The latest medical research on Prostate Cancer
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Request AccessClinicopathological Significance of Extranodal Adipose Tissue Invasion in Metastatic Lymph Nodes in Patients With Prostate Cancer.
ProstateLymph node (LN) metastasis is a poor prognostic factor in patients with prostate cancer. Elucidating the mechanisms underlying cancer progression in the metastatic microenvironment of LNs is crucial to establishing novel therapies. Adipocytes interact with cancer cells and regulate cancer progression. In this study, we aimed to clarify the clinicopathological significance of extranodal adipose tissue invasion in metastatic LNs and preoperative adipokine concentration in patients with prostate cancer exhibiting metastatic LNs.
We examined the pathological findings of primary and metastatic nodes and clinical information of 66 specimens from 46 patients with prostate cancer. A sub-analysis was performed to assess the relationship between preoperative adiponectin/leptin concentrations and clinical/pathological findings in the blood samples of 56 patients with prostate cancer who either did or did not show LN metastasis.
The number of metastatic LNs in patients correlated with the involvement of adipose tissue and lymphovascular invasion (p = 0.039 and < 0.001, respectively). Preoperative adiponectin concentration was lower in patients with resected margin-positive and extraprostatic extension-positive primary cancers (p = 0.0071 and 0.02, respectively). Preoperative adiponectin concentrations were significantly lower in patients with metastatic LNs than in patients without LN metastasis (p < 0.001). Moreover, leptin concentrations were significantly higher in patients with metastatic LNs than in patients without LN metastasis (p < 0.001). In patients with metastatic LNs, preoperative adiponectin concentrations were significantly lower in patients with biochemical recurrence than in patients without biochemical recurrence (p = 0.031). There was no correlation between biochemical recurrence and pathological findings.
This is the first report on the detailed histopathological characteristics of prostate cancer with LN metastases and the significance of preoperative adiponectin concentration in predicting the pathological features of primary cancers. Also, adipokines are a significant prediction factor of LN metastases for prostate cancer patients. Adipose tissue and adipose-secreting factors may be involved in the progression of metastatic and primary prostate cancer.
Single-port transvesical simple prostatectomy for the surgical treatment of benign prostatic hyperplasia: functional and continence outcomes.
Prostate Cancer and Prostatic DiseasesRobot-Assisted Simple Prostatectomy (RASP) is recommended for the treatment of large prostate glands. The introduction of the Single-Port (SP) platform in 2018 has enabled transvesical approach to SP-RASP with promising outcomes. Our aim was to describe the functional and urinary continence outcomes of SP-RASP.
Clinical and surgical data from all consecutive patients who underwent transvesical SP-RASP between February 2020 and March 2024 were collected in a prospectively maintained institutional dataset and retrospectively analyzed. All procedures were performed using the da Vinci SP platform without any conversions to open surgery. Postoperative outcomes were gathered and analyzed, with a particular focus on the incidence of urinary incontinence (UI) and the time to continence recovery.
Overall, 89 patients underwent SP-RASP, with a median prostate size of 110 grams (90-171.5) and a median PSA level of 5.5 mg/dl (2.77-10.93). All patients were on at least one prostate medication prior to surgery. Preoperative evaluations showed a median International Prostate Symptoms Score (IPSS) of 23 (20-27), Quality of Life (QoL) of 4 (3-5), and Post-voiding Residual (PVR) of 153 ml (60-400). The median operative time was 180 min (164-200), with a median estimated blood loss of 100 ml (30-180). Postoperatively, no patients required continuous bladder irrigation. The median postoperative opioid intake was 6.5 morphine equivalents (0-10), with over 78% not requiring narcotics after discharge. Overall, 77.5% were same day discharged. No Clavien-Dindo > 2 complications were recorded. The median follow-up time was 18 (7-35) months. At the last postoperative urological evaluation, the median IPSS was 5 (3-7), QoL was 1 (0-2), and PVR was 10 ml (0-25). Only 4 patients (4.5%) experienced UI postoperatively, and all were continent within 3 months.
The UI incidence rate and functional outcomes of SP-RASP are very encouraging, likely due to precise adenoma and urethra dissection and bladder neck reconstruction. This approach also allows for same-day discharge.
Safety and Efficacy of Intra-Prostatic Injection of Betamethasone for Refractory Chronic Nonbacterial Prostatitis: A Prospective Cohort Clinical Study.
ProstateWe aimed to assess the safety and effectiveness of TRUS guided betamethasone injections in refractory cases of chronic nonbacterial prostatitis.
