Abstract Context There is controversy regarding the therapeutic role of pelvic lymph node dissection (PLND) in patients undergoing radical prostatectomy for prostate cancer (PCa). Objective To ...systematically review the relevant literature assessing the relative benefits and harms of PLND for oncological and non-oncological outcomes in patients undergoing radical prostatectomy for PCa. Evidence acquisition MEDLINE, MEDLINE In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched up to December 2015. Comparative studies evaluating no PLND, limited, standard, and (super)-extended PLND that reported oncological and non-oncological outcomes were included. Risk-of-bias and confounding assessments were performed. A narrative synthesis was undertaken. Evidence synthesis Overall, 66 studies recruiting a total of 275,269 patients were included (44 full-text articles and 22 conference abstracts). Oncological outcomes were addressed by 29 studies, one of which was a randomized clinical trial (RCT). Non-oncological outcomes were addressed by 43 studies, three of which were RCTs. There were high risks of bias and confounding in most studies. Conflicting results emerged when comparing biochemical and clinical recurrence, while no significant differences were observed among groups for survival. Conversely, the majority of studies showed that the more extensive the PLND, the greater the adverse outcomes in terms of operating time, blood loss, length of stay, and postoperative complications. No significant differences were observed in terms of urinary continence and erectile function recovery. Conclusions Although representing the most accurate staging procedure, PLND and its extension are associated with worse intraoperative and perioperative outcomes, whereas a direct therapeutic effect is still not evident from the current literature. The current poor quality of evidence indicates the need for robust and adequately powered clinical trials. Patient summary Based on a comprehensive review of the literature, this article summarizes the benefits and harms of removing lymph nodes during surgery to remove the prostate because of PCa. Although the quality of the data from the studies was poor, the review suggests that lymph node removal may not have any direct benefit on cancer outcomes and may instead result in more complications. Nevertheless, the procedure remains justified because it enables accurate assessment of cancer spread.
Abstract Objective To present a summary of the 2016 version of the European Association of Urology (EAU) – European Society for Radiotherapy & Oncology (ESTRO) – International Society of Geriatric ...Oncology (SIOG) Guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (CRPC). Evidence acquisition The working panel performed a literature review of the new data (2013–2015). The guidelines were updated, and the levels of evidence and/or grades of recommendation were added based on a systematic review of the literature. Evidence synthesis Relapse after local therapy is defined by a rising prostate-specific antigen (PSA) level >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir after radiation therapy (RT).11 C-choline positron emission tomography/computed tomography is of limited importance if PSA is <1.0 ng/ml; bone scans and computed tomography can be omitted unless PSA is >10 ng/ml. Multiparametric magnetic resonance imaging and biopsy are important to assess biochemical failure following RT. Therapy for PSA relapse after RP includes salvage RT at PSA levels <0.5 ng/ml and salvage RP, high-intensity focused ultrasound, cryosurgical ablation or salvage brachytherapy of the prostate in radiation failures. Androgen deprivation therapy (ADT) remains the basis for treatment of men with metastatic prostate cancer (PCa). However, docetaxel combined with ADT should be considered the standard of care for men with metastases at first presentation, provided they are fit enough to receive the drug. Follow-up of ADT should include analysis of PSA, testosterone levels, and screening for cardiovascular disease and metabolic syndrome. Level 1 evidence for the treatment of metastatic CRPC (mCRPC) includes, abiraterone acetate plus prednisone (AA/P), enzalutamide, radium 223 (Ra 223), docetaxel at 75 mg/m2 every 3 wk and sipuleucel-T. Cabazitaxel, AA/P, enzalutamide, and radium are approved for second-line treatment of CRPC following docetaxel. Zoledronic acid and denosumab can be used in men with mCRPC and osseous metastases to prevent skeletal-related complications. Conclusions The knowledge in the field of advanced and metastatic PCa and CRPC is changing rapidly. The 2016 EAU-ESTRO-SIOG Guidelines on PCa summarise the most recent findings and advice for use in clinical practice. These PCa guidelines are the first endorsed by the European Society for Therapeutic Radiology and Oncology and the International Society of Geriatric Oncology and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office or online ( http://uroweb.org/guideline/prostate-cancer/ ). Patient summary In men with a rise in their PSA levels after prior local treatment for prostate cancer only, it is important to balance overtreatment against further progression of the disease since survival and quality of life may never be affected in many of these patients. For patients diagnosed with metastatic castrate-resistant prostate cancer, several new drugs have become available which may provide a clear survival benefit but the optimal choice will have to be made on an individual basis.
