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2.
Eur J Endocrinol ; 186(1): 9-23, 2021 Nov 30.
Artículo en Inglés | MEDLINE | ID: covidwho-2325951

RESUMEN

OBJECTIVE: Indirect evidence suggests that the effects of testosterone on fat mass in men are dependent on aromatization to estradiol (E2). However, no controlled study has assessed the effects of E2 in the absence of testosterone. DESIGN: Six-month randomized, placebo-controlled trial with the hypothesis that men randomized to E2 would reduce their fat mass. METHODS: Seventy-eight participants receiving androgen deprivation therapy for prostate cancer were randomized to 0.9 mg of 0.1% E2 gel per day, or matched placebo. Dual x-ray absorptiometry body composition was measured at baseline, month 3, and month 6. The primary outcome was total fat mass. RESULTS: Serum E2 increased in the estradiol group over 6 months compared to placebo, and mean-adjusted difference (MAD) was 207 pmol/L (95% CI: 123-292), P < 0.001. E2 treatment changed total fat mass, MAD 1007 g (95% CI: 124-1891), but not significantly, so P = 0.09. There were other consistent non-significant trends toward increased proportional fat mass, MAD 0.8% (95% CI: 0.0-1.6), P= 0.15; gynoid fat, MAD 147 g (95% CI: 2-293), P = 0.08; visceral fat, 53 g (95% CI: 1-105) P = 0.13; and subcutaneous fat, MAD 65 g (95% CI: 5-125), P = 0.11. Android fat increased, MAD 164 g (95% CI: 41-286), P = 0.04. CONCLUSION: Contrary to our hypothesis, we provide suggestive evidence that E2 acting in the absence of testosterone, may increase total and regional fat mass in men. Given the premature closure of clinical trials due to the COVID pandemic, this potentially important observation should encourage additional studies to confirm or refute whether E2 promotes fat expansion in the absence of testosterone.


Asunto(s)
Tejido Adiposo/efectos de los fármacos , Antagonistas de Andrógenos/uso terapéutico , Estradiol/farmacología , Absorciometría de Fotón , Anciano , Antagonistas de Andrógenos/efectos adversos , Australia , Composición Corporal/efectos de los fármacos , Método Doble Ciego , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/tratamiento farmacológico
3.
Clin Genitourin Cancer ; 21(2): 273-277, 2023 04.
Artículo en Inglés | MEDLINE | ID: covidwho-2245445

RESUMEN

BACKGROUND: In metastatic hormone sensitive prostate cancer (mHSPC), treatment intensification with either docetaxel or an androgen-receptor-axis targeted therapy (ARAT), added to androgen deprivation therapy (ADT) is the new standard of care. To better understand patterns of treatment intensification in Canada and specifically how it has been influenced by the COVID-19 pandemic, we conducted a national survey of genitourinary medical oncologists from across Canada. METHODS: Using SurveyMonkey, we conducted an online survey of 119 medical oncologists in Canada from January 15 to January 27, 2021. The survey consisted of 16 questions, including demographics, and asked specifically about their approach to managing mHSPC before and during the pandemic. RESULTS: Overall there were 50/119 (42%) respondents. Most were male (65%), from Ontario (35%), practicing in academic centers (71%), with 45% reporting their practices focused primarily on genitourinary malignancies and one other tumor site. The majority were in practice 1 to 5 years (34%). Overall 65% indicated their practice patterns had changed since the pandemic, with 51% offering more ARATs and less docetaxel chemotherapy. In low volume mHSPC, the use of ARATs increased from 73% to 79%, while the use of docetaxel remained unaltered at 2%. In high volume disease, the use of ARATs increased from 63% to 84%, while the use of docetaxel decreased from 37% to 14%. Use of granulocyte colony stimulating factor (G-CSF) with docetaxel chemotherapy increased by 35%. Post-pandemic, 45% reported they intend to maintain these changes. Only 18% reported they had prostate cancer patients test positive for COVID-19, and all patients recovered. CONCLUSION: Management of patients with mHSPC in Canada has changed during the pandemic, with increased uptake of ARATs and reduced use of docetaxel, a trend expected to continue beyond the pandemic. How this trend will impact uptake of triplet therapy (ADT + ARAT + Docetaxel), downstream treatment choices and overall outcomes remains to be seen.


