Prostate Cancer Patients Research Articles

MiRNA Signatures as Predictors of Therapy Response in Castration-Resistant Prostate Cancer: Insights from Clinical Liquid Biopsies and 3D Culture Models

Background/Objectives: Prostate cancer (PCa) patients who do not respond to androgen deprivation therapy (ADT), referred to as castration-resistant prostate cancer (CRPC), remain a clinical challenge due to confirm the aggressive nature of CRPC and its resistance to conventional therapies. This study aims to investigate the potential of microRNAs (miRNAs) as biomarkers for predicting therapeutic response in CRPC patients. Methods: We performed miRNA and mRNA expression analyses using publicly available datasets and applied 3D cell culture models to replicate more physiologically relevant tumor conditions. Genetic analysis techniques were employed on publicly available data, and expression profiles from 3D cell culture models were examined. Results: Eighteen miRNAs with differential expression were identified between patients who responded favorably to abiraterone therapy (responders) and those with advanced CRPC (non-responders). Specifically, miRNAs such as hsa-miR-152-3p and hsa-miR-34a-3p were found to be associated with critical pathways, including TGF-β signaling and P53, which are linked to therapeutic resistance. Several miRNAs were identified as potential predictors of treatment efficacy, including therapies like abiraterone. Conclusions: These results indicate that miRNAs could serve as non-invasive biomarkers for predicting therapeutic outcomes, facilitating a more personalized approach to CRPC treatment. This study provides a novel perspective on treatment strategies for CRPC, emphasizing the role of miRNAs in improving therapeutic precision and efficacy in this complex disease.

Prognostic Stratification Using Early Prostate-specific Antigen Kinetics in Men With Metastatic Hormone-sensitive Prostate Cancer.

The prognostic significance of prostate-specific antigen (PSA) kinetics in metastatic castration-sensitive prostate cancer (mCSPC) patients treated with upfront therapy remains unclear. This study investigated the correlation between early PSA response and clinical outcomes in patients with mCSPC who received upfront therapy. We analyzed 106 patients with mCSPC who received upfront therapies [abiraterone acetate (ABI), enzalutamide (ENZ), apalutamide (APA), and docetaxel (DOC)] at Kurume University Hospital and its affiliated hospitals. Thirty-nine, 15, 38, and 14 patients were treated with ABI, DOC, ENZ, and APA, respectively. Among the total number of patients, 67 met the criteria for high-volume disease. Additionally, 83 patients were categorized as high risk. Patients with a PSA decline rate of ≥90% at 4 and 12 weeks post-upfront therapies had a significantly longer time to develop CRPC than those with a PSA decline of <90%. PSA cutoff values >26 ng/ml at 4 weeks post-upfront therapies and a PSA decline rate of ≥90% at 12 weeks post-upfront therapies were independent predictors of poor prognosis. Furthermore, patients were stratified into three groups based on PSA levels at 4 weeks and PSA decline rate at 12 weeks. A larger PSA decline within three months of initiating upfront therapy is significantly associated with a longer time to CRPC in patients with mCSPC treated with upfront therapy. A combination of early PSA kinetics can be used to stratify the risk of CRPC progression in patients with mCSPC treated with upfront therapies.

Effects of hypoxia and iron on ascorbic acid-mediated cytotoxicity in prostate cancer cell lines.

