Biochemical Recurrence-free Survival Research Articles

TET2 gene mutation status associated with poor prognosis of transition zone prostate cancer: a retrospective cohort study based on whole exome sequencing and machine learning models

BackgroundProstate cancer (PCa) in the transition zone (TZ) is uncommon and often poses challenges for early diagnosis, but its genomic determinants and therapeutic vulnerabilities remain poorly characterized.MethodsTumor mutational landscape was characterized in nine patients with TZ PCa, identifying somatic variants through whole-exome sequencing (WES). Novel candidate variants relevant to driver gene were selected using rare-variant burden analysis. Kaplan-Meier curves with log-rank testing and Cox regression models were applied to evaluate the prognostic significance of selected mutant driver gene and clinicopathological characteristics in a cohort of 132 patients with TZ PCa. Significant prognostic determinants were integrated into a validated nomogram for individualized prediction of 3-, 4-, and 5-year biochemical recurrence-free survival (BRFS) and overall survival (OS) probabilities. Eight machine learning algorithms were employed to develop BRFS and OS prediction models in a cohort.ResultsA total of 5,036 somatic single nucleotide variants (SNVs) and 587 somatic insertion and deletion (INDELs) were discovered. Among eight driver gene mutations which were verified through Sanger sequencing, TET2 gene, with high mutation frequency and potential targeted drug relevance (bromodomain inhibitors and DOT1L inhibitors) was selected for further validation. Retrospective cohort study demonstrated that TET2 mutant status was significantly associated with Gleason score (p = 0.004) and distant metastasis (p = 0.002). Furthermore, TET2 mutant status was significantly correlated with inferior BRFS and OS and served as an independent predictor. Comparative evaluation of eight algorithms revealed the GBM model achieved superior discriminative ability for BRFS (AUC for 3-year: 0.752, 4-year: 0.786, 5-year: 0.796). The predictive model based on the GBM machine learning algorithm achieved the best predictive performance for OS (AUC for 3-year: 0.838, 4-year: 0.915, 5-year: 0.868). The constructed predictive nomogram provided evidence that TET2 mutant status integration conferred statistically significant improvements in model accuracy and clinical predictive value.ConclusionOur study elucidated the distinct genetic basis of prostate cancer in the transition zone and identified TET2 mutation as an independent prognostic determinant in TZ PCa. However, the limited sample size of this study necessitates cautious interpretation of these findings, and further validation in larger cohorts is warranted to confirm their generalizability.

Long-term outcomes of PSMA PET/CT-guided radiotherapy in biochemical failure patients post-radical prostatectomy: a 5-year follow-up analysis

Abstract Purpose To evaluate the role of PSMA PET/CT-guided salvage radiotherapy (sRT) in improving long-term biochemical recurrence-free survival (bRFS) in patients with biochemical recurrence (BCR) or PSA persistence (PERS) after radical prostatectomy (RP) for localized prostate cancer. Methods This single-center retrospective study included 100 patients with BCR or PERS after RP who underwent [⁶⁸Ga]Ga-PSMA-11 PET/CT and sRT according to EAU guidelines. The primary endpoint was bRFS (PSA ≤ 0.2 ng/ml). Results Sixty-three patients had BCR and 37 had PERS. Fifteen patients had PSA pre-RT < 0.5 ng/ml, while 75 had PSA pre-RT ≥ 0.5 ng/ml. [⁶⁸Ga]Ga-PSMA-11 PET/CT was positive in 52 patients, with BCR patients more frequently exhibiting local recurrence while PERS patients showed more nodal involvement. Patients with PERS received sRT and androgen deprivation therapy (ADT) in 57% of cases. The hazard ratio (HR) of treatment failure for patients with PSA pre-RT ≥ 0.5 ng/ml vs. < 0.5 ng/ml was 2.2 (p < 0.039). With a median follow-up of 59 months, treatment failure occurred in 36% of patients, with no difference between BCR and PERS groups. Among those with treatment failure, 64% were [⁶⁸Ga]Ga-PSMA-11 PET/CT positive at recurrence, and 39% received a new PSMA PET/CT-based RT. All patients were alive at the last analysis. Conclusion [⁶⁸Ga]Ga-PSMA-11 PET/CT-guided sRT demonstrates significant long-term efficacy in patients with BCR or PERS after RP, leading to durable PSA response and guiding further treatment decisions. Trial registration 244/2016/O/Oss8 November 2016 retrospectively registered.

