OBJECTIVE: The use and duration of androgen deprivation therapy (ADT) with postoperative radiotherapy (RT) have been uncertain. RADICALS-HD compared adding no (\"None\"), 6-months (\"Short\"), or 24-mo (\"Long\") ADT to study efficacy in the long term.
METHODS: Participants with prostate cancer were indicated for postoperative RT and agreed randomisation between all durations. ADT was allocated for 0, 6, or 24 mo. The primary outcome measure (OM) was metastasis-free survival (MFS). The secondary OMs included freedom from distant metastasis, overall survival, and initiation of nonprotocol ADT. Sample size was determined by two-way comparisons. Analyses followed standard time-to-event approaches and intention-to-treat principles.
UNASSIGNED: Between 2007 and 2015, 492 participants were randomised one of three groups: 166 None, 164 Short, and 162 Long. The median age at randomisation was 66 yr; Gleason scores at surgery were as follows: <7 = 64 (13%), 3+4 = 229 (47%), 4+3 = 127 (26%), and 8+ = 72 (15%); T3b was 112 (23%); and T4 was 5 (1%). The median follow-up was 9.0 yr and, with MFS events reported for 89 participants (32 None, 31 Short, and 26 Long), there was no evidence of difference in MFS overall (logrank p = 0.98), and, for Long versus None, hazard ratio = 0.948 (95% confidence interval 0.54-1.68). After 10 yr, 80% None, 77% Short, and 81% Long patients were alive without metastatic disease. The three-way randomisation was not powered to conventional levels for assessment, yet provides a fair comparison.
CONCLUSIONS: Long-term outcomes after radical prostatectomy are usually favourable. In those indicated for postoperative RT and considered suitable for no, short-term, or long-term ADT, there was no evidence of improvement with addition of ADT. Future research should focus on patients at a higher risk of metastases in whom improvements are required more urgently.

BACKGROUND: The aim of this study was to determine the proportion of patients with prostate cancer (PCa) who remained on primary androgen deprivation therapy (ADT) after starting treatment for castration-resistant prostate cancer (CRPC) and to describe their treatment patterns.
METHODS: The study comprises a retrospective analysis of 609,308 patients in urological practices in Germany from 2011 to 2020 based on anonymized secondary data from the UROscience webserver. PCa patients were eligible for inclusion if they received ADT after a 6-month prescription-free pre-index period.
RESULTS: A total of 3,112 patients (mean age 75.5 [±8.0] years) were included. Most patients received gonadotropin-releasing hormone (GnRH) agonists (72.3%), followed by antiandrogens (24.9%). The median duration of ADT treatment was 25.9 months. The estimated probabilities of continuing ADT 3, 6, and 8 years after starting treatment were 40.7%, 20.1%, and 12.7%, respectively. Interruption across all ADTs occurred in 42.7% of patients, switching of primary ADT in 52.2% and discontinuation in 82.2% of patients. After starting ADT, 14.6% of patients received treatment for CRPC, of whom 76.4% continued primary ADT. The median duration of CRPC treatment was 11.0 months. The estimated probabilities of developing CRPC 3, 6, and 8 years after starting ADT were 11.1%, 20.1%, and 25.9%, respectively.
CONCLUSIONS: This study has shown that a relevant proportion of patients discontinued primary ADT after starting treatment for CRPC, although guidelines recommend continuing ADT if the disease progresses.
UNASSIGNED: HINTERGRUND: Ziel dieser Studie war die Bestimmung des Anteils der Patienten mit einem Prostatakarzinom (PCa), die nach Beginn einer Therapie für ein kastrationsresistentes Prostatakarzinom (KRPCa) die primäre Androgendeprivationstherapie (ADT) beibehielten sowie die Beschreibung ihrer Behandlungsmuster.
METHODS: Retrospektive Analyse von 609.308 Patienten in urologischen Praxen in Deutschland von 2011 bis 2020 auf Basis von anonymisierten Sekundärdaten des Webservers UROscience. PCa-Patienten waren für die Studie geeignet, wenn sie nach einer 6‑monatigen verschreibungsfreien Prä-Indexperiode eine ADT erhielten.
UNASSIGNED: Insgesamt wurden 3.112 Patienten (Durchschnittsalter: 75,5 [± 8,0] Jahre) eingeschlossen. Die meisten Patienten erhielten Gonadotropin-Releasing-Hormon (GnRH)-Agonisten (72,3 %), gefolgt von Antiandrogenen (24,9 %). Die mediane Dauer der ADT-Behandlung betrug 25,9 Monate. Die geschätzten Wahrscheinlichkeiten, die ADT 3, 6 und 8 Jahre nach Behandlungsbeginn fortzusetzen, lagen bei 40,7 %, 20,1 % bzw. 12,7 %. Eine Unterbrechung über alle ADT hinweg erfolgte bei 42,7 % der Patienten, eine Umstellung der primären ADT bei 52,2 % und ein Abbruch bei 82,2 % der Patienten. Nach Beginn der ADT erhielten 14,6 % der Patienten eine Therapie für KRPCa, von denen 76,4 % die primäre ADT fortsetzten. Die mediane Dauer der KRPCa-Behandlung betrug 11,0 Monate. Die geschätzten Wahrscheinlichkeiten, 3, 6 und 8 Jahre nach Beginn der ADT ein KRPCa zu entwickeln, lagen bei 11,1 %, 20,1 % und 25,9 %.
UNASSIGNED: Diese Studie hat gezeigt, dass bei einem relevanten Anteil der Patienten die primäre ADT nach Beginn der Therapie für KRPCa abgesetzt wurde, obwohl Leitlinien die Fortsetzung der ADT bei Fortschreiten der Erkrankung empfehlen.