Ascorbic acid (ASC) has long been proposed as a potential cancer co-treatment due to its specific toxicity towards cancer cells, but discrepancies between in vitro and in vivo studies suggest that external factors may modulate its cytotoxicity. Here, we investigate the impact of hypoxia and iron on the therapeutic effectiveness of ASC on prostate cancer cell lines. Hypoxia-induced increases in the EC50 of ASC in the prostate cancer cell lines PC-3, DU 145, LNCaP, and CWR22Rv1 but not in the prostate non-cancer cell lines RWPE-1 and TERT-PrECs. The synthetic androgen dihydrotestosterone did not modify ASC's effectiveness in either normoxia or hypoxia, which was tested because both early and advanced prostate cancer maintain the androgen receptor pathway. The effects of hypoxia on cytotoxicity depend on the drug. Hypoxia did not affect the EC50 for the DNA-damaging agent etoposide but decreased the sensitivity for the anti-microtubule agent paclitaxel in PC-3 and DU 145 cells. Although hypoxic cells were iron deficient, adding iron back to cells did not reverse the effects of the hypoxic atmosphere. Interestingly, the EC50 for ASC was approximately two-fold higher in iron-treated cells than non‑iron-treated cells for the PC-3 line. The higher EC50 was not observed by knocking down ferritin heavy chain mRNA. In summary, both hypoxia and iron attenuate the effectiveness of high concentrations of ASC in prostate cancer cell lines, which may affect the therapeutic benefit of ASC for prostate cancer patients.

Prostate Cancer Bone Metastasis: Molecular Mechanisms of Tumor and Bone Microenvironment.

Prostate cancer is prevalent among men aged 65 and older. Bone metastasis occurs in up to 90% of advanced prostate cancer patients, metastatic prostate cancer is generally considered a non-curative condition which can impact quality of life. The tumor microenvironment, comprising diverse cellular and non-cellular elements, interacts with prostate cancer cells to affect tumor growth and bone metastasis. Within the bone microenvironment, different cell types, including osteoblasts, osteoclasts, adipocytes, endothelial cells, hematopoietic stem cells, and immune cells, engage with tumor cells. Some cells alter tumor behavior, while others are impacted or overpowered by tumor cells, leading to different phases of tumor cell movement, dormancy, latency, resistance to treatment, and advancement to visible bone metastasis. This review summarizes recent research on the tumor microenvironment and bone microenvironment in prostate cancer bone metastasis, exploring underlying mechanisms and the potential value of targeting these environments for treatment.

Optimizing the dose-averaged linear energy transfer for the dominant intraprostatic lesions in high-risk localized prostate cancer patients

Optimizing the dose-averaged linear energy transfer for the dominant intraprostatic lesions in high-risk localized prostate cancer patients

Clinical, Diagnostic and Therapeutic Framework of mHSPC and nmCRPC: A Multidisciplinary Consensus Project of the Italian Society for Uro-Oncology (SIUrO).

The recent evidences provided in metastatic hormone sensitive prostate cancer (nmHSPC) and in nonmetastatic castration resistant (nmCRPC) introduced the possibility to adopt Androgen Receptor Signaling inhibitor (ARSi) alone (both settings) or with chemotherapy (in mHSPC). In daily clinical practice there are some opening questions regarding the inclusion of next generation imaging, mainly PSMA-PET, how integrate local treatment as radiotherapy, how to select patients or drugs in a multiple-choice scenario, and how to manage patients with comorbidities and polypharmacy. These issues led the Italian Society for Uro-Oncology (SIUrO) to develop a consensus project involving all of the most important Italian scientific societies engaged in the multidisciplinary and multiprofessional management of the disease. This paper describes the items and statements approved, with the aim to support clinicians in managing metastatic hormone sensitive and nonmetastatic castration resistant prostate cancer patients.

Implementing and Optimizing Universal Germline Genetic Testing for Patients with Prostate Cancer in Clinical Practice Consider.

To advocate for universal germline genetic testing (UGGT) in prostate cancer and provide practical recommendations for its implementation. Although guidelines for germline genetic testing (GGT) in prostate cancer have progressed, usage remains limited and inconsistent due to barriers including access, cost, and variable guideline adherence. These issues prevent some patients with germline pathogenic/likely pathogenic variants from benefiting from risk assessment, precision therapies (e.g., PARP inhibitors, PD-1 inhibitors) and potential clinical trials. Despite these benefits, studies indicate that GGT use remains low, especially in prostate cancer care. The PROCLAIM trial (Shore et al., 2023) highlighted that nearly half of patients with pathogenic variants are missed under NCCN guidelines, particularly impacting non-white patients and those with incomplete family history data. Additional racial and socioeconomic disparities further hinder access and variant interpretation accuracy. Given these challenges, UGGT for all prostate cancer patients has been proposed to improve care equity and decision-making. In March 2024, prostate cancer experts convened to discuss strategies for UGGT implementation. The outcome of that meeting includes recommendations for integrating UGGT into oncology and urology practices and have been outlined in this paper. To maximize the benefits while mitigating the potential risks of UGGT, it is essential to address implementation details, including careful gene panel selection, VUS reporting and management, appropriate genetics follow-up, and seamless integration of test reports into EMRs for accessibility by patients and providers.

