Prostate Cancer Receiving Androgen Deprivation Research Articles

Precarious Bodies and Masculinities: The Experience of Exercise During Hormonal Treatment for Prostate Cancer

This study focuses on ageing men treated for prostate cancer receiving androgen deprivation therapy (ADT) linked to a spectrum of side effects, sometimes understood as emasculating. To understand the consequences of ADT and how to counteract side effects related to masculinity, interviews were conducted with treated men participating in an exercise programme. The aim was to analyse how participants experienced and embodied the exercise programme in relation to ageing, illness and masculinity. Findings show that the men experience their bodies as changing, loosing habituated abilities. The beginning of the programme evoked feelings of precarious bodies, whereas further along these feelings evolved into those of bodily remedy. Participation was seen as opportunity to meet other men in the same situation and created a sense of fellowship.

MANCAN2: A multicentre randomised controlled trial of self-help cognitive behavioural therapy (CBT) to manage hot flush and night sweats (HFNS) symptoms in patients with prostate cancer receiving androgen deprivation therapy (ADT).

LBA5004 Background: Up to 80% of patients receiving ADT suffer HFNS which impacts quality of life (QOL) and potentially ADT compliance. Mitigation options are limited. Prior research has found self-help CBT, with minimal guidance, reduced HFNS due to ADT at 6 weeks. We tested the longer term impact of self-help CBT, guided and delivered by prostate Cancer Nurse Specialist (CNS) teams. Methods: MANCAN2 is a multicentre randomised controlled trial and process evaluation within UK prostate cancer units. Eligibility: localised/advanced prostate cancer; on ADT with ≥ 6 months further planned; HFNS Problem Rating Scale ≥ 2. Patients were randomised (1:1) in groups of 6 to 8 to treatment as usual (TAU) or CBT + TAU, by permuted block, stratified by site, cohort and treatment intent. CBT was a 4-week self-help intervention (booklet and relaxation audio) with pre- and post-intervention group workshops by the prostate CNS team. Primary objective: does adding CBT to TAU reduce 6 month HFNS Problem Rating Scale versus baseline (mixed linear regression). Secondary endpoints: 6 week HFNS Problem Rating Scale, HFNS frequency, HFNS beliefs and behaviours, QOL (EORTC QLQ-C30, symptoms (rating scales for anxiety, depression, mood and sleep) by mixed logistic regression), ADT compliance (chi-squared test). A 6 month mean HFNS Problem Rating Scale difference of ≥ 1.5 points was deemed clinically relevant, and required data from 111 patients (90% power, 5% type 1 error, 6 to 8 patients per group, intra-class correlation 0.01, anticipating 26% patient loss). Results: 162 patients were randomly assigned (81/arm) and 117 returned 6 month HFNS Problem Rating Scale data. Baseline characteristics were balanced. Mean CBT delivery adherence was 85%. 6 month mean HFNS Problem Rating Scale score was not significantly different for the TAU alone versus CBT + TAU (mean 4.08 vs 4.04, 95% CI for difference: -0.89, 0.80; p=0.97), although a difference was observed at 6 weeks (mean 4.47 vs 3.79, 95% CI: -1.26, -0.09; p=0.03). At 6 weeks, CBT patients had higher weekly HFNS frequency (median 54.2 vs 59.4, 95% CI: 0.22, 10.19; p=0.04), lower depression score (median 7.19 vs 6.19, 95% CI: -1.88, -0.12; p=0.03) and lower anxiety score (median 4.25 vs 3.39, 95% CI: -1.64, -0.08; p=0.03). CBT patients had more positive beliefs about openness and humour scores at 6 months (median 4.92 vs 4.59, 95% CI: -0.63, -0.03; p=0.03). There was no significant difference for other measures of HFNS beliefs and behaviours, quality of life, anxiety, mood, sleep quality and treatment compliance. Conclusions: Adding CBT to TAU in prostate cancer patients receiving ADT improved short-term HFNS severity but was not maintained at 6 months. Future research should investigate whether initial CBT benefit could be made sustainable in this setting. Clinical trial information: 58720120.

11-Ketotestosterone and time to castration resistance in patients with recurrent non-metastatic prostate cancer receiving androgen deprivation therapy.

