Doxorubicin induces cardiotoxicity in a pluripotent stem cell model of aggressive B cell lymphoma cancer patients.

Cancer therapies with anthracyclines have been shown to induce cardiovascular complications. The aims of this study were to establish an in vitro induced pluripotent stem cell model (iPSC) of anthracycline-induced cardiotoxicity (ACT) from patients with an aggressive form of B-cell lymphoma and to examine whether doxorubicin (DOX)-treated ACT-iPSC cardiomyocytes (CM) can recapitulate the clinical features exhibited by patients, and thus help uncover a DOX-dependent pathomechanism. ACT-iPSC CM generated from individuals with CD20+ B-cell lymphoma who had received high doses of DOX and suffered cardiac dysfunction were studied and compared to control-iPSC CM from cancer survivors without cardiac symptoms. In cellular studies, ACT-iPSC CM were persistently more susceptible to DOX toxicity including augmented disorganized myofilament structure, changed mitochondrial shape, and increased apoptotic events. Consistently, ACT-iPSC CM and cardiac fibroblasts isolated from fibrotic human ACT myocardium exhibited higher DOX-dependent reactive oxygen species. In functional studies, Ca2+ transient amplitude of ACT-iPSC CM was reduced compared to control cells, and diastolic sarcoplasmic reticulum Ca2+ leak was DOX-dependently increased. This could be explained by overactive CaMKIIδ in ACT CM. Together with DOX-dependent augmented proarrhythmic cellular triggers and prolonged action potentials in ACT CM, this suggests a cellular link to arrhythmogenic events and contractile dysfunction especially found in ACT engineered human myocardium. CamKIIδ inhibition prevented proarrhythmic triggers in ACT. In contrast, control CM upregulated SERCA2a expression in a DOX-dependent manner, possibly to avoid heart failure conditions. In conclusion, we developed the first human patient-specific stem cell model of DOX-induced cardiac dysfunction from patients with B-cell lymphoma. Our results suggest that DOX-induced stress resulted in arrhythmogenic events associated with contractile dysfunction and finally in heart failure after persistent stress activation in ACT patients.

Brain metastases in gastroesophageal cancers-an underestimated complication.

BACKGROUND: Brain metastases represent a severe complication in many gastrointestinal malignancies especially those arising from the upper gastrointestinal tract, including cancer of the esophagus, gastroesophageal junction, and stomach (GEC). However, there is little knowledge about the onset or potential risk factors for brain metastases (BRMs) in upper gastrointestinal cancers resulting in a lack of screening guidelines for BRMs. METHODS: We analyzed 827 patients from our cancer registry suffering from gastroesophageal cancer (GEC) and treated at the University Medical Center Göttingen between January 2013 and December 2019 for the presence of BRMs. RESULTS: From 827 patients with GEC we found 54 patients with BRMs, resulting in an incidence of 6.5%. BRMs are more frequent in male patients (90.74% vs 9.26%, p = 0.0051) and in adenocarcinomas (90.74% vs 9.26%, p = 0.0117). Mean duration for the onset of BRMs from initial cancer diagnoses was 20.9 months in limited disease (curative approach) and 9.3 months in advanced disease (palliative approach) (p = 0.0026). However, early detection of BRMs is a prognostic factor since patients with successful resection of BRMs have a better prognosis compared to those with unresectable BRMs (5.93 vs 2.07 months, p = 0.0091). CONCLUSION: In this single-center retrospective study, brain metastases (BRMs) occur with a high frequency (6.5%) in gastroesophageal cancer (GEC), significantly more often in male patients and adenocarcinomas. Since survival of these patients considerably correlates with successful BRMs resection, our observations propose further prospective trails to validate our hypothesis and ultimately the implementation of routine screening procedures to detect asymptomatic brain metastases.

Post-migration acquisition of HIV: Estimates from four European countries, 2007 to 2016.