Forty-five patients with refractory CNP were included in a prospective cohort clinical trial. Six injections of betamethasone sodium sulfate were guided by TRUS. After injection: assessment of NIH-CPSI, IPSS, IIEF, GRA and VAS were performed 1, 4, and 12 weeks after injection. Prostatitis symptoms were measured by NIH-CPSI. We considered the minimal clinically important difference (MCID) as a 25% decrease or a six-point reduction from baseline. We considered the MCID of the IIEF to be at least an increase of 4 points. We considered the MCID of the IPSS score to be three points and the MCID for the VAS score to be a 25%-35% change of the initial score. Regarding the global response assessment (GRA), scores 5-7 means significant success rate of perceived treatment.
According to total NIH CPSI score, the success rate of injected cases was 71% after 1 week, dropping to 55.6% after 4 weeks and 44.4% after 12 weeks. According to IPSS questionnaire, the MD (mean difference) is -4.09 ± 3.5, -3.8 ± 3.83 and -3.47 ± 3.92. According to the IIEF questionnaire, the success rate was 22% and 26.7% after 4 and 12 weeks respectively. According to GRA, successful pain control was reported in 82%, 71% and 64.4% after 1, 4 and 12 weeks, respectively.
Intraprostatic betamethasone injection is a simple, safe, and feasible procedure in refractory cases with CNP with predominant pain and urinary symptoms.
Enhancing risk stratification models in localized prostate cancer by novel validated tissue biomarkers.
Prostate Cancer and Prostatic DiseasesLocalized prostate cancer (PCa) is a largely heterogeneous disease regarding its clinical behavior. Current risk stratification relies on clinicopathological parameters and distinguishing between indolent and aggressive cases remains challenging. To improve risk stratification, we aimed to identify new prognostic markers for PCa.
We performed an in silico analysis on publicly available PCa transcriptome datasets. The top 20 prognostic genes were assessed in PCa tissue samples of our institutional cohort (n = 92) using the NanoString nCounter technology. The three most promising candidates were further assessed by immunohistochemistry (IHC) in an institutional (n = 121) and an independent validation cohort from the EMPACT consortium (n = 199). Cancer-specific survival (CSS) and progression-free survival (PFS) were used as endpoints.
Our in silico analysis identified 113 prognostic genes. The prognostic values of seven of the top 20 genes were confirmed in our institutional radical prostatectomy (RPE) cohort. Low CENPO, P2RX5, ABCC5 as well as high ASF1B, NCAPH, UBE2C, and ZWINT gene expressions were associated with shorter CSS. IHC analysis confirmed the significant associations between NCAPH and UBE2C staining and worse CSS. In the external validation cohort, higher NCAPH and ZWINT protein expressions were associated with shorter PFS. The combination of the newly identified tissue protein markers improved standard risk stratification models, such as D'Amico, CAPRA, and Cambridge prognostic groups.
We identified and validated high tissue levels of NCAPH, UBE2C, and ZWINT as novel prognostic risk factors in clinically localized PCa patients. The use of these markers can improve routinely used risk estimation models.
Reactive Stroma and Acinar Morphology in Prostate Cancer: Implications for Progression and Prognostic Assessment.
ProstateProstate cancer (PC) remains a significant global health concern, with prognostic assessments largely reliant on the Gleason Classification System. While it has proven effective, subjectivity in interpretation persists, prompting the need for complementary approaches. Reactive stroma (RS) has emerged as a potential candidate for enhancing PC characterization, as it reflects intricate interactions among stromal, epithelial, and extracellular matrix components. To shed light on this, we conducted a comprehensive study.
Two expert pathologists independently analyzed consecutive prostate biopsies (n = 120 patients), categorized into four groups based on Gleason scores. Four acinar patterns were described, denoted as A, B, C, and D. Our study uncovered a noteworthy presence of RS, predominantly within poorly differentiated tumors. Stromogenic tumors, characterized by high RS content, were particularly associated with Gleason scores of 4 + 3 and ≥ 8. Intriguingly, acinar patterns, including the distinctive B and D patterns, exhibited strong correlations with stromogenic tumors. Incorporating quantitative imaging techniques (Second Harmonic Generation and Two-Photon Excitation Fluorescence Microscopy), we examined collagen fiber density within the stroma.
Our analysis revealed a direct relationship between RS intensity and collagen fiber counts, particularly prominent in patterns B and D. These findings suggest that the stromal reaction in PC is closely linked to acinar morphology and collagen deposition. Moreover, rudimentary microacini at the tumor periphery, associated with intense RS and patterns B and D, may signify an unfavorable prognosis.
Our study highlights the potential of RS as an additional prognostic factor in PC. It underscores the intricate interplay between acinar patterns, RS intensity, and collagen fiber density, providing valuable insights for future prognostic assessments and therapeutic strategies. Further exploration of these relationships is essential for a comprehensive understanding of PC progression and management.
Prostatic stents: a systematic review and analysis of functional outcomes and complication rate.