209 Background: The contribution of 11-oxygenated androgens to disease progression in men receiving androgen deprivation therapy (ADT) for recurrent non-metastatic prostate cancer (PCa) remains unresolved. We hypothesized that evaluating circulating levels of 11-oxygenated androgens, such as the potent androgen receptor (AR) agonist 11-ketotestosterone (11KT), could serve as a potential predictor for the onset of castration resistance (CRPC). Methods: The multi-institutional prospective PROCURE cohort involves 2,026 patients who underwent radical prostatectomy for localized PCa. In this cohort, a subset of 145 patients who received ADT therapy for recurrent disease and had available plasma samples post-surgery were included in this study. The effect of therapy on steroid levels was assessed in paired samples obtained before and after the initiation of ADT (n=50), and samples from patients under combined ADT with AR pathway inhibitors, enzalutamide (n=10) and abiraterone (n =15). 11-oxygenated androgens (n=7) and canonical steroids, such as testosterone (T) and dihydrotestosterone (DHT), were quantified by mass spectrometry. Kaplan-Meier survival analyses were used to investigate relationships of androgen levels with the occurrence of CRPC. Results: 11-oxygenated androgens remained unaffected by ADT, which stands in contrast to the observed changes in T, DHT and other steroids. In men with castrated T levels, 11KT was the most abundant androgen. Elevated 11KT was associated with a sooner time to CRPC ( P=0.023). The 10-year CRPC event-free rate was 63% vs. 84% for 11KT levels above and below the median, respectively. The initiation of enzalutamide had no impact on 11-oxygenated androgen levels, whereas abiraterone significantly reduced 11KT levels owing to the adrenal origin of its precursor. Conclusions: Our findings indicate that 11KT is a significant component of the hormonal profile predictive of an earlier onset of CRPC and inhibition of its production by the CYP17A1 inhibitor abiraterone.

Probability of Cardiovascular Death in Patients with Prostate Cancer Receiving Androgen Deprivation Therapy (ADT): A Comprehensive Analysis

Probability of Cardiovascular Death in Patients with Prostate Cancer Receiving Androgen Deprivation Therapy (ADT): A Comprehensive Analysis

Statin use and mortality risk in Asian patients with prostate cancer receiving androgen deprivation therapy: A population-based cohort study.

This study aimed to examine the associations between the use of statins concurrent with androgen deprivation therapy (ADT) and the risks of mortality in Asian patients diagnosed with prostate cancer (PCa). Adult patients (≥18 years old) diagnosed with PCa who were receiving any form of ADT and were being treated at public hospitals in Hong Kong from December 1999 to March 2021 were retrospectively identified, with follow-up conducted until September 2021. Patients who had received medical castration for <180 days without subsequent bilateral orchidectomy, those who had used statins concurrently with ADT for <180 days, and those with missing baseline total cholesterol levels were excluded. Statin users were defined as individuals who had used statins for ≥180 days concurrent with ADT, while non-users were those who had not used any statins. PCa-related mortality was the primary outcome, while all-cause mortality served as the secondary outcome. Inverse probability treatment weighting was employed to balance the covariates. A total of 4920 patients were included, consisting of 2578 statin users and 2342 non-users (mean age 76.1 ± 8.2 years). Over a mean follow-up period of 4.2 ± 3.3 years, it was observed that statin users had significantly lower risks of both PCa-related mortality (weighted hazard ratio [wHR] 0.56 [95% confidence interval (CI) 0.48, 0.65], p < 0.001) and all-cause mortality (wHR 0.57 [95% CI 0.51, 0.63], p < 0.001), regardless of the type of ADT used. Notably, these associations were more pronounced among patients with less advanced PCa, as indicated by the absence of androgen receptor antagonist or chemotherapy usage (p value for interaction <0.001 for both outcomes). The use of statins concurrent with ADT was associated with reduced mortality risks among Asian patients with PCa. These findings suggest the need for additional research to explore the potential role of statins in the treatment of PCa patients.

Associations between patient reported fatigue and remotely monitored activity in patients with prostate cancer receiving androgen deprivation therapy.

