OBJECTIVE: Androgen deprivation therapy (ADT) is a mainstay of treatment for prostate cancer (PCa) and is associated with increased risks of osteoporosis and fragility fractures. Despite international guidelines to mitigate fracture risk, osteoporosis is under-diagnosed and under-treated due to poor implementation. This scoping review aims to synthesise knowledge surrounding the implementation of guidelines to inform health service interventions to reduce fracture risk in men with PCa-taking ADT (PCa-ADT).
METHODS: Four databases and additional literature were searched for studies published between January 2000 and January 2023. Studies that provided evidence influencing guidelines implementation were included. The i-PARIHS (Promoting Action on Research Implementation in Health Services) implementation framework was used to inform the narrative synthesis.
RESULTS: Of the 1229 studies identified, 9 studies met the inclusion criteria. Overall, an improvement in fracture risk assessment was observed across heterogeneous study designs and outcome measures. Six studies were from Canada. Two studies involved family physicians or a community healthcare programme. Two studies incorporated patient or specialist surveys. One utilised an implementation framework. Implementation barriers included the lack of knowledge for both patients and clinicians, time constraints, unsupportive organisational structures, and challenges in transferring patient care from specialists to primary care. Effective strategies included education, novel care pathways using a multidisciplinary approach, incorporating a healthy bone prescription tool into routine care, point-of-care interventions, and bespoke clinics.
CONCLUSIONS: There is an unmet need to provide evidence-based bone healthcare in men with PCa receiving ADT. This study highlights barriers and strategies in the implementation of fracture risk assessment for PCa-ADT patients.
CONCLUSIONS: Primary care clinicians can play a significant role in the management of complications from long-term cancer treatment such as treatment-induced bone loss. Future studies should consult patients, families, specialists, and primary care clinicians in service re-design.

OBJECTIVE: Biochemical recurrence (BCR) after primary definitive treatment for prostate cancer (PCa) is a heterogeneous disease state. While BCR is associated with worse oncologic outcomes, risk factors that impact outcomes can vary significantly, necessitating avenues for risk stratification. We sought to identify prognostic risk factors at the time of recurrence after primary radical prostatectomy or radiotherapy, and prior to salvage treatment(s), associated with adverse oncologic outcomes.
METHODS: We performed a systematic review of prospective studies in EMBASE, MEDLINE, and ClinicalTrials.gov (from January 1, 2000 to October 16, 2023) according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (CRD42023466330). We reviewed the factors associated with oncologic outcomes among patients with BCR after primary definitive treatment.
UNASSIGNED: A total of 37 studies were included (total n = 10 632), 25 after prostatectomy (total n = 9010) and 12 after radiotherapy (total n = 1622). Following recurrence after prostatectomy, factors associated with adverse outcomes include higher pathologic T stage and grade group, negative surgical margins, shorter prostate-specific antigen doubling time (PSADT), higher prostate-specific antigen (PSA) prior to salvage treatment, shorter time to recurrence, the 22-gene tumor RNA signature, and recurrence location on molecular imaging. After recurrence following radiotherapy, factors associated with adverse outcomes include a shorter time to recurrence, and shorter PSADT or higher PSA velocity. Grade group, T stage, and prior short-term hormone therapy (4-6 mo) were not clearly associated with adverse outcomes, although sample size and follow-up were generally limited compared with postprostatectomy data.
CONCLUSIONS: This work highlights the recommendations and level of evidence for risk stratifying patients with PCa recurrence, and can be used as a benchmark for personalizing salvage treatment based on prognostics.