Prognostic Impact of Seminal Vesicle Mucosal Invasion in pT3b Prostate Cancer Following Radical Prostatectomy

Purpose: The extent of seminal vesicle invasion (SVI) in prostate cancer can be classified into muscle layer invasion (SVI-muscle) and mucosal layer invasion (SVI-mucosa). This study aimed to evaluate the prognostic significance of the extent of SVI after radical prostatectomy.Materials and Methods: SVI-mucosa data were prospectively collected since 2014. Among 1,659 radical prostatectomy specimens from 2014 to 2023, 259 cases (15.6%) with extraprostatic SVI were enrolled. A total of 252 cases with available follow-up data were included in the final analysis.Results: SVI-mucosa was identified in 63 cases (25.0%), and SVI-muscle was identified in all 252 cases. Extracapsular extension was present in nearly all SVI cases (99.6%). The mean tumor volume percentage in final specimens was significantly higher in patients with SVI-mucosa (50%) compared to those without it (35%) (p<0.001). A high Gleason score (≥8) was more common in men with SVI-mucosa (p=0.021). Only 10 (5.3%) and 4 patients (6.3%) with and without SVI-mucosa, respectively, received adjuvant therapy (p=0.544). Biochemical recurrence-free survival did not significantly differ between men with SVI-mucosa and those with SVI-muscle alone (log-rank test, p=0.309). The 5-year metastasis-free survival and prostate cancerspecific survival rates were 86.0% vs. 91.6% (p=0.654) and 99.5% vs. 100% (p=0.865) in patients with and without SVI-mucosa, respectively.Conclusion: The prognosis of patients with SVI is not uniformly poor. SVI-mucosa was associated with more aggressive pathological features. In most cases, SVI-muscle appears to develop first following extracapsular extension, with subsequent progression to SVI-mucosa. However, the presence of SVI-mucosa, an advanced status of SVI, did not significantly impact biochemical recurrence and metastasis-free survival rates.

MRI-guided biopsy reduces biochemical recurrence in prostate cancer patients undergoing radiation therapy: a single-center study from Thailand

Accurate diagnosis of significant prostate cancer (PCa) is essential for effective treatment. Multiparametric magnetic resonance imaging (mpMRI) is increasingly used for lesion detection and biopsy guidance, but its impact on outcomes following radiotherapy remains uncertain. This study assesses the effect of MRI-guided biopsy on biochemical recurrence (BCR) following definitive external beam radiotherapy (EBRT). This single-center, retrospective review included 102 patients with localized PCa who received primary EBRT between 2018 and 2021. The MRI-guided biopsy group underwent both targeted and systematic biopsies, while the non-MRI-guided biopsy group underwent systematic biopsy alone. All patients underwent pre-treatment MRI (pre-RT MRI). Kaplan-Meier analysis compared BCR-free survival between the MRI-guided and non-MRI-guided biopsy groups. Among the 102 patients, 57 underwent MRI-guided biopsy, with 52.9% classified as intermediate-risk. The median follow-up period was 57.2 months. The proportion of very-high-risk patients was significantly greater in the non-MRI-guided biopsy group (24.4% vs. 3.5%, p = 0.01). Seventeen patients in the non-guided biopsy group were staged as T3 with the assistance of the pre-RT MRI. Despite the use of pre-RT MRI in all non-MRI-guided biopsy cases, four patients experienced BCR, whereas no BCR was observed in the MRI-guided biopsy group. The MRI-guided biopsy group demonstrated superior BCR-free survival (p < 0.01) across both intermediate- and higher-risk groups. MRI-guided biopsy was associated with a reduced risk of BCR following definitive EBRT, particularly in intermediate-risk patients. In contrast, systematic random biopsies, even when combined with pre-RT MRI, were linked to poorer intermediate oncologic outcomes.

Preoperative MRI-based predictive model for biochemical recurrence following radical prostatectomy.