Prostate cancer (PCa) is initially sensitive to androgen deprivation therapy (ADT) but ultimately develops resistance and progresses to castration-resistant prostate cancer (CRPC) with a poor prognosis. This study indicated that some PCa patients and mice were more sensitive to ADT and entered CRPC later, which was related to the gut microbiota, especially the enrichment of Akkermansia muciniphila (AKK). Untargeted metabolomics analysis found that serum inosine level was upregulated in the treatment-sensitive group and significantly correlated with AKK. Furthermore, we revealed that intestinal permeability and serum lipopolysaccharide (LPS) levels increased in treatment-resistant mice. LPS stimulated the upregulation of p-NF-κB p65 and AR in tumors. Supplementing AKK metabolite inosine could alleviate intestinal barrier damage and reduce serum LPS level, ultimately inhibiting castration resistance via the LPS/NF-κB/AR axis. Finally, we constructed a predictive model for CRPC combining gut microbiota and clinical information (AUC = 0.729). This study revealed the potential mechanism of gut microbiota on CRPC and provided potential therapeutic targets and prognostic indicators.

BACKGROUND: In metastatic hormone-sensitive prostate cancer (mHSPC), androgen deprivation therapy and standard of care treatment intensification with docetaxel and/or an androgen receptor signaling inhibitor (ARSI) are associated with improved survival outcomes for appropriate patients.
METHODS: This retrospective study selected patients with de novo mHSPC diagnosed between 2014 and 2023 from CancerLinQ Discovery®, a United States (US)-based, de-identified clinical database. Patient-level data, including clinical characteristics, treatments, and demographics, were collected from CancerLinQ. Treatment intensification was defined as the use of docetaxel, abiraterone, apalutamide, enzalutamide, or docetaxel plus abiraterone or darolutamide. Patient characteristics and treatment intensification data were analyzed descriptively and using multivariable logistic regression.
RESULTS: Of the 3,684 patients with mHSPC, the overall rate of treatment intensification was 58.4% but increased from 32.5% in 2014 to 67.5% in 2023. A relative decline in docetaxel use was accompanied by an increase in ARSI use. Black patients with mHSPC were less likely to receive treatment identification (OR 0.78, 95% CI 0.64-0.95, P = 0.013). Treatment intensification was also less likely for patients of older age and increased ECOG performance status. Despite increasing treatment intensification for Black patients with mHSPC over time, rates of docetaxel use are disproportionately declining relative to White patients.
CONCLUSIONS: Treatment intensification rates are increasing to include the majority of patients with mHSPC. However, treatment disparities exist for Black patients, who are less likely to receive intensification. These findings illustrate the importance of promoting treatment intensification in appropriate patients and addressing racial treatment disparities.

OBJECTIVE: In patients with metastatic castration-sensitive prostate cancer (mCSPC), upfront treatment intensification with the addition of new hormonal agents and/or docetaxel to androgen deprivation therapy (ADT) is recommended. However, this modality is potentially excessive in a subset of these patients. This study aimed to identify patients who may be eligible to omit upfront treatment intensification.
METHODS: Patients with mCSPC who underwent ADT were enrolled. The association between undetectable prostate-specific antigen (PSA) (<0.2 ng/ml) after ADT initiation and overall or castration-resistance-free survival was evaluated.
RESULTS: Ninety-seven out of the 242 enrolled patients had low-risk and/or low-volume cancer and were further analyzed. Of these, 45 (46.4%) patients achieved undetectable PSA. The median follow-up period after ADT initiation was 70 months. The median overall survival among patients with undetectable PSA was quite long, reaching 226 months and significantly longer than that among patients with detectable PSA [71 months, hazard ratio (HR)=0.27, 95% confidence interval (CI)=0.15-0.49, p<0.001]. Time to development of castration-resistance was also long and significantly longer in the undetectable PSA group than that in the detectable PSA group (median: 124 vs. 17 months, HR=0.20, 95% CI=0.12-0.34, p<0.001).
CONCLUSIONS: Patients with low-risk and/or low-volume mCSPC showed long-term survival when undetectable PSA was achieved during conventional ADT. In these patients, skipping upfront treatment intensification does not seem to negatively impact survival.

