Systematic Reviews and Meta-analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery.

OBJECTIVE: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. BACKGROUND: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. METHODS: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. RESULTS: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. CONCLUSIONS: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.

Expected impact of MRI-targeted biopsy interreader variability among uropathologists on ProScreen prostate cancer screening trial: a pre-trial validation study.

PURPOSE: Prostate cancer (PCa) histology, particularly the Gleason score, is an independent prognostic predictor in PCa. Little is known about the inter-reader variability in grading of targeted prostate biopsy based on magnetic resonance imaging (MRI). The aim of this study was to assess inter-reader variability in Gleason grading of MRI-targeted biopsy among uropathologists and its potential impact on a population-based randomized PCa screening trial (ProScreen). METHODS: From June 2014 to May 2018, 100 men with clinically suspected PCa were retrospectively selected. All men underwent prostate MRI and 86 underwent targeted prostate of the prostate. Six pathologists individually reviewed the pathology slides of the prostate biopsies. The five-tier ISUP (The International Society of Urological Pathology) grade grouping (GG) system was used. Fleiss' weighted kappa (κ) and Model-based kappa for associations were computed to estimate the combined agreement between individual pathologists. RESULTS: GG reporting of targeted prostate was highly consistent among the trial pathologists. Inter-reader agreement for cancer (GG1-5) vs. benign was excellent (Model-based kappa 0.90, Fleiss' kappa κ = 0.90) and for clinically significant prostate cancer (csPCa) (GG2-5 vs. GG0 vs. GG1), it was good (Model-based kappa 0.70, Fleiss' kappa κ 0.67). CONCLUSIONS: Inter-reader agreement in grading of MRI-targeted biopsy was good to excellent, while it was fair to moderate for MRI in the same cohort, as previously shown. Importantly, there was wide consensus by pathologists in assigning the contemporary GG on MRI-targeted biopsy suggesting high reproducibility of pathology reporting in the ProScreen trial.

Population-based randomized trial of screening for clinically significant prostate cancer ProScreen: a pilot study.

OBJECTIVES: To evaluate the feasibility of a population-based screening trial using prostate-specific antigen (PSA), a kallikrein panel and multiparametric magnetic resonance imaging (MRI) aimed at minimizing overdiagnosis, while retaining mortality benefit. PATIENTS AND METHODS: Feasibility of the screening algorithm was evaluated in terms of participation, screening test results and cancer detection. A random sample of 400 men aged 65 years was identified from the population registry and invited for screening with three stepwise tests (PSA, kallikrein panel and MRI). Men with PSA levels ≥3 ng/mL were further tested with the kallikrein panel, and those with positive findings (risk >7.5%) were referred for prostate MRI. Men with positive MRI (Prostate Imaging Reporting and Data System [PI-RADS] score 3-5) had targeted biopsies only. Men with negative MRI, but PSA density ≥0.15 underwent systematic biopsies. RESULTS: Of the 399 men invited, 158 (40%) participated and 27 had PSA levels ≥3 ng/mL (7% of the invited and 17% of the participants). Of these, 22 had a positive kallikrein panel (6% of the invited and 81% of the PSA-positive men). Finally, 10 men (3% of the invited and 45% of 4Kscore [kallikrein panel]-positive) had a suspicious MRI finding (PI-RADS score ≥3) and five were diagnosed with a clinically significant prostate cancer (Gleason Grade Group [GG] ≥2) at fusion biopsy (3% of the participants), with two GG 1 cases (1%). Additional testing (kallikrein panel and MRI) after PSA reduced biopsies by 56%. CONCLUSION: The findings constitute proof of principle for our screening protocol, as we achieved a substantial detection rate for clinically significant cancer with few clinically insignificant cases. Participation, however, was suboptimal.

Bias-corrected estimates of effects of PSA screening decisions on the risk of prostate cancer diagnosis and death: Analysis of the Finnish randomized study of screening for prostate cancer.