Abstract Context It remains unclear whether patients with a suspicion of prostate cancer (PCa) and negative multiparametric magnetic resonance imaging (mpMRI) can safely obviate prostate biopsy. ...Objective To systematically review the literature assessing the negative predictive value (NPV) of mpMRI in patients with a suspicion of PCa. Evidence acquisition The Embase, Medline, and Cochrane databases were searched up to February 2016. Studies reporting prebiopsy mpMRI results using transrectal or transperineal biopsy as a reference standard were included. We further selected for meta-analysis studies with at least 10-core biopsies as the reference standard, mpMRI comprising at least T2-weighted and diffusion-weighted imaging, positive mpMRI defined as a Prostate Imaging Reporting Data System/Likert score of ≥3/5 or ≥4/5, and results reported at patient level for the detection of overall PCa or clinically significant PCa (csPCa) defined as Gleason ≥7 cancer. Evidence synthesis A total of 48 studies (9613 patients) were eligible for inclusion. At patient level, the median prevalence was 50.4% (interquartile range IQR, 36.4–57.7%) for overall cancer and 32.9% (IQR, 28.1–37.2%) for csPCa. The median mpMRI NPV was 82.4% (IQR, 69.0–92.4%) for overall cancer and 88.1% (IQR, 85.7–92.3) for csPCa. NPV significantly decreased when cancer prevalence increased, for overall cancer ( r = –0.64, p < 0.0001) and csPCa ( r = –0.75, p = 0.032). Eight studies fulfilled the inclusion criteria for meta-analysis. Seven reported results for overall PCa. When the overall PCa prevalence increased from 30% to 60%, the combined NPV estimates decreased from 88% (95% confidence interval 95% CI, 77–99%) to 67% (95% CI, 56–79%) for a cut-off score of 3/5. Only one study selected for meta-analysis reported results for Gleason ≥7 cancers, with a positive biopsy rate of 29.3%. The corresponding NPV for a cut-off score of ≥3/5 was 87.9%. Conclusions The NPV of mpMRI varied greatly depending on study design, cancer prevalence, and definitions of positive mpMRI and csPCa. As cancer prevalence was highly variable among series, risk stratification of patients should be the initial step before considering prebiopsy mpMRI and defining those in whom biopsy may be omitted when the mpMRI is negative. Patient summary This systematic review examined if multiparametric magnetic resonance imaging (MRI) scan can be used to reliably predict the absence of prostate cancer in patients suspected of having prostate cancer, thereby avoiding a prostate biopsy. The results suggest that whilst it is a promising tool, it is not accurate enough to replace prostate biopsy in such patients, mainly because its accuracy is variable and influenced by the prostate cancer risk. However, its performance can be enhanced if there were more accurate ways of determining the risk of having prostate cancer. When such tools are available, it should be possible to use an MRI scan to avoid biopsy in patients at a low risk of prostate cancer.
Summary Background Sentinel-lymph-node (SLN) surgery was designed to minimise the side-effects of lymph-node surgery but still offer outcomes equivalent to axillary-lymph-node dissection (ALND). The ...aims of National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-32 were to establish whether SLN resection in patients with breast cancer achieves the same survival and regional control as ALND, but with fewer side-effects. Methods NSABP B-32 was a randomised controlled phase 3 trial done at 80 centres in Canada and the USA between May 1, 1999, and Feb 29, 2004. Women with invasive breast cancer were randomly assigned to either SLN resection plus ALND (group 1) or to SLN resection alone with ALND only if the SLNs were positive (group 2). Random assignment was done at the NSABP Biostatistical Center (Pittsburgh, PA, USA) with a biased coin minimisation approach in an allocation ratio of 1:1. Stratification variables were age at entry (≤49 years, ≥50 years), clinical tumour size (≤2·0 cm, 2·1–4·0 cm, ≥4·1 cm), and surgical plan (lumpectomy, mastectomy). SLN resection was done with a blue dye and radioactive tracer. Outcome analyses were done in patients who were assessed as having pathologically negative sentinel nodes and for whom follow-up data were available. The primary endpoint was overall survival. Analyses were done on an intention-to-treat basis. All deaths, irrespective of cause, were included. The mean time on study for the SLN-negative patients with follow-up information was 95·6 months (range 70·1–126·7). This study is registered with ClinicalTrials.gov , number NCT00003830. Findings 5611 women were randomly assigned to the treatment groups, 3989 had pathologically negative SLN. 309 deaths were reported in the 3986 SLN-negative patients with follow-up information: 140 of 1975 patients in group 1 and 169 of 2011 in group 2. Log-rank comparison of overall survival in groups 1 and 2 yielded an unadjusted hazard ratio (HR) of 1·20 (95% CI 0·96–1·50; p=0·12). 8-year Kaplan-Meier estimates for overall survival were 91·8% (95% CI 90·4–93·3) in group 1 and 90·3% (88·8–91·8) in group 2. Treatment comparisons for disease-free survival yielded an unadjusted HR of 1·05 (95% CI 0·90–1·22; p=0·54). 8-year Kaplan-Meier estimates for disease-free survival were 82·4% (80·5–84·4) in group 1 and 81·5% (79·6–83·4) in group 2. There were eight regional-node recurrences as first events in group 1 and 14 in group 2 (p=0·22). Patients are continuing follow-up for longer-term assessment of survival and regional control. The most common adverse events were allergic reactions, mostly related to the administration of the blue dye. Interpretation Overall survival, disease-free survival, and regional control were statistically equivalent between groups. When the SLN is negative, SLN surgery alone with no further ALND is an appropriate, safe, and effective therapy for breast cancer patients with clinically negative lymph nodes. Funding US Public Health Service, National Cancer Institute, and Department of Health and Human Services.
