Introduction:Prostate cancer (PCa) is one of the most common cancers among men and a major cause of cancer-related mortality worldwide. In the Democratic Republic of the Congo (DRC), PCa represents an important public health challenge, with limited data available on environmental factors that may be associated with disease occurrence. Recent evidence suggests that trace element exposure may influence prostate carcinogenesis. This study aimed to compare urinary trace element concentrations between PCa patients and age-matched controls in the DRC. Methodology:This case-control analytical study was conducted between April 5, 2018, and April 5, 2023, in Haut-Katanga Province, DRC. The study included 94 PCa patients and 94 controls matched according to age and sociodemographic characteristics. Urinary concentrations of 12 selected trace elements were measured using inductively coupled plasma optical emission spectrometry. Statistical comparisons were performed using the Wilcoxon-Mann-Whitney U test due to the non-normal distribution of trace element concentrations. Results:Compared with controls, PCa patients showed significantly higher urinary concentrations of arsenic, cadmium, cobalt, chromium, copper, manganese, selenium and zinc (p < 0.05), whereas aluminium concentrations were significantly lower. No significant differences were observed for nickel, lead or strontium. These findings indicate distinct urinary trace element profiles among PCa patients and controls. Conclusion:Altered urinary concentrations of several trace elements, including toxic and essential elements, were associated with PCa status in this Congolese population. Because urinary concentrations mainly reflect recent exposure, further studies using complementary biological matrices and longitudinal designs are needed to clarify the biological significance and potential role of trace elements in PCa development.
Background:Prostate-specific antigen (PSA) levels are influenced by demographic and ethnic factors, but data from Azerbaijani men remain limited. PSA screening for prostate cancer must consider regional and ethnic variations. This study aimed to describe PSA levels and examine their clinical correlates in a hospital-based cohort of Azerbaijani men presenting to a urology clinic. Methods:This retrospective cross-sectional study included 1175 Azerbaijani men aged 40-75 years who presented to a urology clinic without a known diagnosis of prostate cancer between January 2023 and December 2024. Data collected included age, total PSA, digital rectal examination (DRE)-estimated prostate size category, prostate volume (via ultrasound), maximum urinary flow rate (Q max), and International Prostate Symptom Score (IPSS). Multivariate logistic regression was used to identify predictors of PSA elevation. Results:The median PSA level was 1.15 ng/mL (range: 0.001-112.1), with 85.1% of patients exhibiting levels below 4 ng/mL. PSA levels increased with age: 0.86 ng/mL in men aged 40-49, 1.2 ng/mL in those 50-64, and 1.44 ng/mL in men 65-75 years (p < 0.001). PSA correlated positively with age, IPSS, and prostate volume and negatively with Q max (all p < 0.001). PSA levels varied with DRE-estimated prostate size category, showing significant differences between Categories 2 and 3 (p = 0.002). Multivariate analysis identified age as an independent predictor of PSA ≥ 4 ng/mL. Conclusions:In this hospital-based cohort of Azerbaijani men, PSA levels were positively associated with age, and age was independently associated with PSA ≥ 4 ng/mL. These findings provide important regional data and support further investigation of age-specific PSA patterns in the Azerbaijani population.
Background:mpMRI is now widely used before prostate biopsy and has improved the detection of clinically significant prostate cancer (csPCa). However, the subsequent risk of csPCa among men with both negative mpMRI and negative systematic biopsy (SBx) remains uncertain. Purpose:To evaluate the observed medium-term risk of csPCa in biopsy-naïve men with initially negative mpMRI and negative SBx. Methods:This post hoc longitudinal follow-up subanalysis included biopsy-naïve men from the prospective multicenter MULTIPROS trial who had negative baseline mpMRI (PI-RADS ≤ 2) and negative SBx. Of the 582 enrolled men, 169 had negative mpMRI; 138 underwent baseline SBx, of whom 8 had csPCa, and 31 had < 12 months of follow-up, leaving 99 men for analysis. Follow-up was PSA-based, with repeat mpMRI and biopsy performed when clinically indicated. Kaplan-Meier analysis estimated csPCa-free survival. Results:During a mean follow-up of 61.8 ± 22.1 months, four patients were diagnosed with csPCa (4/99; 4.0%). The mean time from initial negative mpMRI to csPCa diagnosis was 68.3 ± 22.4 months. Repeat biopsy was performed in 16 patients. csPCa-free survival was 100% at 24 months and 97.3% at 60 months (95% CI: 93.7%-100%). Conclusion:In this selected cohort of biopsy-naïve men with both negative mpMRI and negative SBx, the observed incidence of csPCa during medium-term follow-up was low but based on only four events. Because repeat imaging and biopsy were selectively triggered rather than systematically performed, the true incidence of csPCa may be underestimated. Continued PSA-based monitoring, with repeat mpMRI and biopsy when clinically indicated, remains important.