More information is needed about effects of prostate-specific antigen (PSA) screening for informed decision making. The objective of our study is to evaluate the effects of an implemented screening decision on the risk of prostate cancer (PC) diagnosis and PC death. In a randomized trial, 31,867 Finnish men aged 55-67 years were allocated to the screening arm and 48,282 to the control arm during 1996-1999. Two to three screening rounds were offered to the screening arm with a PSA cut-off of 4.0 ng/ml. A counterfactual exclusion method was used to adjust for the effects of screening noncompliance and PSA contamination on risk of PC death and PC incidence by prognostic group at 15 years of follow up. After correcting for noncompliance and contamination, PSA screening led to 32.4 (95% CI 26.4, 38.6) more PC diagnoses per 1,000 men after 15 years and 1.4 (95% CI 0.0, 2.8) fewer PC deaths compared to the control arm. The corresponding results of an intention-to-screen analysis were 16.5 (95% CI 12.3, 20.7) and 0.8 (95% CI 0.5, 2.0), respectively. These results can be used for patient counseling in informed decision making about PC screening. A limitation of the study was the lack of comprehensive data on contamination.

Evolving Clinical Picture of Renal Cell Carcinoma: A Population-Based Study from Helsinki.

BACKGROUND: There is a lack of detailed population-based data for renal cell carcinoma (RCC). OBJECTIVES: The study aimed to examine the contemporary changes in the clinical picture and treatment of RCC. METHODS: A total of 1,719 consecutive patients living in the Helsinki metropolitan area with a solid or cystic renal mass (Bosniak 3-4) ≥10 mm were identified. Data from medical records was evaluated for clinical characteristics and treatments in the periods I (2006-2008), II (2009-2011), III (2012-2014), and IV (2015-2016). RESULTS: The proportions of patients with comorbidities (Charlson index ≥2) and frailty (Eastern Co-operative Oncology Group classification ≥2) increased significantly during the study period. The percentage of clinical stage I patients, cystic tumors and use of needle biopsies increased significantly. Use of observation increased from 9% (I) to 32% (IV; p < 0.001). First-line oncological treatments within 6 months were given to 47% of 262 patients with metastases and -cytoreductive nephrectomy (CN) was delivered to 54% of those patients. CONCLUSIONS: The size of renal tumors continued to decrease, while the percentage of patients with significant comorbidity or frailty increased. Active surveillance emerged as the initial strategy. Tyrosine kinase inhibitors with CN remained the primary option in patients with metastatic RCC.

Estimate of Opportunistic Prostate Specific Antigen Testing in the Finnish Randomized Study of Screening for Prostate Cancer.

PURPOSE: Screening for prostate cancer remains controversial, although ERSPC (European Randomized Study of Screening for Prostate Cancer) showed a 21% relative reduction in prostate cancer mortality. The Finnish Randomized Study of Screening for Prostate Cancer, which is the largest component of ERSPC, demonstrated a statistically nonsignificant 16% mortality benefit in a separate analysis. The purpose of this study was to estimate the degree of contamination in the control arm of the Finnish trial. MATERIALS AND METHODS: Altogether 48,295 and 31,872 men were randomized to the control and screening arms, respectively. The screening period was 1996 to 2007. The extent of prostate specific antigen testing was analyzed retrospectively using laboratory databases. The incidence of T1c prostate cancer (impalpable prostate cancer detected by elevated prostate specific antigen) was determined from the national Finnish Cancer Registry. RESULTS: Approximately 1.4% of men had undergone prostate specific antigen testing 1 to 3 years before randomization. By the first 4, 8 and 12 years of followup 18.1%, 47.7% and 62.7% of men in the control arm had undergone prostate specific antigen testing at least once and in the screening arm the proportions were 69.8%, 81.1% and 85.2%, respectively. The cumulative incidence of T1c prostate cancer was 6.1% in the screening arm and 4.5% in the control arm (RR 1.21, 95% CI 1.13-1.30). CONCLUSIONS: A large proportion of men in the control arm had undergone a prostate specific antigen test during the 15-year followup. Contamination is likely to dilute differences in prostate cancer mortality between the arms in the Finnish screening trial.

Prostate Cancer and Socioeconomic Status in the Finnish Randomized Study of Screening for Prostate Cancer.

Prostate cancer (PC) screening remains controversial. We investigated whether screening reduces the difference in prostate cancer risk by socioeconomic status (SES). In 1996-2011, a total of 72,139 men from the Finnish Randomized Study of Screening for Prostate Cancer were analyzed. Outcome measures were PC incidence, mortality, and participation in screening. SES indicators were educational level, income, and home ownership status (data obtained from the Statistics Finland registry). The mean duration of follow-up was 12.7 years. Higher SES was associated with a higher incidence of low- to moderate-risk PC but with a lower risk of advanced PC. Higher education was associated with significantly lower PC mortality in both control and screening arms (risk ratio = 0.48-0.69; P < 0.05). Higher income was also associated with lower PC mortality but only in the control arm (risk ratio = 0.45-0.73; P < 0.05). There were no significant differences in SES gradient by arm (Pinteraction = 0.33 and Pinteraction = 0.47 for primary vs. secondary education and primary vs. tertiary education, respectively; Pinteraction = 0.65 and Pinteraction = 0.09 for low vs. intermediate income and low vs. high income, respectively; and Pinteraction = 0.27 among home ownership status strata). Substantial gradients by SES in PC incidence and mortality were observed in the control arm. Higher SES was associated with overdiagnosis of low-risk PC and, conversely, lower risk of incurable PC and lower PC mortality. Special attention should be directed toward recruiting men with low SES to participate in population-based cancer screening.

