Early Stage Prostate Cancer Research Articles

Gold–Graphene Quantum Dot Hybrid Nanoparticle for Smart Diagnostics of Prostate Cancer

Prostate cancer is one of the most prevalent cancers afflicting men worldwide, often detected at advanced stages, leading to increased mortality rates. Addressing this challenge, we present an innovative approach employing electrochemical biosensing for early-stage prostate cancer detection. This study used Indium–Tin Oxide (ITO) as a substrate and a deposited gold–graphene quantum dot (Au–GQD) nanohybrid to establish electrochemical sensing platforms for DNA-hybridization assays. A capturing DNA probe, PCA3, was covalently immobilized on the surface of the Au–GQDs and deposited electrochemically onto the ITO electrode surface. The Au–GQDs enabled the capturing of the target PCA3 biomarker probe. The sensor achieved a limit of detection (LoD) of up to 211 fM and presented a linear detection range spanning 1 µM to 100 fM. A rapid 5-min response time was also achieved. The tested shelf life of the pre-immobilized sensor was approximately 19 ± 1 days, with pronounced selectivity for its intended target amidst various interferants. The sensing device has the potential to revolutionize prostate cancer management by facilitating early-stage detection and screening with enhanced treatment efficacy.

Comparative Cardiovascular Risks of Radical Prostatectomy and External Beam Radiation Therapy in Early-Stage Prostate Cancer: A Comprehensive Retrospective Analysis.

The risk of cardiac disease mortality has recently become a focal point of concern within the medical community for patients with prostate cancer (PCa). Given that radical prostatectomy (RP) and external beam radiation therapy (EBRT) are the main treatment modalities for localized PCa, their specific impact on cardiovascular-specific mortality (CSM) remains unclear. This study explored the specific effects of RP and EBRT on CSM risk to guide clinical treatment decisions. Data from patients aged 45-74years, who were diagnosed with T1-2N0M0 stage PCa from the SEER database (2010-2015), were used. Multivariate statistical methods, including propensity score matching (PSM), competing risk regression, COX regression analysis, and Fine-Gray testing, were applied to assess the impact of RP and EBRT on CSM risk. Among 146,082 T1-2 stage PCa patients, cardiac disease emerged as the primary cause of death, surpassing PCa itself. Multifactorial COX regression and competing risk regression analyses indicated that local treatments do not increase CSM risk. Further analysis revealed a significant increase in CSM risk for patients undergoing only EBRT compared with those undergoing only RP (hazard ratio [HR] = 2.71, 95% confidence interval [CI] 1.96-3.74, P < 0.001), with subsequent PSM adjustment, further confirming a significantly reduced risk in the RP treatment group (HR 0.23, 95% CI 0.13-0.40, P < 0.001). T1-2 stage PCa patients face a significant risk of CSM, with RP offering a potential advantage over EBRT in reducing this risk. These findings encourage clinicians to comprehensively consider the potential impact on cardiac health when formulating treatment plans, providing crucial guidance for optimizing treatment strategies.

ASO Author Reflections: Evaluating Cardiovascular Mortality in Localized Treatments for Early-Stage Prostate Cancer.

ASO Author Reflections: Evaluating Cardiovascular Mortality in Localized Treatments for Early-Stage Prostate Cancer.

PI3K/Akt inhibition promotes AR activity and prostate cancer cell proliferation through p35-CDK5 modulation

Aberrant PI3K/Akt activation is linked to prostate cancer (PCa) malignancy, while androgen receptor (AR) is critical in early-stage PCa development. Investigating the interaction between these pathways is crucial for PCa malignancy. Our previous study demonstrated that p35-CDK5 mediates post-translational modifications of AR, STAT3, and p21CIP1, eventually promoting PCa cell growth. This study revealed the role of p35-CDK5 in between PI3K/Akt and AR by utilizing LNCaP and 22Rv1 cells. Through the TCGA database analysis, we observed a positive correlation between PTEN and p35 expression, implying a potential negative correlation between PI3K/Akt activation and p35-CDK5. Inhibiting PI3K/Akt with LY294002, Capivasertib (AZD5363), or using an inactive Akt mutant significantly increased p35 expression and subsequently enhanced AR stability and activation in PCa cells. On the other hand, CDK5-knockdown reversed these effects. The involvement of the β-catenin/Egr1-axis was observed in regulating PI3K/Akt inhibition and p35-CDK5 activation, implying a possible mechanistic connection. Importantly, CDK5 knockdown further reduced PI3K/Akt-inhibition-induced AR and cell viability maintenance, suggesting a compensatory role for CDK5-AR in maintaining cell viability under Akt inhibition. In conclusion, PI3K/Akt inhibition could trigger p35-CDK5-dependent AR activation and cell viability, highlighting p35-CDK5 as a critical link connecting PI3K/Akt inhibition to AR activation and pivotal in PCa cell resistance to PI3K/Akt blockade.