Asunto(s)
COVID-19 , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/patología , Docetaxel/uso terapéutico , Pandemias , Antagonistas de Andrógenos/uso terapéutico , Andrógenos , COVID-19/epidemiología , Canadá/epidemiología , Resultado del Tratamiento
4.
Viruses ; 14(12)2022 12 07.
Artículo en Inglés | MEDLINE | ID: covidwho-2155307

RESUMEN

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), is estimated to have caused over 6.5 million deaths worldwide. The emergence of fast-evolving SARS-CoV-2 variants of concern alongside increased transmissibility and/or virulence, as well as immune and vaccine escape capabilities, highlight the urgent need for more effective antivirals to combat the disease in the long run along with regularly updated vaccine boosters. One of the early risk factors identified during the COVID-19 pandemic was that men are more likely to become infected by the virus, more likely to develop severe disease and exhibit a higher likelihood of hospitalisation and mortality rates compared to women. An association exists between SARS-CoV-2 infectiveness and disease severity with sex steroid hormones and, in particular, androgens. Several studies underlined the importance of the androgen-mediated regulation of the host protease TMPRSS2 and the cell entry protein ACE2, as well as the key role of these factors in the entry of the virus into target cells. In this context, modulating androgen signalling is a promising strategy to block viral infection, and antiandrogens could be used as a preventative measure at the pre- or early hospitalisation stage of COVID-19 disease. Different antiandrogens, including commercial drugs used to treat metastatic castration-sensitive prostate cancer and other conditions, have been tested as antivirals with varying success. In this review, we summarise the most recent updates concerning the use of antiandrogens as prophylactic and therapeutic options for COVID-19.


Asunto(s)
COVID-19 , Masculino , Humanos , Femenino , SARS-CoV-2/metabolismo , Antagonistas de Andrógenos/uso terapéutico , Andrógenos/fisiología , Pandemias , Peptidil-Dipeptidasa A/metabolismo , Antivirales/uso terapéutico
5.
Am J Mens Health ; 16(4): 15579883221115593, 2022.
Artículo en Inglés | MEDLINE | ID: covidwho-1993293

RESUMEN

Due to the COVID-19 pandemic, major congresses and many teaching opportunities as well as the usual visits from medical advisors of pharmaceutical firms have been postponed and canceled. The major trials of prostate cancer in the last 5 years in each state are shortly discussed providing a panoramic overview of the available evidence and data on prostate cancer treatment. Apalutamide, enzalutamide, and darolutamide have proven to have clinical benefits when added to androgen deprivation therapy for patients with nonmetastatic castration-resistant prostate cancer. In patients in the metastatic hormone-sensitive setting, next to docetaxel, abiraterone, enzalutamide, and apalutamide have been shown to significantly improve overall survival and progression-free survival in comparison to standard hormone therapy. In addition, docetaxel abiraterone and enzalutamide are widely used in the metastatic setting. For second-line therapy of metastasized prostate cancer patients who have received either docetaxel or abiraterone or enzalutamide, olaparib, cabazitaxel, radium, and lutetium therapy have been shown to be beneficial in selected patient groups.


Asunto(s)
COVID-19 , Neoplasias de la Próstata Resistentes a la Castración , Antagonistas de Andrógenos/uso terapéutico , Docetaxel/uso terapéutico , Hormonas , Humanos , Masculino , Pandemias , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Resultado del Tratamiento
8.
JNCI Cancer Spectr ; 6(3)2022 05 02.
Artículo en Inglés | MEDLINE | ID: covidwho-1878801

