Search Results (530)

Background: Although the relationship between androgen deprivation therapy (ADT) for prostate cancer (PC) and the biological mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unequivocally unclear, it is possible that exposure to the virus may influence PC evolution by altering TMPRSS2 expression. This study aims to evaluate the long-term oncological outcomes of patients with metastatic PC who were undergoing medical therapy at the time of contracting SARS-CoV-2 and who resumed/continued anticancer treatment after recovery. Methods: We retrospectively evaluated a consecutive series of 151 metastatic PC patients who developed SARS-CoV-2 infection while receiving one active systemic anticancer therapy (125 metastatic castration-resistant PC (mCRPC) patients and 26 metastatic hormone-sensitive PC (mHSPC) patients). We evaluated variables that influence the ability to maintain or resume the ongoing therapy. For the maintained/resumed therapies, we calculated the post-infection overall survival (piOS) and the overall survival (OS). Results: Of the patients, 12.6% died due to SARS-CoV-2 infection, 10.6% recovered from the infection but failed to maintain/resume the ongoing anticancer treatment, and the remaining 76.8% maintained/resumed the treatment after recovery. Hospitalization, duration of infection, and the type of ongoing anticancer agent influenced these treatment changes. In the cohort of mCRPC patients, the median piOS was 32 months, and the median OS was 67.8 months. The median piOS was not achieved in the cohort of mHSPC patients, while the median OS was 122 months. The outcomes of single anticancer agents were in line with those of pivotal trials. Conclusions: Although observed in a highly selected population of PC patients who survived SARS-CoV-2 infection and were able to resume/maintain anticancer therapy, the survival outcomes of this study appear to be in line with those reported in pivotal studies, and SARS-CoV-2 infection does not seem to have adversely affected long-term oncological outcomes. Full article

Prostate cancer (PCa) is a common malignancy in men worldwide, with incidence projected to rise in the coming years. Traditional screening and diagnostic methods, such as prostate-specific antigen (PSA) testing and biopsy, face limitations in specificity and invasiveness. Circulating microRNAs (miRNAs) have emerged as stable, non-invasive biomarkers obtainable via liquid biopsies (blood, urine, semen) that could transform PCa management. These small regulatory RNAs reflect underlying tumor biology and are detectable at early disease stages, enabling improved early detection when used alongside or in place of PSA. Distinct miRNA expression patterns correlate with tumor aggressiveness. For example, miR-141 and miR-375 are elevated in metastatic cases, whereas let-7 family members and miR-326 are upregulated in aggressive disease, highlighting their prognostic value. Moreover, dynamic changes in reported miRNAs during therapy provide real-time insights into treatment response. In androgen-deprivation therapy (ADT), oncogenic miRNAs, such as miR-21 and miR-125b, increase upon resistance, whereas a decline in tumor-suppressive miRNAs, such as miR-23b/-27b, flags the transition to castration-resistant PCa (CRPC). Similarly, baseline levels of miRNAs (e.g., miR-200b/c, miR-20a) can predict chemotherapy outcomes. Integrating multi-miRNA panels has demonstrated superior accuracy for risk stratification and monitoring, paving the way for personalized treatment. Although promising, clinical implementation of miRNA-based assays requires further validation, standardization of protocols, and large-scale prospective studies. Harnessing circulating miRNAs could usher in a new era of precision oncology for PCa, improving early diagnosis, prognostication, and real-time therapeutic guidance. Full article

High-risk and locally advanced prostate cancer represents 20–25% of new diagnoses of prostate cancer and is associated with high rates of recurrence, morbidity, and mortality. The neoadjuvant window provides a unique opportunity for systemic control prior to definitive therapy with radical prostatectomy or radiotherapy (RT). Early trials with first-generation androgen deprivation therapy (ADT) achieved pathological downstaging but no survival benefit. In the 2000s, the advent of chemohormonal regimes using docetaxel provided excitement but mixed results tempered expectations and is now not recommended prior to surgery. Second-generation androgen receptor pathway inhibitors (ARPIs) combined with ADT have demonstrated significant survival benefit in metastatic prostate cancer and are currently being evaluated in large phase III trials in the neoadjuvant setting. RT remains an alternative curative modality, and recent data highlights similar issues to surgery in eradicating micrometastatic disease despite excellent local control. This has driven parallel efforts to evaluate intensified systemic therapy in the pre-RT/neoadjuvant settings. In addition to the excitement surrounding ARPIs, radioligand therapy, such as [¹⁷⁷Lu]Lu-PSMA-617 has shown promise in the neoadjuvant setting and continues to be investigated. Future research aims to incorporate genomic and molecular factors to enable personalised neoadjuvant therapies by identifying damage immunologically responsive subtypes that may derive greater benefit from immune-directed therapies in the peri-operative setting. This narrative review synthesises current evidence for neoadjuvant therapies in high-risk prostate cancer and future directions. Full article

