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BACKGROUND: No new agent has improved overall survival in patients with unresectable or metastatic urothelial carcinoma when added to first-line cisplatin-based chemotherapy. METHODS: In this phase 3, multinational, open-label trial, we randomly assigned patients with previously untreated unresectable or metastatic urothelial carcinoma either to receive intravenous nivolumab (at a dose of 360 mg) plus gemcitabine-cisplatin (nivolumab combination) every 3 weeks for up to six cycles, followed by nivolumab (at a dose of 480 mg) every 4 weeks for a maximum of 2 years, or to receive gemcitabine-cisplatin alone every 3 weeks for up to six cycles. The primary outcomes were overall and progression-free survival. The objective response and safety were exploratory outcomes. RESULTS: A total of 608 patients underwent randomization (304 to each group). At a median follow-up of 33.6 months, overall survival was longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for death, 0.78; 95% confidence interval [CI], 0.63 to 0.96; P = 0.02); the median survival was 21.7 months (95% CI, 18.6 to 26.4) as compared with 18.9 months (95% CI, 14.7 to 22.4), respectively. Progression-free survival was also longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for progression or death, 0.72; 95% CI, 0.59 to 0.88; P = 0.001). The median progression-free survival was 7.9 months and 7.6 months, respectively. At 12 months, progression-free survival was 34.2% and 21.8%, respectively. The overall objective response was 57.6% (complete response, 21.7%) with nivolumab-combination therapy and 43.1% (complete response, 11.8%) with gemcitabine-cisplatin alone. The median duration of complete response was 37.1 months with nivolumab-combination therapy and 13.2 months with gemcitabine-cisplatin alone. Grade 3 or higher adverse events occurred in 61.8% and 51.7% of the patients, respectively. CONCLUSIONS: Combination therapy with nivolumab plus gemcitabine-cisplatin resulted in significantly better outcomes in patients with previously untreated advanced urothelial carcinoma than gemcitabine-cisplatin alone. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 901 ClinicalTrials.gov number, NCT03036098.).
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células de Transição , Cisplatino , Gencitabina , Nivolumabe , Neoplasias da Bexiga Urinária , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Gencitabina/administração & dosagem , Gencitabina/efeitos adversos , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Administração IntravenosaRESUMO
BACKGROUND: Co-inhibition of poly(ADP-ribose) polymerase (PARP) and androgen receptor activity might result in antitumour efficacy irrespective of alterations in DNA damage repair genes involved in homologous recombination repair (HRR). We aimed to compare the efficacy and safety of talazoparib (a PARP inhibitor) plus enzalutamide (an androgen receptor blocker) versus enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: TALAPRO-2 is a randomised, double-blind, phase 3 trial of talazoparib plus enzalutamide versus placebo plus enzalutamide as first-line therapy in men (age ≥18 years [≥20 years in Japan]) with asymptomatic or mildly symptomatic mCRPC receiving ongoing androgen deprivation therapy. Patients were enrolled from 223 hospitals, cancer centres, and medical centres in 26 countries in North America, Europe, Israel, South America, South Africa, and the Asia-Pacific region. Patients were prospectively assessed for HRR gene alterations in tumour tissue and randomly assigned (1:1) to talazoparib 0·5 mg or placebo, plus enzalutamide 160 mg, administered orally once daily. Randomisation was stratified by HRR gene alteration status (deficient vs non-deficient or unknown) and previous treatment with life-prolonging therapy (docetaxel or abiraterone, or both: yes vs no) in the castration-sensitive setting. The sponsor, patients, and investigators were masked to talazoparib or placebo, while enzalutamide was open-label. The primary endpoint was radiographic progression-free survival (rPFS) by blinded independent central review, evaluated in the intention-to-treat population. Safety was evaluated in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (NCT03395197) and is ongoing. FINDINGS: Between Jan 7, 2019, and Sept 17, 2020, 805 patients were enrolled and randomly assigned (402 to the talazoparib group and 403 to the placebo group). Median follow-up for rPFS was 24·9 months (IQR 21·9-30·2) for the talazoparib group and 24·6 months (14·4-30·2) for the placebo group. At the planned primary analysis, median rPFS was not reached (95% CI 27·5 months-not reached) for talazoparib plus enzalutamide and 21·9 months (16·6-25·1) for placebo plus enzalutamide (hazard ratio 0·63; 95% CI 0·51-0·78; p<0·0001). In the talazoparib group, the most common treatment-emergent adverse events were anaemia, neutropenia, and fatigue; the most common grade 3-4 event was anaemia (185 [46%] of 398 patients), which improved after dose reduction, and only 33 (8%) of 398 patients discontinued talazoparib due to anaemia. Treatment-related deaths occurred in no patients in the talazoparib group and two patients (<1%) in the placebo group. INTERPRETATION: Talazoparib plus enzalutamide resulted in clinically meaningful and statistically significant improvement in rPFS versus standard of care enzalutamide as first-line treatment for patients with mCRPC. Final overall survival data and additional long-term safety follow-up will further clarify the clinical benefit of the treatment combination in patients with and without tumour HRR gene alterations. FUNDING: Pfizer.