Background and Objective:Accurate risk stratification in localized prostate cancer is essential for guiding treatment decisions. Conventional National Comprehensive Cancer Network (NCCN) risk groups rely on prostate-specific antigen (PSA), Gleason grade group, and clinical stage, while artificial intelligence (AI) methods, including radiomics, digital pathology, and multimodal prediction models, are increasingly being evaluated as alternatives or complements. This systematic review aims to assess studies published between 2020 and 2025 that directly compare AI-based models with traditional NCCN risk stratification methods in localized prostate cancer. Methods:A systematic search of PubMed/MEDLINE, Scopus, and Cochrane Library (January 2020-September 2025) was conducted. Eligible studies focused on localized prostate cancer, used AI-based models, compared them with NCCN risk stratification or its components, and reported outcomes such as the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, calibration, or decision-curve analysis. Case reports, nonhuman studies, and abstracts without full data were excluded. Title/abstract and full-text screening was performed independently by two reviewers. Risk of bias was assessed using PROBAST, and reporting transparency was benchmarked against TRIPOD-AI. Results:Out of 686 records, 100 duplicates were removed. Of the 586 screened, 95 were excluded. A total of 491 records mapped to NCCN components and compared AI with conventional methods; 43 full-text studies met inclusion criteria. AI approaches combining MRI radiomics, PET imaging, and histopathology whole-slide analysis consistently showed higher discrimination than NCCN models, especially for predicting adverse pathology and biochemical recurrence. However, calibration, external validation, and reporting quality were addressed inconsistently. Conclusions:AI-based methods show promise in improving NCCN risk stratification for localized prostate cancer, delivering better prognostic accuracy than traditional approaches. However, variability in methods, limited external validation, and gaps in transparent reporting highlight the need for larger, multiinstitutional prospective studies before these methods can be widely adopted in clinical practice.
Background:Considering the hepatotoxicity and other side effects associated with flutamide as a first-line treatment for prostate cancer (PCa), this study aimed to evaluate metformin as a potential anticancer agent to reduce the required dose of flutamide and thereby minimize its adverse effects. Method:We assessed the influence of metformin, flutamide, and metformin-flutamide combination therapy on LNCaP, DU145, and PC3 cell lines, which represent human PCa. The tests include wound-healing assay, colony formation assay (CFA), analysis of apoptosis (programmed cell death) and cell cycle by flow cytometry, gene expression at the mRNA level by real-time PCR (BAX/BCL2, E-cadherin, Snail, HIF1α, VEGFC, and KLK3 genes), and assessment of the treatments' hepatotoxicity potential via measuring AST and ALT values. Result:To determine the IC50 (half-maximal inhibitory concentration) values, cell lines were treated with different concentrations of the drugs. The IC50 values for metformin (800 μM) in the three cell lines and for flutamide (12 μM for PC3 and 10 μM for LNCaP/DU145), as determined by MTT assay, were confirmed by flow cytometry, indicating significant cell cycle arrest at the G0/G1 phase. The combination of metformin and flutamide significantly increased the BAX/BCL2 mRNA ratio in all three cell lines (p < 0.0001) and downregulated the expression of KLK3 (p < 0.01), HIF1α (p < 0.01), VEGFC (p < 0.001), and EMT pathway genes in PC3 and LNCaP (p < 0.01). Liver injury assessment reported a reduction in flutamide's hepatotoxicity in combination with metformin. Conclusion:Metformin in combination with flutamide reduced its dose and increased the sensitivity of PCa cells to treatment. Additionally, it mitigated the hepatotoxic effects of flutamide. Therefore, this combination may represent a new treatment strategy for PCa.