Advancing prostate cancer detection: High-accuracy urine test distinguishes between high and low-risk cancers

Prostate cancer remains one of the leading causes of cancer-related deaths among men. The standard method for early detection involves measuring Prostate-specific antigen (PSA) levels in the blood, with elevated PSA levels prompting further diagnostic procedures, such as a prostate biopsy. While effective, biopsies can be painful and carry risks of complications such as fever and urinary tract infections. To reduce unnecessary biopsies, researchers have sought alternative diagnostic methods. In recent years, a urine test was developed for early-stage prostate cancer detection. However, this test struggled to differentiate between aggressive and slow-growing cancers, the latter of which often require minimal treatment and are managed through active surveillance. To address this limitation, scientists at Wunderkind University have significantly enhanced the urine test. By analysing the genomes of thousands of prostate cancer patients, they identified a panel of 16 genes detectable in urine that can effectively distinguish between high-risk and low-risk cancers. When applied to individuals with elevated PSA levels, this improved test demonstrated an impressive 97% accuracy in identifying advanced prostate cancer. This advancement holds great promise for reducing unnecessary biopsies and improving patient outcomes by accurately identifying those needing aggressive treatment versus those suitable for observation. This review paper will explore the development, validation, and clinical implications of this novel urine test, highlighting its potential to transform prostate cancer diagnostics and patient management.

Targeted Biopsy Is Sufficient for Men on Active Surveillance for Early-Stage Prostate Cancer.

Serial biopsy is a mainstay for patients on active surveillance (AS) for prostate cancer. mpMRI targeting has become a standard. It is unclear whether targeted biopsy alone reliably identifies the dominant lesion, thereby obviating the need for systematic sampling. Participants enrolled in AS with early-stage prostate cancer (PSA < 20, cT1-2, GG1-2) and underwent 2+ systematic biopsy sessions with or without MR-targeted sampling. The findings for dominant Gleason Grade (GG) and tumor localization were assessed. Among 821 men who underwent MR fusion biopsies, 82% were diagnosed with GG1 and 18% with GG2. Sixty-two percent had their first MR fusion biopsy as diagnostic or confirmatory. Across all fusion biopsies, MRI-targeted detection of GG and/or tumor location overlapped with systematic sampling for 95% of cases. For 5% of cases, systematic biopsy was unique in detecting GG and location outside the target. Most unique lesions detected outside the target had marginally aggressive features: 73% GG2 of low-volume and favorable histologic subtypes. In men with MR fusion biopsies, targeting alone identified the dominant GG and location most of the time (95%); 25% of dominant lesions were contiguous to the target, suggesting that better sampling of the target improves detection. The remaining 5% of men had higher-grade, low-volume disease outside the targeted lesion of which only 2% had aggressive risk features. MR fusion targeting, without systematic sampling, may be sufficient to monitor men on AS. Few high-risk cancers are missed, all of limited volume and favorable histology.

Histopathological Study Of Prostate Cancer According To Gleason Score

The aim of this study was to histopathological alternation prostate cancer according Gleason systems . The total number of study samples was (60 ) that taken from men who suffered prostate cancer .patients diagnosed by a specialist doctor. Blood samples taken from all groups for estimation of levels of PSA. Second type of samples was biopsy and paraffin block that taken from PC patients for detection of histopathological alternations depending Gleason score. The result obtained from histopathology method that the prostate cancer in early stage poorly differentiated gland to loss gland formation in advanced early stage.

