The latest medical research on Prostate Cancer
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Request AccessUndetected Cribriform and Intraductal Prostate Cancer at biopsy is associated with adverse outcomes.
Prostate Cancer and Prostatic DiseasesIntraductal carcinoma (IDC) and cribriform pattern (Crib) of prostate cancer are increasingly recognized as independent prognosticators of poor outcome, both in prostate biopsies and radical prostatectomy (RP) specimens.
The aim of our project is to assess the impact of false negative biopsies for these two characteristics on oncological outcomes.
Patients who underwent RP between January 2015 and December 2022 were included in the study. Predictors of Biochemical Failure were examined using a multivariate Cox proportional hazards model.
Among the 836 patients who underwent RP, 233 (27.9%) had Crib, and 125 (15.0%) had IDC on prostate biopsy, with 71 (8.5%) patients having both IDC and Crib. Concerning IDC/Crib status at biopsy, 217 (26%) patients had a false-negative biopsy, 332 (39.7%) had a true-negative biopsy, 256 (30.6%) showed a true-positive biopsy, and 24 (3.7%) exhibited a false-positive biopsy, with respect to either pattern. When comparing false-negative, false-positive, true-negative and true-positive biopsies for IDC/Crib, we found that patients with a false-negative biopsy for IDC/Crib versus those with a true-negative biopsy for IDC/Crib disclosed a rate of advanced pathological stage (≥pT3) which was twice that of patients with a true-negative biopsy for IDC/Crib: 56.8% versus 28.1%, respectively (p < 0.001). On multivariate Cox analysis, log PSA before RP (hazard ratio [HR] 2.07, 95% CI 1.53-2.82; p < 0.001), a higher percentage of positive cores at biopsy ( ≥ 33%) (HR 1.68, 95% CI 1.07-2.63; p = 0.024), and false negative biopsy for IDC/Crib (HR 2.14, 95% CI 1.41-3.25; p < 0.001), were each significantly associated with an increased risk of BCR.
A false-negative biopsy for IDC/Crib is independently associated with higher risk of BCR and advanced pathological stage compared to a true negative biopsy.
Prostate cancer screening and management in patients candidate for endoscopic enucleation of the prostate: an international survey.
Prostate Cancer and Prostatic DiseasesTo explore how urologists manage prostate cancer (PCa) screening and treatment in patients undergoing endoscopic enucleation of the prostate (EEP).
A team of experts in EEP collaboratively formulated the survey questions through an interactive process. The survey opened in January 2024 and closed in February 2024.
102 urologists responded, revealing that most use PSA and digital rectal examination for screening, with high PSA and abnormal DRE prompting prostate MRI. 75% perform pre-EEP biopsies. For incidental low-grade PCa, active surveillance is preferred. For intermediate-grade PCa, most use PSA and MRI for workup, often choosing active surveillance if post-EEP biopsies are negative. There's no consensus on abnormal post-operative PSA thresholds.
While urologists are aware of PCa management in EEP candidates, future work should focus on developing optimal post-EEP screening protocols.
Protein kinase D1 mitigation against etoposide induced DNA damage in prostate cancer is associated with increased α-Catenin.
ProstateThe E-cadherin, α- and β-Catenin interaction at the cell adherens junction plays a key role in cell adhesion; alteration in the expression and function of these genes are associated with disease progression in several solid tumors including prostate cancer. The membranous β-Catenin is dynamically linked to the cellular cytoskeleton through interaction with α-Catenin at amino acid positions threonine 120 (T120) to 151 of β-Catenin. Nuclear presence of α-Catenin modulates the sensitivity of cells to DNA damage. The objective of this study is to determine the role of α-Catenin and protein kinase D1 (PrKD1) in DNA damage response.
Prostate cancer cells; LNCaP, LNCaP (Sh-PrKD1; silenced PrKD1), C4-2 and C4-2 PrKD1 were used for various sets of experiments to determine the role of DNA damage in PrKD1 overexpression and silencing cells. These cells were treated with compound-10 (100 nM) and Etoposide (30 µM), total cell lysates, cytosolic and nuclear fractions were prepared to observe various protein expressions. We performed single cell gel electrophoresis (COMET assay) to determine the etoposide induce DNA damage in C4-2 and C4-2 PrKD1 cells. The animal experiments were carried out to determine the tolerability of compound-10 by mice and generate preliminary data on efficacy of compound-10 in modulating the α-Catenin and PrKD1 expressions in inhibiting tumor progression.