RESUMEN

BACKGROUND: TMPRSS2, a cell surface protease regulated by androgens and commonly upregulated in prostate cancer (PCa), is a necessary component for SARS-CoV-2 viral entry into respiratory epithelial cells. Previous reports suggested a lower risk of SARS-CoV-2 among PCa patients on androgen deprivation therapy (ADT). However, the impact of ADT on severe COVID-19 illness is poorly understood. METHODS: We performed a multicenter study across 7 US medical centers and evaluated patients with PCa and SARS-CoV-2 detected by polymerase-chain-reaction between March 1, 2020, and May 31, 2020. PCa patients were considered on ADT if they had received appropriate ADT treatment within 6 months of COVID-19 diagnosis. We used multivariable logistic and Cox proportional-hazard regression models for analysis. All statistical tests were 2-sided. RESULTS: We identified 465 PCa patients (median age = 71 years) with a median follow-up of 60 days. Age, body mass index, cardiovascular comorbidity, and PCa clinical disease state adjusted overall survival (hazard ratio [HR] = 1.16, 95% confidence interval [CI] = 0.68 to 1.98, P = .59), hospitalization status (HR = 0.96, 95% CI = 0.52 to 1.77, P = .90), supplemental oxygenation (HR 1.14, 95% CI = 0.66 to 1.99, P = .64), and use of mechanical ventilation (HR = 0.81, 95% CI = 0.25 to 2.66, P = .73) were similar between ADT and non-ADT cohorts. Similarly, the addition of androgen receptor-directed therapy within 30 days of COVID-19 diagnosis to ADT vs ADT alone did not statistically significantly affect overall survival (androgen receptor-directed therapy: HR = 1.27, 95% CI = 0.69 to 2.32, P = .44). CONCLUSIONS: In this retrospective cohort of PCa patients, the use of ADT was not demonstrated to influence severe COVID-19 outcomes, as defined by hospitalization, supplemental oxygen use, or death. Age 70 years and older was statistically significantly associated with a higher risk of developing severe COVID-19 disease.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Neoplasias de la Próstata , Anciano , Antagonistas de Andrógenos/uso terapéutico , Andrógenos/uso terapéutico , Prueba de COVID-19 , Humanos , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Receptores Androgénicos/uso terapéutico , Estudios Retrospectivos , SARS-CoV-2
9.
Am J Health Syst Pharm ; 79(15): 1224-1235, 2022 07 22.
Artículo en Inglés | MEDLINE | ID: covidwho-1778882

RESUMEN

PURPOSE: This article summarizes current androgen receptor (AR)-directed therapies that have received regulatory approval for the treatment of advanced prostate adenocarcinoma (herein referred to as prostate cancer, PC). SUMMARY: PC is an androgen-dependent malignancy in which ligands including testosterone and dihydrotestosterone bind to AR, initiating androgen-AR complex translocation to the nucleus followed by AR-mediated transcription of target genes. Androgen deprivation therapy (ADT), including gonadotropin hormone-releasing hormone (GnRH) agonists with or without AR antagonists (antiandrogens), GnRH antagonists, or bilateral orchiectomy, forms the backbone of treatment for patients with metastatic castration-naive PC and/or castration-resistant PC (CRPC). ADT is also an option for high-risk, early-stage PC after prostatectomy and/or radiation. While ADT is often very effective as initial therapy, resistance ultimately develops despite suppression of gonadal and/or adrenal androgens, leading to CRPC, which is characterized by mechanisms such as reactivation of the AR signaling pathway, AR gene overexpression, and mutations in the ligand-binding domain of AR that lead to disease progression, resulting in increased symptom burden and ultimately death. However, disease in patients with CRPC is still dependent on androgen signaling, and these patients continue on ADT to maintain a castrate level of serum testosterone. Novel hormonal therapies including agents that target AR directly (eg, AR antagonists) are often added to ADT in this setting. Targeting the AR signaling pathway led to the development of second-generation AR antagonists, examples of which include enzalutamide, apalutamide, and darolutamide. These agents do not exhibit partial agonism, possess a higher affinity for AR, and are postulated to improve survival outcomes relative to their first-generation counterparts for patients with CRPC. Lastly, the emergence of ADT, including second-generation AR antagonists, has led to the development of supportive care for treatment-related adverse effects. CONCLUSION: Major advances have been made in targeting the AR signaling pathway in patients with advanced PC. Further studies are warranted to identify the optimal sequencing of therapies to maximize treatment benefit. Mitigation of treatment-related adverse effects presents new opportunities to advance clinical pharmacy practice.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Receptores Androgénicos , Antagonistas de Andrógenos/uso terapéutico , Antagonistas de Receptores Androgénicos/uso terapéutico , Andrógenos/metabolismo , Hormona Liberadora de Gonadotropina/agonistas , Hormona Liberadora de Gonadotropina/antagonistas & inhibidores , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Transducción de Señal , Testosterona
10.
Eur Urol ; 82(1): 6-11, 2022 07.
Artículo en Inglés | MEDLINE | ID: covidwho-1768076