Cabazitaxel is a second-generation semisynthetic taxane approved for the treatment of prostate cancer. Vitamin K, an essential nutrient involved in blood coagulation and bone metabolism, has also been shown to have antineoplastic effects. However, no information is currently available regarding the combinatorial effects of cabazitaxel and menadione (VK3, a derivative of vitamin K) on prostate cancer cells. Therefore, we investigated the in vitro effects of cabazitaxel, VK3, and their combination on growth, mitochondrial bioenergetics, and glycolytic parameters using the human prostate cancer cell lines PC-3 and DU 145. All treatments inhibited the cell growth, but the combination of cabazitaxel and VK3 produced a synergistic effect that was stronger than either compound alone, and these effects were accompanied by cell line-specific bioenergetic changes and glycolytic responses. Furthermore, high-throughput transcriptomic profiling of PC-3 cells revealed distinct sets of differentially expressed genes for each treatment, with the greatest effect established by the combinatorial treatment, followed by VK3, and then cabazitaxel. Gene ontology analyses showed that the combinatorial treatment was associated with biological processes such as positive regulation of reactive oxygen species metabolic process, steroid metabolic process, proteolysis, and signal transduction. Notably, the treatments altered the gene expression of several tumorigenic and immunologic mediators, including MSXI, ZRSR2, GALNTL6, IL24, and IL18R1, which may impact cancer cell behavior. In conclusion, these in vitro findings indicate that the combination of cabazitaxel with VK3 is more effective in inhibiting prostate cancer cell growth than either agent alone and provide exploratory mechanistic insight into their effects on cancer cell metabolism and gene expression.
Background:Prostate cancer (PCa) ranks as the fourth most prevalent form of cancer overall and imposes a substantial financial burden on individuals and communities. Given information on the costs of this disease and the factors influencing them, the present study analyzed factors affecting the costs of medical and nonmedical services for patients with PCa in southern Iran. Methods:Factors affecting the cost of PCa were identified through a scoping review of international databases (ISI Web of Science, Scopus, PubMed, ProQuest, Magiran, and SID) and consultation with PCa experts. Subsequently, data on 254 PCa patients were collected between March 2020 and March 2022 using a two-stage stratified random sampling method. Patients were randomly selected from the provincial Cancer Registry Center lists within strata defined by healthcare catchment areas. Multiple regression analysis using SPSS 13.0 was employed to determine the factors influencing costs. Results:The findings from the multiple regression analysis indicated that premature mortality, grade, and monthly income (all p value < 0.001) were important factors affecting PCa patients' costs. Conclusions:In line with the results, implementing low-cost screening systems for early detection and effective treatment of PCa at all income levels, and directing targeted subsidies to the health sector, especially to low-income patients, can help reduce costs for PCa patients.
Background:Prostate cancer is the second most commonly diagnosed cancer worldwide. Although androgen deprivation therapy initially demonstrates clinical benefit, disease relapse with more aggressive phenotypes frequently occurs. The acidic tumor microenvironment in solid tumors may alter drug responsiveness. This study investigates how extracellular pH influences the cytotoxic effects of bicalutamide in human prostate cancer cell lines. Methods:PC3 and LNCaP cells were exposed to bicalutamide at varying concentrations at pH 7.4 and pH 6.8. IC50 values were determined using the MTT assay. Cell migration, apoptosis, and cell cycle distribution were evaluated by wound-healing assay, annexin V/PI staining, and DNA content analysis, respectively. The expression of BAX, BCL2, E-cadherin, N-cadherin, SNAI1, AR, and VEGF-C was quantified by qPCR. Results:Bicalutamide (140 μg/mL) reduced PC3 cell viability to 39.62% at pH 7.4 compared with 51.36% at pH 6.8. In LNCaP cells, viability declined to 33.64% at pH 7.4% and 56.09% at pH 6.8. Treated PC3 cells exhibited significantly greater migration at pH 6.8 (p < 0.01). Early apoptosis in treated LNCaP cells was significantly reduced at pH 6.8 (p < 0.001). Both cell lines demonstrated enhanced S phase accumulation and reduced G1-phase distribution at pH 6.8. The BAX/BCL2 ratio was significantly decreased at pH 6.8, indicating the suppression of proapoptotic signaling. Additionally, genes associated with epithelial-mesenchymal transition (EMT) were upregulated, and VEGF-C and AR expression increased at pH 6.8 (p < 0.05). Conclusion:The efficacy of bicalutamide in prostate cancer cells is significantly influenced by extracellular pH. The drug exerts stronger cytotoxic, antimigratory, and proapoptotic effects at physiological pH (7.4) compared with acidic conditions (6.8).