593 Background: Androgen deprivation therapy (ADT) is commonly used for the management of prostate cancer (PCa). Despite its benefits, ADT can lead to a range of side effects that have prominent determents on patient quality of life, specifically fatigue. Fatigue is a multidimensional symptom that influences a patient’s psychological and physical well-being, including the inability to perform daily activities due to lack of energy. This analysis evaluates associations between patient-reported fatigue and remotely monitored objective activity in PCa patients. Methods: This is a secondary analysis ofa multi-site observational cohort study (DigiPRO) among men diagnosed with advanced PCa, initiating ADT within 6 months, conducted between 12/2020 and 4/2023. Eligible patients wore an activity monitor (Fitbit Charge HR 4) continuously for the 12-week study and completed NIH PROMIS fatigue surveys via REDCap, which included Likert-scale questions (8 items, range 1-5 (worse)) about fatigue severity and interference, at baseline, 4, 8, and 12 weeks. PROMIS scores were converted to standardized T-scores (mean 50: SD: 10). Pearson correlation coefficients were calculated, and multivariable logistic regression models were fit to evaluate associations between activity and fatigue T-scores. Results: 40 patients were included in the analysis (median age: 70 yrs, range 51-85; 37% Black or African American/63% White, 10% Hispanic/90% non-Hispanic White). 11 patients reported high levels of fatigue (T-Score&gt;60) at least once over the course of the study and 20% of patients experienced an increase &gt; 5 T-score points from baseline, indicating clinically meaningful deterioration. Higher fatigue T-scores were negatively correlated with higher daily step counts (r=-0.6, p=0.003) and calories expended (r=-0.5, p=0.002) and positively correlated with increased sedentary time (r=0.5, p=0.002) at baseline. Lower baseline step counts were significantly associated with any occurrence of worsening patient fatigue over the study period (OR: 2.08, 95% CI 1.12-3.8, per 1000 step decrease, p=0.02) after adjusting for age and race. Patients who reported worsening fatigue had a mean step count of 3,426 compared to 5,664 steps/day among those who reported stable or improving fatigue (p=0.02). Conclusions: Findings from this analysis suggest that objective measures of daily activityare correlated with patient-reported fatigue and predict worsening fatigue over time. Routine collection and monitoring of patient-reported fatigue and daily activity during ADT may help identify patients at increased risk for worsening fatigue. More research is needed to determine the role of wearable activity monitors as potential interventions and for real time monitoring to help manage fatigue and other symptoms during ADT. Clinical trial information: NCT04575402 .

The Impact Of Creatine Supplementation And Resistance Training On Body Composition And Physical Function In Men With Prostate Cancer Receiving Androgen Deprivation Therapy

The Impact Of Creatine Supplementation And Resistance Training On Body Composition And Physical Function In Men With Prostate Cancer Receiving Androgen Deprivation Therapy

Nutritional program among patients with prostate cancer receiving androgen deprivation therapy (ADT).

12072 Background: Treatment with ADT can lead to changes in body composition, including an increase in body fat and a decrease in muscle mass. To minimize the nutritional risks associated with ADT, a nutritional program was developed. Thus, this study sought to determine the benefit of this program among patients with prostate cancer receiving ADT. Methods: Patients were recruited in a cancer center located in Brasilia, Brazil. Patients were eligible if they were diagnosed with prostate cancer, and about to initiate treatment with ADT. They were assessed before starting ADT and at follow-up assessment (3 months). Based on their risk, patients were instructed to follow either a normocaloric (20-25 kcal/kg) or a hypocaloric (18-20 kcal/kg) diet, and both groups were required to consume a hyperproteic diet (1-1.2 g/kg), including the use of whey protein supplementation as needed. Outcomes measures included nutritional risk (Patient-Generated Subjective Global Assessment; PG-SGA), body composition (Medical software Lookin’Body120), and muscle strength (Jamar Hydraulic Hand Dynamometer). Descriptive statistics were generated, and paired T-test, Wilcoxon signed rank on paired samples and ANOVA-RM were used to evaluate changes in variables over time. Results: A total of 62 patients were included in this program. Participants had a median age of 75 years (range from 41-97) and were predominantly married (87%). A great proportion of patients (65%) were diagnosed with a stage IV disease. Notably, 23% were diagnosed with moderate to severe nutritional risk at baseline; 47% were overweight, 13% were obese and 14% were with sarcopenia. The nutritional program resulted in maintenance of total body weight (median 74.1 vs 75.6 kg, P=0.12), lean body weight (median 29.1 vs 29.4 kg, P=0.11), and muscle strength (median 30 vs 30 kg, P=0.62), while a statistically significant loss of body fat weight (median 22.0 vs 20 kg, P=0.003) was found over the 12-week period. Despite no change in the PG-SGA scores were noted overtime, the rate of sarcopenia has decreased (15% vs 13%, P=0.03) and the proportion of eutrophic patients has increased (18% vs 27%, P=0.001), as seen in the contingency table below. Conclusions: These findings suggest that this program may improve body composition and maintain muscle strength in men receiving treatment with ADT after only three months of intervention. Future studies should validate the benefit of this program in randomized trial with a longer follow-up assessment (6 and 12 months after treatment initiation). [Table: see text]