Prostate Cancer and Prostatic DiseasesThis review aims to identify and summarize the current literature on the use of prostatic stents or nitinol devices as minimally invasive techniques for the management of lower urinary tract symptoms (LUTS) resulting from benign prostatic hyperplasia (BPH).
A comprehensive search of the literature was conducted until October 2023. Only original articles written in English were considered for inclusion. This review has been registered in PROSPERO (registration number CRD42023474884).
Thirty-eight articles were included (2618 patients). Generally, the risk of bias was deemed as high or very high. The most frequently investigated stents were the UroLume, followed by the Memokath/Memotherm. The mean age was 72.01 ± 5.6 years, with a mean prostate volume of 48.27 ± 12.8 cc and a mean urethral length of 40.53 ± 9.16 mm. Surgeries were usually performed under local anesthesia. The rates of catheter-free status and complications were 85.2% and 30.83%, respectively. The primary complications included urinary tract infections (17.2%), followed by calcifications (12.6%), irritative symptoms (12.2%), and acute urinary retention (10.4%). During a follow-up period of 12 months, the failure rate intended as stent removal or repositioning was 14.8%. The International Prostate Symptom Score (IPSS) showed an overall improvement of 9.85 points. The mean improvement in maximum flow rate and post-void residual volume were 6.62 ml/sec and 147 ml, respectively.
Prostatic stents remain an efficient choice for addressing obstructive symptoms from BPH, offering the advantage of being performed under local anaesthesia, relieving symptoms with good functional outcomes and a low incidence of major complications. Prospective studies are needed to corroborate these results.
Quality of Chatbot Information Related to Benign Prostatic Hyperplasia.
ProstateLarge language model (LLM) chatbots, a form of artificial intelligence (AI) that excels at prompt-based interactions and mimics human conversation, have emerged as a tool for providing patients with information about urologic conditions. We aimed to examine the quality of information related to benign prostatic hyperplasia surgery from four chatbots and how they would respond to sample patient messages.
We identified the top three queries in Google Trends related to "treatment for enlarged prostate." These were entered into ChatGPT (OpenAI), Bard (Google), Bing AI (Microsoft), and Doximity GPT (Doximity), both unprompted and prompted for specific criteria (optimized). The chatbot-provided answers to each query were evaluated for overall quality by three urologists using the DISCERN instrument. Readability was measured with the built-in Flesch-Kincaid reading level tool in Microsoft Word. To assess the ability of chatbots to answer patient questions, we prompted the chatbots with a clinical scenario related to holmium laser enucleation of the prostate, followed by 10 questions that the National Institutes of Health recommends patients ask before surgery. Accuracy and completeness of responses were graded with Likert scales.
Without prompting, the quality of information was moderate across all chatbots but improved significantly with prompting (mean [SD], 3.3 [1.2] vs. 4.4 [0.7] out of 5; p < 0.001). When answering simulated patient messages, the chatbots were accurate (mean [SD], 5.6 [0.4] out of 6) and complete (mean [SD], 2.8 [0.3] out of 3). Additionally, 98% (39/40) had a median score of 5 or higher for accuracy, which corresponds to "nearly all correct." The readability was poor, with a mean (SD) Flesch-Kincaid reading level grade of 12.1 (1.3) (unprompted).
LLM chatbots hold promise for patient education, but their effectiveness is limited by the need for careful prompting from the user and by responding at a reading level higher than that of most Americans (grade 8). Educating patients and physicians on optimal LLM interaction is crucial to unlock the full potential of chatbots.
Comparative Evaluation of Detection Rates for Clinically Significant Prostate Cancer Using MRI-Targeted Biopsy Alone Versus in Combination With Systematic Biopsies: Development of a Risk-Stratification Scoring System.
ProstateTo compare the detection rates for clinically significant prostate cancer (csPCa; grade group 2 or higher disease) using MRI-targeted biopsy (MRI-TB) versus systematic biopsy (SB) or their combination, and identify risk factors for detecting csPCa in MRI-TB with systematic transrectal (TR)/transperineal (TP) biopsies (sTR/TP-bx) and MRI-TB with sTP-bx.
We retrospectively analyzed 216 patients who underwent MRI-TB with SB at our hospital between September 2020 and December 2023 and compared clinical characteristics for patients with and without prostate cancer.
csPCa was detected in 132 (61.1%) patients by MRI-TB with sTR/TP-bx, in 121 (56.0%) patients using MRI-TB with sTP-bx, and in 101 (46.8%) patients using MRI-TB. Older age, higher PSA density (PSAD), smaller prostate volume, region of interest in the peripheral zone, higher Prostate Imaging-Reporting and Data System (PI-RADS), and administration of dutasteride were more common in csPCa cases. A scoring system was constructed based on odds ratios for PSAD, PI-RADS ≥ 4, and administration of dutasteride; accordingly, the detection rate of csPCa was 20.3% (14/69) in the low-risk group (RG) and 95.5% (42/44) in high RG for MRI-TB with sTR/TP-bx, and 16.7% (12/72) in the low RG and 97.8% (45/46) in high RG for MRI-TB with sTP-Bx.