Background Although treatment options for metastatic castration-resistant prostate cancer (mCRPC) have been increasing since 2014, the actual treatment sequences of each drug in clinical practice in Japan have only been reported in a limited number of patients and facilities. The primary objective of this database study was to investigate the general situation and the transition of prior and post-mCRPC treatments. Methods Using Medical Data Vision's medical record database across Japan, patients diagnosed with mCRPC from January 2015 to December 2022 based on defined criteria were extracted. Treatment sequences before and after mCRPC diagnosis were analyzed. Results Analysis of 4967 patients revealed that the most common pretreatment for mCRPC was classical vintage hormone therapy (77.1%), followed by androgen receptor signaling inhibitors (ARSI), including enzalutamide (7.8%) and abiraterone (7.4%). The most common treatments for first-line mCRPC were enzalutamide (43.1%), abiraterone (28.3%), and docetaxel (10.7%). When the treatment prior to mCRPC was ARSI, docetaxel was the most common first-line treatment for mCRPC, but another ARSI that had not been used as treatment prior to mCRPC was also selected as first-line mCRPC treatment at a similar rate to docetaxel. Regarding annual changes, the proportion of vintage hormone therapy for mCRPC has been decreasing annually, and there has been a trend to replace it with ARSIs. Conclusion In terms of the treatment sequence for mCRPC in Japan, vintage hormone therapy was the most common pretreatment for mCRPC, and ARSIs were the most common first-line treatments for mCRPC.
Background:Both healthy and malignant prostate tissues express the glycoprotein marker known as prostate-specific antigen (PSA). When checking for prostate lesions, serum total PSA levels are a major factor. However, the exact levels to rely on are not explicit. Objective:To ascertain the relationship between histopathological findings and serum levels of the PSA in patients in southwest Uganda. Methods:This cross-sectional study involved 71 participants in southwestern Uganda from January to July 2023, who underwent histological examinations. Blood samples were taken off for total serum PSA level measurement. Stained formalin-fixed paraffin-embedded sections were examined. Histological results and PSA levels were correlated using Spearman's correlation coefficient. Results:The study involved 74 participants with an average age of 74.20 ± 9.40 years and average Gleason score of 7.73 ± 1.04. Only 1/71 (1.41%) had prostatic intraepithelial neoplasia (PIN), 36/71 (50.70%) had benign prostate hyperplasia (BPH), and 34/71 (47.89%) had prostate adenocarcinoma (PAC). A significant correlation was observed between PSA levels above 100 ng/mL (p = 0.001, rho = 0.5955) and prostate cancer and between PSA levels up to 20 ng/mL (p = 0.010, rho = 0.03033). AUC of 0.85 (95% CI: 0.77-0.94) showed good predictive power of the test. PSA optimal cut off was 103.4 ng/mL, at sensitivity of 68% and specificity of 92% with maximum Youden index (J): 0.595. Conclusion:There was a significant correlation between BPH with PSA levels up to 20 ng/mL and above 100 ng/mL for prostate adenocarcinoma. In some of the cases, however, total serum PSA levels were high for BPH and low for prostate adenocarcinoma. PSA test usefulness cannot be nullified, but its accuracy and specificity have to be ascertained in order to increase its reliability. Future researches are argued to focus more on how to refine PSA-based diagnostics through identifying any underlying unknown hereditary factors and probably better biomarkers that could be influencing PSA levels. With this, dependability increases and unnecessary biopsing reduces, thus alleviating anxiety in patients and probably their caregivers. Contributions of this study:The study provides additional insights into the importance and clarity of total serum PSA levels in prostate screening and diagnosis.
Background:At the height of the COVID-19 pandemic, healthcare utilization among cancer patients, including those with prostate cancer, was limited due to inadequate healthcare resources and concern for disease transmission among patients and medical personnel. While publications with treatment recommendations during the pandemic exist, there is limited real-life data comparing prostate cancer management pre-COVID to during the pandemic. Objective:The primary aim of this study is to determine the effect of the COVID-19 pandemic on prostate cancer management at a tertiary medical center by comparing patients receiving treatment preceding the pandemic to those receiving treatment during the height of the pandemic. Methods:Prostate cancer patients treated with definitive intent (surgery, definitive radiation (RT), or salvage RT) in 2019-2020 were retrospectively reviewed. Analysis was performed with the following timeframes: pre-COVID as 1/3/19 to 2/28/20 and COVID as 3/1/20 to 9/30/20. Time-to-treatment (TT) for surgery and definitive RT was defined from the date of diagnosis (biopsy or decision to treat if active surveillance) to the date of surgery or RT start, respectively. TT for salvage RT was defined as the date of PSA failure to RT start. Descriptive statistics such as medians and interquartile ranges (IQRs) were reported for continuous variables, while frequency counts and percents were reported for categorical variables. Chi-squared tests (Fisher's exact when appropriate) along with Wilcoxon rank sum tests were used to compare two timeframes. Two adjusted binary logistic regressions assessed the associations of NCCN risk groups, as well as grade group (GG), on the outcome of receipt of treatment during COVID compared to those in pre-COVID timeframes. Results:This study sample included 565 prostate cancer patients treated with surgery (n = 303), definitive RT (n = 151), or salvage RT (n = 111). There was a statistically significant difference in TT by timeframe for all patients (median 111 days pre-COVID v 126.5 days COVID, p = 0.007). For patients who received definitive or salvage RT with ADT, there were significant differences in time from ADT initiation to treatment start between pre-COVID vs. COVID (definitive RT: median 78 days v 147 days, p = 0.001; salvage RT: median 67 days v 84 days, p = 0.004). A significantly higher proportion of patients received ADT prior to surgery in the COVID cohort compared to those in pre-COVID (9.8% v 0.5%, p < 0.001). Patients with clinically more aggressive prostate cancer had higher odds of being treated in the COVID timeframe (HR or VHR, adjusted OR [aOR] 1.62, 95% CI: 1.02-2.55). Conclusions:The COVID-19 pandemic changed prostate cancer management in various ways including longer TT, prolonged time from ADT initiation to RT, increased utilization of ADT for patients planned for surgery, and prioritizing treatment for higher-risk disease. Analysis of treatment outcomes for these patients may direct action in future global pandemics.