The Finnish prostate cancer screening trial: analyses on the screening failures.

Prostate cancer (PC) screening with prostate-specific antigen (PSA) has been shown to decrease PC mortality in the European Randomized Study of Screening for Prostate Cancer (ERSPC). However, in the Finnish trial, which is the largest component of the ERSPC, no statistically significant mortality reduction was observed. We investigated which had the largest impact on PC deaths in the screening arm: non-participation, interval cancers or PSA threshold. The screening (SA) and control (CA) arms comprised altogether 80,144 men. Men in the SA were screened at four-year intervals and referred to biopsy if the PSA concentration was ≥ 4.0 ng/ml, or 3.0-3.99 ng/ml with a free/total PSA ratio ≤ 16%. The median follow-up was 15.0 years. A counterfactual exclusion method was applied to estimate the effect of three subgroups in the SA: the non-participants, the screen-negative men with PSA ≥ 3.0 ng/ml and a subsequent PC diagnosis, and the men with interval PCs. The absolute risk of PC death was 0.76% in the SA and 0.85% in the CA; the observed hazard ratio (HR) was 0.89 (95% confidence interval (CI) 0.76-1.04). After correcting for non-attendance, the HR was 0.78 (0.64-0.96); predicted effect for a hypothetical PSA threshold of 3.0 ng/ml the HR was 0.88 (0.74-1.04) and after eliminating the effect of interval cancers the HR was 0.88 (0.74-1.04). Non-participating men in the SA had a high risk of PC death and a large impact on PC mortality. A hypothetical lower PSA threshold and elimination of interval cancers would have had a less pronounced effect on the screening impact.

Pros and Cons of Noninferiority Trials.

Clinical trials are essential for establishing the benefits and harms of various treatments. Among the various trial designs, superiority trials aim to establish the superiority of one treatment over another, while noninferiority trials demonstrate that a new treatment is not inferior to an established one while minimizing harms or patient burdens. In recent years, noninferiority trials have gained prominence. This mini-review explores noninferiority trials, focusing on challenges in their interpretation. Ultimately, we argue that the focus should be on the results from trials rather than their design, as clinicians and other stakeholders primarily seek evidence that helps patients and clinicians in trade-offs of the benefits and harms and burdens of treatment options. PATIENT SUMMARY: Our mini-review shows that looking at the overall treatment benefits and harms in noninferiority trials is better than focusing on the trial design. This approach would help patients and clinicians to better understand trial results and their implications.

Practice Variation in the Management of Adult Hydroceles: A Multinational Survey.

Background: Although hydrocele is one of the most common urologic pathologies, it is seldom studied, and the major urologic associations have no guidelines for the management of adult hydroceles. Objective: To characterize international practice variation in the treatment of adult hydroceles. Design setting and participants: An international survey was conducted addressing the management of hydroceles among urologists in Belgium, Denmark, Finland, Iceland, Japan, and the Netherlands from September to December 2020. We invited a random sample of 170 urologists from each country (except Iceland). Outcome measurements and statistical analysis: Urologists' treatment options, factors relevant for decision-making, expected patient satisfaction, and outcomes after aspiration versus surgery were assessed. Results and limitations: Of the 864 urologists contacted, 437 (51%) participated. Of the respondents, 202 (53%) performed both hydrocelectomies and aspiration, 147 (39%) performed hydrocelectomies only, and 30 (8%) performed aspiration only. In Belgium (83%), the Netherlands (75%), and Denmark (55%), urologists primarily performed hydrocelectomies only, whereas in Finland (84%), Japan (61%), and Iceland (91%), urologists performed both hydrocelectomies and aspiration. Urologists favored hydrocelectomy for large hydroceles (78.8% vs 37.5% for small), younger patients (66.0% for patients <50 yr vs 41.2% for ≥70 yr), patients with few or no comorbidities (62.3% vs 23.1% with multiple comorbidities), and patients without antithrombotic agents (53.5% vs 36.5% with antithrombotic agents). Most urologists considered patient satisfaction to be highest after hydrocelectomy (53.8% vs 9.9% after aspiration) despite believing that hydrocelectomy is more likely to cause complications (hematoma 77.8% vs 8.8% after aspiration). Estimates varied between countries. Conclusions: We found a large variation in the treatment of adult hydroceles within and between countries. Optimization of hydrocele management globally will require future studies. Patient summary: Our international survey shows that treatment of adult hydrocele varies considerably within and between countries.