Periprostatic adipose tissue inhibits tumor progression by secreting apoptotic factors: A natural barrier induced by the immune response during the early stages of prostate cancer.

Prostate cancer (PCa) is the second most prevalent malignancy in men worldwide. The risk factors for PCa include obesity, age and family history. Increased visceral fat has been associated with high PCa risk, which has prompted previous researchers to investigate the influence of body composition and fat distribution on PCa prognosis. However, there is a lack of studies focusing on the mechanisms and interactions between periprostatic adipose tissue (PPAT) and PCa cells. The present study investigated the association between the composition of pelvic adipose tissue and PCa aggressiveness to understand the role played by this tissue in PCa progression. Moreover, PPAT-conditioned medium (CM) was prepared to assess the influence of the PPAT secretome on the pathophysiology of PCa. The present study included 50 patients with localized PCa who received robot-assisted radical prostatectomy. Medical records were collected, magnetic resonance imaging scans were analyzed and body compositions were calculated to identify the associations between adipose tissue volume and clinical PCa aggressiveness. In addition, CM was prepared from PPAT and perivesical adipose tissue (PVAT) collected from 25 patients during surgery, and its effects on the PCa cell lines C4-2 and LNCaP, and the prostate epithelial cell line PZ-HPV-7, were investigated using a cell proliferation assay and RNA sequencing (RNA-seq). The results revealed that the initial prostate-specific antigen level was significantly correlated with pelvic and periprostatic adipose tissue volumes. In addition, PPAT volume was significantly higher in patients with extracapsular tumor extension. PCa cell proliferation was significantly reduced when the cells were cultured in PPAT-CM compared with when they were cultured in control- and PVAT-CM. RNA-seq revealed that immune responses, and the cell death and apoptosis pathways were enriched in PPAT-CM-cultured cells indicating that the cytokines or other factors secreted from PPAT-CM induced PCa cell apoptosis. These findings revealed that the PPAT secretome may inhibit PCa cell proliferation by activating immune responses and promoting cancer cell apoptosis. This mechanism may act as a first-line defense during the early stages of PCa.

Development of transition metal oxide platforms for aptasensing of PSA in cell cultures.

In this study, a novel aptasensor based on a transition metal oxide-modified pencil graphite electrode (PGE) was developed for the diagnosis of early-stage prostate cancer (PCa) via monitoring the prostate-specific antigen (PSA), which is the main biomarker for PCa. Single-use PGEs modified with pulsed deposited manganese oxide (MnOx) film were used to attach the amino-terminated aptamer specific to the PSA via carbodiimide chemistry. The designed aptasensor was placed in an electrochemical cell containing ferri/ferrocyanide ions as a redox probe to measure the charge transfer resistances (Rct) of the electrode surface by electrochemical impedance spectroscopy (EIS) to follow the response of each modification step. The effect of the medium pH on the ionic structure of the aptamer molecule according to its pI value and, thus, the reversing of the direction of the response (ΔRct) by the pH change was also discussed. The level of PSA secreted from PCa cells was investigated using impedimetric transduction. The specificity of the aptasensor was validated through selectivity studies against non-specific tumor markers like VEGF and different cancer cell lines including breast cancer and androgen-insensitive prostate cancer. The developed system showcases a label-free, fast, specific, and cost-effective approach for PSA detection, highlighting the importance of medium pH and the electrostatic environment on the aptamer's response. Our work emphasizes the potential for such aptasensors in clinical diagnostics and paves the way for further exploration into using transition metal oxides in biosensing applications.

Lifestyle and risk factors associated with elevated prostate-specific antigen levels in rural men: implications for health counseling.

