Real-world use of first-generation antiandrogens: impact on patient outcomes and subsequent therapies in metastatic castration-resistant prostate cancer.

OBJECTIVES: To investigate the recent real-world use of first-generation antiandrogens (FGAs) in metastatic castration-resistant prostate cancer (mCRPC) using a retrospective multicentre cohort study. PATIENTS AND METHODS: The electronic CRPC Australian Database (ePAD) was interrogated to identify patients with mCRPC. Clinicopathological features, treatment and outcome data, stratified by FGA use, were retrieved and reported through descriptive statistics. Survival analyses were calculated using the Kaplan-Meier method and groups compared using log-rank tests. Factors influencing overall survival (OS) were analysed using Cox proportional hazards regression model. RESULTS: We identified 634 patients with mCRPC, enrolled in ePAD between January 2016 and March 2019, including 322 (51%) who received FGAs. The median follow-up was 21.9 months. Patients treated with FGAs were more likely to have lower International Society of Urological Pathologists (ISUP) grade group (P = 0.04), longer median time to CRPC (25.6 vs 16.0 months, P < 0.001), and were less likely to have visceral metastases (5.0% vs 11.2%, P = 0.005) or to have received upfront docetaxel (P < 0.001). A ≥50% reduction from pre-treatment prostate-specific antigen (PSA) level (PSA50 response) during FGA treatment occurred in 119 (37%) patients and was independently associated with improved OS (hazard ratio 0.233, P < 0.001). Prior FGA treatment did not significantly influence the selection of subsequent life-prolonging treatments for mCRPC or their PSA50 response rates. CONCLUSION: In our present cohort, FGAs were commonly used in lower-risk mCRPC and their use did not significantly influence the choice or duration of subsequent systemic therapy. A PSA50 response to FGA therapy was an independent favourable prognostic marker associated with improved OS.

Association between low total serum testosterone and body mass index in Australian survivors of testicular cancer: a retrospective analysis.

BACKGROUND: Primary hypogonadism is a recognised complication in survivors of testicular cancer. However, secondary hypogonadism can result from other causes that suppress the hypothalamic-pituitary axis, including obesity, high dose glucocorticoids, chronic end organ failure, and diabetes. The aim of this study was to explore low total serum testosterone in Australian survivors of testicular cancer and examine associations with body mass index, age, and prior chemotherapy use. METHODS: Clinical data including height, weight, diagnosis, treatment, and hormonal evaluations during follow-up were extracted from the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group Chemocog study (2007-2012), accompanied by data from two Australian, high-volume testicular cancer centres included in the iTestis testicular cancer registry (2012-2019). Low testosterone was defined by a serum concentration of testosterone (T) < 10 nmol/L, and was classified as primary by a serum concentration of luteinising hormone (LH) > 8 IU/L, otherwise as secondary. RESULTS: Two hundred eighty-five individuals with either stage 1 or advanced testicular cancer were included. Of these, 105 (37%) were treated with orchidectomy and chemotherapy. Forty-nine (17%) met criteria for low testosterone during follow-up: 21 (43%) had primary and 27 (55%) had secondary low testosterone. Survivors of testicular cancer with higher body mass index were more likely to display low testosterone, both primary (p = 0.032) and secondary (p = 0.028). Our data did not show evidence of an association between older age or chemotherapy use and low testosterone in our cohort. CONCLUSIONS: Low total serum testosterone was common in survivors of testicular cancer, and associated with a higher body mass index prior to orchidectomy, suggesting that elevated body mass index may contribute to low testosterone in this population, and that body weight, diet, and exercise should be addressed in testicular cancer follow-up.