Reporting of costs and economic impacts in randomized trials of de-implementation interventions for low-value care: a systematic scoping review.

BACKGROUND: De-implementation of low-value care can increase health care sustainability. We evaluated the reporting of direct costs of de-implementation and subsequent change (increase or decrease) in health care costs in randomized trials of de-implementation research. METHODS: We searched MEDLINE and Scopus databases without any language restrictions up to May 2021. We conducted study screening and data extraction independently and in duplicate. We extracted information related to study characteristics, types and characteristics of interventions, de-implementation costs, and impacts on health care costs. We assessed risk of bias using a modified Cochrane risk-of-bias tool. RESULTS: We screened 10,733 articles, with 227 studies meeting the inclusion criteria, of which 50 included information on direct cost of de-implementation or impact of de-implementation on health care costs. Studies were mostly conducted in North America (36%) or Europe (32%) and in the primary care context (70%). The most common practice of interest was reduction in the use of antibiotics or other medications (74%). Most studies used education strategies (meetings, materials) (64%). Studies used either a single strategy (52%) or were multifaceted (48%). Of the 227 eligible studies, 18 (8%) reported on direct costs of the used de-implementation strategy; of which, 13 reported total costs, and 12 reported per unit costs (7 reported both). The costs of de-implementation strategies varied considerably. Of the 227 eligible studies, 43 (19%) reported on impact of de-implementation on health care costs. Health care costs decreased in 27 studies (63%), increased in 2 (5%), and were unchanged in 14 (33%). CONCLUSION: De-implementation randomized controlled trials typically did not report direct costs of the de-implementation strategies (92%) or the impacts of de-implementation on health care costs (81%). Lack of cost information may limit the value of de-implementation trials to decision-makers. TRIAL REGISTRATION: OSF (Open Science Framework): https://osf.io/ueq32 .

Risk of Complications After Hydrocele Surgery: A Retrospective Multicenter Study in Helsinki Metropolitan Area.

Background: Despite being one of the most frequent urological procedures, the risk estimates for complications after hydrocele surgery (hydrocelectomy) are uncertain. Decision-making about hydrocelectomy involves balancing the risk of complications with efficacy of surgery-a tradeoff that critically depends on the complication risks of hydrocele surgery. Objective: To examine the 90-d risks of complications of hydrocele surgery in a large, contemporary sample. Design setting and participants: We retrospectively reviewed all surgeries performed for nonrecurrent hydroceles conducted in all five Helsinki metropolitan area public hospitals from the beginning of 2010 till the end of 2018, and evaluated the complication outcomes. Outcome measurements and statistical analysis: The following outcomes were evaluated: (1) risk of moderate or severe (Clavien-Dindo II-V) hydrocele surgery complications, (2) risk of reoperation due to a surgical complication, and (3) risk of an unplanned postoperative visit to the emergency room or outpatient clinic, all within 90 d after surgery. Results and limitations: We identified 866 hydrocele operations (38 [4.3%] bilateral operations). A total of 139 (16.1%) patients had moderate or severe hydrocele surgery complications within 90 d after surgery. Of the 139 complications, 94 were (10.9% of all or 67.6% of patients with moderate or severe complications) Clavien-Dindo grade II, 43 (5.0% and 30.9%, respectively) grade III, two (0.2% and 1.4%, respectively) grade IV, and none grade V. A total of 45 patients (5.2% of all and 32.4% of those who had moderate or severe complications) required immediate reoperation due to complications. All together 219 operated patients (25.3% of all operated patients) had an unplanned visit to the emergency room. The retrospective study design limits the reliability of the results. Conclusions: Complications after hydrocele surgery are common and warrant further research. These estimates can be useful in shared decision-making between clinicians and patients. Patient summary: We investigated the complication rates after hydrocele surgery and found that complications are common after a procedure often considered minor: every ninth patient had a moderate and every 20th a severe complication. Every fourth patient had an unplanned postoperative visit to the emergency room.