Background and Objectives: Chemical androgen deprivation and estrogenization are essential components of clinical treatment for advanced prostate cancer and male-to-female sex transition. The aim of this study was to determine the effects of these therapies on anthropometric parameters, liver histology, and biochemical parameters, with the goal of establishing experimental models that accurately represent current clinical practice. Materials and Methods: Young adult Wistar rats were divided into nine groups: intact control (IC), control vehicle (CV), cyproterone acetate-treated (CA), flutamide-treated (F), control sesame oil (CO), estradiol valerate-treated (E), combined control (CC), flutamide + estradiol valerate (F + E), and cyproterone acetate + estradiol valerate (CA + E)-treated groups. Treatments were administered by subcutaneous injection for four weeks. Results: The administration of estradiol valerate, alone or combined with antiandrogens, reduced final body mass and white adipose tissue mass. Notable changes were observed in absolute and relative pituitary, liver, prostate, and testis mass in the E, F + E and CA + E groups. There were no significant changes in liver histology or glycogen deposition; however, the combined treatment groups showed an increased volume density of binucleated hepatocytes and fibrotic tissue. Regarding biochemical parameters, androgen deprivation and/or estrogenization caused marked changes in serum triglyceride, LDL (low-density lipoproteins), ALP (alkaline phosphatase), AST (aspartate aminotransferase), ALT (alanine aminotransferase), Bil-T (bilirubin), creatinine, and urea levels. Conclusions: Given the importance of these therapies in clinical practice, providing a model based on the evaluated parameters offers a solid platform for future research. Full article

Background: Men treated with androgen deprivation therapy (ADT) for prostate cancer are at risk for cognitive decline. Patient genetics and endocrine state may shape gut microbiome features that relate to cognition. Methods: We studied a subsample of 79 prostate cancer survivors with prior ADT exposure previously enrolled in a randomized controlled exercise trial comparing three training modalities (strength training, Tai Chi training, or stretching control) who completed an additional food-frequency questionnaire and remote Montreal Cognitive Assessment (MoCA) and provided saliva and stool for APOE genotyping, salivary testosterone, and 16S rRNA sequencing. We used beta regression for MoCA (scaled 0–1), linear models for testosterone, alpha diversity regressions, PERMANOVA for beta diversity, and DESeq2 for genus-level differential abundance, with false-discovery correction. Results: Compared to post-stretching control, post-strength training testing was associated with higher MoCA scores whereas post-Tai Chi testing was not. APOE ε4 carriers exhibited a greater testosterone increase with strength training than non-carriers. Testosterone, and its interactions with exercise modality and APOE ε2 status, was related to presence/absence-based community structure; APOE ε4 interacted with exercise intervention to influence alpha diversity. At the genus level, exercise was linked to lower levels of Bacteroidota taxa (including Muribaculaceae) and higher levels of Enterobacteriaceae; APOE ε4 status was linked to higher Megamonas and lower Rikenellaceae RC9 levels; and higher salivary testosterone levels were linked to higher Prevotellaceae taxa and Succinivibrio levels. Higher MoCA scores were associated with lower abundances of several Firmicutes genera. Conclusions: Endocrine state and APOE genotype may condition the gut microbiome’s response to exercise intervention in ADT-treated prostate cancer survivors, with downstream associations with cognition. These findings could inform precision survivorship strategies pairing strength training with genotype- and hormone-informed microbiome monitoring to optimize cognitive performance. Full article

Background: High-risk prostate cancer is often treated with combined androgen deprivation therapy (ADT) and radiotherapy (RT). Blood biomarkers may enable treatments to be tailored to individual patients. Metabolomics, the study of small-molecule alterations in blood, is promising, and lipids are emerging as potential markers of poor prognosis. This study aims to investigate metabolic changes during prostate cancer treatment and their correlation to disease outcome. Methods: This study included 136 blood plasma samples from 35 patients with high-risk prostate cancer treated with RT and ADT, recruited from the Uppsala/Umeå Comprehensive Cancer Consortium (U-CAN) project. Blood samples were collected before, during, and after treatment and analyzed at Metabolon Inc. (Durham, NC, USA). To study differences in metabolic levels during treatment, three different sampling time points were considered: before ADT, in-between ADT and RT, and after RT. Both multivariate (orthogonal projections to latent structures, OPLS) and univariate analyses were performed, where statistical significance in combination with a large fold change was considered indicative of a substantial change. Results: Significant changes in metabolite levels were observed. Many of the significant metabolites for the whole course of treatment were also significant during ADT but not during RT, indicating that changes during ADT dominated the overall treatment. Changes were found to be especially common in steroids and fatty acids. Multivariate analysis revealed significant differences in metabolites between relapsing and non-relapsing patients. Among the significant metabolites were cholesterol and epiandrosterone. Conclusions: Metabolomics can identify biomarkers for prostate cancer treatment response and relapse. Further studies are needed to identify patterns and individual metabolites to personalize treatment strategies for prostate cancer. Full article