BackgroundThe assumption that migrants acquire human immunodeficiency virus (HIV) before migration, particularly those from high prevalence areas, is common.AimWe assessed the place of HIV acquisition of migrants diagnosed in four European countries using surveillance data.MethodsUsing CD4+ T-cell count trajectories modelled to account for seroconversion bias, we estimated infection year of newly HIV-diagnosed migrants residing in the United Kingdom (UK), Belgium, Sweden and Italy with a known arrival year and CD4+ T-cell count at diagnosis. Multivariate analyses identified predictors for post-migration acquisition.ResultsBetween 2007 and 2016, migrants constituted 56% of people newly diagnosed with HIV in the UK, 62% in Belgium, 72% in Sweden and 29% in Italy. Of 23,595 migrants included, 60% were born in Africa and 70% acquired HIV heterosexually. An estimated 9,400 migrants (40%; interquartile range (IQR): 34-59) probably acquired HIV post-migration. This proportion was similar by risk group, sex and region of birth. Time since migration was a strong predictor of post-migration HIV acquisition: 91% (IQR: 87-95) among those arriving 10 or more years prior to diagnosis; 30% (IQR: 21-37) among those 1-5 years prior. Younger age at arrival was a predictor: 15-18 years (81%; IQR: 74-86), 19-25 years (53%; IQR: 45-63), 26-35 years (37%; IQR: 30-46) and 36 years and older (25%; IQR: 21-33).ConclusionsMigrants, regardless of origin, sex and exposure to HIV are at risk of acquiring HIV post-migration to Europe. Alongside accessible HIV testing, prevention activities must target migrant communities.

Establishing an ad hoc COVID-19 mortality surveillance during the first epidemic wave in Belgium, 1 March to 21 June 2020.

BackgroundCOVID-19-related mortality in Belgium has drawn attention for two reasons: its high level, and a good completeness in reporting of deaths. An ad hoc surveillance was established to register COVID-19 death numbers in hospitals, long-term care facilities (LTCF) and the community. Belgium adopted broad inclusion criteria for the COVID-19 death notifications, also including possible cases, resulting in a robust correlation between COVID-19 and all-cause mortality.AimTo document and assess the COVID-19 mortality surveillance in Belgium.MethodsWe described the content and data flows of the registration and we assessed the situation as of 21 June 2020, 103 days after the first death attributable to COVID-19 in Belgium. We calculated the participation rate, the notification delay, the percentage of error detected, and the results of additional investigations.ResultsThe participation rate was 100% for hospitals and 83% for nursing homes. Of all deaths, 85% were recorded within 2 calendar days: 11% within the same day, 41% after 1 day and 33% after 2 days, with a quicker notification in hospitals than in LTCF. Corrections of detected errors reduced the death toll by 5%.ConclusionBelgium implemented a rather complete surveillance of COVID-19 mortality, on account of a rapid investment of the hospitals and LTCF. LTCF could build on past experience of previous surveys and surveillance activities. The adoption of an extended definition of 'COVID-19-related deaths' in a context of limited testing capacity has provided timely information about the severity of the epidemic.

Second brazilian consensus on the treatment of advanced prostate cancer - a SBOC-SBU-SBRT panel review.

Prostate cancer is the second most common cancer and the fi fth leading cause of cancer deaths. In Brazil, it is likewise the second most common cancer among men, second only to non-melanoma skin cancers. The aim of this consensus is to align different opinions and interpretations of the medical literature in a practical and patient-oriented approach. The fi rst Brazilian Consensus on the Treatment of Advanced Prostate Cancer was published in 2017, with the goal of reducing the heterogeneity of therapeutic conduct in Brazilian patients with metastatic prostate cancer. We acknowledge that in Brazil the incorporation of different technologies is a big challenge, especially in the Sistema Único de Saúde (SUS), which allows for the disparity in the options available to patients treated in different institutions. In order to update the recommendations and to make them objective and easily accessible, once more a panel of specialists was formed in order to discuss and elaborate a new Brazilian Consensus on Advanced Prostate Cancer. This Consensus was written through a joint initiative of the Brazilian Society of Clinical Oncology (SBOC) and the Brazilian Society of Urology (SBU) to support the clinical decisions of physicians and other health professionals involved in the care of patients with prostate cancer.

WITHDRAWN: Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma.