A Modular Customizable Ligand-Conjugate (LC) System Targeting Ghrelin O-Acyltransferase

Ghrelin is a 28 amino acid peptide hormone that impacts a wide range of biological processes, including appetite regulation, glucose metabolism, growth hormone regulation, and cognitive function. To bind and activate its cognate receptor, ghrelin must be acylated on a serine residue in a post-translational modification performed by ghrelin O-acyltransferase (GOAT). GOAT is a membrane-bound O-acyltransferase (MBOAT) responsible for the catalysis of the addition of an octanoyl fatty acid to the third serine of desacyl ghrelin. Beyond its canonical role for ghrelin maturation in endocrine cells within the stomach, GOAT was recently reported to be overexpressed in prostate cancer (PCa) cells and detected at increased levels in the serum and urine of PCa patients. This suggests GOAT can serve as a potential route for the detection and therapeutic targeting of PCa and other diseases that exhibit GOAT overexpression. Building upon a ghrelin mimetic peptide with nanomolar affinity for GOAT, we developed an antibody-conjugate-inspired system for customizable ligand-conjugate (LC) synthesis allowing for the attachment of a wide range of cargoes. The developed synthetic scheme allows for the easy synthesis of the desired LCs and demonstrates that our ligand system tolerates an extensive palette of cargoes while maintaining nanomolar affinity against GOAT.

Roles of CDK12 mutations in PCa development and treatment.

Prostate cancer (PCa) is one of the most common cancers in men, and cyclin-dependent kinase 12 (CDK12) is emerging as a novel star player in the PCa tumorigenesis and progression to castration-resistant prostate cancer (CRPC). In PCa, CDK12 alterations are mostly loss-of-function mutations featuring intronic polyadenylation (IPA), focal tandem duplications (FTDs), and R-loops formation and transcription-replication conflicts (TRCs). The occurrence of IPA can result in homologous recombination deficiency (HRD) and androgen receptor (AR) variation. FTDs induce neoantigens and increase the expression of the AR, MYC, and other hotspot- associated genes. R-loops lead to TRCs and influence various cellular processes, including gene expression and genome stability. Due to the poor prognosis of CDK12-mutant PCa patients and the mediocre response to classic standard therapies, HRD and increased neoantigen levels have provided clinicians with new insights into alternative systematic treatments for this novel PCa phenotype. In this review, we summarize the roles of CDK12 mutations in PCa and discuss their clinical value, suggesting that CDK12 potentially represents a target for further research and the development of clinical strategies for PCa.

Sociodemographic landscape of suspected prostate cancer referrals and diagnoses across North East London.