RESUMEN

Patients with advanced prostate cancer (APC) may be at greater risk for severe illness, hospitalisation, or death from coronavirus disease 2019 (COVID-19) due to male gender, older age, potential immunosuppressive treatments, or comorbidities. Thus, the optimal management of APC patients during the COVID-19 pandemic is complex. In October 2021, during the Advanced Prostate Cancer Consensus Conference (APCCC) 2021, the 73 voting members of the panel members discussed and voted on 13 questions on this topic that could help clinicians make treatment choices during the pandemic. There was a consensus for full COVID-19 vaccination and booster injection in APC patients. Furthermore, the voting results indicate that the expert's treatment recommendations are influenced by the vaccination status: the COVID-19 pandemic altered management of APC patients for 70% of the panellists before the vaccination was available but only for 25% of panellists for fully vaccinated patients. Most experts (71%) were less likely to use docetaxel and abiraterone in unvaccinated patients with metastatic hormone-sensitive prostate cancer. For fully vaccinated patients with high-risk localised prostate cancer, there was a consensus (77%) to follow the usual treatment schedule, whereas in unvaccinated patients, 55% of the panel members voted for deferring radiation therapy. Finally, there was a strong consensus for the use of telemedicine for monitoring APC patients. PATIENT SUMMARY: In the Advanced Prostate Cancer Consensus Conference 2021, the panellists reached a consensus regarding the recommendation of the COVID-19 vaccine in prostate cancer patients and use of telemedicine for monitoring these patients.


Asunto(s)
COVID-19 , Neoplasias de la Próstata , Antagonistas de Andrógenos/uso terapéutico , Vacunas contra la COVID-19 , Humanos , Masculino , Pandemias/prevención & control , Neoplasias de la Próstata/patología
12.
Clin Genitourin Cancer ; 20(2): 123-131, 2022 04.
Artículo en Inglés | MEDLINE | ID: covidwho-1654189

RESUMEN

BACKGROUND: Prostate stereotactic body radiotherapy (SBRT), which delivers high-dose precision treatment in ≤5 fractions, is a shorter, more convenient, and less expensive alternative to conventionally fractionated radiotherapy (CRFT; ∼44 fractions) or moderately hypofractionated radiotherapy (MFRT; 20-28 fractions). SBRT has not been widely adopted but may have radiobiologic advantages over CFRT/MFRT. We hypothesized that SBRT would be associated with improved overall survival (OS) versus CFRT or MFRT ± androgen deprivation therapy (ADT) for unfavorable-intermediate-risk prostate cancer (UIR-PCa). METHODS: Men with UIR-PCa treated with SBRT (35-40Gy in ≤5 fractions) or biologically equivalent doses of CFRT (72-86.4Gy in 1.8-2.0Gy/fraction) or MRFT (≥60Gy in 2.4-3.2Gy/fraction; biologically effective doses ≥120) were identified in the National Cancer Database (NCDB). Unweighted and propensity-weighted multivariable Cox analysis (MVA) was used to compare OS hazard ratios. RESULTS: Of 28,028 men with UIR-PCa who received CFRT with (n = 12,872) or without ADT (n = 12,984); MFRT with (n = 251) or without ADT (n = 281); and SBRT with (n = 212) or without ADT (n = 1,428) were identified. Relative to CFRT without ADT, CFRT+ ADT (HR 0.92, 95% CI 0.87-0.97, P = .002) and SBRT without ADT (HR 0.74, 95% CI 0.61-0.89, P = .002) were both associated with improved OS on MVA. Relative to CFRT+ADT, SBRT without ADT correlated with improved OS on MVA (HR:0.81, 95% CI 0.67-0.99, P = .04). Propensity-weighted MVA demonstrated that SBRT (HR:0.80, 95% CI 0.65-0.98, P = .036) and ADT (HR:0.91, 95% CI 0.86-0.97, P = .002) correlated with improved OS. SBRT was not associated with improved OS versus MFRT. CONCLUSION: SBRT, which offers a cheaper and shorter treatment course that mitigates COVID-19 exposure, was associated with improved OS versus CFRT for UIR-PCa. These results confirm guideline-based recommendations that SBRT is a viable option for UIR prostate cancer. The results from this large retrospective study require further validation in clinical trials.


