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BACKGROUND: The urinary microbiota of patients with benign prostatic hyperplasia (BPH) has been associated with lower urinary tract symptoms (LUTS), however, little is known about urinary microbiota correlations with clinicopathological parameters associated with BPH. Here, we investigate associations between the urinary microbiota and clinical parameters of patients with BPH undergoing surgery. METHODS: Forty-one patients with BPH undergoing surgery were recruited from two medical centers. Catheterized urine specimens were collected and the microbiota was characterized by 16S rRNA gene sequencing. Patients were segregated into two groups according to each clinical parameter and differences in urinary microbiota diversity and composition were evaluated. RESULTS: Higher prostate weight and prostate-specific antigen (PSA) levels were associated with higher alpha diversity in the urinary microbiota of BPH patients. At the specific microbe level, we found that the greater the prostatic weight, the lower the relative abundance of Streptococcus, while the greater the PSA levels, the higher the abundance of Lactobacillus. Treatment with 5-α-reductase inhibitor was associated with overall urinary microbiota composition, in part due to a higher abundance of Corynebacterium and Anaerococcus in this group. CONCLUSIONS: We demonstrated that the urinary microbiota of BPH patients is associated with clinicopathological features, paving the way for larger studies in which causality between urinary microbiota and BPH can be appropriately explored.
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Síntomas del Sistema Urinario Inferior , Hiperplasia Prostática , Masculino , Humanos , Hiperplasia Prostática/tratamiento farmacológico , Antígeno Prostático Específico/uso terapéutico , ARN Ribosómico 16S/genética , Próstata , Síntomas del Sistema Urinario Inferior/etiologíaRESUMEN
INTRODUCTION: Bladder microbiota dysbiosis has been associated with several urological disorders. However, dysbiosis markers in bladder cancer have not been identified and little is known about the effect of Bacillus Calmette-Guérin (BCG) intravesical therapy on the bladder microbiota. In this study, we compared the bladder microbiota of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing BCG therapy to nononcological controls. We also longitudinally analyzed the impact of BCG therapy on the bladder microbiota of NMIBC patients and addressed whether bladder microbiota is associated with BCG efficacy. METHODS: We collected catheterized urine samples from males with intermediate/high-risk NMIBC (cancer group, nâ¯=â¯32) or benign prostatic hyperplasia (control group, nâ¯=â¯41). The cancer group also provided urine samples during and after BCG induction. We used 16S rRNA gene sequencing to characterize the bladder microbiota. Bladder microbiota parameters, such as diversity and taxonomic composition, were compared between groups and associated with clinicopathological data and BCG efficacy. RESULTS: We observed no significant differences between the bladder microbiota of NMIBC patients and controls. BCG intravesical instillations did not significantly alter the bladder microbiota of NMIBC patients, and BCG was rarely detected in the bladder during and after BCG therapy. Microbiota diversity and overall composition before BCG induction did not influence disease persistence at 3 months. However, higher abundance of Lactobacillus, Streptococcus, and Cutibacterium in the pre-BCG bladder microbiota was associated with BCG effectiveness. CONCLUSION: We were unable to identify markers of bladder microbiota dysbiosis among male NMIBC patients. Moreover, we demonstrated for the first time using longitudinally collected samples that BCG cannot persist in the bladder microbiota nor significantly alter its diversity and composition. The associations found between bladder microbes and BCG efficacy highlight the potential of microbial-based therapeutic and risk-stratification strategies in the intermediate/high-risk NMIBC setting.