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Anemia , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Adolescente , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Receptores Androgênicos , Antagonistas de Androgênios/uso terapêutico , Anemia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Método Duplo-CegoRESUMO
OBJECTIVE: To describe age-specific prostate-specific antigen (PSA) distributions and resulting prostate cancer diagnoses that arise from population-wide opportunistic PSA testing. PATIENTS AND METHODS: Over 8 million PSA tests were performed on >1.4 million Norwegian men from 2000 to 2020. During this period 43 486 men were diagnosed with localised prostate cancer. Most of the PSA testing reflected opportunistic testing. Age-specific PSA value distributions were constructed for men aged 45-75 years with and without prostate cancer. RESULTS: The distributions of PSA values in men with and without prostate cancer widened with age and overlapped extensively from 3 to 7 ng/mL. Localised prostate cancer diagnoses increased 10-fold from the age of 45 to 75 years. PSA testing identified intermediate- or high-grade cancers in 21% (95% confidence interval [CI] 19-23%) of men aged 50-54 years and 42% (95% CI 41-43%) of men aged 70-74 years. Grade group (GG)1, GG2, GG3 and ≥GG4 constituted 49%, 31%, 10% and 10% of cancers identified at age 50-54 years and 26%, 26%, 18%, and 30% of cancers identified at age 70-74 years. CONCLUSION: Opportunistic PSA testing increases with ageing and often generates values that cannot discriminate benign prostate enlargement from prostate cancer. A clinical cascade using additional imaging or serum tests is necessary to avoid negative biopsies and the overdiagnosis of indolent disease. The declining specificity of PSA testing with ageing poses a significant public health challenge especially among older men aged ≥70 years.
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Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Idoso , Pessoa de Meia-Idade , Saúde Pública , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Biópsia , Programas de RastreamentoRESUMO
WHAT IS THIS SUMMARY ABOUT?: This summary describes the results from the TALAPRO-2 research study (also known as a clinical trial). The TALAPRO-2 study tested the combination of two medicines called talazoparib plus enzalutamide. This combination of medicines was used as the first treatment for adult patients with metastatic castration-resistant prostate cancer. The combination of talazoparib plus enzalutamide was compared with a placebo plus enzalutamide. WHAT IS METASTATIC CASTRATION-RESISTANT PROSTATE CANCER?: Metastatic castration-resistant prostate cancer is a type of cancer that starts in the prostate and has spread to other parts of the body. Castration-resistant means that the cancer continues to grow even when testosterone levels in the blood are reduced to very low levels. Taking medicines to lower testosterone levels in the blood is a standard treatment for men with advanced prostate cancer. WHAT ARE THE AIMS OF THE TALAPRO-2 TRIAL?: TALAPRO-2 looked at if combining talazoparib plus enzalutamide would increase the length of time patients lived before their cancer got worse or they died compared with a placebo plus enzalutamide. Researchers looked at how treatment affected the size and number of tumors and the length of time before patients needed to change to a new cancer medicine. Researchers also looked at any side effects patients had during the study. WHAT ARE THE KEY TAKEAWAYS?: A total of 805 patients with metastatic castration-resistant prostate cancer took part in the study. Compared with patients who took a placebo plus enzalutamide, the group of patients who took talazoparib plus enzalutamide had a 37% reduced risk of their cancer getting worse or dying. Some patients had tumors that at the start of the study could be measured with scans. Sixty-two percent of patients who took talazoparib plus enzalutamide had their tumors decrease or shrink to the point that they could no longer be seen on scans versus 44% of patients who took a placebo plus enzalutamide. Patients who took talazoparib plus enzalutamide were more likely to have a longer time before they needed to change to a new cancer medicine. The most common side effects of talazoparib plus enzalutamide were low levels of red blood cells (66% of patients) and neutrophils (36% of patients), and excessive tiredness or exhaustion (34% of patients).Clinical Trial Registration: NCT03395197 (TALAPRO-2) (ClinicalTrials.gov).
