Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer : An International Multidisciplinary Systematic Review

Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.Peer reviewedPostprin

A Systematic Review of the Efficacy and Toxicity of Brachytherapy Boost Combined with External Beam Radiotherapy for Nonmetastatic Prostate Cancer

CONTEXT: The optimum use of brachytherapy (BT) combined with external beam radiotherapy (EBRT) for localised/locally advanced prostate cancer (PCa) remains uncertain.OBJECTIVE: To perform a systematic review to determine the benefits and harms of EBRT-BT.EVIDENCE ACQUISITION: Ovid MEDLINE, Embase, and EBM Reviews-Cochrane Central Register of Controlled Trials databases were systematically searched for studies published between January 1, 2000 and June 7, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Eligible studies compared low- or high-dose-rate EBRT-BT against EBRT ± androgen deprivation therapy (ADT) and/or radical prostatectomy (RP) ± postoperative radiotherapy (RP ± EBRT). The main outcomes were biochemical progression-free survival (bPFS), severe late genitourinary (GU)/gastrointestinal toxicity, metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS), at/beyond 5 yr. Risk of bias was assessed and confounding assessment was performed. A meta-analysis was performed for randomised controlled trials (RCTs).EVIDENCE SYNTHESIS: Seventy-three studies were included (two RCTs, seven prospective studies, and 64 retrospective studies). Most studies included participants with intermediate-or high-risk PCa. Most studies, including both RCTs, used ADT with EBRT-BT. Generally, EBRT-BT was associated with improved bPFS compared with EBRT, but similar MFS, CSS, and OS. A meta-analysis of the two RCTs showed superior bPFS with EBRT-BT (estimated fixed-effect hazard ratio [HR] 0.54 [95% confidence interval {CI} 0.40-0.72], p &lt; 0.001), with absolute improvements in bPFS at 5-6 yr of 4.9-16%. However, no difference was seen for MFS (HR 0.84 [95% CI 0.53-1.28], p = 0.4) or OS (HR 0.87 [95% CI 0.63-1.19], p = 0.4). Fewer studies examined RP ± EBRT. There is an increased risk of severe late GU toxicity, especially with low-dose-rate EBRT-BT, with some evidence of increased prevalence of severe GU toxicity at 5-6 yr of 6.4-7% across the two RCTs.CONCLUSIONS: EBRT-BT can be considered for unfavourable intermediate/high-risk localised/locally advanced PCa in patients with good urinary function, although the strength of this recommendation based on the European Association of Urology guideline methodology is weak given that it is based on improvements in biochemical control.PATIENT SUMMARY: We found good evidence that radiotherapy combined with brachytherapy keeps prostate cancer controlled for longer, but it could lead to worse urinary side effects than radiotherapy without brachytherapy, and its impact on cancer spread and patient survival is less clear.</p

Beach litter sources around Nuuk, Greenland: An analysis by UArctic summer school graduate course students

Modeling studies illustrate the potential for long-range transport of plastics into the Arctic, although the degree to which this occurs remains relatively undocumented. We utilised a teaching exercise at a UArctic summer school graduate course in Nuuk, Greenland to conduct a preliminary in-depth analysis of beach litter sources in the Nuup Kangerlua fjord. Students and instructors collected and analysed 1800 litter items weighing 200 kg from one location in the fjord and another at its mouth. The results suggest a predominance of local sources to macrolitter, rather than long-range transport from Europe. Fisheries-related items and rope were common. Packaging which could be identified was largely suspected to be products distributed in Greenland, and soft plastics, which rarely disperse far from its source, were also common. The results suggest local measures to reduce mismanaged waste and emissions from fisheries are important for reducing marine litter in West Greenland.publishedVersio

Systematic Review of Active Surveillance for Clinically Localised Prostate Cancer to Develop Recommendations Regarding Inclusion of Intermediate-risk Disease, Biopsy Characteristics at Inclusion and Monitoring, and Surveillance Repeat Biopsy Strategy