Long-term prognostic impact of cardiovascular comorbidities in patients with prostate cancer receiving androgen deprivation therapy: A population-based competing risk analysis.

Our study investigated how adverse cardiovascular outcomes are impacted by cardiovascular comorbidities in patients with prostate cancer treated by androgen deprivation therapy (ADT). Using prospective, population-based data, all Hong Kong patients with prostate cancer who received ADT during 1 January 1993 to 3 March 2021 were identified and followed up for the endpoint of cardiovascular hospitalization/mortality until 31 September 2021, whichever earlier. Multivariable competing risk regression was used to compare the endpoint's cumulative incidence between different combinations of major cardiovascular comorbidities (heart failure [HF], myocardial infarction [MI], stroke and/or arrhythmia), with noncardiovascular death as competing event. Altogether, 13 537 patients were included (median age 75.9 [interquartile range 70.0-81.5] years old; median follow-up 3.3 [1.5-6.7] years). Compared to those with none of prior HF/MI/stroke/arrhythmia, the incidence of the endpoint was not different in those with only stroke (subhazard ratio [SHR] 1.06 [95% confidence interval (CI): 0.92-1.23], P = .391), but was higher in those with only HF (SHR 1.67 [1.37-2.02], P < .001), arrhythmia (SHR 1.63 [1.35-1.98], P < .001) or MI (SHR 1.43 [1.14-1.79], P = .002). Those with ≥2 of HF/MI/stroke/arrhythmia had the highest incidence of the endpoint (SHR 1.94 [1.62-2.33], P < .001), among whom different major cardiovascular comorbidities had similar prognostic impacts, with the number of comorbidities present being significantly prognostic instead. In conclusion, in patients with prostate cancer receiving ADT, the sole presence of HF, MI or arrhythmia, but not stroke, may be associated with elevated cardiovascular risks. In those with ≥2 of HF/MI/stroke/arrhythmia, the number of major cardiovascular comorbidities may be prognostically more important than the type of comorbidities.

Temporal trends in cardiovascular burden among patients with prostate cancer receiving androgen deprivation therapy: a population-based cohort study

BackgroundAlthough androgen deprivation therapy (ADT) is associated with cardiovascular risks, the extent and temporal trends of cardiovascular burden amongst patients with prostate cancer receiving ADT are unclear.MethodsThis retrospective cohort study analyzed adults with PCa receiving ADT between 1993–2021 in Hong Kong, with follow-up until 31/9/2021 for the primary outcome of major adverse cardiovascular events (MACE; composite of cardiovascular mortality, myocardial infarction, stroke, and heart failure), and the secondary outcome of mortality. Patients were stratified into four groups by the year of ADT initiation for comparisons.ResultsAltogether, 13,537 patients were included (mean age 75.5 ± 8.5 years old; mean follow-up 4.7 ± 4.3 years). More recent recipients of ADT had more cardiovascular risk factors and used more cardiovascular or antidiabetic medications. More recent recipients of ADT had higher risk of MACE (most recent (2015–2021) vs least recent (1993–2000) group: hazard ratio 1.33 [1.11, 1.59], P = 0.002; Ptrend < 0.001), but lower risk of mortality (hazard ratio 0.76 [0.70, 0.83], P < 0.001; Ptrend < 0.001). The 5-year risk of MACE and mortality for the most recent group were 22.5% [20.9%, 24.2%] and 52.9% [51.3%, 54.6%], respectively.ConclusionsCardiovascular risk factors were increasingly prevalent amongst patients with prostate cancer receiving ADT, with increasing risk of MACE despite decreasing mortality.