The objective of this study is to identify healthcare inequities in referrals and diagnoses of suspected prostate cancer (PCa) in an ethnically diverse and socially deprived large urban region. Retrospective cohort study of 2-Week Wait (2WW) suspected PCa patients (n= 12 947) referred to two acute NHS Trusts in North East London (NEL) from February 2019 to August 2023. Sociodemographics, diagnosis and pretreatment staging data were collected from patient records. We examined referral and diagnosis statistics, age at referral, radiological T-stage at diagnosis, levels of deprivation by ethnicity and the impact of COVID-19 pandemic lockdowns on proportion of referrals and diagnoses by ethnicity and T-stage at diagnosis. Uni- and multivariable logistic regression was performed to identify predictors of locally advanced (T-stage ≥T3) disease. Of all referrals, 22% were diagnosed with PCa. There were no statistically significant differences in referrals, diagnoses or T-stage of PCa by ethnicity during COVID lockdown versus non-lockdown periods (p> 0.05). Compared to men from any other ethnicity, Black men (from Black British, Black African and Black Caribbean ethnic groups) were diagnosed at a younger age (mean = 65 years), had the highest age-adjusted PCa incidence rate of 149 per 100 000 person-years, were from the most deprived backgrounds, and were diagnosed with the highest proportion of localised PCa (74%). Multivariable analysis of a patient subgroup revealed age bands 71-80 years (OR 2.01, 95% CI 1.31-3.07) and >80 (OR 4.27, 95% CI 2.25-8.08) as independent positive predictors of locally advanced PCa, and Black ethnicity as an independent predictor of localised disease (OR 0.66, 95% CI 0.43-1.00). Limitations of this study include the exclusion of PCa cases diagnosed outside the 2WW pathway, as well as missing data on Prostate-Specific Antigen (PSA) levels, distant radiological staging and histopathological findings. We identify disparities in PCa incidence, stage and age at presentation, as well as socio-economic deprivation among Black men in NEL. Targeted efforts are needed to mitigate these healthcare inequities.

Use of erectile dysfunction treatments after prostate cancer treatment and their perceived impact on men’s sex life: an analysis of patient reported outcome survey data

BackgroundAlthough sexual dysfunction is a common treatment side-effect affecting men’s quality of life, many prostate cancer patients do not receive or seek out treatments for erectile dysfunction (ED). The aims of this study are to investigate the extent and patterns of use of ED treatments and their perceived impact at different times following prostate cancer treatment.MethodsThis retrospective cohort study included all men on the South Australian prostate cancer registry who completed one or more Patient Reported Outcome Measures (PROMs) survey from 2016 to 2023 (n = 5561). Outcomes included self-reported use of ED treatment (oral medications, intra-cavernosal injections (ICI) and vacuum pumps) and their impact men’s sex life at various time points after treatment. The type and timing of ED treatments used was analysed descriptively. Sociodemographic and clinical characteristics associated with utilisation and self-reported satisfaction were examined using multivariable mixed-effects binomial logistic regression.ResultsPost-treatment use of ED treatments did not exceed 43% at any timepoint, with utilisation rates decreasing over time. Oral medications were most frequently used, while vacuum pump and ICI use was limited. Oral medications were more likely to be used at three-months (odds ratio [OR] = 2.48; 95% confidence interval [95%CI] = 1.88–3.27) and six-months (OR = 2.10; 95%CI = 1.63–2.27) than at 12-months post-treatment, and among men from higher socioeconomic areas (OR = 2.41; 95%CI = 1.47–3.93, highest vs. lowest quintile), and following prostatectomy (OR = 4.37; 95%CI = 2.92–6.42), and less likely among older men (OR = 0.08; 95%CI = 0.05–0.13, < 60yrs vs. 70-79yrs). Men were more likely to report an improved sex life with oral medication use at two-years (OR = 3.79; 95%CI = 1.69–8.47) and five-years (OR = 3.07; 95%CI = 1.51–6.25) post-treatment compared with 12-months or if they were socioeconomically advantaged (OR = 3.22; 95%CI = 1.30–7.96, highest vs. lowest quintile).ConclusionsA substantial proportion of Australian men do not access or continue to use ED treatments after prostate cancer treatment, with many users reporting only modest effects on their sex life. There is a need to improve access to and maintenance of ED treatments following prostate cancer treatment.

Immunohistochemical Analysis of Androgen Receptor Expression Predicts the Prognosis of Metastatic Castration-Sensitive Prostate Cancer Patients Receiving Abiraterone Acetate.