To determine the biochemical recurrence (BCR)-related pelvic anatomic characteristics before radical prostatectomy (RP) and to establish a new predictive model for BCR-free survival (BCRFS). The study involved 170 patients who underwent RP between January 2015 and December 2022. Kaplan-Meier plots were applied to estimate survival probabilities. Multivariate Cox regression models were employed to identify predictors for BCRFS, which were subsequently incorporated into an MRI-based nomogram to visualize the model. The Harrell's concordance index (C-index) was employed to evaluate the discrimination, and compared with a basic model without incorporating pelvic anatomy. Time-dependent receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were applied to identify the advantage of the new predictive model. Three risk categories were created. Multifactorial analysis revealed that age, capsule contact length (CCL), tumor's distance to the proximal membranous urethra (UD), urethral width, and annual surgery volume were independent risk factors for BCR (all p < 0.05). The established predictive model yielded a C-index of 0.850 that was superior to aforementioned basic model with C-index of 0.771 (p < 0.001). Our new model with an area under the ROC curve (AUC) of 0.893 revealed better predictive ability in BCRFS than basic model with the AUC of 0.823 (p = 0.01), and DCA demonstrated that our model generated more net benefits. UD and urethral width are independent predictors of BCRFS. Our new model exhibits superior predictive accuracy with respect to BCRFS relative to the basic model. Apart from tumor features, pelvic anatomical features should also be considered before the treatment decision making of PCa patients.

Bi-parametric MRI-based quantification radiomics model for the noninvasive prediction of histopathology and biochemical recurrence after prostate cancer surgery: a multicenter study.

To develop and evaluate the performance of a noninvasive radiomics combined model based on preoperative bi-parametric MRI to assess biochemical recurrence (BCR) risk factors and to predict biochemical recurrence free survival in PCa patients. Pretreatment bp-MRI and clinicopathology data of 666 (discovery cohort, 545; test cohort, 121) PCa patients from four centers between January 2015 to March 2023 were retrospectively included. To predict BCR, extracapsular extension (ECE), pelvic lymph node metastasis (PLNM), and Gleason Grade group (GG), the pred-BCR, pred-ECE, pred-PLNM, and pred-GG models were developed, respectively. Subsequently, a logistic regression algorithm was used to combine one or more radiomics models and clinicopathology variables into radiomics-clinicopathology combined models (M1, M2) and radiomics-clinical combined model without pathology results (M3) for predicting BCR. In the test cohort, the AUCs for the pred-BCR, pred-ECE, pred-PLNM, and pred-GG models were 0.841, 0.764, 0.896, and 0.698. Of the three combined models, M3 has the best prediction performance with an AUC of 0.884, M2 is the following with an AUC of 0.863, and M1 has the lowest performance with an AUC of 0.838 (95% CI 0.750-0.925) in the test cohort. Delong's test showed that the M3 was significantly higher (M1 vs. M3, p = 0.028; M2 vs. M3, p = 0.044). The combined model developed in this study, which is not dependent on pathologic biopsies, can noninvasively predict postoperative histopathology and BCR after PCa, therefore may provide decision support for follow-up and treatment strategies for patients in the postoperative period.

Prostate-Specific Antigen Decline Rate in the First Month Is a Timely Predictive Factor for Biochemical Recurrence After Robot-Assisted Radical Prostatectomy.

Objectives: We attempt to assess whether prostate-specific antigen decline rate in the first month (PSADR1M = postoperative PSA in the first month/initial PSA) acts as a predictor for biochemical recurrence (BCR) and to evaluate other preoperative and postoperative variables that may predict BCR following robot-assisted laparoscopic prostatectomy (RARP). Method: Based on the D'Amico risk classification system, 777 patients who underwent RARP for localized prostate cancer were classified into a low/intermediate-risk group (n = 435) and a high-risk group (n = 342). The predictors of BCR were identified by univariate and multivariate logistic regression analyses. The area under the curve (AUC) and optimal cutoff values of PSADR1M were determined by receiver operating characteristic (ROC) analysis. Kaplan-Meier curves for biochemical recurrence-free survival (BRFS) rates were stratified by optimal cutoff values of PSADR1M. Results: Effective predictors of BCR in the entire cohort included pT3 (p < 0.001), pathological Grade Group (pGG3, pGG4+5) compared to pGG1+2 (p < 0.001, p = 0.017), positive surgical margins (PSM) (p < 0.001), seminal vesicle invasion (SVI) (p = 0.006), and PSADR1M ≥ 0.62% (p < 0.001). ROC analysis showed that PSADR1M as a predictor for BCR had an AUC of 0.762 for the whole cohort, and 0.821 for the high-risk group, respectively. The optimal cutoff values of PSADR1M were 0.62% in the whole cohort, and 0.68% in high-risk group. Conclusions: As an effective predictor of BCR, PSADR1M can assess the tumor status of prostate cancer patients intuitively and effectively after RARP, especially in the high-risk group.