none38siContext: There is uncertainty regarding the most appropriate criteria for recruitment, monitoring, and reclassification in active surveillance (AS) protocols for localised prostate cancer (PCa). Objective: To perform a qualitative systematic review (SR) to issue recommendations regarding inclusion of intermediate-risk disease, biopsy characteristics at inclusion and monitoring, and repeat biopsy strategy. Evidence acquisition: A protocol-driven, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-adhering SR incorporating AS protocols published from January 1990 to October 2020 was performed. The main outcomes were criteria for inclusion of intermediate-risk disease, monitoring, reclassification, and repeat biopsy strategies (per protocol and/or triggered). Clinical effectiveness data were not assessed. Evidence synthesis: Of the 17 011 articles identified, 333 studies incorporating 375 AS protocols, recruiting 264 852 patients, were included. Only a minority of protocols included the use of magnetic resonance imaging (MRI) for recruitment (n = 17), follow-up (n = 47), and reclassification (n = 26). More than 50% of protocols included patients with intermediate or high-risk disease, whilst 44.1% of protocols excluded low-risk patients with more than three positive cores, and 39% of protocols excluded patients with core involvement (CI) >50% per core. Of the protocols, ≥80% mandated a confirmatory transrectal ultrasound biopsy; 72% (n = 189) of protocols mandated per-protocol repeat biopsies, with 20% performing this annually and 25% every 2 yr. Only 27 protocols (10.3%) mandated triggered biopsies, with 74% of these protocols defining progression or changes on MRI as triggers for repeat biopsy. Conclusions: For AS protocols in which the use of MRI is not mandatory or absent, we recommend the following: (1) AS can be considered in patients with low-volume International Society of Urological Pathology (ISUP) grade 2 (three or fewer positive cores and cancer involvement ≤50% CI per core) or another single element of intermediate-risk disease, and patients with ISUP 3 should be excluded; (2) per-protocol confirmatory prostate biopsies should be performed within 2 yr, and per-protocol surveillance repeat biopsies should be performed at least once every 3 yr for the first 10 yr; and (3) for patients with low-volume, low-risk disease at recruitment, if repeat systematic biopsies reveal more than three positive cores or maximum CI >50% per core, they should be monitored closely for evidence of adverse features (eg, upgrading); patients with ISUP 2 disease with increased core positivity and/or CI to similar thresholds should be reclassified. Patient summary: We examined the literature to issue new recommendations on active surveillance (AS) for managing localised prostate cancer. The recommendations include setting criteria for including men with more aggressive disease (intermediate-risk disease), setting thresholds for close monitoring of men with low-risk but more extensive disease, and determining when to perform repeat biopsies (within 2 yr and 3 yearly thereafter).noneWillemse, Peter-Paul M; Davis, Niall F; Grivas, Nikolaos; Zattoni, Fabio; Lardas, Michael; Briers, Erik; Cumberbatch, Marcus G; De Santis, Maria; Dell'Oglio, Paolo; Donaldson, James F; Fossati, Nicola; Gandaglia, Giorgio; Gillessen, Silke; Grummet, Jeremy P; Henry, Ann M; Liew, Matthew; MacLennan, Steven; Mason, Malcolm D; Moris, Lisa; Plass, Karin; O'Hanlon, Shane; Omar, Muhammad Imran; Oprea-Lager, Daniela E; Pang, Karl H; Paterson, Catherine C; Ploussard, Guillaume; Rouvière, Olivier; Schoots, Ivo G; Tilki, Derya; van den Bergh, Roderick C N; Van den Broeck, Thomas; van der Kwast, Theodorus H; van der Poel, Henk G; Wiegel, Thomas; Yuan, Cathy Yuhong; Cornford, Philip; Mottet, Nicolas; Lam, Thomas B LWillemse, Peter-Paul M; Davis, Niall F; Grivas, Nikolaos; Zattoni, Fabio; Lardas, Michael; Briers, Erik; Cumberbatch, Marcus G; De Santis, Maria; Dell'Oglio, Paolo; Donaldson, James F; Fossati, Nicola; Gandaglia, Giorgio; Gillessen, Silke; Grummet, Jeremy P; Henry, Ann M; Liew, Matthew; Maclennan, Steven; Mason, Malcolm D; Moris, Lisa; Plass, Karin; O'Hanlon, Shane; Omar, Muhammad Imran; Oprea-Lager, Daniela E; Pang, Karl H; Paterson, Catherine C; Ploussard, Guillaume; Rouvière, Olivier; Schoots, Ivo G; Tilki, Derya; van den Bergh, Roderick C N; Van den Broeck, Thomas; van der Kwast, Theodorus H; van der Poel, Henk G; Wiegel, Thomas; Yuan, Cathy Yuhong; Cornford, Philip; Mottet, Nicolas; Lam, Thomas B