The efficacy of abiraterone acetate varies among patients with high-risk metastatic castration-sensitive prostate cancer (mCSPC). Both androgen receptor (AR) and cytokeratin 18 (CK18) are markers of the luminal lineage of prostate cancer, and their expression levels have been suggested to affect the response to androgen deprivation therapy (ADT). This study aimed to predict the efficacy of abiraterone acetate in high-risk mCSPC via immunohistochemical staining of biopsy specimens obtained at the time of prostate cancer diagnosis. We retrospectively analyzed 44 patients treated with abiraterone acetate in combination with ADT. AR and CK18 expression in prostate biopsy specimens were assessed using immunohistochemical staining. AR and CK18 staining was not significantly associated with overall survival (OS). However, low AR staining was significantly associated with a shorter time to castration-resistant prostate cancer (TTCRPC) compared with high AR staining (log-rank test, p = 0.018). Similarly, low CK18 staining was significantly associated with a shorter TTCRPC compared with high CK18 staining (log-rank test, p = 0.037). Immunohistochemical analysis of AR or CK18 expression in biopsy specimens may serve as a predictive biomarker of high-risk mCSPC treated with abiraterone acetate. None.

External Validation of Nomograms for the Identification of Pelvic Nodal Dissection Candidates Among Prostate Cancer Patients with Negative Preoperative Prostate-specific Membrane Antigen Positron Emission Tomography.

Extended pelvic lymph node dissection (ePLND) is recommended in selected radical prostatectomy (RP) prostate cancer (PCa) patients for staging purposes. We aim to externally validate available tools to predict lymph node invasion (LNI) in men with negative preoperative prostate-specific membrane antigen positron emission tomography (miN0). Overall, 282 intermediate- to high-risk PCa patients with miN0 disease undergoing RP and ePLND at ten centers between 2016 and 2023 were identified. The Memorial Sloan Kettering Cancer Center (MSKCC); Amsterdam-Brisbane-Sydney; and Briganti 2017, 2019, and 2023 tools predicting LNI were validated externally using calibration plots, C-indexes, and decision-curve analyses to assess calibration, discrimination, and net benefit. Overall, 36 (13%) patients had LNI. The C-indexes of the MSKCC, Briganti 2017, Briganti 2019, Amsterdam-Brisbane-Sydney, and Briganti 2023 nomograms were 64%, 69%, 72%, 64%, and 77%, respectively. The Briganti 2023 nomogram exhibited higher net benefit than the other available nomograms, and the use of a 5% cutoff would have spared 47% ePLND procedures (vs 14% and 4.3% for the Briganti 2019 and Amsterdam-Brisbane-Sydney nomograms, respectively) at the cost of missing only five (3.8%) LNI cases. Heterogeneity in patient selection and imaging protocols represents the main limitations. The Briganti 2023 nomogram outperformed other available tools in predicting LNI in men with miN0 PCa. The use of this tool resulted in a considerable number of unnecessary ePLND procedures spared and optimization of ePLND recommendations in a contemporary clinical setting.

Effects on Quality of Life and Self-Efficacy of Instant Messaging Services in Self-Management Programs for Prostate Cancer: A Systematic Review and Meta-Analysis

Background: Prostate cancer is one of the most common cancers among men worldwide. Management options include active surveillance, surgery, radiation, and chemotherapy, while self-management and behavioral interventions have shown promise in improving health-promoting behaviors and addressing barriers to care. Mobile health interventions, particularly instant messaging platforms, offer a growing opportunity for effective therapeutic support, but evidence on their role in self-management remains limited. The objective was to investigate the efficacy of self-management interventions based on instant messaging on quality of life and self-efficacy in patients diagnosed with prostate cancer through a systematic review and meta-analysis. Methods: A search was conducted of three databases from their inception to November 2024. Randomized controlled trials were included. Two reviewers performed independent data extraction and methodologic quality assessment of the studies. Results: A total of seven studies were included in the review. Instant messaging interventions were recognized by a previously published taxonomy of collaborative technologies. The meta-analysis showed that self-management interventions based on instant messaging have an effect on quality of life and self-efficacy. Conclusions: This systematic review highlights the potential benefits of self-management interventions incorporating instant messaging for improving quality of life and self-efficacy in prostate cancer patients.

Transcriptome-Wide Association Study Identified Novel Blood Tissue Gene Biomarkers for Prostate Cancer Risk.