Development of a risk model for bcr-free prognosis in prostate cancer patients linked to nucleotide metabolism

Introduction: Prostate cancer is a prevalent malignancy among elderly men, with bioinformatics playing a crucial role in advancing diagnosis and treatment paradigms. Recent studies have highlighted the significance of nucleotide metabolism (NM) in Prostate cancer development and progression, linking it to aggressive cancer phenotypes characterized by uncontrolled proliferation and metastasis. Understanding NM-related genes (NMRGs) could provide insights into Prostate cancer pathogenesis and therapeutic targets.Methods: This paper analyzed TCGA-PRAD and GSE70769 datasets to identify critical modules associated with NMRGs using weighted gene co-expression network analysis (WGCNA). Differentially expressed genes (DEGs) between Prostate cancer and control samples were extracted from the TCGA-PRAD dataset, with overlaps identified as NM-related DEGs (DE-NMRGs). A biochemical recurrence (BCR)-free risk model was constructed from 396 Prostate cancer samples, and patients were classified into high- and low-risk groups based on median risk scores. A nomogram model integrating key prognostic factors was developed to predict BCR rates.Results: This paper identified 5 prognostic genes: RGS11, KAT2A, MXD3, TARBP1, and WFIKKN. The low-risk group exhibited significantly higher BCR-free survival rates, ESTIMATE scores, and immunophenoscore (IPS) scores compared to the high-risk group. Additionally, potential therapeutic agents, including KU-55933 and Wee1 inhibitors, were proposed. Conclusions: The identified prognostic genes present promising targets for Prostate cancer diagnosis and treatment, emphasizing their importance in predicting biochemical recurrence and tailoring personalized therapeutic strategies for patients.

Efficacy and safety of neoadjuvant chemohormonal therapy for high-risk prostate cancer treated with robot-assisted laparoscopic radical prostatectomy: a propensity score-matched analysis (the MSUG94 group).

The optimal neoadjuvant regimen before radical prostatectomy (RP) in patients with high-risk (HR) prostate cancer (PCa) remains to be determined. This retrospective multicenter cohort study assessed the effectiveness and safety of neoadjuvant chemohormonal therapy (NCHT) in patients with HR-PCa undergoing robot-assisted laparoscopic radical prostatectomy (RALP). We reviewed the datasets of 1023 subjects who underwent RALP at nine Japanese facilities between September 2012 and October 2023. The enrolled patients were divided into two groups using propensity score matching: a RALP-alone group and those who underwent NCHT followed by RALP (NCHT group). The NCHT regimen consisted of a luteinizing hormone-releasing hormone antagonist and tegafur-uracil for at least 3months before RALP. The primary endpoint was biochemical recurrence (BCR) after RALP. The secondary endpoint was the surgical specimen pathology findings. Propensity score matching identified 139 individuals for each group. Median follow-up was 18.2months. During follow-up, BCR was observed in 41 patients (29.5%) in the RALP-alone group and 22 patients (15.8%) in the NCHT group (p = 0.010). Pathological results showed significantly more organ-confined PCa and significantly fewer positive surgical margins or lymphovascular invasion in the NCHT group than in the RALP-alone group. The 2-yr biochemical recurrence-free survival (BRFS) was 72.7% and 74.7% in the RALP-alone and NCHT groups, respectively (p = 0.086). Two patients (1.4%) experienced grade 3 liver disorder as an NCHT-related adverse event. The results suggest that NCHT can safely treat HR-PCa and may reduce the incidence of BCR when combined with RALP.

Safety and early outcomes of proton therapy and low-dose rate brachytherapy boost for patients with prostate cancer.

Safety and early outcomes of proton therapy and low-dose rate brachytherapy boost for patients with prostate cancer.

LAMP5, One of Four Genes Related to Oxidative Stress That Predict Biochemical Recurrence-Free Survival, Promotes Proliferation and Invasion in Prostate Cancer [Retraction

[This retracts the article DOI: 10.2147/AABC.S489131.].

PCBP2 promotes immune evasion via cGAS-STING pathway in biochemical recurrence of prostate cancer.