Asunto(s)
COVID-19 , Neoplasias de la Próstata , Radiocirugia , Antagonistas de Andrógenos/uso terapéutico , Humanos , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Radiocirugia/métodos , Estudios Retrospectivos , Análisis de Supervivencia
13.
Scand J Urol ; 56(2): 104-111, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: covidwho-1585249

RESUMEN

BACKGROUND: Androgens facilitate entrance of the severe acute respiratory syndrome coronavirus 2 into respiratory epithelial cells, and male sex is associated with a higher risk of death from corona virus disease (COVID-19). Androgen deprivation therapy (ADT) could possibly improve COVID-19 outcomes. METHODS: In a case-control study nested in the Prostate Cancer data Base Sweden (PCBaSe) RAPID 2019, we evaluated the association between ADT and COVID-19 as registered cause of death in men with prostate cancer. Each case was matched to 50 controls by region. We used conditional logistic regression to adjust for confounders and also evaluated potential impact of residual confounding. RESULTS: We identified 474 men who died from COVID-19 in March-December 2020. In crude analyses, ADT exposure was associated with an increased risk of COVID-19 death (odds ratio [OR] 5.05, 95% CI: 4.18-6.10); however, the OR was substantially attenuated after adjustment for age, comorbidity, prostate cancer characteristics at diagnosis, recent healthcare use, and indicators of advanced cancer (adjusted OR 1.25, 95% CI: 0.95-1.65). If adjustment has accounted for at least 85% of confounding, then the true effect could be no more than a 5% reduction of the odds for COVID-19 death. CONCLUSIONS: The increased mortality from COVID-19 in men with prostate cancer treated with ADT was mainly related to high age, comorbidity, and more advanced prostate cancer. There was no evidence to support the hypothesis that ADT is associated with improved COVID-19 outcomes.


Asunto(s)
COVID-19 , Neoplasias de la Próstata , Antagonistas de Andrógenos/uso terapéutico , Andrógenos , Estudios de Casos y Controles , Comorbilidad , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/tratamiento farmacológico
14.
Eur Urol ; 81(3): 285-293, 2022 03.
Artículo en Inglés | MEDLINE | ID: covidwho-1568696

RESUMEN

BACKGROUND: Men are more severely affected by COVID-19. Testosterone may influence SARS-CoV-2 infection and the immune response. OBJECTIVE: To clinically, epidemiologically, and experimentally evaluate the effect of antiandrogens on SARS-CoV-2 infection. DESIGNS, SETTINGS, AND PARTICIPANTS: A randomized phase 2 clinical trial (COVIDENZA) enrolled 42 hospitalized COVID-19 patients before safety evaluation. We also conducted a population-based retrospective study of 7894 SARS-CoV-2-positive prostate cancer patients and an experimental study using an air-liquid interface three-dimensional culture model of primary lung cells. INTERVENTION: In COVIDENZA, patients were randomized 2:1 to 5 d of enzalutamide or standard of care. OUTCOME MEASUREMENTS: The primary outcomes in COVIDENZA were the time to mechanical ventilation or discharge from hospital. The population-based study investigated risk of hospitalization, intensive care, and death from COVID-19 after androgen inhibition. RESULTS AND LIMITATIONS: Enzalutamide-treated patients required longer hospitalization (hazard ratio [HR] for discharge from hospital 0.43, 95% confidence interval [CI] 0.20-0.93) and the trial was terminated early. In the epidemiological study, no preventive effects were observed. The frail population of patients treated with androgen deprivation therapy (ADT) in combination with abiraterone acetate or enzalutamide had a higher risk of dying from COVID-19 (HR 2.51, 95% CI 1.52-4.16). In vitro data showed no effect of enzalutamide on virus replication. The epidemiological study has limitations that include residual confounders. CONCLUSIONS: The results do not support a therapeutic effect of enzalutamide or preventive effects of bicalutamide or ADT in COVID-19. Thus, these antiandrogens should not be used for hospitalized COVID-19 patients or as prevention for COVID-19. Further research on these therapeutics in this setting are not warranted. PATIENT SUMMARY: We studied whether inhibition of testosterone could diminish COVID-19 symptoms. We found no evidence of an effect in a clinical study or in epidemiological or experimental investigations. We conclude that androgen inhibition should not be used for prevention or treatment of COVID-19.


Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , Anilidas/uso terapéutico , Benzamidas/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Nitrilos/uso terapéutico , Feniltiohidantoína/uso terapéutico , SARS-CoV-2/aislamiento & purificación , Compuestos de Tosilo/uso terapéutico , Anciano , Anciano de 80 o más Años , Andrógenos/uso terapéutico , COVID-19/diagnóstico , COVID-19/epidemiología , Prueba de Ácido Nucleico para COVID-19 , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Suecia/epidemiología , Testosterona , Resultado del Tratamiento
15.
JAMA Netw Open ; 4(11): e2134330, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: covidwho-1513769

RESUMEN

Importance: Androgen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissue-based expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2). Objective: To examine whether ADT is associated with a decreased rate of 30-day mortality from SARS-CoV-2 infection among patients with prostate cancer. Design, Setting, and Participants: This cohort study analyzed patient data recorded in the COVID-19 and Cancer Consortium registry between March 17, 2020, and February 11, 2021. The consortium maintains a centralized multi-institution registry of patients with a current or past diagnosis of cancer who developed COVID-19. Data were collected and managed using REDCap software hosted at Vanderbilt University Medical Center in Nashville, Tennessee. Initially, 1228 patients aged 18 years or older with prostate cancer listed as their primary malignant neoplasm were included; 122 patients with a second malignant neoplasm, insufficient follow-up, or low-quality data were excluded. Propensity matching was performed using the nearest-neighbor method with a 1:3 ratio of treated units to control units, adjusted for age, body mass index, race and ethnicity, Eastern Cooperative Oncology Group performance status score, smoking status, comorbidities (cardiovascular, pulmonary, kidney disease, and diabetes), cancer status, baseline steroid use, COVID-19 treatment, and presence of metastatic disease. Exposures: Androgen deprivation therapy use was defined as prior bilateral orchiectomy or pharmacologic ADT administered within the prior 3 months of presentation with COVID-19. Main Outcomes and Measures: The primary outcome was the rate of all-cause 30-day mortality after COVID-19 diagnosis for patients receiving ADT compared with patients not receiving ADT after propensity matching. Results: After exclusions, 1106 patients with prostate cancer (before propensity score matching: median age, 73 years [IQR, 65-79 years]; 561 (51%) self-identified as non-Hispanic White) were included for analysis. Of these patients, 477 were included for propensity score matching (169 who received ADT and 308 who did not receive ADT). After propensity matching, there was no significant difference in the primary end point of the rate of all-cause 30-day mortality (OR, 0.77; 95% CI, 0.42-1.42). Conclusions and Relevance: Findings from this cohort study suggest that ADT use was not associated with decreased mortality from SARS-CoV-2 infection. However, large ongoing clinical trials will provide further evidence on the role of ADT or other androgen-targeted therapies in reducing COVID-19 infection severity.


Asunto(s)
Antagonistas de Andrógenos/efectos adversos , COVID-19/complicaciones , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/mortalidad , Anciano , Anciano de 80 o más Años , Antagonistas de Andrógenos/uso terapéutico , COVID-19/epidemiología , COVID-19/mortalidad , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/epidemiología , Factores de Riesgo , Tennessee/epidemiología
16.
Urology ; 155: 179-185, 2021 09.
Artículo en Inglés | MEDLINE | ID: covidwho-1411044