To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European ...Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on screening, diagnosis, and local treatment of clinically localised prostate cancer (PCa).
The panel performed a literature review of new data, covering the time frame between 2016 and 2020. The guidelines were updated and a strength rating for each recommendation was added based on a systematic review of the evidence.
A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. Risk-adapted screening should be offered to men at increased risk from the age of 45 yr and to breast cancer susceptibility gene (BRCA) mutation carriers, who have been confirmed to be at risk of early and aggressive disease (mainly BRAC2), from around 40 yr of age. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is performed, a combination of targeted and systematic biopsies must be offered. There is currently no place for the routine use of tissue-based biomarkers. Whilst prostate-specific membrane antigen positron emission tomography computed tomography is the most sensitive staging procedure, the lack of outcome benefit remains a major limitation. Active surveillance (AS) should always be discussed with low-risk patients, as well as with selected intermediate-risk patients with favourable International Society of Urological Pathology (ISUP) 2 lesions. Local therapies are addressed, as well as the AS journey and the management of persistent prostate-specific antigen after surgery. A strong recommendation to consider moderate hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term hormonal treatment.
The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for their use in clinical practice. These PCa guidelines reflect the multidisciplinary nature of PCa management.
Updated prostate cancer guidelines are presented, addressing screening, diagnosis, and local treatment with curative intent. These guidelines rely on the available scientific evidence, and new insights will need to be considered and included on a regular basis. In some cases, the supporting evidence for new treatment options is not yet strong enough to provide a recommendation, which is why continuous updating is important. Patients must be fully informed of all relevant options and, together with their treating physicians, decide on the most optimal management for them.
The 2020 European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on prostate cancer (PCa) summarise the most recent findings and provide recommendations for clinical practice, addressing screening, diagnosis, and local treatment with curative intent. Key stakeholders in PCa management were involved in their development, including a patient representative. A full version is available at the EAU office and online at http://uroweb.org/guideline/prostate-cancer/. A separate publication will address the management of relapsing-, metastatic-, and castration-resistant PCa.
To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy & Oncology (ESTRO)-European ...Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (CRPC).
The working panel performed a literature review of the new data (2016–2019). The guidelines were updated, and the levels of evidence and/or grades of recommendation were added based on a systematic review of the literature.
Prostate-specific membrane antigen positron emission tomography computed tomography scanning has developed an increasingly important role in men with biochemical recurrence after local therapy. Early salvage radiotherapy after radical prostatectomy appears as effective as adjuvant radiotherapy and, in a subset of patients, should be combined with androgen deprivation. New treatments have become available for men with metastatic hormone-sensitive prostate cancer (PCa), nonmetastatic CRPC, and metastatic CRPC, along with a role for local radiotherapy in men with low-volume metastatic hormone-sensitive PCa. Also included is information on quality of life outcomes in men with PCa.
The knowledge in the field of advanced and metastatic PCa and CRPC is changing rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for use in clinical practice. These PCa guidelines are first endorsed by the EANM and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office or online (http://uroweb.org/guideline/prostate-cancer/).
This article summarises the guidelines for the treatment of relapsing, metastatic, and castration-resistant prostate cancer. These guidelines are evidence based and guide the clinician in the discussion with the patient on the treatment decisions to be taken. These guidelines are updated every year; this summary spans the 2017–2020 period of new evidence.
The knowledge in the field of advanced and metastatic prostate cancer (PCa) and castration-resistant prostate cancer is changing rapidly. The 2020 European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy & Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on PCa summarise the most recent findings and advice for use in clinical practice. These PCa guidelines are first endorsed by the EANM and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office or online (http://uroweb.org/guideline/prostate-cancer/).