Immunotherapy resistance is a significant obstacle in the treatment of prostate cancer (PCa), primarily due to immune evasion mechanisms. This study aims to explore cancer-intrinsic immune evasion-related genes (CIERGs) in PCa and develop a predictive signature for biochemical recurrence (BCR). Bulk RNA-seq data and single-cell RNA-sequencing (scRNA-seq) were obtained from TCGA and Gene Expression Omnibus database. The scRNA-seq data analysis revealed higher immune evasion scores in tumor cells compared to normal cells. Differentially expressed genes from TCGA-PRAD and GSE70769 cohorts were intersected with 182 core immune evasion genes, followed by univariate Cox regression, identifying 48 CIERGs significantly associated with BCR. Nonnegative matrix factorization (NMF) clustering revealed two immune evasion-related PCa subtypes. A risk signature based on CIERGs was developed using LASSO regression, and a nomogram was created to predict BCR-free survival. Among the 48 identified CIERGs, poly(C)-binding protein 2 (PCBP2) emerged as a key risk factor associated with poor prognosis in PCa, and its function was validated in vitro. NMF clustering identified two subtypes, with the C1 subtype having a poorer prognosis. Gene Set Variation Analysis highlighted enrichment in cell cycle, extracellular matrix receptor interaction, and transforming growth factor-beta signaling pathways in the C1 subtype. A CIERGs-based risk signature, including six key genes, was developed and validated, with the nomogram showing high predictive accuracy. In vitro experiments showed PCBP2 promotes PCa cell proliferation, migration, and invasion by inhibiting the cyclic GMP-AMP synthase-STING pathway. The CIERGs signature provides a precise prediction of BCR, with PCBP2 emerging as a potential therapeutic target due to its inhibition of the cGAS-STING pathway in PCa.

Management Based on Pretreatment PSMA PET of Patients with Localized High-Risk Prostate Cancer Part 2: Prediction of Recurrence—A Systematic Review and Meta-Analysis

Background and objectives: For patients with prostate cancer (PCa), PSMA PET better diagnose metastases than conventional imaging. In a systematic review and meta-analysis (INPLASY register, 2024311004), we aimed to summarize findings with pretreatment PSMA PET in patients with PCa that was localized according to conventional imaging and summarize how pretreatment PSMA PET had influence on biochemical recurrence (BCR)-free survival and overall survival (OS). Methods: We searched for publications in Pubmed, Google Scholar, ClinicalTrials.gov, and reference lists between 2016 and February 2025. We summarized biochemical recurrence-free survival in Forest plots. Results: Nine publications reported 1908 patients and showed that pretreatment PSMA PET was associated with survival. Three publications reported that pretreatment PSMA PET gave better 3–5-year BCR-free survival than conventional imaging (74% versus 57%). Two publications reported PSMA PET-risk for 389 patients. Those with PSMA PET-low-risk lived 5 years longer often than those with PSMA PET high-risk (84% versus 20%). Conclusions: Pretreatment PSMA PET is widely used in the real world. Pretreatment PSMA PET supports personalized treatment and may explain why pretreatment PSMA PET improved BCR-free survival and OS. It is believed that pretreatment PSMA PET may facilitate future progress in care of patients with high-risk PCa.

Effect of the PI-RADS score on adverse surgical outcomes in patients with prostate cancer after radical prostatectomy