The use of prostate-specific antigen (PSA) for early detection of prostate cancer (PCa) is common but controversial. In rural areas, PSA is widely used for screening because it is convenient and early-stage PCa often shows no symptoms. Studies suggest that PSA levels are linked to factors like unhealthy lifestyles, obesity, lack of exercise, inflammation, and aging. Proper use and interpretation of PSA are crucial for healthcare providers, especially in primary care settings. This study aims to explore the prevalence and factors linked to higher PSA levels in rural men. We conducted a community-based cross-sectional study from March to December 2023 in the western coastal region of Taiwan. Men aged 40-75 years participated, completing a lifestyle questionnaire and providing blood samples for cardiometabolic biomarkers and PSA levels. PSA levels of ≥ 4.0 ng/mL were considered elevated. We used propensity score matching (PSM) and genetic matching (GM) for analysis, followed by regression analysis. In total, 3347 male adults with a mean age of 56.3 years (SD=11.8, range 40-75), and without cancer-related diseases, were enrolled. Findings indicated that 3.9% (n=130) of men aged 40-75 years had a PSA ≥ 4 ng/mL. and many of them did not adopt health-related behaviors, including inadequate servings of vegetables, water intake, and engaging in regular exercise. Furthermore, more than half of the participants had high blood pressure, and over one-quarter exhibited a higher waist-hip ratio and cardiometabolic diseases. After employing propensity score matching (PSM) and genetic matching (GM) with respect to age and education, the multivariate logistic regression model indicated that less water intake (p<0.01), higher waist-hip ratio (> 0.95) (p<0.05), and being diagnosed with cardiometabolic diseases (p<0.05) were significantly associated with a higher serum PSA level. This study revealed that inadequate water intake and obesity related diseases are significant risk factors associated with elevated PSA levels among male adults living in rural areas. It is important for frontline healthcare providers to carefully interpret the meaning of a high PSA level. Additionally, launching a longitudinal study is necessary to further investigate its relation to PCa.

Genitourinary tumors and liver transplantation: A comprehensive review.

Liver transplantation is as a crucial therapeutic option for patients with end-stage liver disease, but the persistent organ shortage emphasizes a need to explore unconventional donor sources, including individuals with a history of malignancies. This review investigates the viability of liver donation from individuals with current or past genitourinary malignancies, focusing on renal, prostate and urinary bladder cancers. The rising incidence of urogenital malignancies among potential donors is thought to result from increasing donor age. Analysis of transmission risks reveals low rates of donor-derived cancer transmission, particularly for early-stage renal and prostate cancers. Recipients with a history of genitourinary malignancy pose complex challenges regarding post-transplant immunosuppression and cancer recurrence. Nonetheless, the evidence suggests acceptable outcomes can be achieved with careful patient selection and tailored management strategies. Recommendations for pre-transplant evaluation and post-transplant surveillance are discussed, highlighting the need for individualized approaches in this patient population. Further prospective studies are warranted to refine guidelines and optimize outcomes in liver transplantation for patients with genitourinary malignancies.

Hypoxic Regulation of the KLK4 Gene in two Different Prostate Cancer Cells Treated with TGF- β.

The human kallikrein-related peptidase (KLK) family which consists of 15 members is associated with prostate cancer and other cancers. It has been reported that overexpression of KLK4 in prostate cancer correlates with bone metastasis or advanced stage. Hypoxia occurs in the early stages of prostate cancer due to the accumulation of acidic metabolites or reactive oxygen species (ROS). In our study, KLK4 gene expression in hypoxic conditions in PC-3 and LNCaP cells which are treated with TGF-β was evaluated with mRNA, protein, and promoter activity levels. A chemical hypoxia model was created and confirmed at mRNA and protein level. No statistically significant cytotoxic effect of CoCl2 and TGF-β was observed in PC-3 and LNCaP cells with the MTT test. Four different truncated KLK4 gene promoter constructs were cloned in pmetLuc expression vector and basal activities of all promoter fragments were analyzed. The activities of P1 (-447/ + 657), P2 (-103/ + 657), and P3 (-267/ + 657) promoter fragments increased in hypoxic conditions except P4 (+555/ + 657), which does not contain the SMAD and HRE region. KLK4 mRNA levels in both PC-3 and LNCaP cells increased in the hypoxia and hypoxia/TGF groups compared to the non-treated groups. The stimulating effect of TGF-β is correlated with the increase in SMAD2/3 mRNA levels. KLK4 expression is up-regulated by TGF-β, especially under hypoxic conditions, and its interaction with the SMAD pathway is determined with different inhibitor experiments. HIF-1α and SMAD transcription factors bind to the KLK4 promoter showing the direct interaction of HIF-1α (-80/-52) and SMAD (+163/+194) regions with EMSA.