A number of susceptibility genes in prostate tissue have been identified to be associated with prostate cancer (PCa) risk. However, the reported genes based on assessing prostate tissue could not fully explain PCa genetic susceptibility. It is believed that genes functioning in the immune system may fill in the gap of some missing heritability. To study potential susceptibility genes acting in such pathways, we performed a transcriptome-wide association study (TWAS) of 79,194 PCa cases and 61,112 control of European ancestry by using three sets of gene expression prediction models of blood tissue. A total of 470 genes were associated at false discovery rates-corrected p-value < 0.05, of which 51 were implicated as likely causal genes based on fine-mapping analysis. Compared with previous literature, 133 novel genes were reported for the first time. Of the identified genes, five (CREB3L4, GSTP1, MAPK3, NKX3-1, and PIK3C2B) were enriched in a PCa signaling pathway, and 128 genes were enriched in five PCa categories. Importantly, 13 genes (SCP2, LMNA, ZNF148, H2AFV, TACC1, FLII, SUPT4H1, CD300LF, MYO9B, COX6B1, CTSA, EP300, and TSPO) showed consistent effect directions for the measured levels in circulating immune cells between PCa cases and controls, and 14 genes (SLC39A1, ZBTB7B, TRIM59, NCEH1, N4BP2, TAGAP, TACC1, TRAF1, AIP, SECTM1, C18orf54, ZNF793, YIF1B, and TSPO) showed consistency for levels in blood exosomes between PCa patients and controls. The identified blood-based candidate susceptibility genes provide further insights into the genetic basis of PCa risk.

Comprehensive analysis of the interaction microbiome and prostate cancer: an initial exploration from multi-cohort metagenome and GWAS studies

IntroductionProstate cancer is one of the most common cancers in the United States with a high mortality rate. In recent years, the traditional opinion about prostate microbiome was challenged. Although there still are some arguments, an escalating number of researchers are shifting their focus toward the microbiome within the prostate tumor environment.MethodsWe mined the data of the microbiome extracted from the metagenome, and it offers a broader taxonomic coverage and accurate functional profiling. We used Kraken2, a mapping tool, to mine the gut microbiota of prostate cancer patients. A two-sample Mendelian Randomization was conducted to reflect the association between gut microbiome and cancer.ResultsIn the study, we found the consistency of the special intratumor microbiome of both non-metastatic tumors and metastatic tumors. And we dig the gut microbiome in patients with different treatments. We found that some microbiotas may be associated with prostate cancer progression and a special microbiome in metastatic prostate cancer may exist. The anti-androgen therapy can significantly change both the intratumor and gut microbiome.ConclusionWith the progression and metastasis of prostate cancer, some intratumor microbiome changes. And anti-androgen influences both the intratumor and gut microbiome. Our discovery may help researchers further understand the progression, metastasis, and resistance of prostate cancer from the perspective of microbiome level.

Tegaserod maleate exerts anti-tumor effects on prostate cancer via repressing sonic hedgehog signaling pathway

Prostate cancer (PCa) is a highly common type of malignancy and affects millions of men in the world since it is easy to recur or emerge therapy resistance. Therefore, it is urgent to find novel treatments for PCa patients. In the current study, we found that tegaserod maleate (TM), an FDA-approved agent, inhibited proliferation, colony formation, migration as well as invasion, caused the arrest of the cell cycle, and promoted apoptosis of PCa cells in vitro. In addition, TM suppressed the tumor growth in the cell-derived xenograft (CDX) mouse model in vivo. Mechanistically, TM exerted anti-tumor effects via downregulating GLI2, and its downtream targets, thus inhibiting the sonic hedgehog (SHH) signaling pathway. In brief, our findings demonstrated that TM effectively inhibited the activities of PCa cells by suppressing the SHH signaling pathway and provided a potential new agent for the treatment of PCa.