Background. Multiparametric magnetic resonance imaging and Prostate Imaging Reporting and Data System (PI-RADS) are widely used to diagnose clinically significant prostate cancer. Meanwhile, PI-RADS diagnostic accuracy varies between 30 % for PI-RADS score 3 to 80 % for PI-RADS score 5. The value of PI-RADS scores in patients already diagnosed with prostate cancer remains unclear.Aim. To evaluate the impact of PI-RADS score on adverse surgical outcomes: prostate cancer upstaging, increased Gleason score, lymph node metastases, positive surgical margin, and oncological outcomes in patients of the ISUP grade 1 group per the International Society of Urological Pathology (ISUP) scale who underwent radical prostatectomy.Materials and methods. Forty patients with ISUP grade 1 prostate cancer underwent radical prostatectomy (robotic or laparoscopic). All patients underwent diagnostic multiparametric magnetic resonance imaging with PI-PADS score v2 (v2.1) prior to radical prostatectomy. PI-RADS 3 was determined in 14 (35 %), PI-RADS 4 – in 10 (25 %) and PI-RADS 5 – in 16 (40 %) patients, respectively. The age of patients was 62.7 ± 6.6 years. Stage cT2a was diagnosed in 19 (47.5 %), cT2b – in 5 (12.5 %), cT2c – in 11 (27.5 %), cT3a – in 5 (12.5 %) patients, respectively. Pelvic lymph node dissection was performed in 23 (57.5 %) cases. The median follow-up was 12.6 months.Results. Upstaging events to pT3a occurred in 2 (15.2 %) patients with PI-RADS 3 lesions, in 5 (31.3 %) patients with PI-RADS 5 lesions; upstaging events to pT3b occurred in 1 (10 %) patient with PI-RADS 4 lesions, and in 1 (6.25 %) patient with PI-RADS 5 lesions. Increased Gleason score (GS) was observed in 22 (55 %) patients: GS increase ≥2 was diagnosed in 8 (57.1 %) patients with PI-RADS 3 lesions, in 3 (30 %) patients with PI-RADS 4 lesions, in 11 (68.7 %) patients with PI-RADS 5 lesions, respectively. Lymph node metastases were observed only in 1 (4.3 %) patient with PI-RADS 5 lesions. Positive surgical margin (&gt;3 mm) was observed in 2 (12.4 %) patients with PI-RADS 5 lesions. Biochemical recurrence occurred in 1 (2.5 %) patient with PI-RADS 3 lesions. One-year biochemical recurrence-free survival was 97.5 %.Conclusion. Increased PI-RADS score from 3 to 5 is accompanied by increased frequency of prostate cancer upstaging and Gleason score increase in patients with ISUP grade 1 prostate cancer. PI-RADS scores 3–5 can be important in selecting patients for nerve-sparing prostatectomy, pelvic lymph node dissection, and play a part in prediction of biochemical recurrence and lymph node metastasis.

Impact of Pelvic Lymph Node Dissection on Early Oncological Outcomes in Intermediate-Risk Prostate Cancer Patients With Node-Negative PSMA PET.

PSMA PET/CT has previously shown superior performance in nodal staging of prostate cancer (PCa) and may be used to reduce the number of unnecessary PLND procedures. This study aims to assess the performance of PSMA PET/CT in nodal staging of intermediate-risk prostate cancer and to evaluate the effect of PLND on oncological outcomes of intermediate-risk prostate cancer patients with a negative PSMA PET/CT. A total of 308 patients with intermediate-risk PCa who underwent PSMA PET/CT for nodal staging between January 2014 and July 2024 were included in the study. Patients who underwent PLND had higher PSA and higher rates of PIRADS-5 and biopsy grade-group 3 disease. A 1:1 propensity score matching was performed to eliminate patient characteristics differences between groups and 140 patients were included in the final analysis. PSA persistence rates ( ≥ 0.1 ng/dL) and biochemical recurrence (BCR; ≥ 0.2 ng/dL) rates after RP were recorded. Kaplan-Meier curves were constructed to evaluate oncological outcomes. Log-rank test was utilized to compare oncological outcomes in patients with and without PLND. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PSMA PET/CT on nodal staging were 53.3%, 95%, 47.1%, and 96.1%, respectively. The NPV of PSMA PET/CT in patients with biopsy GG3 disease (96.3%) was similar to those with biopsy GG2 disease (95.6%). The median follow-up after propensity score matching was 20.7 months. The 24-month BCR-free survival rates were 83.7% and 86.9% in the PLND-RP group and RP-only groups, respectively (p = 0.078). NPV of PSMA PET/CT in determining LNI was remarkable in patients with intermediate-risk PCa and PLND was found to have no impact on oncological outcomes. Therefore PLND may be omitted to decrease surgery-related complications in patients with intermediate-risk PCa a negative PSMA PET/CT for nodal staging.

The Diagnostic Value of Plasma Small Extracellular Vesicle-Derived CAIX Protein in Prostate Cancer and Clinically Significant Prostate Cancer: A Study on Predictive Models.