Background:Multiparametric magnetic resonance imaging (mpMRI) has been widely utilized in clinical practice for identifying clinically significant prostate cancer (csPCa). Although mpMRI demonstrates a pooled negative predictive value (NPV) of 90%, additional clinical parameters require evaluation to enhance this metric specifically for the Chinese population-given the rising incidence of PCa in China, as well as ethnic differences in average prostate volume (PV) and chronic prostatitis prevalence that may impact mpMRI's diagnostic performance. Methods:A retrospective analysis was conducted on 543 patients who underwent transrectal ultrasound-guided prostate biopsy at Beijing Tsinghua Changgung Hospital between November 2014 and March 2025. After applying exclusion criteria, 412 patients were enrolled, all of whom had completed prebiopsy mpMRI within 1 month prior to biopsy. Patients were stratified into four groups based on the results of MRI examination and the pathological outcomes of biopsy: MRI (-) PCa (-), MRI (+) PCa (-), MRI (-) PCa (+), and MRI (+) PCa (+) groups. Multivariate logistic regression analyses were used to assess the odd ratios (ORs) of potential predictors for csPCa, comparing the MRI (-) PCa (+) and MRI (-) PCa (-) groups. Receiver operating characteristic curves were generated to analyze the predictive values of total PSA (tPSA), free PSA (fPSA), free-to-total (f/t) PSA, PV, PSA density (PSAD), and adjusted PSAD (PSADadj, defined as PSAD × weight) for csPCa in patients with negative MRI. Results:The patient distribution was as follows: MRI (-) PCa (-) group: 27.9% (115/412), MRI (+) PCa (-) group: 36.9% (152/412), MRI (-) PCa (+) group: 2.4% (10/412), and MRI (+) PCa (+) group: 32.8% (135/412). The NPV of MRI for csPCa was 92%. Multivariate analyses indicated that PV was negatively associated with the presence of csPCa (OR = 0.940, 95% CI: 0.896-0.986, p = 0.012), while PSAD and PSADadj were positively associated with csPCa occurrence (OR = 10.288, 95% CI: 1.569-67.46, p = 0.015; OR = 1.027, 95% CI: 1.001-1.053, p = 0.043, respectively). For MRI-negative patients, PV > 55.25 mL (sensitivity = 100%, specificity = 63.2%), PSAD < 0.100 ng/mL2 (sensitivity = 100%, specificity = 25.4%), or PSADadj < 7.24 ng/mL (sensitivity = 100%, specificity = 28.1%) enhanced MRI's NPV to 100%, while PSAD < 0.205 ng/mL2 (sensitivity = 77.8%, specificity = 71.9%) and PSADadj < 24.97 ng/mL (sensitivity = 55.6%, specificity = 90.4%) improved NPV to 97.6% and 92.6%, respectively. Conclusion:In Chinese men with negative prostate MRIs, PV > 55.25 mL, PSAD < 0.100 ng/mL2, or PSADadj < 7.24 ng/mL may elevate mpMRI's NPV from 92% to 100%, enabling safe avoidance of unnecessary biopsies. Prospective multicenter validation is required to confirm these findings.