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BACKGROUND: The long-term toxicities after cisplatin-based chemotherapy (CBCT) reveal a remarkable inter-individual variation among testicular cancer survivors (TCSs). Therefore, we assessed long-term platinum (Pt) changes and their associations with CBCT-related late effects in TCSs. MATERIAL AND METHODS: In 77 TCSs treated with CBCT from 1984 to 1990, blood samples for analyses of Pt and a questionnaire including self-reported neuro- and ototoxicity (NTX) symptoms were collected during two follow-up surveys at median 12 (Survey I; SI) and 20 (Survey II; SII) years after treatment. Information about second cancers after SII was retrieved from the Norwegian Cancer Registry. RESULTS: A larger Pt decline from SI to SII was associated with a decreased risk of a second cancer diagnosis (HR 0.78, 95% CI 0.62-0.99 per 10 ng/L/year), and worsening of paresthesias in hands (OR 1.98, 95% CI 1.09-3.59 per 10 ng/L/year) and tinnitus (OR 1.51, 95% CI 1.01-2.27 per 10 ng/L/year). CONCLUSION: In summary, we found a significant association between a larger Pt decline and a reduced risk of second cancers and deterioration of paresthesias in hands and tinnitus.
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Antineoplásicos/efeitos adversos , Sobreviventes de Câncer , Cisplatino/efeitos adversos , Platina/sangue , Neoplasias Testiculares/tratamento farmacológico , Adolescente , Adulto , Idoso , Cisplatino/farmacocinética , Perda Auditiva/induzido quimicamente , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/mortalidade , Adulto JovemRESUMO
INTRODUCTION: In 1979, the Copenhagen group around Dr. Skakkebaek introduced contralateral biopsy in patients with testicular germ cell tumour (GCT) as a means of early diagnosing a contralateral testicular tumour (Berthelsen et al. in Br Med J 2(6186):363-364, 1). Although the rationale of contralateral biopsies is based on much of scientific evidence, no issue regarding the management of GCTs has been more controversial than the issue of contralateral biopsies (Heidenreich in BJU Int 104(9 Pt B):1346-1350, 2; Grigor and Rorth in Eur Urol 23(1):129-135, 3). A poll conducted during the GCT Consensus Meeting in Berlin 2011 revealed that 43 % of 60 leading experts would not recommend a contralateral biopsy and only 13.7 % would do the biopsy in all cases with GCT (Beyer et al. in Ann Oncol 24(4):878-888, 4). Likewise, the European Association of Urology and the European Society of Medical Oncology offer only weak recommendations with respect to contralateral biopsies in their guidelines of testicular cancer (Albers et al. in Eur Urol 68(6):1054-1068, 5; Oldenburg et al. in Ann Oncol 24(Suppl 6):vi125-vi132, 6). CONCLUSION: This review summarizes contemporary knowledge regarding contralateral biopsies to provide professionals caring for GCT patients with sufficient information to decide for or against the procedure in clinical practice.
