFP in 255 (10.6%) cases and metastatic LNs in the PAFPs were found in 14 (0.6%) cases. Metastatic PAFP LNs were associated with anterior tumours in 11 of the 14 cases (P = 0.01), and were present only in preoperative D'Amico intermediate- (six of 14) and high- (eight of 14) risk patients (P < 0.001). Metastatic PAFP LNs were associated with extraprostatic disease in 13 of the 14 cases, although concomitant pelvic LN involvement was present in only four of the 14 cases. With a mean follow-up of 1.5 years, three of the 14 patients with metastatic PAFP LN developed BCR. Positive LN involvement in either the pelvic LN or PAFP had worse BCR than LN-negative patients (P < 0.001); however, there was no difference in BCR between patients with positive pelvic LN and positive PAFP LN (P = 0.5).

Conclusion: Metastatic PAFP LNs are rare and always occur in the presence of other adverse pathological features. The routine pathological analysis of PAFP as a separate specimen, especially in low-risk disease, may not be warranted.
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http://dx.doi.org/10.1111/bju.13654DOI Listing
March 2017

Prevalence and Prognostic Significance of PTEN Loss in African-American and European-American Men Undergoing Radical Prostatectomy.

Eur Urol 2017 05 28;71(5):697-700. Epub 2016 Jul 28.

Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address:

African-American (AA) men have a higher risk of lethal prostate cancer (PCa) compared to European-American (EA) men. However, the molecular basis of this difference, if any, remains unclear. In EA PCa, PTEN loss, but not ERG rearrangement, has been associated with poor outcomes in most studies. Although ERG rearrangement is less common in AA compared to EA PCa, the relative frequency of PTEN loss and the association of PTEN/ERG molecular subtypes with outcomes is unknown for AA PCa. We examined PTEN/ERG status by immunohistochemistry in self-identified AA patients undergoing radical prostatectomy at Johns Hopkins with tumor tissue available on tissue microarray (TMA; n=169) and matched these cases by pathologic parameters to 169 EA patients from the same TMAs. The rate of PTEN loss was significantly lower in AA compared to EA PCa (18% vs 34%; p=0.001), similar to the lower rate of ERG expression (25% vs 51%; p<0.001). To examine the association of PTEN/ERG status with oncologic outcomes, we created an additional TMA of 87 AA tumors with Gleason score > 4 + 3 = 7. Among the total population of AA men with outcome data from all TMAs (n=222), PTEN loss was associated with higher risk of biochemical recurrence (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.33-3.82) and metastasis (HR 3.90, 95% CI 1.46-10.4) in multivariable models.

Patient Summary: PTEN and ERG alterations in prostate cancer are less likely in African-American than in European-American men. However, PTEN loss remains associated with poor prostate cancer outcomes among African-American men.
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http://dx.doi.org/10.1016/j.eururo.2016.07.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5274596PMC
May 2017

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

BJU Int 2017 05 29;119(5):676-683. Epub 2016 Jul 29.

The James Buchanan Brady Urological Institute and Department of Urology at the Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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.
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http://dx.doi.org/10.1111/bju.13573DOI Listing
May 2017

Rare Renal Incidentaloma in Pregnancy: An Unusual Primitive Neuroectodermal Tumor Presentation.

Urol Case Rep 2015 Mar 23;3(2):12-4. Epub 2015 Jan 23.

The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA.

Peripheral Primitive Neuroectodermal Tumors (PNETs) are rare lesions that arise from outside the central nervous system and normally do not affect the genitourinary system. Primary renal presentations are extremely rare but given their aggressive behavior and characteristic cytomorphologic and genetic features should be considered well-defined distinct clinical entities in order to distinguish them from other primary tumors featuring round cells in the kidney. We report one case of PNET involving the kidney and associated with pregnancy.
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http://dx.doi.org/10.1016/j.eucr.2014.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4714261PMC
March 2015