RESUMEN

OBJECTIVE: To determine the attitudes and education regarding surgical castration in men receiving androgen deprivation therapy (ADT) for metastatic prostate cancer (mCaP). METHODS: We identified 142 patients receiving ADT for mCaP at our institution without prior orchiectomy who were then sent 2 surveys via mail: (1) A questionnaire to assess knowledge and understanding of ADT treatment alternatives and (2) the functional assessment of cancer therapy - prostate (FACT-P) questionnaire which determines health-related quality of life (HRQOL). Two cohorts were created based on the answer to "would you be interested in surgical orchiectomy?" and demographic, CaP and HRQOL were compared between the surgical castration yes (SC+) and surgical castration no (SC-) cohorts. A second analysis identified predictors of worse HRQOL. RESULTS: Of 68 (47.9%) patients that responded to the survey, only 39 (59.1%) recalled a discussion regarding treatment alternatives to ADT and only 22 (33.3%) recalled a discussion regarding orchiectomy. There were 24 (40.0%) patients that stated interest in undergoing orchiectomy (SC+) as an alternative to ADT with the only independent risk factor being "…bother from the number of clinical appointments required for ADT…" Patients most bothered by side effects and cosmetic changes associated with ADT reported lower HRQOL scores on the FACT-P. CONCLUSIONS: Few men on ADT knew about surgical alternatives, implying that educational deficits may be a significant factor in the decline in the utilization of orchiectomy. Changes in healthcare economics, utilization and delivery brought on by a global pandemic should warrant a fresh look at the use of surgical castration.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Orquiectomía/psicología , Neoplasias de la Próstata/terapia , Calidad de Vida , Anciano , Antagonistas de Andrógenos/uso terapéutico , Humanos , Masculino , Metástasis de la Neoplasia , Aceptación de la Atención de Salud , Educación del Paciente como Asunto , Neoplasias de la Próstata/patología , Encuestas y Cuestionarios
17.
Prostate ; 81(16): 1349-1354, 2021 12.
Artículo en Inglés | MEDLINE | ID: covidwho-1404607

RESUMEN

BACKGROUND: The TMPRSS2 protein has been involved in severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2). The production is regulated by the androgen receptor (AR). It is speculated that androgen deprivation therapy (ADT) may protect patients affected by prostate cancer (PC) from SARS-CoV-2 infection. METHODS: This is a retrospective study of patients treated for COVID-19 in our institution who had a previous diagnosis of PC. We analyzed the influence of exposure of ADT on the presence of severe course of COVID-19. RESULTS: A total of 2280 patients were treated in our center for COVID-19 with a worse course of disease in males (higher rates of hospitalization, intense care unit [ICU] admission, and death). Out of 1349 subjects registered in our PC database, 156 were on ADT and 1193 were not. Out of those, 61 (4.52%) PC patients suffered from COVID-19, 11 (18.0%) belonged to the ADT group, and 50 (82.0%) to the non-ADT group. Regarding the influence of ADT on the course of the disease, statistically significant differences were found neither in the death rate (27.3% vs. 34%; p = 0.481), nor in the presence of severe COVID-19: need for intubation or ICU admission (0% vs. 6.3%; p = 0.561) and need for corticoid treatment, interferon beta, or tocilizumab (60% vs. 34.7%; p = 0.128). Multivariate analysis adjusted for clinically relevant comorbidities did not find that ADT was a protective factor for worse clinical evolution (risk ratio [RR] 1.08; 95% confidence interval [CI], 0.64-1.83; p = 0.77) or death (RR, 0.67; 95% CI, 0.26-1.74; p = 0.41). CONCLUSIONS: Our study confirms that COVID-19 is more severe in men. However, the use of ADT in patients with PC was not shown to prevent the risk of severe COVID-19.


Asunto(s)
Antagonistas de Andrógenos/uso terapéutico , COVID-19/epidemiología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/epidemiología , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Anciano , Anciano de 80 o más Años , COVID-19/mortalidad , COVID-19/terapia , Comorbilidad , Hospitalización/estadística & datos numéricos , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Factores de Riesgo
18.
World J Urol ; 40(4): 907-914, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: covidwho-1391851

RESUMEN

PURPOSE: Androgen-regulated enzymes such as the angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are involved in the SARS-CoV-2 infection process. The expression of TMPRSS2 and its fusion gene, which are increased in the epithelium of the human prostate gland during prostate carcinogenesis, are regulated by androgens. Our goal was to assess the risk of the SARS-CoV-2 infection and the severity of the disease in PCa patients treated with androgen deprivation therapy (ADT). METHODS: We conducted a systematic review and meta-analysis according to PRISMA guidelines. We queried PubMed and Web of Science databases on 1 July 2021. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to Cochrane's Q test and I2 statistic, respectively. RESULTS: Six retrospective studies (n = 50,220 patients) were selected after considering inclusion and exclusion criteria for qualitative evidence synthesis. Four retrospective studies were included to assess the SARS-CoV-2 infection risk in PCa patients under ADT vs. no ADT and the summarized risk ratio (RR) was 0.8 (95% confidence intervals (CI) 0.44-1.47). Five retrospective studies were included to assess the severity of coronavirus disease 2019 (COVID-19) in PCa patients under ADT versus no ADT and the summarized RR was 1.23 (95% CI 0.9-1.68). CONCLUSION: We found a non-significant association between the risk of SARS-CoV-2 infection and COVID-19 severity in PCa patients treated with ADT. However, our results suggest that during the COVID-19 pandemic PCa patients can safely undergo ADT as a cancer therapy without worsening COVID-19 risk and trajectory.