What’s the opposite of fragile? : of social capitals, bonding and bridging

Many rural areas in Nordic countries have been declining in population for decades. As a countermovement, Iceland has introduced a program in so called fragile communities to halt this tendency. This thesis investigates the program’s impact and success rate. Furthermore, it assesses the program’s support for innovation and the outcomes. A conclusion was reached through interviews with the Icelandic Regional Development Institute, former project managers and follow-up managers. A case study was performed based on reports published by the Icelandic Regional Development Institute. While the literature review creates a foundation and supports the thesis topics such as regional development concepts and rural innovation. The findings highlight certain program- and project-level discontinuities that act as a barrier to achieving the program’s primary purpose. As such the program’s top-down ‘structure’ and bottom-up approach on project level are in conflict. Thus, the two approaches are currently not combined; rather, they are acting independently or, at most, as loose guidelines. As a result the used empowering bottom-up approach does not accomplish the main goal, which is to stop depopulation. Moreover, the results show that the program frequently favours economic capital over social capital. Nonetheless, two out of four case study communities involved in the case study exhibit a stabilization in population size and a boost in innovation.Áratugum saman hefur orðið fólksfækkun í dreifðum byggðum á Norðurlöndum. Íslensk stjórnvöld hafa brugðist við til varnar þessari þróun með sérstökum verkefnum í svokölluðum „brothættum byggðum“. Í ritgerðinni eru áhrif og árangur verkefnisins skoðuð. Einnig er metið hvernig verkefnið hefur stutt við nýsköpun og hverju hún hefur skilað. Gagnaöflun fór fram með viðtölum við Byggðastofnun og verkefnisstjóra, sem höfðu ýmist starfað við verkefnin í þeim byggðarlögum sem um ræðir, eða fylgt þeim eftir. Gerð var rannsókn byggð á efni sem gefið hefur verið út af Byggðastofnun. Einnig er stuðst við fræðirit og greinar um efni sem tengist viðfangsefninu, svo sem byggðaþróun og nýsköpun í dreifðum byggðum, til að leggja grunn að og varpa frekara ljósi á efni ritgerðarinnar. Niðurstöðurnar sýna fram á ákveðið ósamræmi milli verkefnisins á landsvísu og útfærslu þess í einstökum byggðarlögum, sem stendur í vegi fyrir því að megin markmið verkefnisins nái fram að ganga. Ákveðin þversögn ríkir milli þess að verkefnið er skipulagt „að ofan” en framkvæmd þess í byggðarlögunum byggir á grasrótarnálgun. Þannig ríkir ekki samræmi milli þessara tveggja sjónarhorna; þau virka óháð hvoru öðru, eða skila í besta falli leiðbeiningum sem ekki er fylgt til hlítar. Af því leiðir að sú valdeflandi grasrótarnálgun sem byggt er á, nær ekki fram megin markmiðinu, sem er að stöðva fólksfækkun. Að auki sýna niðurstöðurnar að í verkefninu er oft lögð meiri áhersla á fjárhagslegan ávinning, frekar en félagsauð. Þrátt fyrir það, sýndi athugunin að íbúafjöldi varð stöðugur og nýsköpun jókst, í tveimur byggðarlögum af fjórumFunded by FIER

Biochemical Recurrence in Prostate Cancer : The European Association of Urology Prostate Cancer Guidelines Panel Recommendations

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. Patient summary: 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

Evaluation of Oncological Outcomes and Data Quality in Studies Assessing Nerve-sparing Versus Non–Nerve-sparing Radical Prostatectomy in Nonmetastatic Prostate Cancer: A Systematic Review

Context: Surgical techniques aimed at preserving the neurovascular bundles during radical prostatectomy (RP) have been proposed to improve functional outcomes. However, it remains unclear if nerve-sparing (NS) surgery adversely affects oncological metrics. Objective: To explore the oncological safety of NS versus non-NS (NNS) surgery and to identify factors affecting the oncological outcomes of NS surgery. Evidence acquisition: Relevant databases were searched for English language articles published between January 1, 1990 and May 8, 2020. Comparative studies for patients with nonmetastatic prostate cancer (PCa) treated with primary RP were included. NS and NNS techniques were compared. The main outcomes were side-specific positive surgical margins (ssPSM) and biochemical recurrence (BCR). Risk of bias (RoB) and confounding assessments were performed. Evidence synthesis: Out of 1573 articles identified, 18 studies recruiting a total of 21 654 patients were included. The overall RoB and confounding were high across all domains. The most common selection criteria for NS RP identified were characteristic of low-risk disease, including low core-biopsy involvement. Seven studies evaluated the link with ssPSM and showed an increase in ssPSM after adjustment for side-specific confounders, with the relative risk for NS RP ranging from 1.50 to 1.53. Thirteen papers assessing BCR showed no difference in outcomes with at least 12 mo of follow-up. Lack of data prevented any subgroup analysis for potentially important variables. The definitions of NS were heterogeneous and poorly described in most studies. Conclusions: Current data revealed an association between NS surgery and an increase in the risk of ssPSM. This did not translate into a negative impact on BCR, although follow-up was short and many men harbored low-risk PCa. There are significant knowledge gaps in terms of how various patient, disease, and surgical factors affect outcomes. Adequately powered and well-designed prospective trials and cohort studies accounting for these issues with long-term follow-up are recommended. Patient summary: Neurovascular bundles (NVBs) are structures containing nerves and blood vessels. The NVBs close to the prostate are responsible for erections. We reviewed the literature to determine if a technique to preserve the NVBs during removal of the prostate causes worse cancer outcomes. We found that NVB preservation was poorly defined but, if applied, was associated with a higher risk of cancer at the margins of the tissue removed, even in patients with low-risk prostate cancer. The long-term importance of this finding for patients is unclear. More data are needed to provide recommendations