PrKD1, a novel serine threonine kinase, phosphorylates β-Catenin T120. In silico analysis, confirmed that T120 phosphorylation alters β- to α-Catenin binding. Forced expression of PrKD1 in prostate cancer cells increased β- and α-Catenin protein levels associated with reduced etoposide induced DNA damage. Downregulation of α-Catenin abrogates the PrKD1 mitigation of DNA damage. The in vitro results were corroborated in vivo using mouse prostate cancer patient derived xenograft model by inhibition of PrKD1 kinase activity with compound-10, a selective PrKD inhibitor, demonstrating decreased total β- and α-Catenin protein levels, and β-Catenin T120 phosphorylation.
Alteration in DNA damage response pathways play major role in prostate cancer progression. The study identifies a novel mechanism of α-Catenin dependent DNA damage mitigation role for PrKD1 in prostate cancer.
Navigating therapeutic sequencing in the metastatic castration-resistant prostate cancer patient journey.
Prostate CancerNovel therapies for metastatic castration-resistant prostate cancer (mCRPC) have improved patient outcomes. However, there is uncertainty on the optimal selection of therapeutic agents for subsequent lines of therapy.
We conducted a comprehensive review of published evidence from pivotal clinical trials and recent guidelines for the treatment of mCRPC. We further identify gaps in knowledge and areas for future research.
Key considerations to help guide treatment selection for patients with mCRPC include personal treatment history, individual clinical characteristics, symptoms, prognosis, availability of clinical trials, and other patient-specific factors. Genetic testing and prostate-specific membrane antigen-targeted imaging are important tools to evaluate candidacy for newer therapeutic options such as poly (ADP-ribose) polymerase inhibitors, alone or in combination with androgen receptor pathway inhibitors, and [177Lu]Lu-PSMA-617.
This article provides an overview of the evolving treatment landscape of mCRPC, discussing guideline-recommended treatment options and data from key clinical trials, while highlighting ongoing trials that may impact the future treatment landscape. Recommendations for optimal treatment sequencing based on individual patient factors are provided.
Comparison of abiraterone, enzalutamide, and apalutamide for metastatic hormone-sensitive prostate cancer: A multicenter study.
ProstateWe aimed to assess the differential efficacy and safety of androgen receptor pathway inhibitors (ARPI), such as abiraterone, enzalutamide, and apalutamide, in patients with metastatic hormone-sensitive prostate cancer (mHSPC) in a real-world practice setting.
We retrospectively reviewed the records of consequent 668 patients with mHSPC treated with ARPI plus androgen deprivation therapy between September 2015 and December 2023. Based on the LATITUDE criteria, the comparison among abiraterone, enzalutamide, and apalutamide was exclusively conducted in high-risk patients. Prostate-specific antigen (PSA) responses such as the achievement of 95% and 99% PSA decline, overall survival (OS), cancer-specific survival (CSS), time to castration-resistant prostate cancer (CRPC), and the incidence of adverse events (AEs) were compared. All two-group comparisons relied on propensity score matching (PSM) to minimize the effect on possible confounders.
In total, 297 patients with high-risk mHSPC treated with abiraterone, 127 with enzalutamide, and 142 with apalutamide were compared. There were no differences in time to CRPC (p = 0.13), OS (p = 0.7), and CSS (p = 0.5) among the three ARPIs. No differences were observed in the achievement rates for 95% PSA decline at 3 months among the three ARPIs, while abiraterone was significantly better in 99% PSA decline achievement compared to apalutamide (72% vs. 57%, p = 0.003). The aforementioned oncologic outcomes were sustained even when performing PSM analyzes. Although skin rash for APA (34%) was the highest incidence of AEs, there were no differences in the rates of severe AEs across the three ARPIs. Enzalutamide resulted in the lowest treatment discontinuation rates (10%) other than disease progression compared to the other regimens.
Abiraterone, enzalutamide, and apalutamide have comparable oncologic outcomes in terms of OS, CSS, and time to CRPC in patients with high-risk mHSPC. Our data on differential treatment discontinuation rates, PSA response, and AE profiles can help guide clinical decision-making.
Does size matter? A single institution's comparison of Aquablation in prostates greater than or less than 150 mL.