HbA1c Variability and Cardiovascular Events in Patients with Prostate Cancer Receiving Androgen Deprivation Therapy

BackgroundAndrogen deprivation therapy (ADT) worsens glycaemic control and cardiovascular outcomes. The prognostic value of visit-to-visit HbA1c variability (VVHV) has been unexplored in prostate cancer (PCa) patients receiving ADT. ObjectiveTo explore the effect of ADT on VVHV and the cardiovascular prognostic value of VVHV. Design, setting, and participantsPCa patients receiving ADT in Hong Kong between January 1, 1993 and March 31, 2021 were included in this retrospective cohort study. Those with fewer than three HbA1c results available within 3 yr after ADT initiation, <6 mo of ADT, missing baseline HbA1c, prior diagnosis of any component of major adverse cardiovascular events (MACEs), and MACEs occurring within 3 yr were excluded. Patients were followed up until September 31, 2021. Outcome measurements and statistical analysisThe outcome was MACEs (composite of heart failure, myocardial infarction, stroke, and cardiovascular mortality). VVHV was calculated from HbA1c levels within 3 yr after and, separately where available, before ADT initiation using coefficient of variation (CV; standard deviation [SD] divided by mean) and average real variability (ARV; average difference between consecutive measurements). Results and limitationsAltogether, 1065 patients were analysed (median age 74.4 yr old [interquartile range 68.3–79.5 yr]). In 709 patients with VVHV available before and after ADT initiation, VVHV increased after ADT initiation (p < 0.001), with 473 (66.2%) and 474 (66.9%) having increased CV and ARV, respectively. Over a median follow-up of 4.3 yr (2.8–6.7 yr), higher VVHV was associated with a higher risk of MACEs (adjusted hazard ratio [per SD] for CV 1.21 [95% confidence interval: 1.02, 1.43], p = 0.029; ARV 1.25 [1.06, 1.48], p = 0.008). Limitations included residual confounding and selection bias. ConclusionsIn PCa patients receiving ADT, VVHV increased after ADT initiation. Higher VVHV was associated with an increased risk of MACEs. Patient summaryIn prostate cancer patients receiving androgen deprivation therapy (ADT), glycaemic control is less stable after initiating ADT, which was associated with an increased cardiovascular risk.

Statin Use and Survival Among Men Receiving Androgen-Ablative Therapies for Advanced Prostate Cancer

Epidemiological evidence supports a role for statins in improving survival in advanced prostate cancer, particularly among men receiving androgen-ablative therapies. To study the association between statin use and survival among men with prostate cancer receiving androgen deprivation therapy (ADT) or androgen receptor axis-targeted therapies (ARATs). This systemic review and meta-analysis used sources from MEDLINE, EMBASE, Epub Ahead of Print, Cochrane Clinical Trials, Cochrane Systematic Reviews, and Web of Science from inception to September 6, 2022. Observational studies reporting associations of concurrent statin use and survival outcomes (in hazard ratios [HRs]). Two authors independently abstracted all data. Summary estimates pooled multivariable HRs with 95% CIs using the generic inverse variance method with random-effects modeling. A priori specified subgroup and sensitivity analyses were undertaken, and heterogeneity, study quality, and publication bias were evaluated. Confidence in the evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Overall mortality and prostate cancer-specific mortality (PCSM). Twenty-five cohorts of 119 878 men (65 488 statin users [55%]) with more than 74 416 deaths were included. Concurrent statin use was associated with a 27% reduction in the risk of overall mortality (HR, 0.73 [95% CI, 0.66-0.82]; I2 = 83%) and a 35% reduction in the risk of PCSM (HR, 0.65 [95% CI, 0.58-0.73]; I2 = 74%), with substantial heterogeneity in both estimates. Subgroup analyses identified a PCSM advantage associated with statins for men receiving ARATs compared with ADT alone (HR, 0.40 [95% CI, 0.30-0.55] vs 0.68 [95% CI, 0.60-0.76]; P = .002 for difference). Confidence in the evidence was rated low for both outcomes. The findings of this meta-analysis show that concurrent statin use was associated with reduced overall mortality and PCSM among men receiving androgen-ablative therapies for advanced prostate cancer. These findings are limited by the observational nature of the data and residual unexplained interstudy heterogeneity. Randomized clinical trials are warranted to validate these results.

Discontinuation of denosumab in men with prostate cancer.

