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3.
JNCI Cancer Spectr ; 6(3)2022 05 02.
Article in English | MEDLINE | ID: covidwho-1878801

ABSTRACT

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.


Subject(s)
COVID-19 , Prostatic Neoplasms , Aged , Androgen Antagonists/therapeutic use , Androgens/therapeutic use , COVID-19/drug therapy , COVID-19 Testing , Humans , Male , Prostatic Neoplasms/drug therapy , Receptors, Androgen/therapeutic use , Retrospective Studies , SARS-CoV-2
4.
Nat Rev Urol ; 19(6): 344-356, 2022 06.
Article in English | MEDLINE | ID: covidwho-1795727

ABSTRACT

On 11 March 2020, the WHO declared the coronavirus disease 2019 (COVID-19) outbreak a pandemic and COVID-19 emerged as one of the biggest challenges in public health and economy in the twenty-first century. The respiratory tract has been the centre of attention, but COVID-19-associated complications affecting the genitourinary tract are reported frequently, raising concerns about possible long-term damage in these organs. The angiotensin-converting enzyme 2 (ACE2) receptor, which has a central role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion, is highly expressed in the genitourinary tract, indicating that these organs could be at a high risk of cell damage. The detection of SARS-CoV-2 in urine and semen is very rare; however, COVID-19 can manifest through urological symptoms and complications, including acute kidney injury (AKI), which is associated with poor survival, severe structural changes in testes and impairment of spermatogenesis, and hormonal imbalances (mostly secondary hypogonadism). The effect of altered total testosterone levels or androgen deprivation therapy on survival of patients with COVID-19 was intensively debated at the beginning of the pandemic; however, androgen inhibition did not show any effect in preventing or treating COVID-19 in a clinical study. Thus, urologists have a crucial role in detecting and managing damage of the genitourinary tract caused by COVID-19.


Subject(s)
COVID-19 , Prostatic Neoplasms , Androgen Antagonists , Androgens , Humans , Male , Pandemics , Prostatic Neoplasms/epidemiology , SARS-CoV-2 , Urologists
5.
Am J Health Syst Pharm ; 79(15): 1224-1235, 2022 07 22.
Article in English | MEDLINE | ID: covidwho-1778882

ABSTRACT

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.


Subject(s)
Prostatic Neoplasms, Castration-Resistant , Receptors, Androgen , Androgen Antagonists/therapeutic use , Androgen Receptor Antagonists/therapeutic use , Androgens/metabolism , Gonadotropin-Releasing Hormone/agonists , Gonadotropin-Releasing Hormone/antagonists & inhibitors , Humans , Male , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/genetics , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Signal Transduction , Testosterone
6.
Eur Urol ; 82(1): 6-11, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1768076

ABSTRACT

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.


Subject(s)
COVID-19 , Prostatic Neoplasms , Androgen Antagonists/therapeutic use , COVID-19 Vaccines , Humans , Male , Pandemics/prevention & control , Prostatic Neoplasms/pathology
7.
ESMO Open ; 7(2): 100448, 2022 04.
Article in English | MEDLINE | ID: covidwho-1763725

ABSTRACT

BACKGROUND: Androgen-deprivation therapy (ADT) has been associated with cognitive decline, but results are conflicting. This study describes changes in cognitive performance in patients with prostate cancer, according to ADT, during the first year after prostate cancer diagnosis. PATIENTS AND METHODS: Patients with prostate cancer treated at the Portuguese Institute of Oncology of Porto (n = 366) were evaluated with the Montreal Cognitive Assessment (MoCA), before treatment and after 1 year. All baseline evaluations were performed before the coronavirus disease 2019 (COVID-19) pandemic and 69.7% of the 1-year assessments were completed after the first lockdown. Cognitive decline was defined as the decrease in MoCA from baseline to the 1-year evaluation below 1.5 standard deviations of the distribution of changes in the whole cohort. Participants scoring below age- and education-specific normative reference values in the MoCA were considered to have cognitive impairment. Age- and education-adjusted odds ratios (aORs) were computed for the association between ADT and cognitive outcomes. RESULTS: Mean MoCA scores increased from baseline to the 1-year evaluation (22.3 versus 22.8, P < 0.001). Cognitive decline was more frequent in the ADT group, and even more after the onset of the COVID-19 pandemic (aOR 6.81 versus 1.93, P for interaction = 0.233). The 1-year cumulative incidence of cognitive impairment was 6.9% (9.1% before and 3.7% after the pandemic onset), which was higher among patients receiving ADT, but only after the pandemic (aOR 5.53 versus 0.49, P for interaction = 0.044). CONCLUSIONS: ADT was associated with worse cognitive performance of patients with prostate cancer, mostly among those evaluated after the first COVID-19 lockdown.