Background: Androgen deprivation therapy (ADT) is a fundamental component of treatment for metastatic hormone-sensitive prostate cancer (mHSPC), but it accelerates bone mineral density loss and increases fracture risk. International guidelines recommend calcium and vitamin D supplementation, baseline dual-energy X-ray absorptiometry (DXA), and antiresorptive therapy in patients with osteoporosis. Methods: We conducted a retrospective review of 156 mHSPC patients treated with ADT at a tertiary hospital between January 2022 and December 2024. We assessed adherence to guideline-recommended bone health measures. Collected variables included age, ADT duration, calcium/vitamin D supplementation, DXA testing, antiresorptive treatment, and fracture events. Exploratory stratified analyses were performed, and proportions were reported with 95% confidence intervals (CIs). Results: Calcium/vitamin D supplementation was prescribed in 50.6% of patients (95% CI: 42.9–58.4), baseline DXA was performed in 12.8% (95% CI: 8.5–18.9), and denosumab was administered in 5.1% of the cohort (95% CI: 2.6–9.8). The median follow-up was 23 months, with a fracture incidence of 0.67 events per 100 person-years. Stratified analyses showed lower adherence in older patients, those with prolonged ADT exposure, and those with high metastatic burden. Conclusions: Adherence to guideline-recommended bone health measures in patients with mHSPC receiving ADT was markedly suboptimal. These findings underscore the need to implement standardized institutional protocols to ensure systematic supplementation, routine DXA monitoring, and appropriate antiresorptive therapy. Full article

Introduction. This study aims to conduct a cost-effectiveness analysis comparing two primary treatment approaches: radical prostatectomy versus radiotherapy plus androgen deprivation therapy (ADT) in patients with Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions. Patients and Methods. Data were extracted from two published retrospective cohort studies. Using survival data from two retrospective studies, we reconstructed Kaplan–Meier curves, overlaid them for comparative metasurvival analysis, and developed a cost-function model to assess economic implications alongside clinical outcomes. The primary outcomes included biochemical recurrence-free survival (FFBF) at 2 and 5 years; the area under the survival curve; total cost per treatment strategy; and cost per recurrence-free patient at 5 years. Results. At 5 years, the estimated FFBF was 83% for radiotherapy vs. 28% for prostatectomy. Radiotherapy yielded an AUC of 80.7, while prostatectomy showed 41.9. Radiotherapy yielded a cost of 21,211 € per FFBF patient compared to 113,730 € for prostatectomy. Conclusion. Our study demonstrates that radiotherapy combined with ADT, when selected based on mpMRI stratification, may represent a cost-efficient alternative, pending prospective validation. To radical prostatectomy in patients with PI-RADS 5 prostate cancer, with a favourable cost–benefit profile. Full article

Prostate cancer (PCa) remains one of the most prevalent malignancies among men worldwide and continues to pose significant therapeutic challenges, especially in its metastatic and castration-resistant forms. Over the past two decades, the treatment paradigm has evolved from monotherapy with androgen deprivation therapy (ADT) to a multifaceted approach integrating chemotherapy, androgen receptor axis-targeted therapies (ARATs), radiopharmaceuticals, and precision medicine. This review explores the molecular underpinnings of PCa, including genetic and epigenetic alterations such as BRCA1/2, TP53, and PTEN mutations, and their role in disease progression and treatment resistance. We detail the evidence supporting the integration of systemic agents like abiraterone, enzalutamide, and darolutamide into both hormone-sensitive and castration-resistant settings. Furthermore, we highlight the expanding role of radioligand therapies, including radium-223 and Lutetium-177-labeled PSMA-617 (Lu-PSMA-617), as well as the growing impact of PARP inhibitors in genomically selected patients. The emergence of theranostic strategies and next-generation sequencing has paved the way for personalized treatment algorithms, moving toward a truly precision oncology model in PCa. This comprehensive review synthesizes current therapeutic strategies, clinical trial evidence, and future directions aimed at optimizing outcomes and quality of life for patients with advanced prostate cancer. Full article