BACKGROUND: Malignant melanoma, one of the most aggressive of all skin cancers, is increasing in incidence throughout the world. Surgery remains the cornerstone of curative treatment in earlier stages. Metastatic disease is incurable in most affected people, because melanoma does not respond to most systemic treatments. A number of novel approaches are under evaluation and have shown promising results, but they are usually associated with increased toxicity and cost. The combination of chemotherapy and immunotherapy has been reported to improve treatment results, but it is still unclear whether evidence exists to support this choice, compared with chemotherapy alone. No language restrictions were imposed. OBJECTIVES: To compare the effects of therapy with chemotherapy and immunotherapy (chemoimmunotherapy) versus chemotherapy alone in people with metastatic malignant melanoma. SEARCH METHODS: We searched the Cochrane Skin Group Specialised Register (14 February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (2003 to 30 January 2006 ), EMBASE (2003 to 20 July 2005) and LILACS (1982 to 20 February 2006). References, conference proceedings, and databases of ongoing trials were also used to locate trials. SELECTION CRITERIA: All randomised controlled trials that compared the use of chemotherapy versus chemoimmunotherapy on people of any age, diagnosed with metastatic melanoma. DATA COLLECTION AND ANALYSIS: Two authors independently assessed each study to determine whether it met the pre-defined selection criteria, with differences being resolved through discussion with the review team. Two authors independently extracted the data from the articles using data extraction forms. Quality assessment included an evaluation of various components associated with biased estimates of treatment effect. Whenever possible, a meta-analysis was performed on the extracted data, in order to calculate a weighed treatment effect across trials. MAIN RESULTS: Eighteen studies met our criteria and were included in the meta-analysis, with a total of 2625 participants. We found evidence of an increase of objective response rates in people treated with chemoimmunotherapy, in comparison with people treated with chemotherapy. Nevertheless, the impact of these increased response rates was not translated into a survival benefit. We found no difference in survival to support the addition of immunotherapy to chemotherapy in the systemic treatment of metastatic melanoma, with a hazard ratio of 0.89 (95% CI 0.72 to 1.11, P = 0.31). Additionally, we found increased hematological and non-hematological toxicities in people treated with chemoimmunotherapy. AUTHORS' CONCLUSIONS: We failed to find any clear evidence that the addition of immunotherapy to chemotherapy increases survival of people with metastatic melanoma. Further use of combined immunotherapy and chemotherapy should only be done in the context of clinical trials.

HIV testing within general practices in Europe: a mixed-methods systematic review.

BACKGROUND: Late diagnosis of HIV infection remains a key challenge in Europe. It is acknowledged that general practitioners (GPs) may contribute greatly to early case finding, yet there is evidence that many diagnostic opportunities are being missed. To further promote HIV testing in primary care and to increase the utility of available research, the existing evidence has been synthesised in a systematic review adhering to the PRISMA guidelines. METHODS: The databases PubMed, Scopus and Embase were searched for the period 2006-2017. Two authors judged independently on the eligibility of studies. Through a mixed-methods systematic review of 29 studies, we provide a description of HIV testing in general practices in Europe, including barriers and facilitators. RESULTS: The findings of the study show that although various approaches to target patients are used by GPs, most tests are still carried out based on the patient's request. Several barriers obstruct HIV testing in general practice. Included are a lack of communication skills on sexual health, lack of knowledge about HIV testing recommendations and epidemic specificities, difficulties with using the complete list of clinical HIV indicator diseases and lack of experience in delivering and communicating test results. The findings also suggest that the provision of specific training, practical tools and promotion programmes has an impact on the testing performance of GPs. CONCLUSIONS: GPs could have an increased role in provider-initiated HIV-testing for early case finding. To achieve this objective, solutions to the reported barriers should be identified and testing criteria adapted to primary healthcare defined. Providing guidance and training to better identify priority groups for HIV testing, as well as information on the HIV epidemic's characteristics, will be fundamental to increasing awareness and testing by GPs.

The Human Immunodeficiency Virus Continuum of Care in European Union Countries in 2013: Data and Challenges.