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Neoplasias Vesicales sin Invasión Muscular , Neoplasias de la Vejiga Urinaria , Humanos , Masculino , Vejiga Urinaria/patología , Vacuna BCG/uso terapéutico , Disbiosis/tratamiento farmacológico , ARN Ribosómico 16S/genética , Adyuvantes Inmunológicos/uso terapéutico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Administración Intravesical , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/patologíaRESUMEN
INTRODUCTION: Recent studies about intense neoadjuvant therapy followed by Radical Prostatectomy (RP) lack standardized criteria regarding surgical complications and comparison to a group of patients who underwent RP without the use of neoadjuvant therapy. The aim of this study is to describe and compare the perioperative complication rates. MATERIALS AND METHODS: This was a prospective, single-center phase II trial in patients with high-risk prostate cancer (HRPCa). The control group included HRPCa patients who underwent RP outside the clinical trial during the same study recruitment period. The interventional group was randomized (1:1) to receive neoadjuvant androgen deprivation therapy plus abiraterone with or without apalutamide followed by RP. Complications observed up to 30 days of surgery were classified based on the Clavien-Dindo classification. Uni- and multivariate analyses were carried out to assess predictive factors associated with perioperative complications. RESULTS: In total, 124 patients with HRPCa were underwent to RP between May 27, 2019 and August 6, 2021, including 61 patients in the intervention group and 63 patients in the control group. The general and major complications in the intervention group reached 29.6% and 6.6%, respectively, and 39.7% and 7.9% in the control group, respectively. There was no significant difference between groups. We observed 4.9% of thromboembolic event in the neoadjuvant group. CONCLUSIONS: There was no significant increase in morbidity rate in RP after intense neoadjuvant therapy. The association of intense androgen deprivation neoadjuvant therapy with RP and extended pelvic lymphadenectomy may increase the risk of a perioperative thromboembolic events.
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Terapia Neoadyuvante , Neoplasias de la Próstata , Humanos , Masculino , Antagonistas de Andrógenos/efectos adversos , Andrógenos , Grupos Control , Morbilidad , Terapia Neoadyuvante/efectos adversos , Estudios Prospectivos , Antígeno Prostático Específico , Prostatectomía/efectos adversos , Prostatectomía/métodos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/cirugía , Resultado del TratamientoRESUMEN
INTRODUCTION: Germ-cell tumors (GCTs) are the most common malignancy in young men. There is a paucity of data on GCTs in developing countries. LACOG 0515 study aimed to evaluate clinical characteristics and treatment outcomes in patients with GCTs from Brazilian cancer centers. MATERIALS AND METHODS: This is a retrospective cohort study evaluating male patients diagnosed with GCTs from 2000 to 2018 in 13 Brazilian hospitals. We described baseline characteristics, progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 1232 patients were included, with a median age of 30 years. Histology was seminoma in 47.1% and non-seminoma GCT (NSGCT) in 52.9%. The primary tumor site was testis in 96.5%. At diagnosis, clinical stage I was present in 68.1% and 34.7% and clinical stages IS/II/III in 31.9% and 65.2% of patients with seminoma and NSCGT, respectively. Following orchiectomy, 55.2% of patients with clinical stage I were managed with surveillance. The 5-year disease-free survival rates among patients with stage I were 98.0% in seminoma and 92.3% in NSGCT, with 5-year OS of 99.6% and 97.6%, respectively. Among patients with advanced disease (IS, II, and III), the 5-year PFS were 88.7% in seminoma and 68.7% in NSGCT, with 5y-OS of 97.6% and 82.8%, respectively. CONCLUSION: This is the largest Brazilian cohort of GCTs. Our results show a high rate of adjuvant chemotherapy in patients with clinical stage I. Although our data demonstrate slightly inferior PFS compared with the International Germ Cell Cancer Collaborative Group and other contemporary series, the OS rates were similar.
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Neoplasias de Células Germinales y Embrionarias , Seminoma , Neoplasias Testiculares , Humanos , Masculino , Adulto , Estudios Retrospectivos , América Latina/epidemiología , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Testiculares/diagnóstico , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Seminoma/tratamiento farmacológico , Sistema de RegistrosRESUMEN
Accessibility to next-generation sequencing (NGS) technologies has enabled the profiling of microbial communities living in distinct habitats. 16S ribosomal RNA (rRNA) gene sequencing is widely used for microbiota profiling with NGS technologies. Since most used NGS platforms generate short reads, sequencing the full-length 16S rRNA gene is impractical. Therefore, choosing which 16S rRNA hypervariable region to sequence is critical in microbiota profiling studies. All nine 16S rRNA hypervariable regions are taxonomically informative, but due to variability in profiling performance for specific clades, choosing the ideal 16S rRNA hypervariable region will depend on the bacterial composition of the habitat under study. Recently, NGS allowed the identification of microbes in the urinary tract, and urinary microbiota has become an active research area. However, there is no current study evaluating the performance of different 16S rRNA hypervariable regions for male urinary microbiota profiling. We collected urine samples from male volunteers and profiled their urinary microbiota by sequencing a panel of six amplicons encompassing all nine 16S rRNA hypervariable regions. Systematic comparisons of their performance indicate V1V2 hypervariable regions better assess the taxa commonly present in male urine samples, suggesting V1V2 amplicon sequencing is more suitable for male urinary microbiota profiling. We believe our results will be helpful to guide this crucial methodological choice in future male urinary microbiota studies.