Background:Most therapy options for castration-resistant prostate cancer (CRPCa) target the androgen axis. Human kallikrein-related peptidase (KLK) 2, a serine protease, is a downstream target gene of the androgen receptor (AR) involved in cancer progression, but also known to have an AR-independent function. Tissue KLKs, especially KLK2, are promising targets for therapy in advanced PCa because of their high PCa specificity and their correlation to the rising cancer grade and stage. By inhibition with the recombinant protease inhibitor MDPK67b targeting KLK2 and other trypsin-like KLKs including KLK4 and KLK14, we investigated the antitumor response and the influence on AR downstream target genes with MDPK67b in PCa cell lines in vitro. Methods:Human PCa cells were cultured in a charcoal-stripped media and treated with MDPK67b (0.75 mg/mL). Cell viability was measured by CellTiter-Glo luminescent assay, cell death by flow cytometry. Gene analysis of AR, PSA, and PSMA was performed by qPCR. Correlating protein levels were evaluated by immunoblotting and confirmed by immunocytochemical staining. Results:Treatment with 0.75 mg/mL MDPK67b led to a reduction of cell proliferation of 40% by day 5 in androgen-sensitive LNCaP cells. Immunostaining confirmed the decrease in cell proliferation by antibody labeling of Ki-67. Treatment induced apoptosis, which was visible by flow cytometry of annexin V in LNCaP cells. Further, MDPK67b induced a reduction in AR and PSA gene and protein expression but upregulated PSMA, a target for PCa imaging and therapy. Conclusion:Treatment with MDPK67b demonstrates a significant antitumor effect by relevant reduction in cell proliferation and upregulation of apoptosis in LNCaP cells. Blockage of secreted KLKs can downregulate the AR and thereby influence its downstream target genes like PSA and PSMA. Upregulation of PSMA can lead to a theranostic, that is, therapeutic and diagnostic, advantage in clinics in a CR setting. Therefore, inhibition of KLKs represents a promising and AR-independent approach to treat advanced and CRPCa. Trial Registration:ClinicalTrials.gov ID: NCT04644770.
The first cellular cancer immunotherapy, sipuleucel-T, was approved for metastatic castration-resistant prostate cancer (mCRPC) patients 15 years ago. Since then, the therapeutic landscape of advanced prostate cancer has significantly evolved. Sipuleucel-T is a personalized, autologous immunotherapy that activates the patient's immune system to target prostatic acid phosphatase (PAP)-expressing tumor cells and has demonstrated survival benefit in patients with nonopioid requiring mCRPC. Subsequent clinical trials and abundant real-world data have provided further evidence of this novel immunotherapy's clinical benefit for patients with mCRPC, as well as demonstrating the numerous immune and biologic responses that sipuleucel-T induces. These data have also identified patient-specific factors associated with longer survival, including race, baseline disease burden, and treatment-induced immune responses. Despite the addition of multiple life-prolonging therapeutic modalities now available to treat patients with mCRPC, the mechanism of action of sipuleucel-T remains unique for patients with advanced prostate cancer. Therefore, maximizing the appropriate clinical utilization of sipuleucel-T in patients with mCRPC within current treatment paradigms is essential.
Background:Prostate cancer is the second leading cause of cancer death among men, with a disproportionate burden on Black men. Racial disparities in care delivery for early-stage disease are well documented but less is known about racial gaps in advanced prostate cancer care, a stage where effective therapies can prolong life for years. We sought to evaluate potential treatment disparities among Black and White men with metastatic prostate cancer. Methods:We performed a retrospective cohort study of patients with metastatic prostate cancer receiving treatment at a large public tertiary care health system between 2015 and 2020 using electronic health record data. We estimated the prevalence ratio (PR) of being prescribed each of the recommended treatment options for metastatic prostate cancer as per National Comprehensive Care Network guidelines, including androgen receptor pathway inhibitors (ARPIs) and other antiandrogens, chemotherapy, and bone protection, comparing Black men to White men. Results:We identified 1166 patients with metastatic prostate cancer treated with androgen deprivation therapy (ADT); 370 (32%) were Black. Prescribing of systemic treatments did not differ by race, notably including ARPI (PR: 0.98 95% CI: 0.98-1.1, p=0.8). About 30% of both Black and White patients interacted with our patient navigation team, a group of oncology nurses focused on ensuring patients receive recommended care. Conclusions:In a large public tertiary care health system, we did not observe racial disparities in the prescribing of guideline-recommended therapies for metastatic prostate cancer. High rates of insurance, a robust patient navigation program, and a well-developed pharmacy assistance program may have helped mitigate racial disparities in care. Future studies should prospectively evaluate the delivery of prostate cancer therapies across health systems and the influence of navigation and pharmacy assistance programs.