BACKGROUND.: The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a "90-90-90" target to curb the human immunodeficiency virus (HIV) epidemic by 2020, but methods used to assess whether countries have reached this target are not standardized, hindering comparisons. METHODS.: Through a collaboration formed by the European Centre for Disease Prevention and Control (ECDC) with European HIV cohorts and surveillance agencies, we constructed a standardized, 4-stage continuum of HIV care for 11 European Union countries for 2013. Stages were defined as (1) number of people living with HIV in the country by end of 2013; (2) proportion of stage 1 ever diagnosed; (3) proportion of stage 2 that ever initiated ART; and (4) proportion of stage 3 who became virally suppressed (≤200 copies/mL). Case surveillance data were used primarily to derive stages 1 (using back-calculation models) and 2, and cohort data for stages 3 and 4. RESULTS.: In 2013, 674500 people in the 11 countries were estimated to be living with HIV, ranging from 5500 to 153400 in each country. Overall HIV prevalence was 0.22% (range, 0.09%-0.36%). Overall proportions of each previous stage were 84% diagnosed, 84% on ART, and 85% virally suppressed (60% of people living with HIV). Two countries achieved ≥90% for all stages, and more than half had reached ≥90% for at least 1 stage. CONCLUSIONS.: European Union countries are nearing the 90-90-90 target. Reducing the proportion undiagnosed remains the greatest barrier to achieving this target, suggesting that further efforts are needed to improve HIV testing rates. Standardizing methods to derive comparable continuums of care remains a challenge.

Systematic Review and Network Meta-Analysis of Bevacizumab Plus First-Line Topotecan-Paclitaxel or Cisplatin-Paclitaxel Versus Non-Bevacizumab-Containing Therapies in Persistent, Recurrent, or Metastatic Cervical Cancer.

OBJECTIVE: Despite advances in cervical cancer prevention and diagnosis, outcomes for patients given a diagnosis of advanced and recurrent disease are poor. In the GOG240 trial, the addition of bevacizumab to paclitaxel-topotecan or paclitaxel-cisplatin has been shown to prolong survival compared with paclitaxel-topotecan or paclitaxel-cisplatin in patients with persistent, recurrent, or metastatic disease. However, standards of care vary between regions and countries. The purpose of this systematic review and network meta-analysis was to enable a comparison between bevacizumab + chemotherapy with multiple monotherapy or combination chemotherapy regimens in the treatment for women with advanced, recurrent, or persistent cervical cancer. METHODS/MATERIALS: A systematic literature review was conducted to identify randomized or nonrandomized controlled trials of patients with recurrent, persistent, or metastatic cervical cancer published in English from 1999 to 2015. A feasibility study was performed to assess the heterogeneity of the trials, and a network meta-analysis was conducted. Fixed- and random-effects models were fitted to calculate the hazard ratio for overall survival (OS) for all pairwise comparisons and ranking of all interventions. RESULTS: Twenty-three studies (19 trials) met inclusion criteria and were included in the review. Sample sizes ranged from 69 to 452, and median patient age ranged from 45 to 53 years. There was a trend toward prolonged OS with cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab compared with all non-bevacizumab-containing therapies. Cisplatin-paclitaxel-bevacizumab had the highest probability of being the most efficacious compared with all regimens (68.1%), and cisplatin monotherapy had the lowest (0%). CONCLUSIONS: The results of this network meta-analysis show that bevacizumab in combination with paclitaxel-topotecan or paclitaxel-cisplatin is likely to prolong OS over other non-bevacizumab-containing chemotherapies (eg, paclitaxel-carboplatin), which were not included in the GOG240 trial. In patients with advanced, persistent, and recurrent cervical cancer, cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab showed the highest efficacy in all regimens investigated in this analysis.

First Brazilian Consensus of Advanced Prostate Cancer: Recommendations for Clinical Practice.

INTRODUCTION: Prostate cancer still represents a major cause of morbidity, and still about 20% of men with the disease are diagnosed or will progress to the advanced stage without the possibility of curative treatment. Despite the recent advances in scientific and technological knowledge and the availability of new therapies, there is still considerable heterogeneity in the therapeutic approaches for metastatic prostate cancer. OBJECTIVES: This article presents a summary of the I Brazilian Consensus on Advanced Prostate Cancer, conducted by the Brazilian Society of Urology and Brazilian Society of Clinical Oncology. MATERIALS AND METHODS: Experts were selected by the medical societies involved. Forty issues regarding controversial issues in advanced disease were previously elaborated. The panel met for consensus, with a threshold established for 2/3 of the participants. RESULTS AND CONCLUSIONS: The treatment of advanced prostate cancer is complex, due to the existence of a large number of therapies, with different response profiles and toxicities. The panel addressed recommendations on preferred choice of therapies, indicators that would justify their change, and indicated some strategies for better sequencing of treatment in order to maximize the potential for disease control with the available therapeutic arsenal. The lack of consensus on some topics clearly indicates the absence of strong evidence for some decisions.

