The European Randomized Study of Screening for Prostate Cancer continues to show a 21% reduction in prostate-cancer mortality in the screening group, after 11 years of follow-up. The number of ...cancers that would need to be detected to prevent one prostate-cancer death is 37. Screening does not affect all-cause mortality.
Screening for prostate cancer has remained controversial, despite results showing a significant reduction in the rate of death from prostate cancer (relative reduction, 20%) among men offered screening for prostate-specific antigen (PSA).
1
The European Randomized Study of Screening for Prostate Cancer (ERSPC) is a multicenter trial initiated in 1991 in the Netherlands and in Belgium, with five more European countries (Sweden, Finland, Italy, Spain, and Switzerland) joining between 1994 and 1998. Recruitment was completed in these centers between 1995 and 2003. Later, France also joined, with enrollment in 2000–2005, but data from the French cohort were not included in the . . .
The European Randomized study of Screening for Prostate Cancer (ERSPC) has previously demonstrated that prostate-specific antigen (PSA) screening decreases prostate cancer (PCa) mortality.
To ...determine whether PSA screening decreases PCa mortality for up to 16yr and to assess results following adjustment for nonparticipation and the number of screening rounds attended.
This multicentre population-based randomised screening trial was conducted in eight European countries. Report includes 182160 men, followed up until 2014 (maximum of 16yr), with a predefined core age group of 162389 men (55–69yr), selected from population registry.
The outcome was PCa mortality, also assessed with adjustment for nonparticipation and the number of screening rounds attended.
The rate ratio of PCa mortality was 0.80 (95% confidence interval CI 0.72–0.89, p<0.001) at 16yr. The difference in absolute PCa mortality increased from 0.14% at 13yr to 0.18% at 16yr. The number of men needed to be invited for screening to prevent one PCa death was 570 at 16yr compared with 742 at 13yr. The number needed to diagnose was reduced to 18 from 26 at 13yr. Men with PCa detected during the first round had a higher prevalence of PSA >20ng/ml (9.9% compared with 4.1% in the second round, p<0.001) and higher PCa mortality (hazard ratio=1.86, p<0.001) than those detected subsequently.
Findings corroborate earlier results that PSA screening significantly reduces PCa mortality, showing larger absolute benefit with longer follow-up and a reduction in excess incidence. Repeated screening may be important to reduce PCa mortality on a population level.
In this report, we looked at the outcomes from prostate cancer in a large European population. We found that repeated screening reduces the risk of dying from prostate cancer.
This European Randomized study of Screening for Prostate Cancer trial follow-up reports that repeated screening reduces the risk of dying from prostate cancer for up to 16yr.
There are no published studies on the simultaneous effect of extent and location of positive surgical margins (PSMs) on biochemical recurrence (BCR) after robot-assisted laparoscopic prostatectomy ...(RALP). The aim was to report the incidence, extent, and location of PSMs over the inclusion period as well as the rates of BCR and cancer-related mortality, and determine if BCR is associated with PSM extent and/or location.
Retrospective review of 530 consecutive patients who underwent RALP between 2003 and 2012. Kaplan-Meier (KM) survival analyses and Cox regressions were performed to determine variables associated with BCR.
For the 530 operated patients, evaluated at a median of 92 months (IQR, 87-99), PSMs were observed in 156 (29%), of which 24% were focal. Out of 172 PSMs, 126 (73%) were focal and 46 (27%) were extensive. The KM survival using BCR as endpoint was 0.81 (CI, 0.78-0.85) at 5 years and was 0.67 (CI, 0.61-0.72) at 10 years; and using cancer-related mortality as endpoint was 0.99 (CI, 0.99-1.00) at 5 years and 0.95 (CI, 0.92-0.98) at 10 years. Multi-variable analysis revealed the strongest predictors of BCR to be Gleason score ≥ 8 (HR = 7.97; CI, 4.38-14.51) and 4 + 3 (HR = 3.88; CI, 2.12-7.07), lymph nodes invasion (HR = 3.42; CI, 1.70-6.91), pT stage 3b or 4 (HR = 3.07; CI, 1.93-4.90), and extensive apical PSMs (HR = 2.62; CI, 1.40-4.90) but not focal apical PSMs (HR = 0.86; CI, 0.49-1.50; p = 0.586).