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Microbiota , Bacterias/genética , Cartilla de ADN/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Masculino , Microbiota/genética , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN/métodosAsunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Radio (Elemento) , Antagonistas de Andrógenos/uso terapéutico , Quinasas Ciclina-Dependientes , ADN/uso terapéutico , Daño del ADN , Humanos , Inmunoterapia , Masculino , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Radio (Elemento)/uso terapéuticoRESUMEN
BACKGROUND: Docetaxel has immunostimulatory effects that may promote an immunoresponsive prostate tumour microenvironment, providing a rationale for combination with nivolumab (programmed death-1 inhibitor) for metastatic castration-resistant prostate cancer (mCRPC). METHODS: In the non-randomised, multicohort, global phase II CheckMate 9KD trial, 84 patients with chemotherapy-naive mCRPC, ongoing androgen deprivation therapy and ≤2 prior novel hormonal therapies (NHTs) received nivolumab 360 mg and docetaxel 75 mg/m2 every 3 weeks with prednisone 5 mg twice daily (≤10 cycles) and then nivolumab 480 mg every 4 weeks (≤2 years). The co-primary end-points were objective response rate (ORR) and prostate-specific antigen response rate (PSA50-RR; ≥50% decrease from baseline). RESULTS: The confirmed ORR (95% confidence interval [CI]) was 40.0% (25.7-55.7), and the confirmed PSA50-RR (95% CI) was 46.9% (35.7-58.3). The median (95% CI) radiographic progression-free survival (rPFS) and overall survival (OS) were 9.0 (8.0-11.6) and 18.2 (14.6-20.7) months, respectively. In subpopulations with versus without prior NHT, the ORR was 38.7% versus 42.9%, the PSA50-RR was 39.6% versus 60.7%, the median rPFS was 8.5 versus 12.0 months and the median OS was 16.2 months versus not reached. Homologous recombination deficiency status or tumour mutational burden did not appear to impact efficacy. The most common any-grade and grade 3-4 treatment-related adverse events were fatigue (39.3%) and neutropenia (16.7%), respectively. Three treatment-related deaths occurred (1 pneumonitis related to nivolumab; 2 pneumonias related to docetaxel). CONCLUSIONS: Nivolumab plus docetaxel has clinical activity in patients with chemotherapy-naïve mCRPC. Safety was consistent with the individual components. These results support further investigation in the ongoing phase III CheckMate 7DX trial. CLINICALTRIALS. GOV REGISTRATION: NCT03338790.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Docetaxel/uso terapéutico , Nivolumab/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Estudios de Cohortes , Docetaxel/farmacología , Humanos , Masculino , Persona de Mediana Edad , Nivolumab/farmacologíaRESUMEN
BACKGROUND: Androgen deprivation therapy (ADT) combined with apalutamide, abiraterone acetate plus prednisone, enzalutamide, or docetaxel are the standard treatments for advanced castration-sensitive prostate cancer (CSPC). We investigated ADT-free alternatives for advanced CSPC. PATIENTS AND METHODS: LACOG 0415 is a phase 2, open-label, non-comparative, randomized trial. Patients with advanced CSPC were randomized (1:1:1) to receive goserelin plus abiraterone acetate and prednisone (ADT plus AAP arm), apalutamide (APA arm), or apalutamide plus abiraterone acetate and prednisone (APA plus AAP arm). The primary endpoint was the proportion of patients with PSA of ≤0.2 ng/mL at week 25 in the modified intention-to-treat population. Safety analyses were performed in all patients with at least one dose of the study drug. RESULTS: Of 128 randomized patients, 120 patients were evaluable for PSA response at week 25; 17.2% had a high-risk biochemical recurrence, 8.6% had locally advanced disease, and 74.2% had distant metastases. At week 25, PSA of ≤0.2 ng/mL was observed in 75.6% (95%CI 59.7%-87.6%), 60.0% (95%CI 43.3%-75.1%), and 79.5% (95%CI 63.5%-90.7%) of patients in ADT plus AAP, APA, and APA plus AAP arms, respectively. PSA decline of ≥80% was observed in 100%, 90.0%, and 97.4%, respectively. Grade 3-4 AEs were observed in 31.0%, 21.4% and 36.4%, respectively. Testosterone levels increased significantly in the APA arm and decreased significantly in ADT plus AAP and APA plus AAP arms. CONCLUSIONS: ADT-free alternatives provide a high PSA response in advanced CSPC, although the APA arm did not reach the expected rate of PSA of ≤0.2 ng/mL at week 25. These results warrant further investigation of ADT-free treatments as alternatives in advanced CSPC. SOURCE STUDY REGISTRATION: ClinicalTrials.govNCT02867020.