ProstateSurgical management options for lower urinary tract symptoms due to benign prostatic hypertension have remained limited in prostates of large volume. The advent of the Aquablation has created a potential minimally invasive option for treatment in prostates of all volumes. Thus, this study aims to evaluate outcomes and complications of Aquablation in clinical practice based on prostate volume.
Collected variables included adverse events with Clavien-Dindo classifications, transfusion rates, surgical retreatment rates, continued medication use postoperatively, and International Prostate Symptom Score (IPSS) with Quality-of-Life indicator. Aquablations were stratified by preoperative prostate volume.
One hundred seventy-four men were included in the study. The average postop decrease in IPSS was 10.28, with a 2.02 point decrease in Quality-of-Life at 1 year. Postop increase in peak urinary flow rate was 7.65 mL/s for an average of 16.44 mL/s. Hemoglobin drop average was 1.78 g/dL, but only 2.3% of patients required a transfusion. 12.9% of patients required surgical retreatment. Six months after Aquablation, 22.9% and 12.9% of patients continued taking Alpha-blockers and Androgen receptor inhibitors, respectively. Adverse events occurred in 33 patients (19.0%). Eighteen patients were excluded from secondary analysis due to unrecorded prostate volume, leaving 123 with volumes <150 mL and 33 with volumes ≥150 mL. Groups were comparable with respect to length of stay, adverse events, blood transfusion, IPSS with Quality-of-Life indicator preoperative and postoperative, postop peak urinary flow, and postop alpha-blocker use. Larger prostates had a higher rate of adverse events, retreatment, postop hemoglobin drop, and postop use of finasteride.
Aquablation is a viable treatment option for benign prostatic hyperplasia. Efficacy, safety, subjective outcomes, and adverse event rates were not impacted by prostate volume. However, size does matter as prostates ≥150 mL had higher surgical retreatment rates and postop finasteride use.
Head-to-head comparison of DaVinci and Hugo™ RAS robotic platforms for robot-assisted radical prostatectomy: a systematic review and meta-analysis of comparative studies.
Prostate CancerWe conducted a systematic review and meta-analysis of comparative studies to analyze intra- and postoperative outcomes of robot-assisted radical prostatectomy (RARP) using either DaVinci (DV-RARP) or Hugo™RAS (H-RARP) platforms.
The study was registered in PROSPERO (CRD42024562326) and followed PRISMA guidelines. Literature search was conducted in June 2024 using academic databases, focusing on articles from 2021 to 2024. Research question focused on men with PCa (P) undergoing H-RARP (I) versus DV-RARP (C) to evaluate surgical, pathology, and functional outcomes (O), across comparative studies. Continuous variables were summarized using mean difference (MD) and categorical variables using odds ratio with 95% confidence intervals (CI). Heterogeneity was assessed using Cochran's Q test and I2 statistics. Publication bias was evaluated with Egger's and Begg's tests. Statistical analysis was performed with Stata®17.0, with significance set at p < 0.05. Risk of bias was assessed using the ROBINS-I tool. Methodological quality was evaluated with AMSTAR 2.
Eight studies (three prospective, five retrospective) with 1114 patients (454 H-RARP vs. 660 DV-RARP) were included. Baseline characteristics were comparable between groups. No significant differences were found in overall operative time, console time, blood loss, nerve-sparing, or lymphadenectomy. Docking time was significantly longer for Hugo™RAS (MD:6 min,95% CI 4.2;7.8). Postoperative outcomes, including complications, length of stay, and catheterization time, were similar. Pathological outcomes showed no significant differences in positive surgical margins or staging, but lower node yield was observed with H-RARP (MD:-2,95% CI -3.3;-0.6). Urinary continence recovery was comparable. Risk of bias was moderate to serious.
The meta-analysis suggests H-RARP and DV-RARP perform not statistically different across most of analyzed outcomes, except for docking time and lymph-node yield. The longer docking time associated with the Hugo™RAS suggests demanding setup but does not translate into significantly longer operative time. Although statistically significant, the observed difference in lymph-node yield might be clinically negligible.
Machine learning and explainable artificial intelligence to predict pathologic stage in men with localized prostate cancer.
ProstateThough several nomograms exist, machine learning (ML) approaches might improve prediction of pathologic stage in patients with prostate cancer. To develop ML models to predict pathologic stage that outperform existing nomograms that use readily available clinicopathologic variables.