Several phase II trials have investigated neoadjuvant novel androgen receptor signaling inhibitors (ARSIs) in combination with androgen deprivation therapy (ADT) followed by radical prostatectomy (RP) in prostate cancer (PC) patients. However, data regarding complications of intense hormone therapy and surgical complications are scarce. Our objective was to evaluate the occurrence of cardiovascular (CV) and thromboembolic (TE) adverse events (AE) in patients with localized PC who have received intense neoadjuvant ADT followed by prostatectomy. A comprehensive search in MEDLINE, Embase, Scopus and conference abstracts was performed. The strategies were developed and applied for each electronic database on March 7th, 2023. Eligible studies included randomized and single-arm trials testing ARSIs prior to prostatectomy that adequately reported safety data regarding CV and TE AE, peri-operative complications, and mortality during therapy. Pooled incidence (PI) of AE with 95% confidence interval (95% CI) was estimated using a random effects model. Quality assessment and reporting followed Cochrane Collaboration Handbook and PRISMA guidelines. PROSPERO: CRD42022344104. Nine randomized controlled trials and three single-arm phase II trials were included, comprising 702 patients (702 patients for CV AE and 522 for perioperative complications). The neoadjuvant regimen was classified as monotherapy with ARSI (100 patients), combination therapy with ADT + ARSI (383 patients), or ADT + ARSI + ARSI (219 patients). The PI of TE within the perioperative interval was 4.2% (95% CI = 2.6%-6.6%, I2 = 0.0%, P = .65), and the PI for CV AE was 4.6% (95% CI = 3.1%-6.7%, I2 = 0.0%, P = .71). Seven deaths were reported, resulting in a PI of 2.2% (95% CI = 1.3%-3.8%, I2 = 0.0%, P = .99), of which two were considered treatment-related and occurred within the perioperative period. The PI of hypertension grade 3-5 was 7.3% (95% CI = 4.8%-11.0%, I2 = 38.8%, P = .04). CV and TE AE associated with intense neoadjuvant hormone therapy in patients with localized PC can occur in up to 4.6% of cases. Our data warns for further assessment of thrombotic risk and prophylactic anticoagulation in this setting.

The changes in body composition during androgen deprivation therapy (ADT) in patients suffering from prostate cancer (PCa) are recognized by professionals more often as biomarker for effective treatment. The aim of this study was to investigate the impact of ADT on the sarcopenia development in PCa. The following databases were used: PubMed, Embase, Web of Science and Scopus databases. Out of 2183 studies, 7 were included in this review. The fixed-effect model was used in the meta-analysis. A significant increase in SATI (Subcutaneous Adipose Tissue Index) of 0.32 (95% CI: 0.13-0.51) p = 0.001, decrease in SMI (Skeletal Muscle Index) of -0.38 (95% CI: -0.57 to -0.19) p < 0.0001, and SMD (Skeletal Muscle Density) of -0.46 (95% CI: -0.69 to -0.24) p < 0.0001 were observed. No statistical association was visible between ADT and changes in BMI (Body Mass Index), 0.05 (95% CI: -0.18-0.28), p = 0.686, and VATI (Visceral Adipose Tissue Index): 0.17 (95% CI: -0.02 to 0.37), p = 0.074. In conclusion, the ADT significantly contributes to the body composition changes and sarcopenia development.

BACKGROUND: The addition of androgen receptor signalling inhibitors (ARSIs) to standard androgen deprivation therapy (ADT) has improved survival outcomes in patients with advanced prostate cancer (PCa). Advanced PCa patients have a higher incidence of osteoporosis, compounded by rapid bone density loss upon commencement of ADT resulting in an increased fracture risk. The effect of treatment intensification with ARSIs on fall and fracture risk is unclear.
OBJECTIVE: To assess the risk of falls and fractures in men with PCa treated with ARSIs.
METHODS: A systematic review of EMBASE, MEDLINE, The Cochrane Library, and The Health Technology Assessment Database for randomised control trials between 1990 and June 2023 was conducted in accordance with Preferred Reporting Items for Systematic Review and Meta-analyses guidance. Risk ratios were estimated for the incidence of fracture and fall events. Subgroup analyses by grade of event and disease state were conducted.
RESULTS: Twenty-three studies were eligible for inclusion. Fracture outcomes were reported in 17 studies (N = 18 811) and fall outcomes in 16 studies (N = 16 537). A pooled analysis demonstrated that ARSIs increased the risk of fractures (relative risk [RR] 2.32, 95% confidence interval [CI] 2.00-2.71; p < 0.01) and falls (RR 2.22, 95% CI 1.81-2.72; p < 0.01) compared with control. A subgroup analysis demonstrated an increased risk of both fractures (RR 2.13, 95% CI 1.70-2.67; p < 0.01) and falls (RR 2.19, 95% CI 1.53-3.12; p < 0.0001) in metastatic hormone-sensitive PCa patients, and an increased risk of fractures in the nonmetastatic (RR 2.27, 95% CI 1.60-3.20; p < 0.00001) and metastatic castrate-resistant (RR 2.85, 95% CI 2.16-3.76; p < 0.00001) settings. The key limitations include an inability to distinguish fragility from pathological fractures and potential for a competing risk bias.
CONCLUSIONS: Addition of an ARSI to standard ADT significantly increases the risk of fractures and falls in men with prostate cancer.
RESULTS: We found a significantly increased risk of both fractures and falls with a combination of novel androgen signalling inhibitors and traditional forms of hormone therapy.