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The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has evolved considerably with the introduction of newer agents, such as poly-ADP ribose polymerase (PARP) inhibitors targeting DNA damage repair mutations. Combining and sequencing novel and existing therapies appropriately is necessary for optimizing the management of mCRPC and ensuring better treatment outcomes. The purpose of this review is to provide evidence-based answers to key clinical questions on treatment selection, treatment sequencing patterns, and factors influencing treatment decisions in the management of mCRPC in the era of PARP inhibitors. This article can also serve as a comprehensive guide to clinicians for optimizing genetic testing and counseling and management of patients with mCRPC. Although the PROfound study has validated the concept of PARP sensitivity across multiple genes associated with homologous recombination repair (HRR) in mCRPC and highlighted the importance of genomic testing in this at-risk patient population, it still remains unclear how patients with rarer HRR mutations will respond to PARP inhibitors. Therefore, real-world data obtained through registry-based randomized controlled trials in the future may help produce robust scientific evidence for supporting optimal clinician decision-making in the management of mCRPC.
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PURPOSE: COVID-19 has affected cancer care worldwide. Clinical trials are an important alternative for the treatment of oncologic patients, especially in Latin America, where trials can be the only opportunity for some of them to access novel and, sometimes, standard treatments. METHODS: This was a cross-sectional study, in which a 22-question survey regarding the impact of the COVID-19 pandemic on oncology clinical trials was sent to 350 representatives of research programs in selected Latin American institutions, members of the Latin American Cooperative Oncology Group. RESULTS: There were 90 research centers participating in the survey, with 70 of them from Brazil. The majority were partly private or fully private (n = 77; 85.6%) and had confirmed COVID-19 cases at the institution (n = 57; 63.3%). Accruals were suspended at least for some studies in 80% (n = 72) of the responses, mostly because of sponsors' decision. Clinical trials' routine was affected by medical visits cancelation, reduction of patients' attendance, reduction of other specialties' availability, and/or alterations on follow-up processes. Formal COVID-19 mitigation policies were adopted in 96.7% of the centers, including remote monitoring and remote site initiation visits, telemedicine visits, reduction of research team workdays or home office, special consent procedures, shipment of oral drugs directly to patients' home, and increase in outpatient diagnostic studies. Importantly, some of these changes were suggested to be part of future oncology clinical trials' routine, particularly the ones regarding remote methods, such as telemedicine. CONCLUSION: To our knowledge, this was the first survey to evaluate the impact of COVID-19 on Latin American oncology clinical trials. The results are consistent with surveys from other world regions. These findings may endorse improvements in clinical trials' processes and management in the postpandemic period.