Asunto(s)
COVID-19 , Neoplasias de la Próstata , Antagonistas de Andrógenos/uso terapéutico , Andrógenos , Humanos , Masculino , Pandemias , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/epidemiología , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2 , Índice de Severidad de la Enfermedad
19.
Clin Dermatol ; 39(1): 76-83, 2021.
Artículo en Inglés | MEDLINE | ID: covidwho-1300693

RESUMEN

As of July 9, 2020, there were more than 12 million confirmed cases of coronavirus disease 2019 (COVID-19) across the globe, with more than 550,000 deaths. Many European countries, including Belgium, the United Kingdom, Italy, and Spain, have had the highest numbers of fatalities per capita. This indicates the potential for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus to overwhelm even the most advanced health care systems despite extreme societal interventions. Since its emergence, SARS-CoV-2 has disseminated across the globe, affecting the structure of global societies, infrastructure, and economies. Patients with alopecia are a diverse group who, for various indications, are prescribed a number of antimicrobials and antiandrogen treatments in addition to immunomodulatory therapies such as hydroxychloroquine, oral corticosteroids, and a range of broad immunosuppressants. These drugs are being scrutinized for their capacity to potentially affect SARS-CoV-2 outcomes. We examine these treatments and highlight the critical role that patient registries will play in generating real-world evidence to assess their impact on COVID-19 outcomes.


Asunto(s)
Alopecia/tratamiento farmacológico , Tratamiento Farmacológico de COVID-19 , Alopecia/clasificación , Antagonistas de Andrógenos/uso terapéutico , Antibacterianos/uso terapéutico , Antimaláricos/uso terapéutico , Ciclosporina/uso terapéutico , Glucocorticoides/uso terapéutico , Humanos , Hidroxicloroquina/uso terapéutico , Inmunosupresores/uso terapéutico , Inhibidores de las Cinasas Janus/uso terapéutico , Metotrexato/uso terapéutico , Pronóstico , Sistema de Registros , SARS-CoV-2
20.
Sci Rep ; 11(1): 12470, 2021 06 14.
Artículo en Inglés | MEDLINE | ID: covidwho-1268004

RESUMEN

Lifestyle interventions involving exercise training offset the adverse effects of androgen deprivation therapy in men with prostate cancer. Yet provision of integrated exercise pathways in cancer care is sparse. This study assessed the feasibility and acceptability of an embedded supervised exercise training intervention into standard prostate cancer care in a single-arm, multicentre prospective cohort study. Feasibility included recruitment, retention, adherence, fidelity and safety. Acceptability of behaviourally informed healthcare and exercise professional training was assessed qualitatively. Despite the imposition of lockdown for the COVID-19 pandemic, referral rates into and adherence to, the intervention was high. Of the 45 men eligible for participation, 79% (n = 36) received the intervention and 47% (n = 21) completed the intervention before a government mandated national lockdown was enforced in the United Kingdom. Patients completed a mean of 27 min of aerobic exercise per session (SD = 3.48), at 77% heart rate maximum (92% of target dose), and 3 sets of 10 reps of 3 resistance exercises twice weekly for 12 weeks, without serious adverse event. The intervention was delivered by 26 healthcare professionals and 16 exercise trainers with moderate to high fidelity, and the intervention was deemed highly acceptable to patients. The impact of societal changes due to the pandemic on the delivery of this face-to-face intervention remain uncertain but positive impacts of embedding exercise provision into prostate cancer care warrant long-term investigation.


Asunto(s)
Ejercicio Físico , Neoplasias de la Próstata/patología , Anciano , Antagonistas de Andrógenos/uso terapéutico , Actitud , Estudios de Cohortes , Estudios de Factibilidad , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Neoplasias de la Próstata/tratamiento farmacológico , Entrenamiento de Fuerza
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