Cardiovascular events associated with androgen deprivation therapy in patients with prostate cancer: a systematic review and meta-analysis.

CONTEXT: A recently published meta-analysis of randomized clinical trials (RCT) showed that androgen deprivation therapy (ADT) did not significantly increase cardiovascular mortality in prostate cancer patients. However, cardiovascular morbidity, which can impact quality of life, was not evaluated. OBJECTIVE: To evaluate the risk of cardiovascular morbidity associated with ADT in patients with prostate cancer. METHODS: We conducted a literature search from January 1960 to June 2012. RCT and large cohort studies that evaluated first-line endocrine therapy and ADT longer than 6 months were screened for inclusion. RESULTS: In total, 126,898 patients were included in four cohort studies, and 10,760 patients were included in nine RCTs. Analysis of the RCTs showed no differences in the development of acute myocardial infarction (AMI) (OR 1.23; 95 % CI 0.92-1.64; I (2): 0 %) among the patients receiving ADT or not. The analysis of randomized studies that reported other nonfatal cardiovascular events demonstrated a significant increase in such events in the group receiving ADT (OR 1.55; 95 % CI 1.09-2.20; I (2): 0 %). When the large cohort studies were included in the analysis, an increased risk of AMI among men with ADT was found (OR 2.01, 95 % CI 1.90-2.13; I (2): 91,3 %). CONCLUSION: The use of ADT in prostate cancer patients corresponded with a significant increase in cardiovascular morbidity associated with AMI and with nonfatal events. Therefore, ADT is linked to a significant negative impact on quality of life. Periodic cardiovascular evaluation is required for these patients.

The impact of complete chemotherapy stop on the overall survival of patients with advanced colorectal cancer in first-line setting: A meta-analysis of randomized trials.

BACKGROUND: The impact of the duration of chemotherapy on the overall survival of patients with metastatic colorectal cancer (mCRC) is controversial and studies have failed to define a clear standard. METHODS: We searched medical literature databases and oncology conferences proceedings for randomized controlled trials (RCT) that compared the overall survival of mCRC patients who received continuous first-line chemotherapy until disease progression versus those who were offered complete treatment stop after a fixed number of cycles. Studies including targeted agents were also included. A meta-analysis of reported hazard ratios (HRs) for survival was performed. RESULTS: We retrieved 240 trials, of which six were eligible and five were included in the pooled analysis of overall survival (N = 3061). The overall survival between continuously delivered chemotherapy and complete stop was not statistically different (HR = 0.93, 95% CI 0.85-1.02; p = 0.12; I² = 5%). The results are similar when we analyzed separately the trials performing randomization before versus after induction therapy. The median chemotherapy free interval in the complete stop group was 3.9 months (3.6-4.3 months). Chemotherapy administered until progression was associated with more adverse effects and impaired quality of life. CONCLUSION: Compared with first-line continuous chemotherapy administered until disease progression, complete treatment stop did not have a detrimental impact on the overall survival of patients with mCRC. Identification of predictive biomarkers could help clinicians to select the patients who would benefit from continuous cancer-directed therapies.

Restricted access to antiretroviral treatment for undocumented migrants: a bottle neck to control the HIV epidemic in the EU/EEA.