暂无摘要。

Prostate cancer (PC) is the most frequently diagnosed cancer and second leading cause of cancer-related deaths in men. It is heterogeneous, as is evident from the wide spectrum of therapeutic approaches. Most patients with PC are initially responsive to androgen deprivation therapy; however, the majority of cases are either hormone-sensitive PC or castration-resistant PC. Current therapeutic protocols follow the evolution of PC, a continuously progressive process involving a combination of widespread genomic alterations. These genomic alterations are either hereditary germline mutations, such as mutations in BRCA2, or specific only to tumor cells (somatic). Tumor-specific genomic spectra include genomic structural rearrangements, canonical androgen response genes, and many other specific genes such as TMPRSS2-ERG fusion, SPOP/FOXA1, TP53/RB1/PTEN, and BRCA2. New evidence indicates the involvement of signaling pathways including PI3K, WNT/β-catenin, SRC, and IL-6/STAT, which have been shown to promote epithelial-mesenchymal transition cancer stem cell-like features/stemness, and neuroendocrine differentiation in PC. Over the last decade, our understanding of the genotype-phenotype relationships has been enhanced considerably. The genetic background of PC related to canonical genetic alterations and signaling pathway activation genes has shed more insight into the molecular subtype and disease landscape, resulting in a more flexible role of individual therapies targeting diverse genotypes and phenotypes.

BACKGROUND: Medical androgen deprivation therapy (ADT) options have expanded for patients with advanced prostate cancer (PC). Historically, ADT was primarily available in long-acting injectable formulations. In 2020, the first oral formulation was US Food and Drug Administration-approved for adults with advanced PC. This study\'s aim was to assess patient preferences for attributes of medical ADT, including mode of administration, side effects, impact on sexual interest, and out-of-pocket (OOP) costs, and to segment respondents into distinct groups based on their treatment choice patterns.
METHODS: A cross-sectional survey was conducted among US residents aged > 40 years with PC, employing a discrete choice experiment to assess preferences for ADT attributes. For each choice task, respondents were asked to select the hypothetical treatment profile that they preferred out of two presented. Latent class analysis (LCA) was conducted to estimate attribute-level preference weights and calculate attribute relative importance for groups of respondents with similar treatment preferences.
RESULTS: A total of 304 respondents completed the survey (mean age 64.4 years). LCA identified four preference groups, named according to the attribute each group considered most important: Sexual interest, Cost-sensitive, Favors daily pill, and Favors injection. Most respondents in the Sexual interest group were < 65 years, while the Cost-sensitive group was mostly ≥ 65 years. Favors daily pill had the highest proportion of ADT-naïve individuals. On average, respondents in these groups preferred an oral medication. Favors injection, which had the highest proportion of ADT-experienced individuals, preferred infrequent intramuscular injections, lower chance of post-ADT testosterone recovery, and lower OOP cost.
CONCLUSIONS: Respondents differed in their preferences regarding ADT attributes, highlighting the need for patient involvement in their treatment decisions. Effective communication between healthcare providers and patients about the benefits and risks of available therapies should be encouraged to ensure that patients receive the PC treatment that best meets their needs.
Prostate cancers often depend on the male sex hormone, testosterone, to grow. Androgen deprivation therapy (ADT) is used to lower testosterone levels in patients with advanced prostate cancer. ADT options available to patients have different characteristics, including how they are taken (injection or pill), side effects, impact on sexual interest, and costs. Researchers wanted to understand which ADT characteristics were most important to groups of patients with similar preferences. To do this, they gave 304 patients a series of two hypothetical (meaning not real) examples of ADT options with different characteristics and asked them to choose the option that they preferred most. Researchers found that patients could be separated into four different groups based on their preferences for ADT characteristics. One group preferred an ADT that had the least impact on their interest in sex. These patients were mainly younger than 65 years old. A second group preferred a lower cost ADT. These patients were mainly 65 years or older. A third group preferred a pill that could be taken once a day by mouth. Most of these patients did not take ADT in the past. A fourth group preferred an ADT that was given in a physician’s office as an injection every 6 months. These patients mainly had taken ADT in the past. This study shows that patients have different preferences for ADT treatment characteristics. It is important for doctors to discuss the different ADT options with patients to find the treatment that best meets their needs.

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.

Fracture risk is increased in men with prostate cancer (PCa) receiving Androgen Deprivation Therapy (ADT). However, routine assessment of fracture risk is often not systematically applied. We aimed to establish a comprehensive care pathway for fracture prevention in men with PCa starting ADT. Therefore, a multidisciplinary working group designed and implemented a care pathway using the \'Knowledge to Action\' framework, based on current Dutch guidelines for PCa, osteoporosis and fracture prevention, and an extensive literature review of other guidelines. The pathway was developed according to a five-step clinical approach including case finding, fracture risk assessment based on risk factors, bone mineral density test, vertebral fracture assessment, differential diagnosis, treatment, and annual follow-up. Our fracture prevention care pathway for patients with PCa at the time of ADT initiation was designed to promote a patient-centered, multidisciplinary approach to facilitate the implementation of early fracture prevention measures.