Patients with prostate cancer receiving androgen deprivation therapy (ADT) are treated with denosumab (DMAB) to prevent fractures and preserve bone mass. We wanted to investigate the change in BMD in men with non-metastatic prostate cancer discontinuing DMAB. We conducted a retrospective cohort study based on medical records from patients referred to the Department of Endocrinology from the Department of Urology, Aarhus University Hospital between June 1, 2018, and June 1, 2021. We retrieved information on biochemistry and DXA performed 0-6months after the last DMAB injection and a second DXA performed approximately 12months after the first. In case of a BMD T-score ≤ - 1 at the lumbar spine or total hip at the first DXA, the patients were treated with zoledronate. The primary endpoint was change in lumbar spine BMD. We included 50 patients with non-metastatic prostate cancer. The mean DMAB treatment duration was 5 ± 0.1years. Among the patients treated with zoledronate (n = 9), BMD was maintained at the spine and femoral neck after a mean of 16months. We found a significant decrease in BMD; - 4.9 ± 4.2%, - 1.9 ± 3.5%, and - 2.4 ± 3.6% at the spine, total hip, and femoral neck between the first and second DXA in the patients not treated with zoledronate (n = 24) (p ≤ 0.01 for all). One patient who did not receive ZOL sustained multiple fragility vertebral fractures after DMAB discontinuation. In men with non-metastatic prostate cancer, discontinuation of DMAB after stopping ADT led to an average bone loss of 2-5%. Zoledronate prevented bone loss in men with osteopenia.

A population-based study of factors associated with systemic treatment in advanced prostate cancer decedents.

Life-prolonging therapies (LPTs) are rapidly evolving for the treatment of advanced prostate cancer, although factors associated with real-world uptake are not well characterized. In this cohort of prostate-cancer decedents, we analyzed factors associated with LPT access. Population-level databases from Ontario, Canada identified patients 65 years or older with prostate cancer receiving androgen deprivation therapy and who died of prostate cancer between 2013 and 2017. Univariate and multivariable analyses assessed the association between baseline characteristics and receipt of LPT in the 2 years prior to death. Of 3575 patients who died of prostate cancer, 40.4% (n=1443) received LPT, which comprised abiraterone (66.3%), docetaxel (50.3%), enzalutamide (17.2%), radium-223 (10.0%), and/or cabazitaxel (3.5%). Use of LPT increased by year of death (2013: 22.7%, 2014: 31.8%, 2015: 41.8%, 2016: 49.1%, and 2017: 57.9%, p < 0.0001), driven by uptake of all agents except docetaxel. Adjusted odds of use were higher for patients seen at Regional Cancer Centers (OR: 1.8, 95% CI: 1.5-2.1) and who received prior prostate-directed therapy (OR: 1.3, 95% CI: 1.0-1.5), but lower with advanced age (≥85: OR: 0.54, 95% CI:0.39-0.75), increased chronic conditions (≥6: OR: 0.62, 95% CI: 0.43-0.92), and long-term care residency (OR: 0.38, 95% CI: 0.17-0.89). Income, stage at presentation, and distance to the cancer center were not associated with LPT uptake. In this cohort of prostate cancer-decedents, real-world uptake of novel prostate cancer therapies occurred at substantially higher rates for patients receiving care at Regional Cancer Centers, reinforcing the potential benefits for treatment access for patients referred to specialist centers.

Depression, Anxiety, and Patterns of Mental Health Care Among Men With Prostate Cancer Receiving Androgen Deprivation Therapy.

Androgen deprivation therapy (ADT) use is associated with an increased risk of developing depression and anxiety. Little is known about how the mental health of these men is treated. We identified men with prostate cancer who received ADT between 2001 and 2015 using Optum's de-identified Clinformatics Data Mart Database. We determined the incidence of depression or anxiety diagnoses, mental health treatments, and the specialty of providers initiating psychotropic medications, after the start of ADT. Outcomes were compared with those of men with prostate cancer not receiving ADT and men without prostate cancer. Of 37388 men with prostate cancer treated with ADT, 3964 (10.6%) received a new diagnosis of depression or anxiety. Of those 3964 men, 1892 (47.7%) did not receive a documented treatment, 10 (0.3%) received psychotherapy, 1321 (33.3%) a selective serotonin reuptake inhibitor, and 744 (18.8%) a benzodiazepine. The median time from initiation of ADT to a depression or anxiety diagnosis was 9.3 months. Primary care physicians were the most common prescribers of psychotropic medications (72.2%). The proportion of men not receiving mental health treatments of interest (47.7%) was similar compared to men without prostate cancer (49.1%), but statistically significantly lower compared to men with prostate cancer not receiving ADT (52.7%). In men with prostate cancer receiving ADT with a new diagnosis of depression or anxiety, nearly half are not receiving mental health care while one in five is introduced to a benzodiazepine. Further investigation toward improving the mental health care for men on ADT is needed.