Subject(s)
COVID-19 , Cognitive Dysfunction , Prostatic Neoplasms , Androgen Antagonists/adverse effects , Androgens , Cognitive Dysfunction/complications , Cognitive Dysfunction/etiology , Communicable Disease Control , Humans , Male , Neon , Pandemics , Prospective Studies , Prostatic Neoplasms/complications , Prostatic Neoplasms/drug therapy
8.
Scand J Urol ; 56(2): 112-113, 2022 04.
Article in English | MEDLINE | ID: covidwho-1705257
10.
Curr Opin Urol ; 32(3): 311-317, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-1684904

ABSTRACT

PURPOSE OF REVIEW: The Coronavirus disease 2019 (COVID-19) pandemic has led to uncertainty on the optimal management for prostate cancer (PCa). This narrative review aims to shed light on the optimal diagnosis and management of patients with or suspected to have PCa. RECENT FINDINGS: Faecal-oral or aerosol transmission is possible during prostate procedures; caution must be in place when performing digital rectal examinations, transrectal ultrasound-guided prostate biopsies and prostate surgeries requiring general anaesthesia. Patients must also be triaged using preoperative polymerase chain reaction tests for COVID-19. COVID-19 has accelerated the adoption of multiparametric Magnetic Resonance Imaging (MRI), reducing the need for prostate biopsy unless when absolutely indicated, and the risk of COVID-19 spread can be reduced. Combined with prostate-specific antigen (PSA) density, amongst other factors, multiparametric MRI could reduce unnecessary biopsies in patients with little chance of clinically significant PCa. Treatment of PCa should be stratified by the risk level and preferences of the patient. COVID-19 has accelerated the development of telemedicine and clinicians should utilise safe and effective teleconsultations to protect themselves and their patients. SUMMARY: COVID-19 transmission during prostate procedures is possible. Patients with a Prostate Imaging-Reporting and Data System (PI-RADS) of <3 and PSA density <0.15 ng/ml/ml are deemed low-risk and are safe to undergo surveillance without MRI-targeted biopsy. Intermediate- or high-risk patients should be offered definitive treatment within four months or 30days of diagnosis to avoid compromising treatment outcomes; three-month courses of neoadjuvant androgen deprivation therapy can be considered when a delay of surgery is anticipated.


Subject(s)
COVID-19 , Prostatic Neoplasms , Androgen Antagonists , Humans , Image-Guided Biopsy/methods , Magnetic Resonance Imaging/methods , Male , Prostate-Specific Antigen , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Retrospective Studies
11.
Eur J Endocrinol ; 186(1): 9-23, 2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1686174

ABSTRACT

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.


Subject(s)
Adipose Tissue/drug effects , Androgen Antagonists/therapeutic use , Estradiol/pharmacology , Absorptiometry, Photon , Aged , Androgen Antagonists/adverse effects , Australia , Body Composition/drug effects , Double-Blind Method , Humans , Male , Middle Aged , Obesity/complications , Obesity/drug therapy , Prostatic Neoplasms/complications , Prostatic Neoplasms/drug therapy
12.
Clin Genitourin Cancer ; 20(2): 123-131, 2022 04.
Article in English | MEDLINE | ID: covidwho-1654189

ABSTRACT

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.


Subject(s)
COVID-19 , Prostatic Neoplasms , Radiosurgery , Androgen Antagonists/therapeutic use , Humans , Male , Prostatic Neoplasms/drug therapy , Radiosurgery/methods , Retrospective Studies , Survival Analysis
13.
Scand J Urol ; 56(2): 104-111, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1585249

ABSTRACT

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.


Subject(s)
COVID-19 , Prostatic Neoplasms , Androgen Antagonists/therapeutic use , Androgens , Case-Control Studies , Comorbidity , Humans , Male , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/drug therapy
14.
Eur Urol ; 81(3): 285-293, 2022 03.
Article in English | MEDLINE | ID: covidwho-1568696

ABSTRACT

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.


Subject(s)
Androgen Antagonists/therapeutic use , Anilides/therapeutic use , Benzamides/therapeutic use , COVID-19/drug therapy , Nitriles/therapeutic use , Phenylthiohydantoin/therapeutic use , SARS-CoV-2/isolation & purification , Tosyl Compounds/therapeutic use , Aged , Aged, 80 and over , Androgens/therapeutic use , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Nucleic Acid Testing , Female , Hospitalization , Humans , Male , Middle Aged , Retrospective Studies , Sweden/epidemiology , Testosterone , Treatment Outcome
15.
JAMA Netw Open ; 4(11): e2134330, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1513769

ABSTRACT

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.