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Investigación Biomédica/tendencias , COVID-19 , Oncología Médica/tendencias , Brasil , Ensayos Clínicos como Asunto , Estudios Transversales , Humanos , América Latina/epidemiología , PandemiasRESUMEN
PURPOSE: To present a summary of the treatment and follow-up recommendations for the biochemical recurrence in castration-sensitive prostate cancer (PCa) acquired through a questionnaire administered to 99 PCa experts from developing countries during the Prostate Cancer Consensus Conference for Developing Countries. METHODS: A total of 27 questions were identified as related to this topic from more than 300 questions. The clinician's responses were tallied and presented in a percentage format. Topics included the use of imaging for staging biochemical recurrence, treatment recommendations for three different clinical scenarios, the field of radiation recommended, and follow-up. Each question had 5-7 relevant response options, including "abstain" and/or "unqualified to answer," and investigated not only recommendations but also if a limitation in resources would change the recommendation. RESULTS: For most questions, a clear majority (> 50%) of clinicians agreed on a recommended treatment for imaging, treatment scenarios, and follow-up, although only a few topics reached a consensus > 75%. Limited resources did affect several areas of treatment, although in many cases, they reinforced more stringent criteria for treatment such as prostate-specific antigen values > 0.2 ng/mL and STAMPEDE inclusion criteria as a basis for recommending treatment. CONCLUSION: A majority of clinicians working in developing countries with limited resources use similar cutoff points and selection criteria to manage patients treated for biochemically recurrent castration-sensitive PCa.
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Países en Desarrollo , Neoplasias de la Próstata , Castración , Consenso , Estudios de Seguimiento , Humanos , Masculino , Neoplasias de la Próstata/terapiaRESUMEN
BACKGROUND: The role of extended pelvic lymph node dissection (EPLND) in the surgical management of prostate cancer (PCa) patients remains controversial, mainly because of a lack of randomized controlled trials (RCTs). OBJECTIVE: To determine whether EPLND has better oncological outcomes than limited PLND (LPLND. DESIGN, SETTING AND PARTICIPANTS: This was a prospective, single-center phase 3 trial in patients with intermediate- or high-risk clinically localized PCa. INTERVENTION: Randomization (1:1) to LPLND (obturator nodes) or EPLND (obturator, external iliac, internal iliac, common iliac, and presacral nodes) bilaterally. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was biochemical recurrence-free survival (BRFS). Secondary outcomes were metastasis-free survival (MFS), cancer-specific survival (CSS), and histopathological findings. The trial was designed to show a minimal 15% advantage in 5-yr BRFS by EPLND. RESULTS AND LIMITATIONS: In total, 300 patients were randomized from May 2012 to December 2016 (150 LPLND and 150 EPLND). The median BRFS was 61.4 mo in the LPLND group and not reached in the EPLND group (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.63-1.32; p = 0.6). Median MFS was not reached in either group (HR 0.57, 95% CI 0.17-1.8; p = 0.3). CSS data were not available because no patient died from PCa before the cutoff date. In exploratory subgroup analysis, patients with preoperative biopsy International Society of Urological Pathology (ISUP) grade groups 3-5 who were allocated to EPLND had better BRFS (HR 0.33, 95% CI 0.14-0.74, interaction p = 0.007). The short follow-up and surgeon heterogeneity are limitations to this study. CONCLUSION: This RCT confirms that EPLND provides better pathological staging, while differences in early oncological outcomes were not demonstrated. Our subgroup analysis suggests a potential BCRFS benefit in patients diagnosed with ISUP grade groups 3-5; however, these findings should be considered hypothesis-generating and further RCTs with larger cohorts and longer follow up are necessary to better define the role of EPLND during RP. PATIENT SUMMARY: In this study, we investigated early outcomes in prostate cancer patients undergoing prostatectomy according to the anatomic extent of lymph node resection. We found that extended removal of lymph nodes did not reduce biochemical recurrence of prostate cancer in the expected range.