Transwomen frequently undergo androgen deprivation therapy (ADT) incorporated with oestrogen, but they are still prone to the occurrence of prostatic cancer since the prostate remains intact. The probability of this clinical condition reduces as compared with the general male population. This study aimed to study the occurrence of prostatic malignancy under hormonal therapy such as ADT in transwomen. An extensive literature search was performed using online searches on transgender health, centring on the incidence, diagnosis, treatment and management of prostate cancer in transgender women. Original articles from 1975 to 2022 were searched using PubMed, Scopus, EMBASE, DOAJ and Cochrane databases. Physical, mental and communal deliberation of health development is the major constituent of trans-health. It exhibits a fivefold reduction in prostatic malignancies in transwomen undergoing hormonal therapy contrasted with the extensive male community of indistinguishable age.

Exercise is known to reduce adverse side effects of androgen-deprivation therapy (ADT) on quality of life, bone health and fatigue for prostate cancer (PCa) patients. We conducted a systematic review with meta-analysis to evaluate the effect of multidisciplinary interventions on body composition and metabolic syndrome (MetS) in ADT-treated PCa patients.
A systematic review and meta-analysis were conducted based on searches of EMBASE, MEDLINE, CENTRAL and Scopus databases from inception to March 2023. Participants included ADT-treated PCa patients who received multidisciplinary interventions including exercise, diet, nutrition, pharmacotherapy, bariatric surgery, or psychological/behavioural therapy. Primary outcomes were changes in body composition and MetS, with prostate-specific antigen (PSA) as a secondary outcome. After meta-analysis, results were reported in mean difference, 95% confidence interval and p-value, with forest plots. Additionally, we conducted subgroup analyses to compare the effect of different interventions.
Thirty-three articles met the eligibility criteria out of 1443 articles and 28 studies were included in meta-analysis. Of 33 studies, 17 included exercise-only interventions and 10 included exercise + diet/nutrition interventions, but no studies included diet/nutrition-only interventions. All studies employed multidisciplinary approaches in developing or delivering the interventions. Most studies (85%) had low-moderate risk of bias, thus providing good evidence to this review. Overall, interventions had a positive effect on body composition measures; lean mass (LM):0.82 kg (95% CI:0.47,1.17;p < 0.00001), body fat mass (BFM):-0.68 kg (95% CI:-1.12,-0.24;p = 0.002), fat-free mass:0.75 kg (95% CI:0.14,1.37;p = 0.02) and body fat percentage (BFP):-0.99% (95% CI:-1.29,-0.68;p < 0.00001), as well as on MetS; waist circumference:-1.95 cm (95% CI:-3.10,-0.79;p = 0.0009), systolic blood pressure:-3.43 mmHg (95% CI:-6.36,-0.50;p = 0.02) and diastolic blood pressure:-2.48 mmHg (95% CI:-4.19,-0.76;p = 0.005). Subgroup-analyses showed that a combined approach including exercise + diet/nutrition was most effective in improving BFP, WC, SBP and DBP whereas exercise was more effective in improving LM and BFM.
In ADT-treated PCa patients, multidisciplinary interventions, especially those combining exercise and diet/nutrition, can improve body composition and metabolic health.