BACKGROUND: In the European Union/European Economic Area (EU/EEA), migrants from high-endemic countries are disproportionately affected by HIV. Between 2007 and 2012, migrants represented 39 % of reported HIV cases. There is growing evidence that a significant proportion of HIV acquisition among migrant populations occurs after their arrival in Europe. DISCUSSION: Migrants are confronted with multiple risk factors that shape patterns of population HIV susceptibility and vulnerability, which simultaneously affect HIV transmission. Undocumented migrants incur additional risks for contracting HIV due to limited access to adequate health care services, protection and justice, alongside insecure housing and employment conditions. All EU/EEA countries have ratified a number of international and regional human rights instruments that enshrine access to health care as a human right that should be available to everyone without discrimination. From a clinical and public health perspective, early HIV care and treatment is associated with viral suppression, improved health outcomes and reductions in transmission risks. A current challenge of the HIV epidemic is to reach the highest proportion of overall viral suppression among people living with HIV in order to impact on HIV transmission. Although the majority of EU/EEA countries regard migrants as an important sub-population for their national responses to HIV, and despite the overwhelming evidence of the individual and public health benefits associated with HIV care and treatment, a significant number of EU/EEA countries do not provide antiretroviral treatment to undocumented migrants. HIV transmission dynamics in migrant populations depend on the respective weight of all risk and vulnerability factors to which they are exposed, which act together in a synergistic way. People who are not linked to HIV care will continue to unwillingly contribute to the on-going transmission of HIV. Following the recommendations of the European Union Agency for Fundamental Rights, ensuring access to HIV-care for all sub-populations, including undocumented migrants, would fulfil the human rights of those populations and also strengthen the control of HIV incidence among those not currently able to access HIV care.

Optimal duration of androgen deprivation therapy following radiation therapy in intermediate- or high-risk nonmetastatic prostate cancer: A systematic review and metaanalysis.

OBJECTIVES: To investigate current evidence on the optimal duration of adjuvant hormone deprivation for prostate cancer treated with radiation therapy with curative intent. MATERIALS AND METHODS: A systematic search was performed in electronic databases. Data from randomized trials comparing different durations of hormone blockade was collected for pooled analysis. Overall survival, disease-free survival, disease-specific survival and toxicity were the outcomes of interest. Meta-analyses were performed using random-effects model. RESULTS: Six studies met the eligibility criteria. For overall survival, the pooled data from the studies demonstrated a statistically significant benefit for longer hormone deprivation (Hazard Ratio 0.84; 95% CI 0.74 - 0.96). A statistically significant benefit was also found for disease-free survival (Hazard Ratio 0.74; 95% CI 0.62 - 0.89), and disease-specific survival (Hazard Ratio 0.73; 95% CI 0.62 - 0.85). Studies with longer blockade duration arm demonstrated greater benefit. Toxicity was low, with no increase in cardiovascular events. CONCLUSIONS: Longer duration of androgen deprivation combined to radiotherapy prolongs OS, DFS and DSS in patients with intermediate and high-risk non-metastatic prostate cancer. However, this evidence is based on trials using older radiation techniques, and further research of combination of androgen deprivation and new RT technologies may be warranted.

Prevention strategies for chemotherapy-induced hand-foot syndrome: a systematic review and meta-analysis of prospective randomised trials.

PURPOSE: Hand-foot syndrome (HSF) is a distinctive adverse event relatively frequent to some chemotherapeutic agents as capecitabine, pegylated liposomal doxorubicin, sorafenib and other tyrosine-kinase inhibitors. Since the prevention of HFS would be crucial to avoid treatment interruptions and delays, many studies have been conducted with this purpose. METHODS: The aim of this systematic review and meta-analysis was to analyze the clinical efficacy of prevention strategies for HFS, through a wide search of electronic databases as well as congress abstracts. The endpoints evaluated were the dichotomic data for mild (Grade 1), moderate to severe (Grades 2 to 3) and all-grade HFS. Meta-analysis was calculated through RevMan v5.1 software. RESULTS: Amongst 295 studies identified, only ten met the inclusion criteria. Celecoxib prevented both moderate to severe (odds ratio [OR] 0.39, 95 % confidence interval [CI] 0.20-0.73, P = 0.003) and all-grade HFS (OR 0.47, 95 % CI 0.29-0.78, P = 0.003), whereas pyridoxine and topical urea/lactic acid formulations failed to prove efficacy. There were no proven benefits in mild HFS. The use of topical antiperspirant has not been shown to improve results, according to a single trial. CONCLUSIONS: From all available possibilities for the prevention of HFS, celecoxib appears to be the most promising, with statistically significant results. Larger, multicentric studies are required to reinforce this finding.

Efficacy of immune checkpoint inhibitors combinations as first-line systemic treatment in patients with advanced urothelial carcinoma: A systematic review and network meta-analysis.