Objectives:To assess the validity of magnetic resonance imaging-determined tumor contact area (MRI-TCA) as a predictive factor for pathological extraprostatic extension (EPE) in cT2N0M0 prostate cancer patients. Methods:We retrospectively analyzed 72 cT2N0M0 prostate cancer patients who underwent multiparametric MRI (mpMRI) followed by robot-assisted laparoscopic prostatectomy (RARP) between February 2014 and April 2021. Patients whose MRI-based index lesion did not match the pathological specimens were excluded. MRI-TCA was approximated using an elliptical shape and calculated by two different methods: MRI-TCA1: Calculated using the tumor contact length (TCL) in the axial plane and the longer TCL in either the sagittal or coronal plane, capturing tumor dimensions across two planes. MRI-TCA2: Calculated using the TCL in the axial plane and tumor thickness derived from MRI slice data, reflecting the tumor's contact area within the MRI volume. We compared postoperative prostate-specific antigen (PSA) recurrence-free survival by stratifying patients based on the optimal thresholds of MRI-TCL, MRI-TCA1, MRI-TCA2, pathological-TCL, and pathological-TCA. Results:Sixteen patients (22.2%) were pathologically positive for EPE. MRI-TCL, MRI-TCA1, and MRI-TCA2 were significantly greater in patients with EPE-positive (EPE+) tumors than in those with EPE-negative (EPE-) tumors (p < 0.0001, p < 0.0001, and p = 0.0026, respectively). No statistically significant differences were found between MRI-TCL and MRI-TCA1 (p = 0.914) or between MRI-TCL and MRI-TCA2 (p = 0.112) in predicting pathological EPE. A significant difference in postoperative PSA recurrence rate was observed in the stratified analysis based on pathological-TCA (p = 0.022). Conclusion:Both MRI-TCA1 and MRI-TCA2 are clinically accessible and effective parameters for predicting pathological EPE in cT2N0M0 prostate cancer patients. However, neither method demonstrated clear superiority over MRI-TCL. Pathological-TCA was shown to be a significant predictor of both pathological EPE and postoperative PSA recurrence.
Prostate cancer is the most frequently diagnosed tumor of male reproductive system. Clinically, there is a lack of effective treatment drugs for prostate cancer. Previous studies have shown that AMPK inhibitor dorsomorphin was demonstrated to have potent antitumor effects. However, the effect of dorsomorphin on prostate cancer and its molecular mechanism are still unclear. In this study, the effects of dorsomorphin on the invasion and infiltration, epithelial-mesenchymal transition (EMT), and angiogenesis were investigated in two types of prostate cancer cells (DU145 and PC-3). In addition, nude mouse tumorigenic experiments were performed to confirm the antitumor effect of dorsomorphin. We found that dorsomorphin treatment concentration- and time-dependently inhibited the invasion and infiltration of DU145 and PC-3 cells. In addition, dorsomorphin reduced the expression levels of extracellular matrix components and angiogenesis-related proteins (HIF-1α and VEGF). Further study showed that dorsomorphin inhibited matrix deposition by antagonizing the EMT. Our results from nude mouse tumorigenic experiments further demonstrated dorsomorphin's tumor-growth inhibitory effect, whereas its antimetastatic potential is supported by in vitro invasion and EMT assays. Mechanistically, dorsomorphin treatment suppressed TGF-β1 expression and thereby inhibited the phosphorylation and nucleation of Smad2/3 signaling, which plays a key role in the regulation of EMT. Further study showed that dorsomorphin-triggered inactivation of JAK2/STAT3 and sonic hedgehog (Shh) signaling was involved in the inhibition of TGF-β1-mediated EMT. Interestingly, dorsomorphin inhibited the expression and nucleation of Gli1 and Gli3 but not affected the expression of Gli2. Thus, these findings reveal that the new mechanism of AMPK inhibitor dorsomorphin against prostate cancer metastasis is through synergistically antagonizing JAK2/STAT3 and Gli2-independent Shh activation.