Prostate cancer is the most common malignancy in men, mostly affecting older men who harbor an increased prevalence of cardiovascular disease and metabolic syndrome. Androgen deprivation therapy (ADT), the standard therapy for various stages of prostate cancer, further increases the risk for cardiovascular disease and for metabolic syndrome. Therefore, screening for cardiovascular risk factors should be performed prior to the initiation of ADT, and, if necessary, cardiological evaluation and interdisciplinary management should be provided during and after completion of ADT. Moreover, the use of a gonadotropin-releasing hormone (GnRH) antagonist may help reduce cardiovascular risk in patients with cardiovascular disease.
UNASSIGNED: Das Prostatakarzinom ist die häufigste Tumorerkrankung bei Männern. Es sind insbesondere Männer im fortgeschrittenen Alter mit einer erhöhten Prävalenz für das metabolische Syndrom und kardiovaskuläre Erkrankungen betroffen. Die Androgendeprivationstherapie (ADT) ist seit Jahrzehnten die Standardtherapie in verschiedenen Prostatakarzinomstadien und erhöht zusätzlich das Risiko für kardiovaskuläre Erkrankungen und für das metabolische Syndrom. Aus diesen Gründen sollte vor der Initiierung einer ADT ein Screening auf das Vorhandensein von kardiovaskulären Risikofaktoren sowie ggf. eine kardiologische Vorstellung und Mitbetreuung während und nach Abschluss der ADT erfolgen. Darüber hinaus kann bei Patienten mit kardiovaskulären Vorerkrankungen der Einsatz eines GnRH-Antagonisten („gonadotropin-releasing hormone“) helfen, das kardiovaskuläre Risiko zu reduzieren.

Measuring serum testosterone determination during medical castration is recommended by prostate cancer (PCa) guidelines to assess its efficacy and define castration resistance. It has been suggested that other biochemical compounds, such as free testosterone or luteinising hormone (LH), could also assess castration efficacy. We aimed to analyse the current evidence for serum biochemical compounds that could be appropriate candidates for evaluating medical castration efficacy. A systematic review was conducted after two investigators independently searched the literature in the PubMed, Cochrane Library, and EMBASE databases published between January 1980 and February 2023. Their searches used the medical subject headings \'prostatic neoplasms\', \'testosterone and androgen antagonists\', \'gonadotropin-releasing hormone/analogues and derivatives\', \'free testosterone\', and \'luteinising hormone\'. Studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria, and their eligibility was based on the Participants, Intervention, Comparator, and Outcome strategy. The search was limited to original articles published in English. Among the 6599 initially identified titles, 15 original studies analysing the clinical impact of serum testosterone levels in PCa patients undergoing androgen deprivation therapy (ADT) were selected for evidence acquisition. The risk of bias in individual studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. All selected studies used immunoassays to measure serum testosterone, although only methods based on liquid or gas chromatography and mass spectrometry are recommended to measure low testosterone concentrations. The reported series were not uniform in clinical stage, ADT types, and the time or number of serum testosterone measurements. Only some studies found low serum testosterone levels (<20 or <32 ng/dL) associated with greater survival free of biochemical progression and castration resistance. We conclude that little current evidence justifies the measurement of serum testosterone during ADT using no appropriate methods. No reported longitudinal studies have examined the clinical impact of serum testosterone measured using liquid chromatography with tandem mass spectrometry (LC-MSMS), free testosterone, or LH in PCa patients undergoing medical castration. We conclude that well-designed longitudinal studies examining the clinical impact of serum testosterone measured with LC-MSMS, serum-free testosterone, and LH on biochemical progression and castration resistance in PCa patients undergoing neo-adjuvant castration in radiation therapy or continuous castration are needed.

There is currently no consensus on the optimal treatment for patients with a primary diagnosis of clinically and pathologically node-positive (cN1M0 and pN1M0) hormone-sensitive prostate cancer (PCa). The treatment paradigm has shifted as research has shown that these patients could benefit from intensified treatment and are potentially curable. This scoping review provides an overview of available treatments for men with primary-diagnosed cN1M0 and pN1M0 PCa. A search was conducted on Medline for studies published between 2002 and 2022 that reported on treatment and outcomes among patients with cN1M0 and pN1M0 PCa. In total, twenty-seven eligible articles were included in this analysis: six randomised controlled trials, one systematic review, and twenty retrospective/observational studies. For cN1M0 PCa patients, the best-established treatment option is a combination of androgen deprivation therapy (ADT) and external beam radiotherapy (EBRT) applied to both the prostate and lymph nodes. Based on most recent studies, treatment intensification can be beneficial, but more randomised studies are needed. For pN1M0 PCa patients, adjuvant or early salvage treatments based on risk stratification determined by factors such as Gleason score, tumour stage, number of positive lymph nodes, and surgical margins appear to be the best-established treatment options. These treatments include close monitoring and adjuvant treatment with ADT and/or EBRT.