Extensive apical PSMs significantly increased the risk of BCR, independently from pT stage, Gleason score and lymph nodes invasion, while focal apical PSMs had no significant effect on BCR.
Summary Background Enzalutamide is an oral androgen-receptor inhibitor that has been shown to improve survival in two placebo-controlled phase 3 trials, and is approved for patients with metastatic ...castration-resistant prostate cancer. The objective of the TERRAIN study was to compare the efficacy and safety of enzalutamide with bicalutamide in patients with metastatic castration-resistant prostate cancer. Methods TERRAIN was a double-blind, randomised phase 2 study, that recruited asymptomatic or minimally symptomatic men with prostate cancer progression on androgen-deprivation therapy (ADT) from academic, community, and private health-care provision sites across North America and Europe. Eligible patients were randomly assigned (1:1) via an interactive voice response system to receive enzalutamide 160 mg/day or bicalutamide 50 mg/day, both taken orally, in addition to ADT, until disease progression. Patients were stratified by a permutated block method (block size of four), by whether bilateral orchiectomy or receipt of luteinising hormone-releasing hormone agonist or antagonist therapy started before or after the diagnosis of metastases, and by study site. Participants, investigators, and those assessing outcomes were masked to group assignment. The primary endpoint was progression-free survival, analysed in all randomised patients. Safety outcomes were analysed in all patients who received at least one dose of study drug. The open-label period of the trial is in progress, wherein patients still on treatment at the end of the double-blind treatment period were offered open-label enzalutamide at the discretion of the patient and study investigator. This trial is registered with ClinicalTrials.gov , number NCT01288911. Findings Between March 22, 2011, and July 11, 2013, 375 patients were randomly assigned, 184 to enzalutamide and 191 to bicalutamide. 126 (68%) and 168 (88%) patients, respectively, discontinued their assigned treatment before study end, mainly due to progressive disease. Median follow-up time was 20·0 months (IQR 15·0–25·6) in the enzalutamide group and 16·7 months (10·2–21·9) in the bicalutamide group. Patients in the enzalutamide group had significantly improved median progression-free survival (15·7 months 95% CI 11·5–19·4) compared with patients in the bicalutamide group (5·8 months 4·8–8·1; hazard ratio 0·44 95% CI 0·34–0·57; p<0·0001). Of the most common adverse events, those occurring more frequently with enzalutamide than with bicalutamide were fatigue (51 28% of 183 patients in the enzalutamide group vs 38 20% of 189 in the bicalutamide group), back pain (35 19% vs 34 18%), and hot flush (27 15% vs 21 11%); those occurring more frequently with bicalutamide were nausea (26 14% vs 33 17%), constipation (23 13% vs 25 13%), and arthralgia (18 10% vs 30 16%). The most common grade 3 or worse adverse events in the enzalutamide or bicalutamide treatment groups, respectively, were hypertension (13 7% vs eight 4%), hydronephrosis (three 2% vs seven 4%), back pain (five 3% vs three 2%), pathological fracture (five 3% vs two 1%), dyspnoea (four 2% vs one 1%), bone pain (one 1% vs four 2%), congestive cardiac failure (four 2% vs two 1%), myocardial infarction (five 3% vs none), and anaemia (four 2% vs none). Serious adverse events were reported by 57 (31%) of 183 patients and 44 (23%) of 189 patients in the enzalutamide and bicalutamide groups, respectively. One of the nine deaths in the enzalutamide group was thought to be possibly related to treatment (due to systemic inflammatory response syndrome) compared with none of the three deaths in the bicalutamide group. Interpretation The data from the TERRAIN trial support the use of enzalutamide rather than bicalutamide in patients with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer. Funding Astellas Pharma, Inc and Medivation, Inc.