Erectile Dysfunction and Penile Bulb Dose Following Definitive Prostate Radiation Therapy

Background: Erectile dysfunction (ED) is a common side effect of prostate cancer treatment, affecting up to 50% of patients after radiation therapy. Objectives: This study aims to analyze the correlation between the dose received by the penile bulb (PB) and ED in men who underwent definitive radiation therapy for early-stage prostate cancer without androgen deprivation therapy. Methods: The study included 40 patients who received 3D conformal radiation therapy (3D-CRT) for localized prostate cancer and were reported to be potent before treatment, as determined by the International Index of Erectile Function (IIEF-15) questionnaire. The dose to the PB was measured using dose volume histograms (DVHs), and the IIEF-15 questionnaire was completed again 3 months after 3D-CRT. The Pearson correlation coefficient and linear regression test were used to examine the correlation between the ED score and PB doses. Statistical significance was considered if the P value was less than 0.05. Results: The mean age of the patients was 75.5 ± 5.70 years. The average ED score based on the questionnaire was 15 ± 10.55. Twenty percent of the patients had moderate ED, while 80% had mild ED (all patients reported a decrease in potency after 3D-CRT). However, the correlation between the ED score and the PB mean dose was not statistically significant. Conclusions: This study revealed ED in all prostate cancer patients after 3D-CRT, but no significant correlation was found between the dose received by the PB and radiotherapy-induced impotence.

Searching for Novel HDAC6/Hsp90 Dual Inhibitors with Anti-Prostate Cancer Activity: In Silico Screening and In Vitro Evaluation.

Prostate cancer (PCA) is one of the most prevalent types of male cancers. While current treatments for early-stage PCA are available, their efficacy is limited in advanced PCA, mainly due to drug resistance or low efficacy. In this context, novel valuable therapeutic opportunities may arise from the combined inhibition of histone deacetylase 6 (HDAC6) and heat shock protein 90 (Hsp90). These targets are mutually involved in the regulation of several processes in cancer cells, and their inhibition is demonstrated to provide synergistic effects against PCA. On these premises, we performed an extensive in silico virtual screening campaign on commercial compounds in search of dual inhibitors of HDAC6 and Hsp90. In vitro tests against recombinant enzymes and PCA cells with different levels of aggressiveness allowed the identification of a subset of compounds with inhibitory activity against HDAC6 and antiproliferative effects towards LNCaP and PC-3 cells. None of the candidates showed appreciable Hsp90 inhibition. However, the discovered compounds have low molecular weight and a chemical structure similar to that of potent Hsp90 blockers. This provides an opportunity for structural and medicinal chemistry optimization in order to obtain HDAC6/Hsp90 dual modulators with antiproliferative effects against prostate cancer. These findings were discussed in detail in the study.

Simultaneous noninvasive ultrasensitive detection of prostate specific antigen and lncRNA PCA3 using multiplexed dual optical microfibers with strong plasmonic nanointerfaces

Low accuracy of diagnosing prostate cancer (PCa) was easily caused by only assaying single prostate specific antigen (PSA) biomarker. Although conventional reported methods for simultaneous detection of two specific PCa biomarkers could improve the diagnostic efficiency and accuracy, low detection sensitivity restrained their use in extreme early-stage PCa clinical assay applications. In order to overcome above drawbacks, this paper herein proposed a multiplexed dual optical microfibers separately functionalized with gold nanorods (GNRs) and Au nanobipyramids (Au NBPs) nanointerfaces with strong localized surface plasmon resonance (LSPR) effects. The sensors could simultaneously detect PSA protein biomarker and long noncoding RNA prostate cancer antigen 3 (lncRNA PCA3) with ultrahigh sensitivity and remarkable specificity. Consequently, the proposed dual optical microfibers multiplexed biosensors could detect the PSA protein and lncRNA PCA3 with ultra-low limit-of-detections (LODs) of 3.97 × 10−15 mol/L and 1.56 × 10−14 mol/L in pure phosphorus buffer solution (PBS), respectively, in which the obtained LODs were three orders of magnitude lower than existed state-of-the-art PCa assay technologies. Additionally, the sensors could discriminate target components from complicated physiological environment, that showing noticeable biosensing specificity of the sensors. With good performances of the sensors, they could successfully assay PSA and lncRNA PCA3 in undiluted human serum and urine simultaneously, respectively. Consequently, our proposed multiplexed sensors could real-time high-sensitivity simultaneously detect complicated human samples, that providing a novel valuable approach for the high-accurate diagnosis of early-stage PCa individuals.