Randomized controlled trials in de-implementation research: a systematic scoping review.

BACKGROUND: Healthcare costs are rising, and a substantial proportion of medical care is of little value. De-implementation of low-value practices is important for improving overall health outcomes and reducing costs. We aimed to identify and synthesize randomized controlled trials (RCTs) on de-implementation interventions and to provide guidance to improve future research. METHODS: MEDLINE and Scopus up to May 24, 2021, for individual and cluster RCTs comparing de-implementation interventions to usual care, another intervention, or placebo. We applied independent duplicate assessment of eligibility, study characteristics, outcomes, intervention categories, implementation theories, and risk of bias. RESULTS: Of the 227 eligible trials, 145 (64%) were cluster randomized trials (median 24 clusters; median follow-up time 305 days), and 82 (36%) were individually randomized trials (median follow-up time 274 days). Of the trials, 118 (52%) were published after 2010, 149 (66%) were conducted in a primary care setting, 163 (72%) aimed to reduce the use of drug treatment, 194 (85%) measured the total volume of care, and 64 (28%) low-value care use as outcomes. Of the trials, 48 (21%) described a theoretical basis for the intervention, and 40 (18%) had the study tailored by context-specific factors. Of the de-implementation interventions, 193 (85%) were targeted at physicians, 115 (51%) tested educational sessions, and 152 (67%) multicomponent interventions. Missing data led to high risk of bias in 137 (60%) trials, followed by baseline imbalances in 99 (44%), and deficiencies in allocation concealment in 56 (25%). CONCLUSIONS: De-implementation trials were mainly conducted in primary care and typically aimed to reduce low-value drug treatments. Limitations of current de-implementation research may have led to unreliable effect estimates and decreased clinical applicability of studied de-implementation strategies. We identified potential research gaps, including de-implementation in secondary and tertiary care settings, and interventions targeted at other than physicians. Future trials could be improved by favoring simpler intervention designs, better control of potential confounders, larger number of clusters in cluster trials, considering context-specific factors when planning the intervention (tailoring), and using a theoretical basis in intervention design. REGISTRATION: OSF Open Science Framework hk4b2.

Evidence-based Urology: Subgroup Analysis in Randomized Controlled Trials.

In randomized controlled trials, investigators often explore the possibility that the treatment effects differ between subgroups (eg, women vs men, old vs young, more versus less severe disease). Investigators often inappropriately claim subgroup effects (also called "effect modification" or "interaction") when the likelihood of a true effect modification is low. Criteria for assessing the credibility of subgroup analyses, nicely summarized in a formal Instrument for Assessing the Credibility of Effect Modification Analyses (ICEMAN), include investigator postulation of a priori hypotheses with a specified direction; support from prior evidence; a low likelihood that chance explains the apparent subgroup effect; and only testing a small number of subgroup hypotheses. PATIENT SUMMARY: Randomized clinical trials often use subgroup analyses to explore whether a treatment is more or less effective in a particular patient subgroup (eg, women vs men, old vs young). In this mini-review, we explore the common pitfalls of subgroup analyses.

ARTS: A Large, International Trial of Thromboprophylaxis in Intra-abdominal, Gynecologic, and Urologic Surgery.

ARTS will be the first trial to compare anticoagulation with a direct oral anticoagulant (apixaban) versus no anticoagulation among patients undergoing intra-abdominal, gynecologic, or urologic surgery at sufficiently similar risk of deep vein thrombosis or pulmonary embolism and major bleeding.

A three-feature prediction model for metastasis-free survival after surgery of localized clear cell renal cell carcinoma.

After surgery of localized renal cell carcinoma, over 20% of the patients will develop distant metastases. Our aim was to develop an easy-to-use prognostic model for predicting metastasis-free survival after radical or partial nephrectomy of localized clear cell RCC. Model training was performed on 196 patients. Right-censored metastasis-free survival was analysed using LASSO-regularized Cox regression, which identified three key prediction features. The model was validated in an external cohort of 714 patients. 55 (28%) and 134 (19%) patients developed distant metastases during the median postoperative follow-up of 6.3 years (interquartile range 3.4-8.6) and 5.4 years (4.0-7.6) in the training and validation cohort, respectively. Patients were stratified into clinically meaningful risk categories using only three features: tumor size, tumor grade and microvascular invasion, and a representative nomogram and a visual prediction surface were constructed using these features in Cox proportional hazards model. Concordance indices in the training and validation cohorts were 0.755 ± 0.029 and 0.836 ± 0.015 for our novel model, which were comparable to the C-indices of the original Leibovich prediction model (0.734 ± 0.035 and 0.848 ± 0.017, respectively). Thus, the presented model retains high accuracy while requiring only three features that are routinely collected and widely available.

