Perioperative venous thromboembolism prophylaxis in prostate cancer surgery

Purpose To describe a patient and procedure specific approach to selecting Venous thromboembolism (VTE) prophylaxis for men who undergo radical prostatectomy. Methods We performed a literature search and narrative review of VTE after radical prostatectomy. We describe the current paradigm of perioperative thromboprophylaxis and underlying rationale. Relevant findings from the European Association of Urology thromboprophylaxis guidelines are interpreted and summarized. Results The use of extended post-operative thromboprophylaxis for patients who undergo radical prostatectomy is appropriate when the risk of symptomatic VTE outweighs the risk of major bleeding. Patient and procedure factors impact VTE risk. Patient risk can be stratified as low, moderate or high based on 4 factors; age \u3e 75, BMI \u3e 35, VTE in a first degree relative, and personal history of VTE. Procedure risk of VTE and bleeding can be stratified by modality of surgery (open, laparoscopic, robotic) and extent of pelvic lymphadenectomy. Using these factors, patients at the lowest risk for VTE will have an expected incidence of VTE of 0.4–0.8% and those at highest risk from 1.5 to 15.7%. Incidence of major bleeding ranges from 0.4 to 1.4%. These ranges emphasize the need to consider the net benefit for each specific patient. Use of mechanical prophylaxis is supported by weaker evidence but has fewer harms and is likely reasonable for most patients. Conclusion Many patients who undergo radical prostatectomy will benefit from extended post-operative thromboprophylaxis. Risk of thrombosis is likely higher with open approach and extended lymph node dissection. The net benefit of treatment should be considered using patient- and procedure-specific criteria. When the net benefit is negligible or possibly harmful no pharmacological thromboprophylaxis should be used

Surgery Versus Radiotherapy for Clinically-localized Prostate Cancer: A Systematic Review and Meta-analysis

AbstractContextTo date, there is no Level 1 evidence comparing the efficacy of radical prostatectomy and radiotherapy for patients with clinically-localized prostate cancer.ObjectiveTo conduct a meta-analysis assessing the overall and prostate cancer-specific mortality among patients treated with radical prostatectomy or radiotherapy for clinically-localized prostate cancer.Evidence acquisitionWe searched Medline, EMBASE, and the Cochrane Library through June 2015 without year or language restriction, supplemented with hand search, using Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Meta-analysis of Observational Studies in Epidemiology guidelines. We used multivariable adjusted hazard ratios (aHRs) to assess each endpoint. Risk of bias was assessed using the Newcastle-Ottawa scale.Evidence synthesisNineteen studies of low to moderate risk of bias were selected and up to 118 830 patients were pooled. Inclusion criteria and follow-up length varied between studies. Most studies assessed patients treated with external beam radiotherapy, although some included those treated with brachytherapy separately or with the external beam radiation therapy group. The risk of overall (10 studies, aHR 1.63, 95% confidence interval 1.54–1.73, p<0.00001; I2=0%) and prostate cancer-specific (15 studies, aHR 2.08, 95% confidence interval 1.76–2.47, p < 0.00001; I2=48%) mortality were higher for patients treated with radiotherapy compared with those treated with surgery. Subgroup analyses by risk group, radiation regimen, time period, and follow-up length did not alter the direction of results.ConclusionsRadiotherapy for prostate cancer is associated with an increased risk of overall and prostate cancer-specific mortality compared with surgery based on observational data with low to moderate risk of bias. These data, combined with the forthcoming randomized data, may aid clinical decision making.Patient summaryWe reviewed available studies assessing mortality after prostate cancer treatment with surgery or radiotherapy. While the studies used have a potential for bias due to their observational design, we demonstrated consistently higher mortality for patients treated with radiotherapy rather than surgery

Comparison of MRI- and TRUS-Informed Prostate Biopsy for Prostate Cancer Diagnosis in Biopsy-Naive Men: A Systematic Review and Meta-Analysis.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) with informed targeted biopsies (TGBX) has changed the paradigm of prostate cancer (PCa) diagnosis. Randomized studies have demonstrated a diagnostic benefit of Clinically significant (CS) for TGBX compared to standard systematic biopsies (SBX). We aimed to evaluate whether mpMRI-informed TGBX has superior diagnosis rates of any-, CS-, high-grade (HG)-, and clinically insignificant (CI)-PCa compared to SBX in biopsy-naive men. METHODS: Data was searched in Medline, Embase, Web of Science, and Evidence-based medicine reviews-Cochrane Database of systematic reviews from database inception until 2019. Studies were selected by two authors independently, with disagreements resolved by consensus with a third author. Overall 1951 unique references were identified, and 100 manuscripts underwent full-text review. Data were pooled using random-effects models. The meta-analysis is reported according to the PRISMA statement. The study protocol is registered with PROSPERO (CRD42019128468). RESULTS: Overall 29 studies (13,845 patients) were analyzed. Compared to SBX, use of mpMRI-informed TGBX was associated with a 15% higher rate of any PCa diagnosis (95% CI 10-20%, p\u3c0.00001). This relationship was not affected by the study methodology (p=0.11). Diagnosis of CS and HG PCa were more common in the mpMRI-informed TGBX group (risk difference of 11%, 95% CI 0-20%, p=0.05, and 2%, 95% CI 1-4%; p=0.005, respectively) while there was no difference in diagnosis of CI PCa (risk difference of 0, 95% CI -3-3%, p=0.96). Notably, the exclusion of SBX in the mpMRI-informed TGBX arm significantly modified the association between a mpMRI strategy and lower rates of CI PCa diagnosis (p=0.01) without affecting the diagnosis rates of CS- or HG-PCa. CONCLUSIONS: In comparison to SBX, a mpMRI-informed TGBX strategy results in a significantly higher diagnosis rate of any-, CS-, and HG-PCa. Excluding SBX from mpMRI-informed TGBX was associated with decreased rates of CI-PCa diagnosis without affecting diagnosis of CS- or HG-PCa

Setting the Standards: Examining Research Productivity Among Academic Urologists in the USA and Canada in 2019.