Patients with prostate adenocarcinoma who underwent surgery were identified in the National Cancer Database. Seven ML models were trained to predict organ-confined (OC) disease, extracapsular extension, seminal vesicle invasion (SVI), and lymph node involvement (LNI). Model performance was measured using area under the curve (AUC) on a holdout testing data set. Clinical utility was evaluated using decision curve analysis (DCA). Performance metrics were confirmed on an external validation data set.
The ML-based extreme gradient boosted trees model achieved the best performance with an AUC of 0.744, 0.749, 0.816, 0.811 for the OC, ECE, SVI, and LNI models, respectively. The MSK nomograms achieved an AUC of 0.708, 0.742, 0.806, 0.802 for the OC, ECE, SVI, and LNI models, respectively. These models also performed the best on DCA. Findings were consistent on both a holdout internal validation data set as well as an external validation data set.
Our ML models better predicted pathologic stage relative to existing nomograms at predicting pathologic stage. Accurate prediction of pathologic stage can help oncologists and patients determine optimal definitive treatment options for patients with prostate cancer.
Is prostatic adenocarcinoma detectable by urine cytology-A multicenter retrospective review.
ProstateUrine cytology is robust for the diagnosis of urothelial lesions, but data on the detection rates of prostatic adenocarcinoma in urine cytology is limited. In this study, a multicenter review was performed to define the clinical role of urine cytology in diagnosis of prostatic adenocarcinoma.
Cytologic diagnoses of lower tract urine cytology specimens with histology-proven prostatic adenocarcinoma from three institutions, from a period of over two decades, were reviewed. Clinicopathological parameters-tumor grade, stage, histologic features, and preanalytical factors-prostate-specific antigen (PSA) level and lesion size, were retrieved and compared with cytologic diagnoses.
In total, 2115 urine cytology specimens from 1119 patients were retrieved. The atypia (or above/C3+) and suspicious (or above/C4+) rates were 19.48% and 3.36%. Bilobar and extracapsular involvement, lymphovascular invasion, Gleason score, and International Society of Urological Pathology grade were associated with a positive urine diagnosis (p < 0.05). The atypia (C3+) and suspicious (C4+) rates of urine cytology in patients with a PSA level of ≤4.0 ng/mL was paradoxically higher (p < 0.01), but PSA levels correlated positively with urine diagnosis at higher cutoffs (>10, >20, >50, >100 ng/mL). All these factors remained significant on multivariate analysis (p < 0.05), including a negative correlation with low-PSA (≤4.0 ng/mL, p = 0.001) and positive correlation with high-PSA (>20 ng/mL, p = 0.020). Lesion size and multifocality were not associated with urine cytology diagnosis (p > 0.05).
Urine cytology showed low sensitivity in detection of prostatic adenocarcinoma. Detection rates were largely positively correlated with PSA levels but not for lesion size nor multifocality, limiting its clinical utility.
Retzius-sparing versus standard robot-assisted laparoscopic prostatectomy: A two-year patient-reported and oncological assessment.
ProstateTo evaluate the two-year functional and oncological outcomes of Retzius-sparing robot-assisted laparoscopic prostatectomy (rsRALP) and standard approach (sRALP).
A total of 200 consecutive patients who underwent either sRALP (n = 100) or rsRALP (n = 100) for clinically localized PCa at a single referral European center between 2015 and 2020 were identified from a prospectively cohort, as part of the Belgian Cancer Registry. Primary outcomes included functional outcomes and quality of life (QoL) using validated patient-reported outcome measures (PROMs) assessed at 1-, 3-, 12-, and 24-months post-surgery. Secondary outcomes comprised oncological outcomes reported as positive surgical margins (PSM) and 5-year biochemical recurrence (BCR). Kaplan-Meier analysis with log-rank test and multivariable Cox regression were used.
The median follow-up was 60 months. No significant differences were observed between the surgical approaches in terms of patient and tumor characteristics. Urinary function and QoL were significantly better at each follow-up period (all p ≤ 0.01) with rsRALP, while sexual function was not significantly different 12 months after surgery. No significant difference in positive surgical margins rate was observed between surgical approaches (31% vs 32%, p = 0.9). Retzius-sparing RALP was associated with longer PSM lengths (5 mm vs 2.5 mm, p = 0.02), a higher multifocality rate (34% vs. 13%, p < 0.001), more occurrences in organ-confined disease (59% vs. 39%, p < 0.001) and at anterior locations (37% vs. 16%, p = 0.05). Five-year BCR-free survival was not significantly different, and surgical approach was not a predictor of BCR.