Background/Objectives: There is growing interest in the gut microbiome’s role in cancer, particularly its influence on prostate cancer therapy. This review explores how the gut microbiota modulates treatment outcomes and how prostate cancer therapies affect microbial composition. Methods: A semi-systematic PubMed search was performed for English-language articles published between 2010 and 2025 using relevant keywords related to prostate cancer therapy and the gut microbiome. Both original research and reviews were included, with additional studies identified through citation tracking. Results: The literature reveals a dynamic, bidirectional relationship between the gut microbiome and prostate cancer therapies. Gut microbes can modulate treatment efficacy and toxicity through immune regulation, metabolic activity, and the production of bioactive compounds such as short-chain fatty acids and tryptophan derivatives. These interactions influence responses to androgen deprivation therapy, chemotherapy, radiotherapy, and immunotherapy. In parallel, prostate cancer treatments induce notable shifts in gut microbial composition, reducing diversity, increasing intestinal permeability, and promoting dysbiosis. These changes may impair therapeutic outcomes. Specific microbial taxa, including Akkermansia muciniphila, Faecalibacterium, and Bacteroides, have been linked to both therapeutic response and microbiome alterations. Conclusions: The reciprocal influence between gut microbes and prostate cancer therapies presents a compelling avenue for therapeutic innovation. However, current knowledge is largely derived from preclinical or cross-cancer studies, highlighting a major evidence gap in prostate-specific research. Bridging this gap through well-designed translational studies could inform clinical strategies that harness microbiome modulation to enhance treatment efficacy, reduce toxicity, and personalize prostate cancer therapy. Full article

Treatment-induced neuroendocrine prostate cancer (t-NEPC) is a highly aggressive and therapy-resistant subtype of prostate cancer characterized by lineage plasticity and poor response to standard chemotherapy and androgen deprivation therapy. Although transcriptional mechanisms driving t-NEPC have been extensively studied, the contribution of post-transcriptional regulation remains less defined. Here, we report fibroblast growth factor 12 (FGF12) as a critical post-transcriptional regulator of t-NEPC progression. Transcriptomic analyses of patient biopsies, patient-derived xenografts, and prostate cancer cell models consistently demonstrated elevated FGF12 expression in t-NEPC, which was further validated by immunohistochemistry in archival specimens. Functional assays revealed that FGF12 expression conferred survival of cancer cells to chemotherapeutic agents, including etoposide and camptothecin. Integrative RNA sequencing and affinity purification–mass spectrometry showed that FGF12 mediates these functions mainly through interaction with the RNA-binding protein YB1, leading to stabilization of oncogenic long noncoding RNAs, including NEAT1 and MALAT1, whereas RNA silencing of YB1 abrogated the ability of FGF12 to upregulate these transcripts. Collectively, these findings uncover a previously unrecognized FGF12-YB1-lncRNA signaling axis that drives t-NEPC progression. Targeting this pathway may provide new therapeutic opportunities for patients with this aggressive disease. Full article

Background and Objectives: Prostate cancer (PC) is largely a disease of elderly men, and de novo metastatic presentations are increasingly reported in this population. Yet older patients remain underrepresented in clinical trials, limiting the applicability of guideline-based treatments. Materials and Methods: We retrospectively analyzed 90 patients aged ≥75 years with de novo metastatic castration-sensitive PC (mCSPC) to describe clinical features, treatment patterns, and survival outcomes. Results: Median age was 81 years; high-volume disease and Gleason grade 9–10 tumors predominated. A substantial portion of patients received androgen deprivation therapy (ADT) alone or with bicalutamide despite recommendations for intensified therapy. Enzalutamide was associated with the longest median progression-free survival (PFS, 25.4 months) and overall survival (OS, 30.5 months), though between-group differences were not significant. Castration resistance occurred only in the high-volume group (22.4%). Absence of hypertension was associated with a lower risk of progression (HR 0.46, 95% CI 0.23–0.92, p = 0.028). Conclusions: Elderly patients with de novo mCSPC often have aggressive forms of the disease. Enzalutamide was associated with numerically longer survival compared to other treatments, although the difference was not statistically significant. Additionally, the absence of hypertension appeared to be linked with a lower risk of progression, suggesting that comorbid conditions such as hypertension may influence treatment outcomes in elderly patients. Full article