RéSUMé: CONTEXTE: L'hypogonadisme primaire est une complication reconnue chez les survivants d'un cancer du testicule. Cependant, l'hypogonadisme secondaire peut résulter d'autres causes qui suppriment l'axe hypothalamo-hypophysaire, notamment l'obésité, les glucocorticoïdes à forte dose, la défaillance chronique des organes cibles et le diabète. Le but de cette étude était d'explorer un faible taux de testostérone totale sérique chez les survivants australiens d'un cancer du testicule, et d'examiner les associations avec l'indice de masse corporelle, l'âge et l'utilisation antérieure d'une chimiothérapie. Les données cliniques, y compris la taille, le poids, le diagnostic, le traitement et les évaluations hormonales au cours du suivi, ont été extraites de l'étude Chemocog de l'Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group (2007­2012), accompagnées de données, provenant de deux centres australiens à fort volume de prise en charge de cancers du testicule, incluses dans le registre du cancer du testicule iTestis (2012­2019). Un taux faible de testostérone a été défini par une concentration sérique de testostérone (T) < 10 nmol/L, et a été classé comme primaire pour une concentration sérique d'hormone lutéinisante (LH) > 8 UI/L, sinon comme secondaire. RéSULTATS: Deux cent quatre-vingt-cinq personnes atteintes d'un cancer des testicules de stade 1 ou avancé ont été incluses. Parmi ceux-ci, 105 (37%) ont été traités par orchidectomie et chimiothérapie. Quarante-neuf (17%) répondaient aux critères d'un taux faible de testostérone au cours du suivi: 21 (43%) avaient un taux faible de testostérone primaire et 27 (55%) un faible taux secondaire. Les survivants d'un cancer du testicule avec un indice de masse corporelle plus élevé étaient plus susceptibles de présenter un taux faible de testostérone, à la fois primaire (p = 0,032) et secondaire (p = 0,028). Nos données n'ont pas montré de preuve d'une association entre un âge avancé ou l'utilisation de la chimiothérapie, et un taux faible de testostérone, dans notre cohorte. CONCLUSIONS: Un faible taux de testostérone sérique totale était fréquent chez les survivants d'un cancer du testicule, et associé à un indice de masse corporelle plus élevé avant l'orchidectomie; ceci suggère qu'un indice de masse corporelle élevé peut contribuer à un faible taux de testostérone dans cette population, et que le poids corporel, l'alimentation et l'exercice devraient être pris en compte dans le suivi du cancer du testicule.

Real-world first-line systemic therapy patterns in metastatic castration-resistant prostate cancer.

Introduction: Several systemic therapies have demonstrated a survival advantage in metastatic castration resistant prostate cancer (mCRPC). Access to these medications varies significantly worldwide. In Australia until recently, patients must have received docetaxel first, unless unsuitable for chemotherapy, despite no evidence suggesting superiority over androgen receptor signalling inhibitors (ARSIs). Our study investigated real-world systemic treatment patterns in Australian patients with mCRPC. Methods: The electronic CRPC Australian Database (ePAD) was interrogated to identify mCRPC patients. Clinicopathological features, treatment and outcome data, stratified by first-line systemic therapies, were extracted. Comparisons between groups utilised Kruskal-Wallis tests and Chi-Square analyses. Time-to-event data were calculated using Kaplan-Meier methods and groups compared using log-rank tests. Factors influencing overall survival (OS) and time to treatment failure (TTF) were analysed through Cox proportional hazards regression models. Results: We identified 578 patients who received first-line systemic therapy for mCRPC. Enzalutamide (ENZ) was most commonly prescribed (n = 240, 41%), followed by docetaxel (DOC, n = 164, 28%) and abiraterone (AA, n = 100, 17%). Patients receiving ENZ or AA were older (79, 78.5 years respectively) compared with DOC (71 years, p = 0.001) and less likely to have ECOG performance status 0 (45%, 44%, 59% in ENZ, AA and DOC groups respectively p < 0.0001). Median TTF was significantly higher in those receiving ENZ (12.4 months) and AA (11.9 months) compared to DOC (8.3 months, p < 0.001). PSA50 response rates and OS were not statistically different. Time to developing CRPC > 12 months was independently associated with longer TTF (HR 0.67, p < 0.001) and OS (HR 0.49, p = 0.002). Conclusion: In our real-world population, ENZ and AA were common first-line systemic therapy choices, particularly among older patients and those with poorer performance status. Patients receiving ENZ and AA demonstrated superior TTF compared to DOC, while OS was not statistically different. Our findings highlight the important role of ARSIs, given the variability of access worldwide.

Role for a Web-Based Intervention to Alleviate Distress in People With Newly Diagnosed Testicular Cancer: Mixed Methods Study.