Current diagnostic tools are inaccurate and not specific to prostate cancer (PCa) diagnosis. Cancer-derived small extracellular vehicles (sEVs) play a key role in intercellular communication. In this study, we examined the diagnostic value of plasma sEV-derived carbonic anhydrase IX (CAIX) protein for PCa and clinically significant prostate cancer (csPCa) diagnosis and avoiding unnecessary biopsies. Plasma samples (n = 230) were collected from the patients who underwent prostate biopsy with elevated prostate-specific antigen (PSA) levels. sEVs were isolated and characterized, and sEV protein CAIX was measured using an enzyme-linked immunosorbent assay. Independent predictors of csPCa (Gleason score ≥ 7) were identified, and a predictive model was established. A Nomogram for predicting csPCa was developed using data from the training cohort. The expression of sEV protein CAIX was significantly higher in both PCa and csPCa compared to benign patients and nonsignificant PCa (nsPCa) (Gleason score < 7, p < 0.001). sEV protein CAIX performed well in distinguishing PCa from benign patients. The predictive model defined by sEV protein CAIX and PSA density (PSAD) demonstrated the highest discriminative ability for csPCa (AUC = 0.895), with diagnostic sensitivity and specificity of 82.5% and 85.8%, respectively. Furthermore, sEV protein CAIX is an effective predictor of 2-year biochemical recurrence (BCR) in PCa patients (p = 0.013), and its high expression is significantly associated with poorer BCR-free survival (p < 0.05). Our findings demonstrate the excellent performance of sEV protein CAIX in PCa and csPCa diagnosis. The Nomogram-based csPCa predictive model incorporating sEV protein CAIX and PSAD exhibits strong predictive value. Additionally, assessing plasma sEV protein CAIX expression levels can further aid in evaluating patient prognosis and provide a basis for making effective treatment decisions.

Integration of single-cell and bulk RNA-sequencing data reveals the prognostic potential of epithelial gene markers for prostate cancer.

Prognostic transcriptomic signatures for prostate cancer (PCa) often overlook the cellular origin of expression changes, an important consideration given the heterogeneity of the disorder. Current clinicopathological factors inadequately predict biochemical recurrence, a critical indicator guiding post-treatment strategies following radical prostatectomy. To address this, we conducted a meta-analysis of four large-scale PCa datasets and found 33 previously reported PCa-associated genes to be consistently up-regulated in prostate tumours. By analysing single-cell RNA-sequencing data, we found these genes predominantly as markers in epithelial cells. Subsequently, we applied 97 advanced machine-learning algorithms across five PCa cohorts and developed an 11-gene epithelial expression signature. This signature robustly predicted biochemical recurrence-free survival (BCRFS) and stratified patients into distinct risk categories, with high-risk patients showing worse survival and altered immune cell populations. The signature outperformed traditional clinical parameters in larger cohorts and was overall superior to published PCa signatures for BCRFS. By analysing peripheral blood data, four of our signature genes showed potential as biomarkers for radiation response in patients with localised cancer and effectively stratified castration-resistant patients for overall survival. In conclusion, this study developed a novel epithelial gene-expression signature that enhanced BCRFS prediction and enabled effective risk stratification compared to existing clinical- and gene-expression-derived prognostic tools. Furthermore, a set of genes from the signature demonstrated potential utility in peripheral blood, a tissue amenable to minimally invasive sampling in a primary care setting, offering significant prognostic value for PCa patients without requiring a tumour biopsy.

Impact of Neoadjuvant Chemohormonal Therapy With GnRH Antagonist and Low-Dose Estramustine in Very High-Risk Prostate Cancer Undergoing Robotic Radical Prostatectomy.

High-risk patients with prostate cancer (PC) frequently experience biochemical recurrence (BCR) after surgery. Thus numerous studies have investigated the efficacy of neoadjuvant therapies for high-risk PC patients; however, no protocol has been established. This study aimed to assess the effect of androgen deprivation therapy combined with low-dose estramustine phosphate (EMP) on BCR compared with androgen deprivation therapy (ADT) alone in high- and very high-risk patients with PC. This retrospective study targeted patients with PC meeting the National Comprehensive Cancer Network high-risk criteria (cT1-4N0M0), with 173 patients in the exposure group who received neoadjuvant chemohormonal therapy (gonadotropin-releasing hormone [GnRH] antagonist combined with low-dose EMP), and 490 patients in the control group treated with and neoadjuvant hormone therapy (NHT) (ADT ± first-generation anti-androgens). Data for each group were extracted from a database of patients who underwent robot-assisted laparoscopic prostatectomy at 25 tertiary care centers across Japan between 2011 and 2023. The inverse probability of treatment weighting was used to adjust for baseline differences. The primary outcome was BCR-free survival, with hazard ratios (HRs) calculated using a Cox proportional hazards model between the high-risk and very high-risk groups. After adjustment, the standardized mean difference was < 0.1. The exposure group had 3 and 5-year BCR-free survival rates of 82.1% and 74.6%, respectively, compared with 70.8% and 64.4% in the control group (HR: 0.55; 95% confidence interval [CI]: 0.35-0.88). For high-risk patients, the rates were 87.1% and 84.2% at both 3 and 5 years in the intervention group and 83.5% and 75.0% in the control group (HR: 0.66; 95% CI: 0.30-1.47). For very high-risk patients, the 3-year and 5-year rates were 75.3% and 65.7% in the intervention group and 57.3% and 53.6% in the control group (HR: 0.53; 95% CI: 0.30-0.92). In patients with very high-risk PC undergoing robot-assisted laparoscopic prostatectomy, a GnRH antagonist and low-dose EMP yielded better BCR-free survival outcomes than NHT.