Subject(s)
Androgen Antagonists/adverse effects , COVID-19/complications , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/mortality , Aged , Aged, 80 and over , Androgen Antagonists/therapeutic use , COVID-19/epidemiology , COVID-19/mortality , Cohort Studies , Humans , Male , Middle Aged , Prostatic Neoplasms/epidemiology , Risk Factors , Tennessee/epidemiology
16.
Crit Rev Oncol Hematol ; 167: 103491, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1505718

ABSTRACT

Real-world data suggest a possible interplay between androgen deprivation therapy (ADT) and susceptibility to and the severity of SARS-CoV-2 infection. As ADT is the backbone of prostate cancer treatment, various authors have evaluated different patient cohorts but the evidence provided is conflicting. The aim of this review is to assess the available publications concerning the role of ADT in preventing or reducing the severity of SARS-CoV-2 infection. After a literature search we identified four full papers, five letters, and four meeting abstracts, but these used different search methods and the quality of the evidence varied. They frequently had different endpoints, did not report the status of the prostate cancer patients and evaluated heterogeneous populations. The available data do not support the view that ADT protects against SARS-CoV-2 infection. Larger and more precise studies are warranted, considering variables that affect infection outcomes as these significantly influence the reliability of the findings.


Subject(s)
COVID-19 , Prostatic Neoplasms , Androgen Antagonists , Humans , Male , Prostatic Neoplasms/complications , Prostatic Neoplasms/drug therapy , Reproducibility of Results , SARS-CoV-2
17.
Eur J Endocrinol ; 186(1): 9-23, 2021 Nov 30.
Article in English | MEDLINE | ID: covidwho-1484899

ABSTRACT

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.


Subject(s)
Adipose Tissue/drug effects , Androgen Antagonists/therapeutic use , Estradiol/pharmacology , Absorptiometry, Photon , Aged , Androgen Antagonists/adverse effects , Australia , Body Composition/drug effects , Double-Blind Method , Humans , Male , Middle Aged , Obesity/complications , Obesity/drug therapy , Prostatic Neoplasms/complications , Prostatic Neoplasms/drug therapy
18.
PLoS One ; 16(10): e0255966, 2021.
Article in English | MEDLINE | ID: covidwho-1456078

ABSTRACT

BACKGROUND: Men have a higher risk of death from COVID-19 than women and androgens facilitate entrance of the SARS-CoV-2 virus into respiratory epithelial cells. Thus, androgen deprivation therapy may reduce infection rates and improve outcomes for COVID-19. In the spring of 2020, Sweden was highly affected by COVID-19. The aim was to estimate the impact of androgen deprivation therapy on mortality from COVID-19 in men with prevalent prostate cancer by comparing all-cause mortality in the spring of 2020 to that in previous years. PATIENTS AND METHODS: Using the Prostate Cancer data Base Sweden all men with prostate cancer on March 1 each year in 2015-2020 were followed until June 30 the same year. Exposure to androgen deprivation therapy was ascertained from filled prescriptions for bicalutamide monotherapy, gonadotropin-releasing hormone agonists (GnRH), or bilateral orchidectomy. RESULTS: A total of 9,822 men died in March-June in the years 2015-2020, of whom 5,034 men were on androgen deprivation therapy. There was an excess mortality in 2020 vs previous years in all men. The crude relative mortality rate ratio for 2020 vs 2015-2019 was 0.93 (95% confidence interval (CI) 0.83 to 1.04) in men on GnRH, and 0.90 (95% CI 0.78 to 1.05) in men on bicalutamide monotherapy. After multivariable adjustment these ratios were attenuated to 1.00 (95% CI 0.89 to 1.12) and 0.97 (95% CI 0.84 to 1.12), respectively. When restricting the analysis to the regions with the highest incidence of COVID-19 or to the time period between 2 April to 10 June when mortality in 2020 was increased >30% compared to previous years, the results were similar to the main analysis. CONCLUSIONS: In this large national population-based cohort of men with prevalent prostate cancer, there was no clear evidence in support for an effect of androgen deprivation therapy on COVID-19 mortality.


Subject(s)
Androgen Antagonists/administration & dosage , COVID-19/mortality , Databases, Factual , Pandemics , Prostatic Neoplasms/mortality , Registries , SARS-CoV-2 , Aged , Aged, 80 and over , COVID-19/therapy , Disease-Free Survival , Humans , Male , Middle Aged , Prostatic Neoplasms/therapy , Survival Rate
19.
Urology ; 155: 179-185, 2021 09.
Article in English | MEDLINE | ID: covidwho-1411044

ABSTRACT

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.


Subject(s)
Health Knowledge, Attitudes, Practice , Orchiectomy/psychology , Prostatic Neoplasms/therapy , Quality of Life , Aged , Androgen Antagonists/therapeutic use , Humans , Male , Neoplasm Metastasis , Patient Acceptance of Health Care , Patient Education as Topic , Prostatic Neoplasms/pathology , Surveys and Questionnaires
20.
Prostate ; 81(16): 1349-1354, 2021 12.
Article in English | MEDLINE | ID: covidwho-1404607

ABSTRACT

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.


Subject(s)
Androgen Antagonists/therapeutic use , COVID-19/epidemiology , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/epidemiology , SARS-CoV-2 , Severity of Illness Index , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/therapy , Comorbidity , Hospitalization/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Neoplasm Staging , Prostatic Neoplasms/pathology , Retrospective Studies , Risk Factors
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