Summary Background The goals of axillary-lymph-node dissection (ALND) are to maximise survival, provide regional control, and stage the patient. However, this technique has substantial side-effects. ...The purpose of the B-32 trial is to establish whether sentinel-lymph-node (SLN) resection can achieve the same therapeutic goals as conventional ALND but with decreased side-effects. The aim of this paper is to report the technical success and accuracy of SLN resection plus ALND versus SLN resection alone. Methods 5611 women with invasive breast cancer were randomly assigned to receive either SLN resection followed by immediate conventional ALND (n=2807; group 1) or SLN resection without ALND if SLNs were negative on intraoperative cytology and histological examination (n=2804; group 2) in the B-32 trial. Patients in group 2 underwent ALND if no SLNs were identified or if one or more SLNs were positive on intraoperative cytology or subsequent histological examination. Primary endpoints, including survival, regional control, and morbidity, will be reported later. Secondary endpoints are accuracy and technical success and are reported here. This trial is registered with the Clinical Trial registry, number NCT00003830. Findings Data for technical success were available for 5536 of 5611 patients; 75 declined protocol treatment, had no SLNs removed, or had no SLN resection done. SLNs were successfully removed in 97·2% of patients (5379 of 5536) in both groups combined. Identification of a preincision hot spot was associated with greater SLN removal (98·9% 5072 of 5128). Only 1·4% (189 of 13171) of SLN specimens were outside of axillary levels I and II. 65·1% (8571 of 13 171) of SLN specimens were both radioactive and blue; a small percentage was identified by palpation only (3·9% 515 of 13 171). The overall accuracy of SLN resection in patients in group 1 was 97·1% (2544 of 2619; 95% CI 96·4–97·7), with a false-negative rate of 9·8% (75 of 766; 95% CI 7·8–12·2). Differences in tumour location, type of biopsy, and number of SLNs removed significantly affected the false-negative rate. Allergic reactions related to blue dye occurred in 0·7% (37 of 5588) of patients with data on toxic effects. Interpretation The findings reported here indicate excellent balance in clinical patient characteristics between the two randomised groups and that the success of SLN resection was high. These findings are important because the B-32 trial is the only trial of sufficient size to provide definitive information related to the primary outcome measures of survival and regional control. Removal of more than one SLN and avoidance of excisional biopsy are important variables in reducing the false-negative rate.
The U.S. Environmental Protection Agency’s (EPA) ToxCast program is testing a large library of Agency-relevant chemicals using in vitro high-throughput screening (HTS) approaches to support the ...development of improved toxicity prediction models. Launched in 2007, Phase I of the program screened 310 chemicals, mostly pesticides, across hundreds of ToxCast assay end points. In Phase II, the ToxCast library was expanded to 1878 chemicals, culminating in the public release of screening data at the end of 2013. Subsequent expansion in Phase III has resulted in more than 3800 chemicals actively undergoing ToxCast screening, 96% of which are also being screened in the multi-Agency Tox21 project. The chemical library unpinning these efforts plays a central role in defining the scope and potential application of ToxCast HTS results. The history of the phased construction of EPA’s ToxCast library is reviewed, followed by a survey of the library contents from several different vantage points. CAS Registry Numbers are used to assess ToxCast library coverage of important toxicity, regulatory, and exposure inventories. Structure-based representations of ToxCast chemicals are then used to compute physicochemical properties, substructural features, and structural alerts for toxicity and biotransformation. Cheminformatics approaches using these varied representations are applied to defining the boundaries of HTS testability, evaluating chemical diversity, and comparing the ToxCast library to potential target application inventories, such as used in EPA’s Endocrine Disruption Screening Program (EDSP). Through several examples, the ToxCast chemical library is demonstrated to provide comprehensive coverage of the knowledge domains and target inventories of potential interest to EPA. Furthermore, the varied representations and approaches presented here define local chemistry domains potentially worthy of further investigation (e.g., not currently covered in the testing library or defined by toxicity “alerts”) to strategically support data mining and predictive toxicology modeling moving forward.
Biochemical recurrence (BCR) after primary treatment of localized prostate cancer does not necessarily lead to clinically apparent progressive disease. To aid in prognostication, the European ...Association of Urology prostate cancer guidelines panel undertook a systematic review and successfully developed a novel BCR risk stratification system (groups with a low risk or high risk of BCR) based on disease and prostate-specific antigen characteristics.
Following treatment to cure prostate cancer, some patients can develop recurrence of disease identified via a prostate-specific antigen blood test (ie, biochemical recurrence, or BCR). However, not every man who experiences BCR develops progressive disease (symptoms or evidence of disease progression on imaging). We conducted a review of the literature and developed a classification system for predicting which patients might progress to optimize treatment decisions.
The EAU-EANM-ESTRO-ESUR-SIOG prostate cancer guidelines panel recommends stratifying patients experiencing biochemical recurrence (BCR) after primary treatment for localized prostate cancer into EAU low-risk and high-risk BCR groups. Each patient’s risk profile and life expectancy should be considered when discussing the benefits and toxicities of salvage treatments.
Background. Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent ...tuberculosis infection LTBI). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain. Methods. A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach. Results. Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional. Conclusions. These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances.
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