Understanding Prostate Cancer: Causes, Risks, Diagnosis, and Treatment

Prostate cancer is the most common cancer among men after skin cancer. Most men who get prostate cancer don't die from it. More than 90% of men diagnosed with prostate cancer survive for at least five years. If detected early, while the tumor has not spread outside of the prostate, the survival rate is nearly 100% with treatment. Early-stage prostate cancer rarely causes symptoms, symptoms develop after the disease progresses. Prostate-specific antigen (PSA) blood test and digital rectal exam (DRE) are common screening methods for prostate cancer. However, whether or not to use these screening techniques is still controversial. Active surveillance is a strategy for managing low-risk prostate cancer without immediate treatment. The idea is to avoid unnecessary side effects by carefully watching how the cancer develops over time.

Real‑world retrospective study of early‑stage prostate cancer at a Portuguese Comprehensive Cancer Centre: The PEarlC study.

Despite the high prevalence of localised prostate cancer (LPC) and locally advanced prostate cancer (LAPC), evidence on the characteristics of patients, treatments and clinical outcomes stratified by disease risk is limited. The PEarlC study was conducted to characterise a cohort of patients with early-stage prostate cancer that included real-world clinical outcomes. Retrospective data from a cohort of patients diagnosed with LPC/LAPC between 2015 and 2017 and followed up until December 2020 at a Portuguese comprehensive cancer centre (IPO Porto) was analysed. Patients were classified as LPC (high- or non-high-risk) or LAPC according to European Association of Urology guidelines, were eligible if diagnosed at stage I-III and followed up in Urology, Medical Oncology or Radiation Oncology outpatient clinics of IPO Porto. Data was collected from the medical/administrative records database. Clinical outcomes included prostate-specific antigen (PSA) progression-free survival, metastasis-free survival, disease-free survival, progression-free survival, overall survival (OS), PSA response (palliative) and no evidence of residual tumour (prostatectomy). Time-to-event outcomes were compared between subgroups using the log-rank test. A total of 790 patients were included (54.8% non-high-risk LPC, 30.9% high-risk LPC, 14.3% LAPC) and the median follow-up was 46.7 months. Patients had a median age of 68.0 years. The majority of patients were stage II (52.9%) and Eastern Cooperative Oncology Group 0-1 (99.9%) and received treatment with curative intent (85.4%). The median was only achieved in progression-free survival (29.9 months; 95% CI, 26.5-41.0 months), as evaluated in palliative patients. At year 5, 82.9% were free of PSA progression (curative), 87.5% were metastasis-free, 83.7% were disease-free, all patients in palliative treatment progressed and the 5-year OS rate was 92.9% (CI 95%, 90.2-95.7%). Among patients with LPC, OS was worse in high-risk vs. non-high-risk patients (5-year OS rate, 88.8% vs. 96.8%; hazard ratio=3.34, CI 95%, 1.64-7.05; P=0.001). PSA response rate was 81.4% in the palliative setting. There was no evidence of residual tumour in 61.6% of patients who underwent prostatectomy. Although most patients with early-stage prostate cancer treated at IPO Porto showed positive 5-year real-world outcomes, patients with high-risk LPC showed worse OS compared with patients with non-high-risk LPC and therefore a poorer prognosis. The present large-sample real-world study is an important contribution to reducing the evidence gap on prostate cancer.

New target therapies in prostate cancer: from radioligand therapy, to PARP-inhibitors and immunotherapy.