Associations of PTEN and ERG with Magnetic Resonance Imaging Visibility and Assessment of Non-organ-confined Pathology and Biochemical Recurrence After Radical Prostatectomy.

BACKGROUND: Diagnosing clinically significant prostate cancer (PCa) is challenging, but may be facilitated by biomarkers and multiparametric magnetic resonance imaging (MRI). OBJECTIVE: To determine the association between biomarkers phosphatase and tensin homolog (PTEN) and ETS-related gene (ERG) with visible and invisible PCa lesions in MRI, and to predict biochemical recurrence (BCR) and non-organ-confined (non-OC) PCa by integrating clinical, MRI, and biomarker-related data. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of a population-based cohort of men with PCa, who underwent preoperative MRI followed by radical prostatectomy (RP) during 2014-2015 in Helsinki University Hospital (n = 346), was conducted. A tissue microarray corresponding to the MRI-visible and MRI-invisible lesions in RP specimens was constructed and stained for PTEN and ERG. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations of PTEN and ERG with MRI-visible and MRI-invisible lesions were examined (Pearson's χ2 test), and predictions of non-OC disease together with clinical and MRI parameters were determined (area under the receiver operating characteristic curve and logistic regression analyses). BCR prediction was analyzed by Kaplan-Meier and Cox proportional hazard analyses. RESULTS AND LIMITATIONS: Patients with MRI-invisible lesions (n = 35) had less PTEN loss and ERG-positive expression compared with patients (n = 90) with MRI-visible lesions (17.2% vs 43.3% [p = 0.006]; 8.6% vs 20.0% [p = 0.125]). Patients with invisible lesions had better, but not statistically significantly improved, BCR-free survival probability in Kaplan-Meier analyses (p = 0.055). Rates of BCR (5.7% vs 21.1%; p = 0.039), extraprostatic extension (11.4% vs 44.6%; p < 0.001), seminal vesicle invasion (0% vs 21.1%; p = 0.003), and lymph node metastasis (0% vs 12.2%; p = 0.033) differed between the groups in favor of patients with MRI-invisible lesions. Biomarkers had no independent role in predicting non-OC disease or BCR. The short follow-up period was a limitation. CONCLUSIONS: PTEN loss, BCR, and non-OC RP findings were more often encountered with MRI-visible lesions. PATIENT SUMMARY: Magnetic resonance imaging (MRI) of the prostate misses some cancer lesions. MRI-invisible lesions seem to be less aggressive than MRI-visible lesions.

Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS): introduction and methodology.

BACKGROUND: Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. METHODS: We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. DISCUSSION: This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021234119.

Results of the three rounds of the Finnish Prostate Cancer Screening Trial--the incidence of advanced cancer is decreased by screening.

Screening for prostate cancer (PC) remains a controversial issue despite some new evidence on the mortality benefits of PC screening. We conducted a prospective, randomized screening trial in Finland to investigate whether screening decreases PC incidence. Here, we report the incidence results from three screening rounds during a 12-year period. Of the 80,144 men enrolled, 31,866 men were randomized to the screening arm (SA) and invited for screening with prostate-specific antigen test (cut-off 4.0 ng/ml) every 4 years, while the remaining men formed the control arm (CA) that received no interventions. The mean follow-up time for PC incidence in both arms was over 9 years. The incidence rate of PC (including screen-detected and interval cancers as well as cases among nonparticipants) was 9.1 per 1,000 person-years in the SA and 6.2 in the CA, yielding an incidence rate ratio (IRR) 1.5 (95% confidence interval 1.4-1.5). The incidence of advanced PC was 1.1 in the SA and 1.5 in the CA, IRR = 0.7 (0.6-0.8) and the difference emerges after 5-6 years of follow-up. The incidence of localized PC was 7.5 in the SA and 4.6 in the CA, IRR = 1.6 (1.5-1.7). The results from our large population-based trial indicate that screening for PC decreases the incidence of advanced PC. When compared with the CA, the PC detected in the SA there were substantially more often localized, low-grade PCs due to overdiagnosis.