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Biópsia/métodos , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Primárias Múltiplas/patologia , Lesões Pré-Cancerosas/patologia , Neoplasias Testiculares/patologia , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Primárias Múltiplas/diagnóstico , Lesões Pré-Cancerosas/diagnóstico , Neoplasias Testiculares/diagnósticoRESUMO
BACKGROUND: With the advent of targeted therapies, many treatment options in the first-line setting of metastatic clear cell renal cell carcinoma (mccRCC) have emerged. Guidelines and randomized trial reports usually do not elucidate the decision criteria for the different treatment options. In order to extract the decision criteria for the optimal therapy for patients, we performed an analysis of treatment algorithms from experts in the field. MATERIALS AND METHODS: Treatment algorithms for the treatment of mccRCC from experts of 11 institutions were obtained, and decision trees were deduced. Treatment options were identified and a list of unified decision criteria determined. The final decision trees were analyzed with a methodology based on diagnostic nodes, which allows for an automated cross-comparison of decision trees. The most common treatment recommendations were determined, and areas of discordance were identified. RESULTS: The analysis revealed heterogeneity in most clinical scenarios. The recommendations selected for first-line treatment of mccRCC included sunitinib, pazopanib, temsirolimus, interferon-α combined with bevacizumab, high-dose interleukin-2, sorafenib, axitinib, everolimus, and best supportive care. The criteria relevant for treatment decisions were performance status, Memorial Sloan Kettering Cancer Center risk group, only or mainly lung metastases, cardiac insufficiency, hepatic insufficiency, age, and "zugzwang" (composite of multiple, related criteria). CONCLUSION: In the present study, we used diagnostic nodes to compare treatment algorithms in the first-line treatment of mccRCC. The results illustrate the heterogeneity of the decision criteria and treatment strategies for mccRCC and how available data are interpreted and implemented differently among experts. IMPLICATIONS FOR PRACTICE: The data provided in the present report should not be considered to serve as treatment recommendations for the management of treatment-naïve patients with multiple metastases from metastatic clear cell renal cell carcinoma outside a clinical trial; however, the data highlight the different treatment options and the criteria used to select them. The diversity in decision making and how results from phase III trials can be interpreted and implemented differently in daily practice are demonstrated.
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Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/diagnóstico , Neoplasias Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Árvores de Decisões , Diagnóstico por Computador/métodos , Humanos , Neoplasias Renais/patologia , Metástase NeoplásicaRESUMO
BACKGROUND: A contralateral tumor occurs in 3.5-5% of men diagnosed with testicular germ cell cancer (TGCC). Biopsy of the contralateral testis may detect intratubular germ cell neoplasia ITGCNU, a precursor of TGCC. Biopsy of the contralateral testis to detect ITGCNU is controversial. If adjuvant chemotherapy (ACT) protects against bilateral cancer is debated. MATERIAL AND METHODS: A total of 1003 patients with clinical stage I (CS I) non-seminomatous testicular germ cell cancer (NSGCT) were included in two prospective, population-based protocols. Fifteen patients were excluded. Treatment was either adjuvant chemotherapy (n = 494), or surveillance (n = 494). Contralateral testicular biopsy was recommended for all patients, but was performed only in 282 patients. In case of ITGCNU radiotherapy (RT) to 16 Gy was recommended. RESULTS: During a follow-up of 8.3 years, 31 (3.6%) patients developed contralateral TGCC. ITGCNU was detected in 3.2% (9/282) of biopsied patients. The incidence of bilateral TGCC was similar following ACT, 2.5% (11/494), and surveillance, 3.4% (13/494), p = 0.41. Young age was a risk factor for metachronous TGCC (HR 0.93; 95% CI 0.88-0.99, p = 0.02). In total 2.2% (6/273) of patients without ITGCNU in the biopsy developed contralateral TGCC. One irradiated patient developed contralateral cancer, and one developed contralateral tumor before RT was given. CONCLUSION: ACT did not reduce the incidence of contralateral TGCC. Young patients had the highest risk of developing contralateral TGCC. The proportion of false negatives biopsies was higher than reported in earlier trials, but this may in part be related to patient selection, single biopsies and lack of mandatory immunohistochemistry.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Testiculares/epidemiologia , Adulto , Fatores Etários , Idoso , Biópsia/estatística & dados numéricos , Bleomicina/administração & dosagem , Quimioterapia Adjuvante , Etoposídeo/administração & dosagem , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/prevenção & controle , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Primárias Múltiplas/tratamento farmacológico , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/prevenção & controle , Noruega/epidemiologia , Orquiectomia/estatística & dados numéricos , Estudos Prospectivos , Fatores de Risco , Suécia/epidemiologia , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Neoplasias Testiculares/prevenção & controle , Neoplasias Testiculares/cirurgia , Testículo/patologia , Fatores de Tempo , Vimblastina/administração & dosagem , Conduta ExpectanteRESUMO