Prostate cancer (PCa) remains a significant global health challenge, particularly in its advanced stages. Despite progress in early detection and treatment, PCa is the second most common cancer diagnosis among men. This review aims to provide an overview of current therapeutic approaches and innovations in PCa management, focusing on the latest advancements and ongoing challenges. We conducted a narrative review of clinical trials and research studies, focusing on PARP inhibitors (PARPis), phosphoinositide 3 kinase-protein kinase B inhibitors, immunotherapy, and radioligand therapies (RLTs). Data was sourced from major clinical trial databases and peer-reviewed journals. Androgen deprivation therapy and androgen-receptor pathway inhibitors remain foundational in managing castration-sensitive and early-stage castration-resistant PCa (CRPC). PARPi's, such as olaparib and rucaparib, have emerged as vital treatments for metastatic CRPC with homologous recombination repair gene mutations, highlighting the importance of personalized medicine. Immune checkpoint inhibitors (ICIs) have shown clinical benefit limited to specific subgroups of PCa, demonstrating significant improvement in efficacy in patients with microsatellite instability/mismatch repair or cyclin-dependent kinase 12 alteration, highlighting the importance of focusing ongoing research on identifying and characterizing these subgroups to maximize the clinical benefits of ICIs. RLTs have shown effectiveness in treating mCRPC. Different alpha emitters (like [225Ac]PSMA) and beta emitters compounds (like [177Lu]PSMA) impact treatment differently due to their energy transfer characteristics. Clinical trials like VISION and TheraP have demonstrated positive outcomes with RLT, particularly [177Lu]PSMA-617, leading to FDA approval. Ongoing trials and future perspectives explore the potential of [225Ac]PSMA, aiming to improve outcomes for patients with mCRPC. The landscape of PCa treatment is evolving, with significant advancements in both established and novel therapies. The combination of hormonal therapies, chemotherapy, PARPis, immunotherapy, and RLTs, guided by genetic and molecular insights, opens new possibilities for personalized treatment.

Predictors of time to diagnosis and treatment: A retrospective cohort study of patients with clinically localized prostate cancer in Nigeria.

e23123 Background: Equitable access to the management of early-stage prostate cancer is important for optimal outcome in the diagnostic and curative treatment pathway of patients. This study aimed to identify the predictors of time to treatment and time to diagnosis in these patients. Methods: This was a cohort study of 110 patients with clinically localized prostate cancer (T1-T3a, N0, M0) in three government-funded tertiary hospitals in Nigeria. Retrospective data on sociodemographic status, co-morbid conditions, clinical, pathological and radiological quality metrics, date of first presentation for cancer-related complaint in the tertiary hospital, date of diagnosis of prostate cancer, and the date of commencement of first cancer-directed treatment were collected. Primary endpoint was the time from diagnosis to treatment and the secondary endpoint was the time from presentation to diagnosis. Predictors were determined by Cox proportional hazards using Stata software, version 18.0 with a p-value of less than 0.05 considered significant. Results: Twelve percent (n = 13) of the patients had a family history of prostate cancer. Fifty-four percent (n = 59) had other co-morbid conditions. Nearly one-third, 29% (n = 32) had retired from their primary occupation and 10% (n = 11) were covered by health insurance. The overall median time to diagnosis was 30 (interquartile range (IQR) 10 - 48) days. The median time to treatment commencement was 32 (IQR 19 - 82) days for ADT; 57 (IQR 50 - 63) days for active surveillance; 45 (IQR 21 - 78) days for radical radiotherapy; and 100 (IQR 0 - 127) days for radical prostatectomy. Diagnostic PSA documentation independently predicted delayed time to diagnosis (adjusted HR = 0.22 with 95% CI [0.05,0.97]) while those with guideline concordant imaging investigations independently predicted longer time to treatment (adjusted HR = 0.63 with 95% CI [0.40,0.99]). Conclusions: The documentation of PSA level and use of guideline concordant imaging investigations were significantly associated with delayed time to care. Studies on interventions to reduce barriers associated with these factors is warranted to strengthen equitable access to care in this setting.

Radical prostatectomy versus XRT for early-stage prostate cancer: A retrospective, propensity-matched cohort study of 29,970 patients.

Radical prostatectomy versus XRT for early-stage prostate cancer: A retrospective, propensity-matched cohort study of 29,970 patients.