BACKGROUND: Combinations of immune checkpoint inhibitors (ICI) with platinum-based chemotherapy (PlatinumCT) or with another ICI in the first-line setting for patients with metastatic urothelial carcinoma (mUC) have mixed results. METHODS: Records were searched electronically from January 2019 to January 2024. A meta-analysis was performed to evaluate OS, progression-free survival (PFS), and overall response rate (ORR). RESULTS: Immune-based combinations were associated with an OS (HR: 0.75; 95% CI: 0.61-0.92; p < 0.001; I2= 84.1%) and PFS benefit in the intention-to-treat population (HR: 0.67; 95%CI: 0.51-0.89; p < 0.001; I2 = 89.7%). There was no ORR improvement with immune-based combinations (HR: 1.36; 95% CI:0.84-2.20; p < 0.001; I2 = 92.6%). CONCLUSION: This systematic review and study-level meta-analysis demonstrated that the immune-based combinations in first-line treatment for patients with mUC are associated with survival benefit.

Advanced renal cell carcinoma management: the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG) consensus update.

PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.

Magnetic resonance image in the diagnosis and evaluation of extra-prostatic extension and involvement of seminal vesicles of prostate cancer: a systematic review of literature and meta-analysis.

OBJECTIVE: Systematic review of literature and meta-analysis to evaluate the results of magnetic resonance image 1.5T with endorectal coil in the diagnosis and evaluation of extra-prostatic extension and involvement of seminal vesicles of prostate cancer, compared to the histopathological results of the radical prostatectomy specimen. MATERIALS AND METHODS: It was conducted a systematic review of literature and meta-analyses of all studies data published after 2008. In those studies, the patients with prostate cancer with indication to radical prostatectomy were submitted to magnetic resonance image (MRI) at pre-operatory period and the results were compared to those of histopathological studies after the surgery. The selected terms for research included prostate cancer, magnetic resonance, radical prostatectomy, and prostate cancer diagnosis, in the databases EMBASE, LILACS, PUBMED/MEDLINE and Cochrane Library. The data were collected using a specific qualitative instrument and the meta-analysis data were presented in the forest plot graphics, homogeneity test and sROC curves and funnel plot. RESULTS: A total of seven studies were included, with a total of 603 patients. Among these studies, six evaluated the value of MRI for the detection of prostate cancer, and the median sensitivity of meta-analysis was 0.6 and specificity 0.58, but with heterogeneity among the studies. Three studies evaluated extra-prostatic extension with a median sensitivity of 0.49, specificity 0.82 and heterogeneity only for sensitivity. Three studies evaluated invasion of seminal vesicles, with median sensitivity of 0.45 and specificity 0.96, with heterogeneity in both analysis. CONCLUSION: Magnetic resonance of 1.5T with endocoil showed low values of sensitivity and specificity for the diagnosis and staging of prostate cancer. The reviewed studies showed a significant heterogeneity among them. The best observed result was MRI specificity for invasion of seminal vesicles. More studies are necessary to evaluate new techniques and parameters before recommending the routine use of MRI in clinical practice.

Erratum: Single-center developing country analysis of radium-223 therapy in prostate cancer-preliminary results.

[This corrects the article on p. 352 in vol. 11, PMID: 34754606.].

"Non-metastatic, Castration-resistant Prostate Cancer: Diagnostic and Treatment Recommendations by an Expert Panel from Brazil".

INTRODUCTION: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC. METHODS: A panel of 51 invited medical oncologists and urologists convened in May of 2021 with the aim of discussing and providing recommendations regarding the most relevant issues concerning staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in nmCRPC. Panel members considered the available evidence and their practical experience to address the 73 multiple-choice questions presented. RESULTS: Key recommendations and findings include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel (i.e., positron-emission tomography-based) imaging techniques, the increasing role of ARSis in various settings, the general view that ARSis have similar efficacy. Panelists highlighted the slight preference for darolutamide, when safety is of greater concern, and a continued need to develop high-level evidence to guide the intensity of follow-up in this subset of prostate cancer. DISCUSSION: Despite the limitations associated with a consensus panel, the topics addressed are relevant in current practice, and the recommendations can help practicing clinicians to provide state-of-the-art treatment to patients with nmCRPC in Brazil and other countries with similar healthcare settings.