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Prostatectomía , Neoplasias de la Próstata , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Masculino , Pelvis , Próstata , Neoplasias de la Próstata/cirugíaRESUMEN
INTRODUCTION: Cancer patients may have a higher risk of severe events and unfavourable outcomes in the setting of COVID-19. This review addresses the question of whether to test asymptomatic cancer patients before initiating systemic cancer treatments. METHODS: This systematic review was conducted based on the PRISMA framework. Pubmed, Embase, Web of Science and Cochrane Central Register of Controlled Trials were systematically searched, as well as guidelines from international institutions involved in cancer care and COVID-19 research. Studies published in English, from 1 December 2019 to 27 May 2020 were considered eligible. We included studies which mentioned testing strategies for SARS-CoV-2 of asymptomatic cancer patients before starting immunosuppressive treatments. RESULTS: We identified 1,163 studies and 4 guidelines through the literature search. A total of 18 articles were considered eligible and were included in the final analysis. Two articles were cohort studies, and the remaining were expert consensuses and published guidelines. The most common recommendation among the studies in this systematic review was to test asymptomatic patients for SARS-CoV-2 prior to treatment. CONCLUSION: There is a lack of studies which directly address COVID-19 testing of asymptomatic patients before treatment. Our systematic review showed that most of the published data favours routine test for SARS-CoV-2 before initiating systemic treatment but failed to identify a good level of evidence to support these recommendations. Based upon this review, we proposed local recommendations at our centre. Each institution should consider the pros and cons of testing asymptomatic patients, evaluating accessibility to testing resources and local epidemiology.
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Therapy response assessment is a critical step in cancer management, leading clinicians to optimize the use of therapeutic options during the course of the disease. Imaging is a pivotal biomarker for therapy response evaluation in oncology and has gained wider use through the development of reproducible data-based guidelines, of which the Response Evaluation Criteria in Solid Tumors is the most successful example. Disease-specific criteria have also been proposed, and the Prostate Cancer Working Group 3 criteria are the mainstay for prostate cancer (PC). However, conventional imaging evaluation in metastatic PC has several limitations, including (a) the inability to detect small-volume disease, (b) the high prevalence of bone (nonmeasurable) lesions at imaging, and (c) the established role of serum prostate-specific antigen (PSA) levels as the biomarker of choice for response assessment and disease progression. In addition, there are an increasing number of newer treatment options with various effects on imaging features. Prostate-specific membrane antigen (PSMA) PET has improved patient selection for newer treatments, such as metastasis-directed therapy (MDT) or radionuclide therapy. The role of PSMA PET in response assessment for many metastatic PC therapeutic options (MDT, androgen deprivation therapy, chemotherapy, radionuclide therapy, and immunotherapy) is an evolving issue, with emerging data showing good correlation with PSA levels and clinical outcome. However, there are specific implications of each therapy (especially androgen deprivation therapy and immunotherapy) on PSMA expression by PC cells, leading to potential pitfalls and inaccuracies that must be known by radiologists. Despite some limitations, PSMA PET is addressing gaps left by conventional imaging methods (eg, CT and bone scanning) and nonimaging biomarkers (PSA levels) in metastatic PC therapy response assessment, a role that can be improved with advances like refinement of interpretation criteria and whole-body tumor burden quantification.© RSNA, 2020See discussion on this article by Barwick and Castellucci.
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Tomografía de Emisión de Positrones , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/diagnóstico por imagen , Biomarcadores de Tumor , Humanos , Masculino , Metástasis de la Neoplasia , Selección de Paciente , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Radiofármacos , Criterios de Evaluación de Respuesta en Tumores SólidosRESUMEN
BACKGROUND: The objective of this study was to determine the outcomes of young adults with kidney cancer treated during the targeted therapy era and evaluate the impact of young age on survival. MATERIALS AND METHODS: We reviewed the records from 445 patients younger than 55 years with kidney cancer at a single institution from 2006 to 2017. Overall survival (OS) and recurrence-free survival were estimated with the Kaplan-Meier method and log-rank test. Cox proportional hazards regression was used to determine the impact of clinical and pathologic variables on all-cause mortality. RESULTS: Overall, 104 (23%) patients 40 years or younger were compared with 341 (77%) patients who were 41 to 55 years old. Younger patients presented with more advanced stages of the disease, including metastasis at diagnosis, positive lymph nodes, venous tumor thrombus and had more non-clear cell tumors (54% vs. 30%; P < .001). Young adults had significantly worse OS at 2 and 5 years (67% vs. 82% and 53% vs. 69%, respectively). Younger patients with metastatic disease received targeted agents less often compared with the older group (64% vs. 75%). There was no difference in recurrence-free survival across patients with localized disease. Independent prognostic factors associated with increased mortality were metastasis at diagnosis, pT2 or greater, and age younger than 40 years (hazard ratio, 1.65; 95% confidence interval, 1.0-2.6; P = .03). CONCLUSION: Patients younger than 40 years with kidney tumors treated during the targeted therapy era have worse OS compared with older adults. Young age is an independent predictor of mortality.