Summary Background The European Randomised study of Screening for Prostate Cancer (ERSPC) has shown significant reductions in prostate cancer mortality after 9 years and 11 years of follow-up, but ...screening is controversial because of adverse events such as overdiagnosis. We provide updated results of mortality from prostate cancer with follow-up to 2010, with analyses truncated at 9, 11, and 13 years. Methods ERSPC is a multicentre, randomised trial with a predefined centralised database, analysis plan, and core age group (55–69 years), which assesses prostate-specific antigen (PSA) testing in eight European countries. Eligible men aged 50–74 years were identified from population registries and randomly assigned by computer generated random numbers to screening or no intervention (control). Investigators were masked to group allocation. The primary outcome was prostate cancer mortality in the core age group. Analysis was by intention to treat. We did a secondary analysis that corrected for selection bias due to non-participation. Only incidence and no mortality data at 9 years’ follow-up are reported for the French centres. This study is registered with Current Controlled Trials, number ISRCTN49127736. Findings With data truncated at 13 years of follow-up, 7408 prostate cancer cases were diagnosed in the intervention group and 6107 cases in the control group. The rate ratio of prostate cancer incidence between the intervention and control groups was 1·91 (95% CI 1·83–1·99) after 9 years (1·64 1·58–1·69 including France), 1·66 (1·60–1·73) after 11 years, and 1·57 (1·51–1·62) after 13 years. The rate ratio of prostate cancer mortality was 0·85 (0·70–1·03) after 9 years, 0·78 (0·66–0·91) after 11 years, and 0·79 (0·69–0·91) at 13 years. The absolute risk reduction of death from prostate cancer at 13 years was 0·11 per 1000 person-years or 1·28 per 1000 men randomised, which is equivalent to one prostate cancer death averted per 781 (95% CI 490–1929) men invited for screening or one per 27 (17–66) additional prostate cancer detected. After adjustment for non-participation, the rate ratio of prostate cancer mortality in men screened was 0·73 (95% CI 0·61–0·88). Interpretation In this update the ERSPC confirms a substantial reduction in prostate cancer mortality attributable to testing of PSA, with a substantially increased absolute effect at 13 years compared with findings after 9 and 11 years. Despite our findings, further quantification of harms and their reduction are still considered a prerequisite for the introduction of populated-based screening. Funding Each centre had its own funding responsibility.
Abstract Background Up to a third of patients with localized prostate cancer have unilateral disease that may be suitable for partial treatment with hemiablation. Objective To evaluate the ability of ...high intensity focused ultrasound (HIFU) to achieve local control of the tumor in patients with unilateral localized prostate cancer. Design, setting, and participants The French Urological Association initiated a prospective IDEAL multi-institutional study (2009–2015), to evaluate HIFU-hemiablation as a primary treatment. Intervention Multiparametric magnetic resonance imaging and biopsy were used for unilateral cancer diagnosis and control, and HIFU-hemiablation. Outcome measurements and statistical analysis Primary: absence of clinically significant cancer (CSC) on control biopsy at 1 yr (CSC: Gleason score ≥ 7 or cancer core length > 3 mm regardless of grade or > 2 positive cores). Secondary: presence of any cancer on biopsy, biochemical response, radical treatment free survival, adverse events, continence (no pad), erectile function (International Index of Erectile Function-5 ≥ 16), and quality of life (European Organization for Research and Treatment of Cancer QLQ-C28) questionnaires. Results and limitations One hundred and eleven patients were treated (mean age: 64.8 yr standard deviation 6.2; mean prostate-specific antigen: 6.2 ng/ml standard deviation 2.6; 68% low risk, 32% intermediate risk). Of the 101 patients with control biopsy, 96 (95%) and 94 (93%) had no CSC in the treated and contralateral lobes, respectively. Mean prostate-specific antigen at 2 yr was 2.3 ng/ml (standard deviation 1.7). The radical treatment-free survival rate at 2 years was 89% (radical treatments: six radical prostatectomies, three radiotherapies, and two HIFU). Adverse events were Grade 3 in 13%. At 12 mo continence and erectile functions were preserved in 97% and 78%. No significant decrease in quality of life score was observed at 12 mo. One limitation is the number of low-risk patients included in this study. Conclusions At 1 yr, HIFU-hemiablation was efficient with 95% absence of clinically significant cancer associated with low morbidity and preservation of quality of life. Radical treatment-free survival rate was 89% at 2 yr. Patient summary This report shows that high intensity focused ultrasound half-gland treatment of unilateral prostate cancer provides promising results with high cancer control and low morbidity.