Safety and efficacy of apalutamide in Japanese patients with metastatic castration-sensitive prostate cancer receiving androgen deprivation therapy: Final report for the Japanese subpopulation analysis of the randomized, placebo-controlled, phase III TITAN study.

ObjectivesThe TITAN study is a randomized, double‐blind, placebo‐controlled, multinational trial that evaluated apalutamide with androgen deprivation therapy in patients with metastatic castration‐sensitive prostate cancer. At the first interim analysis in the Japanese subpopulation (median follow‐up 25.7 months), there was an improvement in overall survival and radiological progression‐free survival with apalutamide versus placebo. Here, we report the final analysis results for the Japanese subpopulation.MethodsPatients were randomized 1:1 to receive apalutamide 240 mg or placebo. After the first interim analysis, protocol treatment was unblinded, and crossover was allowed. Efficacy and safety were evaluated in the preplanned, event‐driven final analysis.ResultsFifty‐one patients were Japanese (apalutamide n = 28; placebo n = 23). After a median follow‐up of 46.0 months, the median overall survival was not reached neither in the apalutamide nor the placebo group; the hazard ratio was 0.45, favoring apalutamide, which was consistent with the overall population. Hazard ratios for time to cytotoxic chemotherapy (0.39), time to pain progression (0.87), and time to chronic opioid use (0.82) also favored apalutamide and were comparable with those of the overall population. Time to prostate‐specific antigen progression and progression‐free survival 2, respectively, was favored in the apalutamide group (0.21 and 0.44). Apalutamide was associated with higher incidences of rash and fracture in the Japanese subpopulation compared with the overall population.ConclusionsThe efficacy of apalutamide with androgen deprivation therapy in Japanese patients was consistent with efficacy demonstrated in the overall population. No new safety concerns emerged with long‐term follow‐up.

Feasibility and safety of physical exercise in men with prostate cancer receiving androgen deprivation therapy and radiotherapy: a study protocol

IntroductionAndrogen deprivation therapy (ADT) and radiotherapy (RT) increase survival in selected patients with prostate cancer. Nevertheless, the side effects of these therapies are associated with an increased risk of accidental...

Genetic Analysis Reveals the Prognostic Significance of the DNA Mismatch Repair Gene MSH2 in Advanced Prostate Cancer.

DNA damage repair is frequently dysregulated in advanced prostate cancer and has been linked to cancer susceptibility and survival outcomes. The aim of this study is to assess the influence of genetic variants in DNA damage repair pathways on the prognosis of prostate cancer. Specifically, 167 single nucleotide polymorphisms (SNPs) in 18 DNA damage repair pathway genes were assessed for association with cancer-specific survival (CSS), overall survival (OS), and progression-free survival (PFS) in a cohort of 630 patients with advanced prostate cancer receiving androgen deprivation therapy. Univariate analysis identified four SNPs associated with CSS, four with OS, and two with PFS. However, only MSH2 rs1400633 C > G showed a significant association upon multivariate analysis and multiple testing adjustments (hazard ratio = 0.75, 95% confidence interval = 0.63-0.90, p = 0.002). Furthermore, rs1400633 risk allele C increased MSH2 expression in the prostate and other tissues, which correlated with more aggressive prostate cancer characteristics. A meta-analysis of 31 gene expression datasets revealed significantly higher MSH2 expression in prostate cancer than in normal tissues (p < 0.001), and this high expression was associated with a poor prognosis of prostate cancer (p = 0.002). In summary, we identified MSH2 rs1400633 as an independent prognostic biomarker for prostate cancer survival, and the association of MSH2 with cancer progression lends relevance to our findings.