Preclinical evidence has suggested an interplay between the androgen receptor, which largely drives the growth of prostate cancer cells, and poly(ADP-ribose) polymerase. This association provides a rationale for their co-inhibition for the treatment of metastatic castration-resistant prostate cancer (mCRPC), an area of unmet medical need. The phase 3 TALAPRO-2 study investigated combining the poly(ADP-ribose) polymerase inhibitor talazoparib with enzalutamide versus enzalutamide alone as first-line treatment of mCRPC. Patients were prospectively assessed for tumor alterations in DNA damage response genes involved in homologous recombination repair (HRR). Two cohorts were enrolled sequentially: an all-comers cohort that was enrolled first (cohort 1; N = 805 (169 were HRR-deficient)), followed by an HRR-deficient-only cohort (cohort 2; N = 230). We present results from the alpha-controlled primary analysis for the combined HRR-deficient population (N = 399). Patients were randomized in a 1:1 ratio to talazoparib or placebo, plus enzalutamide. The primary endpoint, radiographic progression-free survival, was met (median not reached at the time of the analysis for the talazoparib group versus 13.8 months for the placebo group; hazard ratio, 0.45; 95% confidence interval, 0.33 to 0.61; P < 0.0001). Data for overall survival, a key secondary endpoint, are immature but favor talazoparib (hazard ratio, 0.69; 95% confidence interval, 0.46 to 1.03; P = 0.07). Common adverse events in the talazoparib group were anemia, fatigue and neutropenia. Combining talazoparib with enzalutamide significantly improved radiographic progression-free survival in patients with mCRPC harboring HRR gene alterations, supporting talazoparib plus enzalutamide as a potential first-line treatment for these patients. ClinicalTrials.gov Identifier: NCT03395197 .
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Antineoplásicos , Benzamidas , Feniltioidantoína , Ftalazinas , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Reparo de DNA por Recombinação , Antineoplásicos/uso terapêutico , NitrilasRESUMO
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 < 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.
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Braquiterapia , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Braquiterapia/métodos , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: 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 Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines provide recommendations for the management of clinically localised prostate cancer (PCa). This paper aims to present a summary of the 2024 version of the EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on the screening, diagnosis, and treatment of clinically localised PCa. METHODS: The panel performed a literature review of all new data published in English, covering the time frame between May 2020 and 2023. The guidelines were updated, and a strength rating for each recommendation was added based on a systematic review of the evidence. KEY FINDINGS AND LIMITATIONS: 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. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is considered, a combination of targeted and regional biopsies should be performed. Prostate-specific membrane antigen positron emission tomography imaging is the most sensitive technique for identifying metastatic spread. Active surveillance is the appropriate management for men with low-risk PCa, as well as for selected favourable intermediate-risk patients with International Society of Urological Pathology grade group 2 lesions. Local therapies are addressed, as well as the management of persistent prostate-specific antigen after surgery. A recommendation to consider hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term intensified hormonal treatment. CONCLUSIONS AND CLINICAL IMPLICATIONS: The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. These PCa guidelines reflect the multidisciplinary nature of PCa management. PATIENT SUMMARY: This article is the summary of the guidelines for "curable" prostate cancer. Prostate cancer is "found" through a multistep risk-based screening process. The objective is to find as many men as possible with a curable cancer. Prostate cancer is curable if it resides in the prostate; it is then classified into low-, intermediary-, and high-risk localised and locally advanced prostate cancer. These risk classes are the basis of the treatments. Low-risk prostate cancer is treated with "active surveillance", a treatment with excellent prognosis. For low-intermediary-risk active surveillance should also be discussed as an option. In other cases, active treatments, surgery, or radiation treatment should be discussed along with the potential side effects to allow shared decision-making.