The rsRALP approach significantly improves both early and short-term urinary function and QoL compared to sRALP. Despite being associated with worse PSM characteristics, no significant decrease in BCR-free survival was observed with rsRALP.
Size and SUVmax define the contribution of nodal metastases to PSA in oligorecurrent prostate cancer.
ProstateTo evaluate how prostate-specific antigen (PSA) levels decrease after removal of isolated prostate cancer (PCa) nodal metastases in relation to their diameter/volume ("PSA-density of PCa-metastases") and maximum standardized uptake value (SUVmax).
A total of 83 consecutive patients with solitary nodal recurrence after radical prostatectomy who underwent prostate-specific membrane antigen-radioguided salvage surgery were retrospectively analyzed. Using multivariable linear regression models, the PSA-decrease after removal of each PCa-metastases (=PSA-contribution of each PCa-metastases) was correlated with the long axis diameter/estimated volume and the SUVmax of each removed metastasis. Sizes were measured by imaging and histopathologic examination.
A total of 83 patients were included with a median (interquartile range [IQR]) PSA-decrease of 0.56 [0.22, 1.31] ng/mL after salvage surgery. The median [IQR] long axis diameters in imaging and histopathological examination were 8.0 [6.0, 11.0] mm and 8.4 [5.5, 11.1] mm, respectively. The median [IQR] estimated volumes were 0.13 [0.05, 0.32] cc (imaging) and 0.05 [0.02, 0.17] cc (pathology). In multivariable linear regression analyses, the estimated PSA-contribution ([95% confidence interval [CI]) of each millimeter of long axis diameter was 0.09 [0.03, 0.14] ng/mL (imaging) or 0.08 [0.03, 0.12] ng/mL (histology). The minimum diameter for biochemical recurrence (PSA ≥ 0.2 ng/mL) was >2.2 mm (imaging) or >2.5 mm (histology). The estimated PSA-contribution [95% CI] of each cc cancer volume was 1.23 [0.51, 1.94] ng/mL (imaging) or 1.46 [0.40, 2.52] ng/mL (histology). SUVmax as surrogate parameter for tissue composition was associated with increased PSA-contribution of PCa-metastases (+0.03-0.05 ng/mL per unit increase).
The diameter/volume and SUVmax of metastatic tissue correlate with its contribution to PSA levels. Therefore, very small metastases may produce too little PSA for biochemical recurrence.
Investigation of pelvic floor influence on prostate displacement in image-guided radiotherapy.
ProstateThe uncertainty of target location during prostate cancer radiotherapy plays an important role in accurate dose delivery and radiation toxicity in adjacent organs. This study analyzed displacement correlations between the prostate and pelvic floor.
We retrospectively analyzed registration results from 467 daily cone-beam computed tomography (CT) in 12 patients with prostate cancer who received radiation therapy. We analyzed prostate displacement and the pelvic floor relative to the pelvic bone's anatomy in the translational and rotational directions and identified statistical correlations.
The systematic (Σ) and random (σ) displacements of the prostate in the three translational directions, anterior-posterior (AP), superior-inferior (SI), and right-left (RL), were 1.49 ± 1.45, 2.10 ± 1.40, and 0.24 ± 0.53 mm, respectively, and in the rotational directions of the pitch, roll, and yaw were 2.10 ± 2.02°, 0.42 ± 0.74°, and 0.42 ± 0.64°, respectively. The pelvic floor displacements were 2.37 ± 1.96, 2.71 ± 2.28, and 0.47 ± 0.84 mm in the AP, SI, and RL directions, respectively, and 0.93 ± 1.49°, 0.98 ± 1.28 °, and 0.87 ± 0.94° in the pitch, roll, and yaw directions, respectively. Additionally, there were statistically significant correlations between the displacement of the prostate and pelvic floor in the AP and SI directions, with correlation coefficients (r) of 0.74 (p < 0.001) and 0.69 (p < 0.001), respectively.
The movement of the pelvic floor may be an important factor that causes prostate displacement, affecting the accuracy of radiotherapy. Therefore, it is necessary to take appropriate measures to ensure that the pelvic floor muscle tension is as consistent as possible in the treatment' CT scan and daily treatment.