Purpose We compared prostate tumor boundaries on magnetic resonance imaging and radical prostatectomy histological assessment using detailed software assisted co-registration to define an optimal ...treatment margin for achieving complete tumor destruction during image guided focal ablation. Materials and Methods Included in study were 33 patients who underwent 3 Tesla magnetic resonance imaging before radical prostatectomy. A radiologist traced lesion borders on magnetic resonance imaging and assigned a suspicion score of 2 to 5. Three-dimensional reconstructions were created from high resolution digitalized slides of radical prostatectomy specimens and co-registered to imaging using advanced software. Tumors were compared between histology and imaging by the Hausdorff distance and stratified by the magnetic resonance imaging suspicion score, Gleason score and lesion diameter. Cylindrical volume estimates of treatment effects were used to define the optimal treatment margin. Results Three-dimensional software based registration with magnetic resonance imaging was done in 46 histologically confirmed cancers. Imaging underestimated tumor size with a maximal discrepancy between imaging and histological boundaries for a given tumor of an average ± SD of 1.99 ± 3.1 mm, representing 18.5% of the diameter on imaging. Boundary underestimation was larger for lesions with an imaging suspicion score 4 or greater (mean 3.49 ± 2.1 mm, p <0.001) and a Gleason score of 7 or greater (mean 2.48 ± 2.8 mm, p = 0.035). A simulated cylindrical treatment volume based on the imaging boundary missed an average 14.8% of tumor volume compared to that based on the histological boundary. A simulated treatment volume based on a 9 mm treatment margin achieved complete histological tumor destruction in 100% of patients. Conclusions Magnetic resonance imaging underestimates histologically determined tumor boundaries, especially for lesions with a high imaging suspicion score and a high Gleason score. A 9 mm treatment margin around a lesion visible on magnetic resonance imaging would consistently ensure treatment of the entire histological tumor volume during focal ablative therapy.
Abstract Background Focal therapy as a treatment option for localized prostate cancer (PCa) is an increasingly popular and rapidly evolving field. Objective To gather expert opinion on patient ...selection, interventions, and meaningful outcome measures for focal therapy in clinical practice and trial design. Design, setting, and participants Fifteen experts in focal therapy followed a modified two-stage RAND/University of California, Los Angeles (UCLA) Appropriateness Methodology process. All participants independently scored 246 statements prior to rescoring at a face-to-face meeting. The meeting occurred in June 2013 at the Royal Society of Medicine, London, supported by the Wellcome Trust and the UK Department of Health. Outcome measurements and statistical analysis Agreement, disagreement, or uncertainty were calculated as the median panel score. Consensus was derived from the interpercentile range adjusted for symmetry level. Results and limitations Of 246 statements, 154 (63%) reached consensus. Items of agreement included the following: patients with intermediate risk and patients with unifocal and multifocal PCa are eligible for focal treatment; magnetic resonance imaging–targeted or template-mapping biopsy should be used to plan treatment; planned treatment margins should be 5 mm from the known tumor; prostate volume or age should not be a primary determinant of eligibility; foci of indolent cancer can be left untreated when treating the dominant index lesion; histologic outcomes should be defined by targeted biopsy at 1 yr; residual disease in the treated area of ≤3 mm of Gleason 3 + 3 did not need further treatment; and focal retreatment rates of ≤20% should be considered clinically acceptable but subsequent whole-gland therapy deemed a failure of focal therapy. All statements are expert opinion and therefore constitute level 5 evidence and may not reflect wider clinical consensus. Conclusions The landscape of PCa treatment is rapidly evolving with new treatment technologies. This consensus meeting provides guidance to clinicians on current expert thinking in the field of focal therapy. Patient summary In this report we present expert opinion on patient selection, interventions, and meaningful outcomes for clinicians working in focal therapy for prostate cancer.