Background: Fibroblast growth factor receptor 1 (FGFR1) signaling is activated by fibroblast growth factors (FGFs) during prostate cancer (PCa) progression. However, the mechanisms by which FGFR1 signaling regulates PCa progression are not fully understood. The objective of this study was to investigate the cross talk between autocrine FGF/FGFR1 loop and aerobic glycolysis in progression of advanced PCa. Method: DU145 cells were used as an advanced PCa model. FGFR1 expression was knockdowned by stable expression of anti-FGFR1 shRNA, and lactate dehydrogenase A (LDHA) levels were rescued by ectopic expression of LDHA cDNA. Protein expression was determined using Western blotting and immunohistochemistry. Tumorigenicity of DU145 cells was defined by cell growth, invasion, and survival in both cultures and xenografts in mice. Results: Here, we showed that DU145 cells in cultures expressed both FGF2 and FGFR1, and knockdown of FGFR1 expression or inactivation of FGFR1 signaling reduced LDHA expression or aerobic glycolysis, which was correlated with suppression of both cell proliferation and invasion, and with promotion of apoptosis. Ectopic expression of LDHA cDNA rescued LDHA levels in FGFR1-deficient cells, restoring their aerobic glycolysis, cell growth, and survival. Similarly, the growth rates of xenografted DU145 cells in mice were decreased by the loss of FGFR1 expression but were rescued by the ectopic expression of LDHA. Conclusion: Our data indicate autocrine FGF/FGFR1 signaling regulates aerobic glycolysis in PCa DU145 cells via LDHA, suggesting the potential of targeting FGFs/FGFRs-LDHA for the management of advanced PCa. The regulation of aerobic glycolysis by other growth factors in PCa remains further investigation.
High-intensity focused ultrasound (HIFU) is a noninvasive modality that is gaining prominence for the localized treatment of malignant tumors. Most current HIFU research utilizes mouse tumor models, where selection of appropriate mouse breed is important for conducting thermal ablation experiments on tumors with consistency. In this study, three breeds (NOD/SCID GammaC -/- (NSG), NSG-SGM3 (NSGS), and Homozygote J:NU (Nude); n = 2 per group) originating from Jackson Laboratory were tested for identifying the breed that has sufficient size for conducting HIFU experiments. Tumors were developed using a human PC3 (CRL-1435) prostate cancer cell line and monitored over 5 to 7 weeks. The surface area and volume of the implanted tumors were determined by assuming the tumor having an ellipsoidal shape. At the end of the growth period, NSG mice exhibited 29% larger tumor surface area than NSGS and 58% larger than Nude mice. Similarly, NSG mice had a 55% larger tumor volume than NSGS mice and 100% larger than Nude mice. Therefore, this research established NSG mice as the superior mouse breed for the PC3 cell-induced tumor growth having established size within a reasonable timeline (5-7 weeks). Subsequently, the NSG model with a larger sample size (n = 48) was selected for HIFU ablation, and histopathological analysis revealed a significantly higher number of apoptotic cells in the HIFU-treated tumors compared to controls. This further confirmed the model's suitability for HIFU research. Tumor surface area and volume compared between the tested (n = 2) and selected (n = 48) groups were statistically insignificant (p = 0.78 for surface area and p = 0.60 for volume).
Background: Prostate cancer (PCa) is a prevalent malignancy in men, with increasing incidence and longer wait times for curative surgery, particularly in public health systems. While the impact of surgical wait time (SWT) on oncological outcomes in PCa remains controversial, its influence on patient-reported outcomes has not been thoroughly evaluated. Objective: To assess the impact of SWT on both oncological and psychological outcomes in patients undergoing robot-assisted radical prostatectomy (RARP) for preoperative ISUP grade 2 and 3 PCa. Methods: This retrospective single-center study included patients who underwent RARP for intermediate risk localized PCa between April 2016 and August 2024. Patients were stratified into two groups based on SWT: < 6 months vs. ≥ 6 months. The primary outcome was recurrence-free survival (RFS) for all patients. Secondary outcomes included RFS in a high-risk subgroup defined by pathological features (pT3 stage, seminal vesicle invasion, extracapsular extension, and positive surgical margins), as well as a comparison of functional outcomes between the two groups. Patient-reported outcomes were evaluated using SF-36 (mental and physical components) and the Decision Regret Scale (DRS) at 6 weeks, 3 months, 6 months, and 1 year. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazard models, and comparative tests with p < 0.05 considered significant. Results: 218 patients have been included. RFS did not significantly differ between groups (p=0.98), including among high-risk patients (p=1.00). No significant differences were found in extraprostatic extension, seminal vesicle invasion, positive surgical margins, or ISUP upgrading between groups. Similarly, changes in both SF-36 physical and mental and DRS scores showed no statistically significant differences at all time points. Conclusion: In this cohort of patients with intermediate-risk PCa, SWT beyond 6 months did not adversely affect oncological or health-related quality of life outcomes.