BACKGROUND: Distress is common immediately after diagnosis of testicular cancer. It has historically been difficult to engage people in care models to alleviate distress because of complex factors, including differential coping strategies and influences of social gender norms. Existing support specifically focuses on long-term survivors of testicular cancer, leaving an unmet need for age-appropriate and sex-sensitized support for individuals with distress shortly after diagnosis. OBJECTIVE: We evaluated a web-based intervention, Nuts & Bolts, designed to provide support and alleviate distress after diagnosis of testicular cancer. METHODS: Using a mixed methods design to evaluate the acceptability, feasibility, and impact of Nuts & Bolts on distress, we randomly assigned participants with recently diagnosed testicular cancer (1:1) access to Nuts & Bolts at the time of consent (early) or alternatively, 1 week later (day 8; delayed). Participants completed serial questionnaires across a 4- to 5-week period to evaluate levels of distress (measured by the National Comprehensive Cancer Network Distress Thermometer [DT]; scored 0-10), anxiety, and depression (Hospital Anxiety and Depression Score [HADS]-Anxiety and HADS-Depression; each scored 0-21). The primary end point was change in distress between consent and day 8. Secondary end points of distress, anxiety, and depression were assessed at defined intervals during follow-up. Optional, semistructured interviews occurring after completion of quantitative assessments were thematically analyzed. RESULTS: Overall, 39 participants were enrolled in this study. The median time from orchidectomy to study consent was 14.8 (range 3-62) days. Moderate or high levels of distress evaluated using DT were reported in 58% (23/39) of participants at consent and reduced to 13% (5/38) after 1 week of observation. Early intervention with Nuts & Bolts did not significantly decrease the mean DT score by day 8 compared with delayed intervention (early: 4.56-2.74 vs delayed: 4.47-2.74; P=.85), who did not yet have access to the website. A higher baseline DT score was significantly predictive of reduction in DT score during this period (P<.001). Median DT, HADS-Anxiety, and HADS-Depression scores reduced between orchidectomy and 3 weeks postoperatively and then remained stable throughout the observation period. Thematic analysis of 16 semistructured interviews revealed 4 key themes, "Nuts & Bolts is a helpful tool," "Maximizing benefits of the website," "Whirlwind of diagnosis and readiness for treatment," and "Primary stressors and worries," as well as multiple subthemes. CONCLUSIONS: Distress is common following the diagnosis of testicular cancer; however, it decreases over time. Nuts & Bolts was considered useful, acceptable, and relevant by individuals diagnosed with testicular cancer, with strong support for the intervention rendered by thematic analyses of semistructured interviews. The best time to introduce support, such as Nuts & Bolts, is yet to be determined; however, it may be most beneficial as soon as testicular cancer is strongly suspected or diagnosed.

E-cigarette use and combustible tobacco cigarette smoking uptake among non-smokers, including relapse in former smokers: umbrella review, systematic review and meta-analysis.

OBJECTIVE: To review and summarise the current evidence on the uptake of combustible cigarette smoking following e-cigarette use in non-smokers-including never-smokers, people not currently smoking and past smokers-through an umbrella review, systematic review and meta-analysis. DESIGN: Umbrella review, systematic review and meta-analysis. DATA SOURCES: PubMed, Scopus, Web of Science, PsychINFO (Ovid), Medline (Ovid) and Wiley Cochrane Library up to April 2020. RESULTS: Of 6225 results, 25 studies of non-smokers-never, not current and former smokers-with a baseline measure of e-cigarette use and an outcome measure of combustible smoking uptake were included. All 25 studies found increased risk of smoking uptake with e-cigarette exposure, although magnitude varied substantially. Using a random-effects model, comparing e-cigarette users versus non-e-cigarette users, among never-smokers at baseline the OR for smoking initiation was 3.25 (95% CI 2.61 to 4.05, I2 85.7%) and among non-smokers at baseline the OR for current smoking was 2.87 (95% CI 1.97 to 4.19, I2 90.1%). Among former smokers, smoking relapse was higher in e-cigarette users versus non-users (OR=2.40, 95% CI 1.50 to 3.83, I2 12.3%). CONCLUSIONS: Across multiple settings, non-smokers who use e-cigarettes are consistently more likely than those avoiding e-cigarettes to initiate combustible cigarette smoking and become current smokers. The magnitude of this risk varied, with an average of around three times the odds. Former smokers using e-cigarettes have over twice the odds of relapse as non-e-cigarettes users. This study is the first to our knowledge to review and pool data on the latter topic. PROSPERO REGISTRATION NUMBER: CRD42020168596.