Abstract Background A systematic literature review of magnetic resonance imaging (MRI)–targeted prostate biopsy demonstrates poor adherence to the Standards for the Reporting of Diagnostic Accuracy ...(STARD) recommendations for the full and transparent reporting of diagnostic studies. Objective To define and recommend Standards of Reporting for MRI-targeted Biopsy Studies (START). Design, setting, and participants Each member of a panel of 23 experts in urology, radiology, histopathology, and methodology used the RAND/UCLA appropriateness methodology to score a 258-statement premeeting questionnaire. The collated responses were presented at a face-to-face meeting, and each statement was rescored after group discussion. Outcome measurements and statistical analysis Measures of agreement and consensus were calculated for each statement. The most important statements, based on group median score, the degree of group consensus, and the content of the group discussion, were used to create a checklist of reporting criteria (the START checklist). Results and limitations The strongest recommendations were to report histologic results of standard and targeted cores separately using Gleason score and maximum cancer core length. A table comparing detection rates of clinically significant and clinically insignificant disease by targeted and standard approaches should also be used. It was recommended to report the recruitment criteria for MRI-targeted biopsy, prior biopsy status of the population, a brief description of the MRI sequences, MRI reporting method, radiologist experience, and image registration technique. There was uncertainty about which histologic criteria constitute clinically significant cancer when the prostate is sampled using MRI-targeted biopsy, and it was agreed that a new definition of clinical significance in this setting needed to be derived in future studies. Conclusions Use of the START checklist would improve the quality of reporting in MRI-targeted biopsy studies and facilitate a comparison between standard and MRI-targeted approaches.
Over the years, several techniques for performing robot-assisted prostatectomy have been implemented in an effort to achieve optimal oncological and functional outcomes.
To provide an evidence-based ...description and video-based illustration of currently available dissection techniques for robotic prostatectomy.
A literature search was performed to retrieve articles describing different surgical approaches and techniques for robot-assisted radical prostatectomy (RARP) and to analyze data supporting their use. Video material was provided by experts in the field to illustrate these approaches and techniques.
Multiple surgical approaches are available: extraperitoneal, transvesical, transperitoneal posterior, transperitoneal anterior, Retzius sparing, and transperineal. Surgical techniques for prostatic dissection sensu strictu are the following: omission of the endopelvic fascia dissection, bladder neck preservation, incremental nerve sparing by means of an antegrade or retrograde approach, and preservation of the puboprostatic ligaments and dorsal venous complex. Recently, techniques for total or partial prostatectomy have been described.
Different surgical approaches and techniques for robotic prostatectomy have been analyzed.
Two randomized controlled trials evaluating the extraperitoneal versus the transperitoneal approach have demonstrated similar results. Level I evidence on the Retzius-sparing approach demonstrated earlier return to continence than the traditional anterior approach. The question whether Retzius-sparing RARP is associated with a higher rate of positive surgical margins is still open due to the intrinsic bias in terms of surgical expertise in the available comparative studies. This technique also offers an advantage in patients who have received kidney transplantation. Retrospective evidence suggests that the more the anatomical dissection (eg., more periprostatic tissue is preserved), the better the functional outcome in terms of continence. Yet, two randomized controlled trials evaluating the different techniques of dissection have so far been produced. Partial prostatectomies should not be offered outside clinical trials.
Several techniques and approaches are available for prostate dissection during RARP. While the Retzius-sparing approach seems to provide earlier return to continence than the traditional anterior transperitoneal approach, no technique has been proved to be superior to other(s) in terms of long-term outcomes in randomized studies.
We have summarized available approaches for the surgical treatment of prostate cancer. Specifically, we described the different techniques that can be adopted for the surgical removal of the prostate using robotic technology.
PDF