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Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/diagnóstico , Detecção Precoce de Câncer/normasRESUMO
BACKGROUND AND OBJECTIVE: 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 Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (PCa) have been updated. Here we provide a summary of the 2024 guidelines. METHODS: The panel performed a literature review of new data, covering the time frame between 2020 and 2023. The guidelines were updated and a strength rating for each recommendation was added on the basis of a systematic review of the evidence. KEY FINDINGS AND LIMITATIONS: Risk stratification for relapsing PCa after primary therapy may guide salvage therapy decisions. New treatment options, such as androgen receptor-targeted agents (ARTAs), ARTA + chemotherapy combinations, PARP inhibitors and their combinations, and prostate-specific membrane antigen-based therapy have become available for men with metastatic PCa. CONCLUSIONS AND CLINICAL IMPLICATIONS: Evidence for relapsing, metastatic, and castration-resistant PCa is evolving rapidly. These guidelines reflect the multidisciplinary nature of PCa management. The full version is available online (http://uroweb.org/guideline/ prostate-cancer/). PATIENT SUMMARY: This article summarises the 2024 guidelines for the treatment of relapsing, metastatic, and castration-resistant prostate cancer. These guidelines are based on evidence and guide doctors in discussing treatment decisions with their patients. The guidelines are updated every year.
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Recidiva Local de Neoplasia , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/terapia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológicoRESUMO
ProBio is the first outcome-adaptive platform trial in prostate cancer utilizing a Bayesian framework to evaluate efficacy within predefined biomarker signatures across systemic treatments. Prospective circulating tumor DNA and germline DNA analysis was performed in patients with metastatic castration-resistant prostate cancer before randomization to androgen receptor pathway inhibitors (ARPIs), taxanes or a physician's choice control arm. The primary endpoint was the time to no longer clinically benefitting (NLCB). Secondary endpoints included overall survival and (serious) adverse events. Upon reaching the time to NLCB, patients could be re-randomized. The primary endpoint was met after 218 randomizations. ARPIs demonstrated ~50% longer time to NLCB compared to taxanes (median, 11.1 versus 6.9 months) and the physician's choice arm (median, 11.1 versus 7.4 months) in the biomarker-unselected or 'all' patient population. ARPIs demonstrated longer overall survival (median, 38.7 versus 21.7 and 21.8 months for taxanes and physician's choice, respectively). Biomarker signature findings suggest that the largest increase in time to NLCB was observed in AR (single-nucleotide variant/genomic structural rearrangement)-negative and TP53 wild-type patients and TMPRSS2-ERG fusion-positive patients, whereas no difference between ARPIs and taxanes was observed in TP53-altered patients. In summary, ARPIs outperform taxanes and physician's choice treatment in patients with metastatic castration-resistant prostate cancer with detectable circulating tumor DNA. ClinicalTrials.gov registration: NCT03903835 .
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Occasionally, medical decisions have to be taken in the absence of evidence-based guidelines. Other sources can be drawn upon to fill in the gaps, including experience and intuition. Authorities or experts, with their knowledge and experience, may provide further input--known as "eminence-based medicine". Due to the Internet and digital media, interactions among physicians now take place at a higher rate than ever before. With the rising number of interconnected individuals and their communication capabilities, the medical community is obtaining the properties of a swarm. The way individual physicians act depends on other physicians; medical societies act based on their members. Swarm behavior might facilitate the generation and distribution of knowledge as an unconscious process. As such, "swarm-based medicine" may add a further source of information to the classical approaches of evidence- and eminence-based medicine. How to integrate swarm-based medicine into practice is left to the individual physician, but even this decision will be influenced by the swarm.