A Systematic Review of the Impact of Surgeon and Hospital Caseload Volume on Oncological and Nononcological Outcomes After Radical Prostatectomy for Nonmetastatic Prostate Cancer

Context: The impact of surgeon and hospital volume on outcomes after radical prostatectomy (RP) for localised prostate cancer (PCa) remains unknown. Objective: To perform a systematic review on the association between surgeon or hospital volume and oncological and nononcological outcomes following RP for PCa. Evidence acquisition: Medline, Medline In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched. All comparative studies for nonmetastatic PCa patients treated with RP published between January 1990 and May 2020 were included. For inclusion, studies had to compare hospital or surgeon volume, defined as caseload per unit time. Main outcomes included oncological (including prostate-specific antigen persistence, positive surgical margin [PSM], biochemical recurrence, local and distant recurrence, and cancer-specific and overall survival) and nononcological (perioperative complications including need for blood transfusion, conversion to open procedure and within 90-d death, and continence and erectile function) outcomes. Risk of bias (RoB) and confounding assessments were undertaken. Both a narrative and a quantitative synthesis were planned if the data allowed. Evidence synthesis: Sixty retrospective comparative studies were included. Generally, increasing surgeon and hospital volumes were associated with lower rates of mortality, PSM, adjuvant or salvage therapies, and perioperative complications. Combining group size cut-offs as used in the included studies, the median threshold for hospital volume at which outcomes start to diverge is 86 (interquartile range [IQR] 35–100) cases per year. In addition, above this threshold, the higher the caseload, the better the outcomes, especially for PSM. RoB and confounding were high for most domains. Conclusions: Higher surgeon and hospital volumes for RP are associated with lower rates of PSMs, adjuvant or salvage therapies, and perioperative complications. This association becomes apparent from a caseload of >86 (IQR 35–100) per year and may further improve hereafter. Both high- and low-volume centres should measure their outcomes, make them publicly available, and improve their quality of care if needed. Patient summary: We reviewed the literature to determine whether the number of prostate cancer operations (radical prostatectomy) performed in a hospital affects the outcomes of surgery. We found that, overall, hospitals with a higher number of operations per year have better outcomes in terms of cancer recurrence and complications during or after hospitalisation. However, it must be noted that surgeons working in hospitals with lower annual operations can still achieve similar or even better outcomes. Therefore, making hospital's outcome data publicly available should be promoted internationally, so that patients can make an informed decision where they want to be treated

Impact of Epithelial Histological Types, Subtypes, and Growth Patterns on Oncological Outcomes for Patients with Nonmetastatic Prostate Cancer Treated with Curative Intent: A Systematic Review.

CONTEXT The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for conventional PCa and so different approaches may be needed. OBJECTIVE To compare oncological outcomes for conventional and UH PCa in men with localized disease treated with curative intent. EVIDENCE ACQUISITION A systematic review adhering to the Referred Reporting Items for Systematic Reviews and Meta-Analyses was prospectively registered on PROSPERO (CRD42022296013) was performed in July 2021. EVIDENCE SYNTHESIS We screened 3651 manuscripts and identified 46 eligible studies (reporting on 1 871 814 men with conventional PCa and 6929 men with 10 different PCa UHs). Extraprostatic extension and lymph node metastases, but not positive margin rates, were more common with UH PCa than with conventional tumors. PCa cases with cribriform pattern, intraductal carcinoma, or ductal adenocarcinoma had higher rates of biochemical recurrence and metastases after radical prostatectomy than for conventional PCa cases. Lower cancer-specific survival rates were observed for mixed cribriform/intraductal and cribriform PCa. By contrast, pathological findings and oncological outcomes for mucinous and prostatic intraepithelial neoplasia (PIN)-like PCa were similar to those for conventional PCa. Limitations of this review include low-quality studies, a risk of reporting bias, and a scarcity of studies that included radiotherapy. CONCLUSIONS Intraductal, cribriform, and ductal UHs may have worse oncological outcomes than for conventional and mucinous or PIN-like PCa. Alternative treatment approaches need to be evaluated in men with these cancers. PATIENT SUMMARY We reviewed the literature to explore whether prostate cancers with unconventional growth patterns behave differently to conventional prostate cancers. We found that some unconventional growth patterns have worse outcomes, so we need to investigate if they need different treatments. Urologists should be aware of these growth patterns and their clinical impact