Genetic ancestry concordant RNA splicing in prostate cancer involves oncogenic genes and associates with recurrence

Black men suffer disproportionately from prostate cancer (PCa) compared to men of other races and ethnicities. Comparing the molecular landscape of PCa among Black and White patients has the potential to identify targets for development of new precision medicine interventions. Herein, we conducted transcriptomic analysis of prostate tumors and paired tumor-adjacent normals from self-reported Black and White PCa patients and estimated patient genetic ancestry. Clinical follow-up revealed increased biochemical recurrence (BCR) among Black patients compared to White patients with high-grade PCa. Transcriptomic analysis identified differential alternative RNA splicing events (ARSs) between Black and White PCa patients. Genes undergoing genetic ancestry-concordant ARSs in high-grade or low-grade tumors involved cancer promoting genes. Most genes undergoing genetic ancestry-concordant ARSs did not exhibit differential aggregate gene expression or alternative polyadenylation. A number of the genetic ancestry-concordant ARSs associated with BCR; thus, genetic ancestry-concordant RNA splice variants may represent unique targets for PCa precision oncology.

18F]PSMA-1007 PET/CT-based radiomics may help enhance the interpretation of bone focal uptakes in hormone-sensitive prostate cancer patients.

We hypothesised that applying radiomics to [18F]PSMA-1007 PET/CT images could help distinguish Unspecific Bone Uptakes (UBUs) from bone metastases in prostate cancer (PCa) patients. We compared the performance of radiomic features to human visual interpretation. We retrospectively analysed 102 hormone-sensitive PCa patients who underwent [18F]PSMA-1007 PET/CT and exhibited at least one focal bone uptake with known clinical follow-up (reference standard). Using matRadiomics, we extracted features from PET and CT images of each bone uptake and identified the best predictor model for bone metastases using a machine-learning approach to generate a radiomic score. Blinded PET readers with low (n = 2) and high (n = 2) experience rated each bone uptake as either UBU or bone metastasis. The same readers performed a second read three months later, with access to the radiomic score. Of the 178 [18F]PSMA-1007 bone uptakes, 74 (41.5%) were classified as PCa metastases by the reference standard. A radiomic model combining PET and CT features achieved an accuracy of 84.69%, though it did not surpass expert PET readers in either round. Less-experienced readers had significantly lower diagnostic accuracy at baseline (p < 0.05) but improved with the addition of radiomic scores (p < 0.05 compared to the first round). Radiomics might help to differentiate bone metastases from UBUs. While it did not exceed expert visual assessments, radiomics has the potential to enhance the diagnostic accuracy of less-experienced readers in evaluating [18F]PSMA-1007 PET/CT bone uptakes.

Lesion-based grading system using clinicopathological and MRI features for predicting positive surgical margins in prostate cancer.

To develop and validate a lesion-based grading system using clinicopathological and MRI features for predicting positive surgical margin (PSM) following robotic-assisted laparoscopic prostatectomy (RALP) among prostate cancer (PCa) patients. Consecutive MRI examinations of patients undergoing RALP for PCa were retrospectively collected from two medical institutions. Patients from center 1 undergoing RALP between January 2020 and December 2021 were included in the derivation cohort and those between January 2022 and December 2022 were allocated to the validation cohort. Patients from center 2 were assigned to the test cohort. PSM associated imaging and clinicopathological predictors were assessed. A grading system was developed through fixed effect logistic regression and classification and regression tree analysis. The area under the curve (AUC), sensitivity and specificity were calculated and compared by Delong test and McNemar test. A total 489 lesions from 396 patientswere included and 82 (29.1%), 32 (35.6%) and 42 (35.9%) of lesions were observed PSM after RALP in the derivation, validation and test cohorts, respectively. The grading system comprised tumor morphology, tumor location, anatomical feature and clinical risk stratification. The grading system demonstrated good prediction performance for PSM in the derivation (AUC 0.82 [95% CI: 0.77, 0.86]), validation (AUC 0.76 [95% CI: 0.66, 0.85]) and test (AUC 0.81 [95% CI: 0.72, 0.88]) cohorts. When compared with Park's model (AUC: 0.73 [95% CI: 0.64, 0.81]) in the test cohort, our grading system demonstrated significantly higher AUC and specificity (P < 0.05). The lesion-based grading system can assess the likelihood of PSM after RALP, assisting surgeons in minimizing the occurrence rate of PSM while optimizing functional preservation.