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Internet , Telemedicina/métodos , Comunicação , Medicina Baseada em Evidências , Humanos , MédicosRESUMO
With the numerous advances and broad applications of mobile health (mHealth), establishing concrete data sharing, privacy, and governance strategies at national (or regional) levels is essential to protect individual privacy and data usage. This article applies the recent Health Data Governance Principles to provide a guiding framework for low- and middle-income countries (LMICs) to create a comprehensive mHealth data governance strategy. We provide three objectives: (1) establish data rights and ownership to promote equitable benefits from health data, (2) protect people through building trust and addressing patients' concerns, and (3) promote health value by enhancing health systems and services. We also recommend actions for realizing each objective to guide LMICs based on their unique mHealth data ecosystems. These objectives require adopting a regulatory framework for data rights and protection, building trust for data sharing, and enhancing interoperability to use new datasets in advancing healthcare services and innovation.
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Privacidade , Telemedicina , Humanos , Países em Desenvolvimento , Promoção da Saúde , Ecossistema , Disseminação de InformaçãoRESUMO
New technologies such as devices, apps, smartphones, and sensors not only enable people to self-monitor their health but also share their health data with healthcare professionals. Data collection and dissemination occur across a wide variety of environments and settings, tracking everything from biometric data to mood and behavior, which has been termed Patient Contributed Data (PCD). In this work, we created a patient journey, enabled by PCD, to shape a connected health model for Cardiac Rehabilitation (CR) in Austria. Consequently, we highlighted the potential PCD benefit, which is a postulated increasing uptake of CR and improved patient outcomes through apps in a home-based setting. Finally, we addressed the related challenges and policy barriers that hinder the implementation of CR-connected health in Austria and identified actions to be taken.
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Reabilitação Cardíaca , Humanos , Áustria , SmartphoneRESUMO
The Journal of Participatory Medicine introduces Extraordinary Lives, a new journal section celebrating the voices and work of steadfast advocates of participatory medicine that we have lost. This inaugural essay spotlights Casey Quinlan, a patient activist who effectively used her humor and incisive analysis of health care to encourage others to strive for meaningful change. A first-generation "professional patient," Casey served as a role model who inspired many to share their stories and achieve genuine partnerships in care delivery. A maker of "good trouble," her voice and stance were part of her power and influence in disrupting the status quo. We present her fight for personal access to health data, her aspiration for personally customized evidence, and her drive for all people to control their health and their health care.
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PURPOSE: To understand the potential impact of new treatment options for urinary tract cancer, recent population trends in incidence, mortality and survival should be elucidated. This study estimated changes in the incidence, mortality and relative survival of urinary tract cancer in the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden) between 1990 and 2019. METHODS: Annual counts of incident cases and deaths due to urinary tract cancer (International Classification of Diseases, Tenth Revision, Clinical Modification codes C65-C68, D09.0-D09.1, D30.1-D30.9 and D41.1-D41.9) in Nordic countries were retrieved in 5-year age categories by sex during the study period. Country-specific time trends (annual rate ratios [RRs]) were estimated using Poisson regression, and RRs were compared between sexes. RESULTS: The incidence rate of bladder and upper urothelial tract cancer was >3-times lower in women than men in all countries across all age groups (incidence RR for women to men ranging from 0.219 [95% CI = 0.213-0.224] in Finland to 0.291 [95% CI = 0.286-0.296] in Denmark). Incidence rates were lowest in Finland and highest in Norway and Denmark. Age-adjusted mortality decreased in Finland, Denmark and Norway and in Swedish men, with the greatest decrease seen in Danish men (annual RR = 0.976; 95% CI = 0.975-0.978). In all countries and age groups, women had a lower relative survival rate than men. CONCLUSION: Between 1990 and 2019, the incidence of urinary tract cancer was stable in the Nordic countries, while mortality rates declined and relative survival increased. This could be due to earlier diagnosis and better treatment.