Prostate cancer (PCa) is the second most common cancer in men, and it is frequently diagnosed at an advanced stage of the disease. Androgen Deprivation Therapy (ADT) has traditionally represented the backbone of therapy for high-risk, recurrent, and metastatic disease; however, in the last ten years a new group of molecules known as androgen receptor pathway inhibitors (ARPIs) have been demonstrated to improve outcomes in metastatic patients when added to ADT. Developed and validated originally in the setting of castration-resistant disease, ARPIs have been implemented progressively earlier in the natural history of PCa, involving patients who have never received ADT before or that are still responsive to this treatment. Considering the strong evidence for treatment intensification in patients with high-risk features, with this review we aim to provide a complete overview of the current indications for the use of ARPIs through all the stages of castration-sensitive prostate cancer (CSPC). Full article

Background/Objectives: Metformin is one of the most frequently used concomitant medications among prostate cancer (PCa) patients. However, the effects of metformin on all-cause and PCa-specific mortality among men diagnosed with advanced/metastatic PCa treated with androgen-deprivation therapy (ADT) remain poorly understood, but they may be specifically explained by emulating a target trial. Methods: We emulated a target trial of metformin therapy and survival using observational data on 7361 patients diagnosed with advanced PCa, who were treated with ADT, from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2008–2019), with completed follow-up until 2020. We included patients with diabetes, and participants were assigned as either “initiator of metformin within 6 months after advanced PCa diagnosis” or “non-initiator of metformin.” We estimated mortality risks using Cox proportional hazards models with adjustment for risk factors via inverse probability weighting using both intention-to-treat and per-protocol analyses. Results: Over 13 years of follow-up, with a maximum 3 years of follow-up after PCa diagnosis, all-cause mortality occurred in 52 metformin initiators (47.7%) versus 3052 non-initiators (42.1%), while PCa-specific mortality occurred in 36 initiators (33.0%) versus 1919 non-initiators (26.5%). In the intention-to-treat analysis, metformin initiation was not associated with all-cause mortality (Hazard Ratio [HR] = 1.38, 95% CI: 0.98–1.95) or PCa-specific mortality (HR = 0.99, 95% CI: 0.63–1.55). Similarly, in per-protocol analysis, there was no evidence of risk reduction with all-cause (HR = 1.20, 95% CI = 0.80–1.81) or PCa-specific mortality (HR = 1.45, 95% CI = 0.88–2.38) after adjusting for time-varying covariates and allowing a 30-day gap for metformin discontinuation, adjusted for via inverse probability weighting. Conclusions: Our findings align with prior randomized trials showing no survival benefit of metformin in advanced PCa patients receiving ADT. Timing of metformin discontinuation also showed no significant effect. However, the small size of the metformin initiator group precluded subgroup analyses for hormone-sensitive (HSPC) and castrate-resistant prostate cancer (CRPC), limiting our ability to explore potential differential effects. Full article

Prostate-specific membrane antigen (PSMA) targeting agents have been the cornerstone of advanced prostate cancer (PCa) management in theranostics due to their high sensitivity for detecting and treating metastatic disease. However, approximately one-third of metastatic castration-resistant PCa (mCRPC) lesions may exhibit low or absent PSMA expression due to tumor heterogeneity, prior androgen deprivation therapy, or loss of androgen receptor expression, subsequently altering their response to PSMA-targeted therapy. The molecular and biological mechanisms underlying PSMA downregulation remain elusive but may include neuroendocrine differentiation or epithelial-to-mesenchymal transition (EMT). This review addresses this knowledge gap by examining recent preclinical and clinical evidence on novel radiotracers with the potential to provide alternative strategies beyond PSMA for imaging and treating PCa. The diagnostic performance and therapeutic potential of three emerging radiotracer classes are discussed, including gastrin-releasing peptide receptor (GRPR) ligands, androgen receptor (AR) ligands, and amino acid analogs. This article further highlights the complementary roles of these radiotracers along with their utility in specific patient populations, such as those with low prostate-specific antigen (PSA), biochemical recurrence (BCR), or confirmed PSMA-negative disease. For instance, GRPR-targeted radiotracers have achieved sensitivity of up to 88% and specificity of up to 90% for detecting primary tumors in PCa. The radiolabeled androgen agonist, fluorine-18 (¹⁸F)-fluoro-5α-dihydrotestosterone (FDHT), has demonstrated 98% true-positive rate in predicting lesions on positron emission tomography (PET) scans of mCRPC patients. On the other hand, the synthetic amino acid analog ¹⁸F-fluciclovine demonstrated a lesion detection rate of 84% for PSA levels at or above 5, and 62.5% for PSA levels ranging from 0.7 to less than 1. This review concludes with future directions on the paradigm of multi-tracer and dual-targeting strategies, which can effectively address challenges associated with PCa tumor heterogeneity and facilitate personalized approaches in theranostics. Full article