BACKGROUND: Research productivity among academic urologists is strongly encouraged, but little data are available on productivity metrics within the field. OBJECTIVE: To provide the first comprehensive survey of research productivity among academic urologists in the USA and Canada. DESIGN, SETTING, AND PARTICIPANTS: Using the Accreditation Council for Graduate Medical Education, the Canadian Resident Matching Service, and individual program websites, all active accredited urology faculties were identified. For each individual, we collected data on American Urological Association section, title, gender, fellowship training, Scopus H-index, and citations. Comprehensive searches were completed during March-May 2019. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive statistics for demographic comparisons were performed using analysis of variance for continuous variables and chi-square test for categorical variables. Multivariable logistic regressions were used to identify the predictors of H-index greater than the median. RESULTS AND LIMITATIONS: A total of 2214 academic urology faculties (2015 in USA and 199 in Canada) were identified. The median and mean H-indices for the entire cohort of physicians were 11 and 16.1, respectively. On multivariable analysis, physicians in the North Central and Western Sections (vs mid-Atlantic), who were fellowship trained (vs no fellowship training), and of higher academic rank (professor and associate professor vs clinical instructor) were more likely to have H-index values greater than the median. Additionally, female physicians (vs male) were more likely to have H-index values less than the median. CONCLUSIONS: This study represents the first comprehensive assessment of research productivity metrics among academic urologists. These represent key benchmarks for trainees considering careers in academics and for practicing physicians gauging their own productivity in relation to their peers. PATIENT SUMMARY: In this study, we provide the first comprehensive assessment of research productivity among academic urologists in the USA and Canada. Our results help provide key benchmarks for trainees considering careers in academics and for practicing physicians gauging their own productivity in relation to peers

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study

Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research

Clinically Significant Prostate Cancer: Biological and Epidemiological Observations to Improve Cancer-Free and Survival Metrics

Background: Due to very high disease-specific survival following prostate cancer treatment, disease progression (metastasis) and treatment-related complications may significantly affect a patientâ s life trajectory. Using distinct epidemiologic methodologies, this thesis sought to (1) identify novel microRNA predictors of metastasis following radical prostatectomy; (2) examine the association between local treatment modality (surgery or radiotherapy) and androgen deprivation therapy (ADT) on non-prostate cancer mortality; and (3) study the association between radiotherapy for prostate cancer and secondary malignancies. Methods: We conducted a matched-case control study of 38 patients who underwent radical prostatectomy using bootstrapping with automated backward selection to identify miRNA sequences which were significantly associated with metastasis. To examine the association between treatment modality and non-prostate cancer mortality, we performed a propensity-score matched, population-based retrospective cohort study of 10,786 men treated for non-metastatic prostate cancer in Ontario between 2002 and 2009. We used the Fine and Gray method with generalized estimating equation survival models with a sandwich variance estimator to calculate the sub-distribution hazard ratio of treatment effect, accounting for ADT exposure in a time-varying manner. To assess the association between radiotherapy for prostate cancer and the development of secondary cancers, we performed a systematic review and meta-analysis utilizing random-effects models and Mantel-Haenszel weighting. Results: We identified a panel of five microRNA which were associated with metastasis following surgery (AUC 89.5%, 95% CI 79.5-99.5). Treatment with radiotherapy was independently associated with an increased risk of non-prostate cancer mortality (HR 1.57, 95% CI 1.35-1.83) though ADT exposure was not (p = 0.26 - 0.87 depending on analytic strategy). Radiotherapy was associated with an increased risk of bladder (aHR 1.67, 95% CI 1.55-1.80), colorectal (aHR 1.79, 95% CI 1.34-2.38) and rectal cancers (aHR 1.79, 95% CI 1.34-2.38) but not hematological (aHR 1.64, 95% CI 0.90-2.99) or lung (aHR 1.45, 95% CI 0.70-3.01) cancers. Conclusions: Varied epidemiologic techniques may be used to characterise outcomes following prostate cancer treatment. These data may inform patients and physicians when making decisions regarding prostate cancer treatment choice.Ph.D

The role of resection of pulmonary metastases from prostate cancer: a case report and literature review

We report a case of a 53-year-old man who presented with two nodules in the lower lobe and one nodule in the upper lobe of the right lung almost 7 years after radical prostatectomy for pT3aN0M0, Gleason 4+5 disease, without evidence of osseous or lymphatic spread. Surgical resection of the lower lung nodules confirmed metastases, but prostate-specific antigen did not drop to undetectable levels. Isolated pulmonary metastases from prostate cancer are rare with only 33 previously described cases in the English-language literature, 18 of which were solitary metastases. We review the principles of management, including metastasectomy and long-term prognosis