Feasibility and Safety of Physical Exercise to Preserve Bone Health in Men With Prostate Cancer Receiving Androgen Deprivation Therapy: A Systematic Review.

ObjectiveMen with prostate cancer (PCa) receiving androgen deprivation therapy (ADT) experience the loss of bone mineral density (BMD) and lean body mass, which can increase their risk of falls and fractures. Physical exercise programs with appropriate components and dosage are suggested to preserve BMD and muscle strength, thereby potentially reducing accidental falls and fractures and associated morbidity and mortality. These benefits can be obtained if exercise programs are feasible and safe and if patient adherence is adequate. This systematic review investigates the feasibility and safety of exercise programs aimed at preventing the risk of accidental falls and fractures and BMD loss in men with PCa undergoing ADT.MethodsMEDLINE, Embase, CINAHL, and the Cochrane Library were searched from database inception to June 7, 2021. Randomized controlled trials were included when they analyzed the feasibility and safety of experimental exercise programs targeting bone health in men with PCa receiving ADT. Two reviewers independently selected the studies, assessed their methodological quality, and extracted the data. Exercise feasibility was measured through recruitment, retention, and adherence rates. Exercise safety was measured through the number, type, and severity of adverse events. Furthermore, the components, setting, intensity, frequency, and duration of exercise programs were extracted.ResultsTen studies were included, with a total of 633 participants. Exercise consisted of a combination of aerobic, resistance, and impact-loading exercise or football training. Exercise is feasible in men with PCa undergoing ADT, although football training should be prescribed with caution for safety reasons.ConclusionMulticomponent exercise programs targeting bone health seem feasible and safe in this population; however, adverse events should be systematically documented according to current guidelines.ImpactThe study shows that men with PCa receiving ADT can safely perform exercise programs to preserve bone health and supports that those programs should become part of lifestyle habits.Lay SummaryMen with PCa who are receiving ADT can safely perform exercise programs to preserve bone health and should make exercise an important part of their lifestyle.

Exercise as a supportive care strategy in men with prostate cancer receiving androgen deprivation therapy at a regional cancer centre: a survey of patients and clinicians.

PurposeTo understand how frequently exercise is discussed and/or prescribed as a supportive care measure and the barriers and facilitators to exercise uptake for men with prostate cancer receiving androgen deprivation therapy (ADT) at a regional cancer centre.MethodsAn observational, cross-sectional study was conducted at a regional cancer centre in three stages: (1) Retrospective chart review of men with prostate cancer undergoing ADT to identify the frequency of discussion and/or prescription of supportive care measures; (2) prospective patient survey exploring barriers and facilitators to exercise; and (3) prospective clinician survey exploring barriers, facilitators and awareness of exercise guidelines in men with prostate cancer.ResultsFiles of 100 men receiving ADT (mean age 73 years; mean ADT duration =12 months) in the medical oncology (n = 50) and radiation oncology (n = 50) clinics were reviewed. Exercise was discussed with 16% of patients and prescribed directly to 5%. Patient survey (n = 49). 44.2% of patients reported participating in exercise at a high level. Common barriers to exercise participation included fatigue (51.0%), cancer/treatment-related weakness (46.9%) and joint stiffness (44.9%). 36.7% of patients reported interest in a supervised exercise program. Clinician survey (n = 22). 36.4% identified one or more exercise guidelines, and 40.9% correctly identified national exercise guidelines. Clinicians reported low knowledge of referral pathways to a supervised exercise program (27.3%). Clinicians believe physiotherapists (95.5%) are most suited to exercise prescription and 72.7% stated that exercise counselling should be part of supportive care. Limited time (63.6%) and patient safety (59.1%) were the two most common barriers to discussing exercise with patients. Clinicians reported that only 21.9% of their patients asked about exercise. The most endorsed facilitators to increase exercise uptake were patient handouts (90.9%) and integration of exercise specialists into the clinical team (86.4%).ConclusionDespite a third of patient respondents indicating an interest in a supervised exercise program, only 16% of patients with prostate cancer undergoing ADT at a regional cancer centre engaged in a discussion about exercise with their treating clinicians. Physical limitations and fatigue were the greatest barriers for patients. Clinicians indicated a need for more clinician education and better integration of exercise specialists into clinical care. A tailored, integrated approach is needed to improve the uptake of exercise in men with prostate cancer.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00520-021-06512-2.