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Neoplasias da Bexiga Urinária , Neoplasias Urológicas , Masculino , Humanos , Feminino , Incidência , Bexiga Urinária , Fatores de Risco , Países Escandinavos e Nórdicos , Neoplasias da Bexiga Urinária/epidemiologia , Finlândia/epidemiologia , Noruega/epidemiologia , Suécia/epidemiologia , Dinamarca/epidemiologia , Sistema de RegistrosRESUMO
BACKGROUND: Prostate-specific antigen (PSA) levels in midlife are strongly associated with the long-term risk of lethal prostate cancer in cohorts not subject to screening. This is the first study evaluating the association between PSA levels drawn as part of routine medical care in the Norwegian population and prostate cancer incidence and mortality. OBJECTIVE: To determine the association between midlife PSA levels <4.0 ng/ml, drawn as part of routine medical care, and long-term risk of prostate cancer death. DESIGN, SETTING, AND PARTICIPANTS: The Norwegian Prostate Cancer Consortium collected >8 million PSA results from >1 million Norwegian males ≥40 yr of age. We studied 176 099 men (predefined age strata: 40-54 and 55-69 yr) without a prior prostate cancer diagnosis who had a nonelevated baseline PSA level (<4.0 ng/ml) between January 1, 1995 and December 31, 2005. INTERVENTION: Baseline PSA. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the 16-yr risk of prostate cancer mortality. We calculated the discrimination (C-index) between predefined PSA strata (<0.5, 0.5-0.9, 1.0-1.9, 2.0-2.9, and 3.0-3.9 ng/ml) and subsequent prostate cancer death. Survival curves were plotted using the Kaplan-Meier method. RESULTS AND LIMITATIONS: The median follow-up time of men who did not get prostate cancer was 17.9 yr. Overall, 84% of men had a baseline PSA level of <2.0 ng/ml and 1346 men died from prostate cancer, with 712 deaths (53%) occurring in the 16% of men with the highest baseline PSA of 2.0-3.9 ng/ml. Baseline PSA levels were associated with prostate cancer mortality (C-index 0.72 for both age groups, 40-54 and 55-69 yr). The fact that the reason for any given PSA measurement remains unknown represents a limitation. CONCLUSIONS: We replicated prior studies that baseline PSA at age 40-69 yr can be used to stratify a man's risk of dying from prostate cancer within the next 15-20 yr. PATIENT SUMMARY: A prostate-specific antigen level obtained as part of routine medical care is strongly associated with a man's risk of dying from prostate cancer in the next two decades.
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CONTEXT: Each year the European Association of Urology (EAU) produce a document based on the most recent evidence on the diagnosis, therapy, and follow-up of testicular cancer (TC). OBJECTIVE: To represent a summarised version of the EAU guidelines on TC for 2023 with a focus on key changes in the 2023 update. EVIDENCE ACQUISITION: A multidisciplinary panel of TC experts, comprising urologists, medical and radiation oncologists, and pathologists, reviewed the results from a structured literature search to compile the guidelines document. Each recommendation in the guidelines was assigned a strength rating. EVIDENCE SYNTHESIS: For the 2023 EAU guidelines on TC, a review and restructure were undertaken. The key changes incorporated in the 2023 update include: new supporting text regarding venous thromboembolism prophylaxis in males with metastatic germ cell tumours receiving chemotherapy; quality of life after treatment; an update of the histological classifications and inclusion of the World Health Organization 2022 pathological classification; inclusion of the revalidation of the 1997 International Germ Cell Cancer Collaborative Group prognostic risk factors; and a new section covering oncology treatment protocols. CONCLUSIONS: The 2023 version of the EAU guidelines on TC include the highest available scientific evidence to standardise the management of TC. Better stratification and optimisation of treatment modalities will continue to improve the high survival rates for patients with TC. PATIENT SUMMARY: This article presents a summary of the European Association of Urology guidelines on testicular cancer published in 2023 and includes the latest recommendations for management of this disease. The guidelines are a valuable resource that may help patients in understanding treatment recommendations.