Extended Lymph Node Dissection May Not Provide a Therapeutic Benefit in Patients with Intermediate-to High-Risk Prostate Cancer Treated with Robotic-Assisted Radical Prostatectomy.

The therapeutic efficacy of extended lymph node dissection (ePLND) for intermediate- and high-risk (IR/HR) prostate cancer remains controversial. This study evaluated whether PLND improved biochemical recurrence (BCR) rates in patients with prostate cancer undergoing robotic-assisted radical prostatectomy (RARP) using a propensity matching method with cases from two facilities. The study included 1002 patients with IR/HR disease who underwent RARP at two facilities with equivalent surgical techniques and hospital size but different ePLND policies for IR/HR between July 2012 and November 2022. We compared perioperative outcomes, complications, and biochemical recurrence-free survival (bRFS) between the centers. After propensity matching, 221 and 124 cases, each at intermediate and high risk, respectively, were compared. Except for age, preoperative clinicopathological variables did not differ significantly between the matched ePLND and non-PLND groups. A median of 18 lymph nodes were assessed in the dissection group. The 3-year bRFS rates did not differ significantly between ePLND and non-PLND among intermediate-risk and high-risk patients. The dissection group had significantly longer operative times and more complications associated with ePLND, including lower extremity edema, pelvic hematoma, and neuropathy. A multivariable Cox regression analysis performed after propensity adjustment identified initial prostate-specific antigens, pathological tumor stage (high-risk only), and positive surgical margins as independent prognostic factors for bRFS while ePLND was not significant. These results suggest that ePLND may not be necessary in intermediate- to high-risk PCa patients undergoing RARP, although further study with a longer follow-up is required.

Evaluating the efficacy and safety of pelvic lymph node dissection in high-risk prostate cancer patients undergoing radical prostatectomy: A systematic review and meta-analysis.

390 Background: Pelvic lymph node dissection (PLND) is currently considered the gold standard for lymph node staging in prostate cancer patients. However, there is a paucity high-quality evidence demonstrating an oncological prognostic benefit of PLND in high-risk prostate cancer (PCa) populations, as defined by D'Amico risk classification. Methods: We conducted a comprehensive systematic literature review utilizing MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE databases. The search encompassed studies up to June 2024, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We identified original articles published in journals that reported survival analyses using Cox regression analysis and differences in hazard ratios (HRs) for the biochemical recurrence (BCR)-free survival (BRFS) (primary outcome) and metastasis-free survival (MFS), overall survival (OS) or cancer specific survival (CSS) (secondary outcomes). A meta-analysis of the effect of PLND on primary and secondary endpoints was performed using a random effects model. Results: Our analysis included seven studies, comprising one prospective and the rest retrospective. Pooled outcome data showed that PLND after radical prostatectomy did not independently predict BRFS (HR: 1.22; 95%CI: 0.99-1.50; p=0.006), MFS (HR: 1.21; 95%CI: 0.86-1.70; p=0.27), OS (HR: 0.91; 95%CI: 0.74-1.12; p=0.37), or CSS(HR: 1.02; 95%CI: 0.74-1.42; p=0.89) in high-risk prostate cancer patients. Heterogeneity was low to moderate. Conclusions: The available pooled analyses suggest that the therapeutic value of PLND is unclear. The high-risk PCa population should be carefully selected for lymph node dissection.