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Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Metástasis Linfática/tratamiento farmacológico , Terapia Molecular Dirigida/estadística & datos numéricos , Recurrencia Local de Neoplasia/epidemiología , Inhibidores de Proteínas Quinasas/uso terapéutico , Adolescente , Adulto , Factores de Edad , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/secundario , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Indazoles , Estimación de Kaplan-Meier , Riñón/patología , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida/métodos , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Pronóstico , Pirimidinas/uso terapéutico , Estudios Retrospectivos , Factores de Riesgo , Sulfonamidas/uso terapéutico , Sunitinib/uso terapéutico , Adulto JovenRESUMEN
The treatment landscape of advanced prostate cancer continues to evolve rapidly, with newer and more active drugs being used in earlier phases of the disease based on improved overall survival. After adoption of docetaxel for metastatic castration-sensitive disease, large trials with next-generation androgen receptor-signaling inhibitors (abiraterone, enzalutamide and apalutamide) have demonstrate significant improvements in survival and important secondary endpoints. For non-metastatic castration-resistant prostate cancer, recent phase III placebo-controlled trials with enzalutamide, apalutamide and darolutamide all demonstrated benefits in improving metastasis-free survival. This review aims to summarize the clinical development of darolutamide, a novel next-generation androgen receptor antagonist, including preclinical data, clinical studies and the potential of darolutamide for the treatment of advanced prostate cancer. To date, darolutamide efficacy and tolerability has been demonstrated in the ARAMIS trial, which demonstrated an improvement in metastasis-free survival compared to placebo for non-metastatic castration-resistant prostate cancer patients with a rapid PSA doubling time. Ongoing studies will further evaluate the role of darolutamide in metastatic castration-sensitive prostate cancer in combination with docetaxel (ARASENS trial) and also in other stages of the disease.
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INTRODUCTION: Non-clear cell renal cell carcinoma (nccRCC) and sarcomatoid renal cell carcinoma (sRCC) are underrepresented in clinical trials. Treatment approaches are frequently extrapolated from data of clear cell renal cell carcinoma, in which pazopanib is non-inferior to sunitinib. We aim to compare the effectiveness of first-line sunitinib and pazopanib for nccRCC and sRCC. METHODS: We evaluated a retrospective cohort of patients with metastatic nccRCC and sRCC treated with first-line sunitinib or pazopanib at an academic cancer centre. Overall survival (OS), progression-free survival (PFS) and response rate were measured. Kaplan-Meier and log-rank analyses were used for time-to-event data. Cox regression was used for prognostic factors. RESULTS: Fifty-three patients were included; 16 (30.1%) treated with sunitinib and 37 (69.9%) with pazopanib. Forty-six (86.8%) patients had nccRCC and 7 (13.2%) had sRCC. The majority had intermediate or poor International Metastatic Renal-Cell Carcinoma Database Consortium risk (93%).Median PFS was 6.6 months with sunitinib and 4.9 months with pazopanib (HR 1.75; P = 0.078). Treatment with pazopanib was associated with inferior OS in comparison with sunitinib (median OS: 30.4 months versus 8.7 months; HR 2.71, 95% CI 1.31-5.58, P = 0.007). These results were confirmed in subgroup analysis of patients with papillary, chromophobe and MiT family translocation histologies (median OS: 38.7 months versus 14.7 months; HR 3.16, 95% CI 1.20-8.29, P = 0.019). Unclassified and sarcomatoid histologies had inferior OS (median: 6.9 and 1.1 months, respectively) regardless of the treatment used. CONCLUSION: In this patient cohort, pazopanib was associated with inferior OS in comparison with sunitinib for metastatic nccRCC. Larger trials are ideally warranted to confirm these results.