The addition of SB increased the detection rate of csPCa compared with MRI-TB alone. PSAD, PI-RADS ≥ 4, and administration of dutasteride significantly affect the detection of csPCa using MRI-TB with SB and can be used for deciding whether to perform a biopsy or include sTR-bx with MRI-TB.
pSTAT3 Expression is Increased in Advanced Prostate Cancer in Post-Initiation of Androgen Deprivation Therapy.
ProstateThe transcription factor Signal Transducer and Activator of Transcription 3 (STAT3) plays a role in carcinogenesis and is involved in processes, such as proliferation, differentiation, drug resistance and immunosuppression. STAT3 can be activated by phosphorylation of tyrosine at position 705 (pSTAT3Tyr705) or serine at 727 (pSTAT3Ser727). High expression levels of pSTAT3 are implicated in advanced stages of prostate cancer (PCa) and are known to interact with the androgen receptor signaling pathway. However, not much is known about how androgen deprivation therapy (ADT) in advanced disease affects pSTAT3 expression. The aim of this study was to determine the influence of ADT on pSTAT3 expression in PCa tissue.
The study cohort came from a PCa tissue microarray resource containing prostate specimens from patients before and post-initiation of ADT. Tissue samples from 111 patients were immunostained for pSTAT3Tyr705 and pSTAT3Ser727. H-score was used to evaluate the intensity and the percentage of pSTAT3 expression in malignant epithelial and stromal compartments. Univariate and multivariable Cox regression analyses were used to assess pSTAT3Tyr705 and pSTAT3Ser727 as biomarkers of oncological outcome in patients undergoing ADT.
Post-ADT PCa samples demonstrated increased nuclear and cytoplasmic levels of pSTAT3Ser727 in the stroma compared to pre-ADT samples, whereas pSTAT3Tyr705 expression was increased significantly in both stromal and malignant epithelial compartments except for stromal cytoplasm. High cytoplasmic pSTAT3Ser727 in stromal compartments correlated with reduced overall survival, shorter time to castration-resistant PCa development, and decreased metastasis-free survival. An increase in nuclear and cytoplasmic pSTAT3Ser727 expression within the stromal compartment of post-ADT samples corresponded to a shorter time to CRPC development, which was not observed for pSTAT3Tyr705. Multivariable survival analysis using Cox's regression identified that high cytoplasmic pSTAT3Ser727 expression in the stroma of post-ADT samples and pT3 or pT4-stage were associated with worse overall survival and 5-year metastasis-free survival (MFS).
This study presents novel insights into the impact of ADT on the expression levels of pSTAT3Tyr705 and pSTAT3Ser727 in PCa. Cytoplasmic pSTAT3Ser727 status of cancer-associated stromal cells in post-ADT samples may serve as an independent prognostic marker for OS and 5-year MFS, identifying prostate cancer patients prone to developing resistance to ADT.
Comprehensive review of cardiovascular disease in prostate cancer: epidemiology, risk factors, therapeutics and prevention strategies.
Prostate CancerThe prevalence of cardiovascular risk factors and disease is high in patients with newly diagnosed prostate cancer (PC). Survivorship of PC patients is often determined by cardiovascular disease (CVD). Our review synthesizes the most recent literature exploring the dynamics between PC and CVD across the disease trajectory and treatments. We review key ongoing clinical trials in the field and highlight avenues for future study.
We conducted a comprehensive narrative review of the literature using various search strategies in three databases (PubMed, Web of Science, ClinicalTrials.gov), focusing on literature published between 2000 and 2024.
We discuss the significance of CVD-related mortality in PC, review the risk factors, and highlight potential mechanisms for accelerated CVD in the androgen-deprivation setting. Furthermore, we summarize key literature of CVD and cardiotoxicity for various therapeutic approaches in PC, including orchiectomy, taxane-based chemotherapy, GnRH-axis targets, and next-generation hormonal agents and PARP inhibitors. Lastly, we discuss prevention strategies and the importance of multi-disciplinary care in this setting.
CVD is a major cause of death in men with PC. Various novel therapeutic approaches have been pivotal in improving oncologic outcomes, but emerging data demonstrate a complex interplay between the androgen axis and CVD that is likely affected by modern treatment strategies. Given the prolonged PC survivorship, unraveling non-oncologic related causes of death and investigating prevention strategies are imperative (Fig. 1). Fig. 1 LANDSCAPE OF PROSTATE CANCER.: Spectrum of prostate cancer disease states (red) and interventions (yellow) with the potential role for optimization (green) to improve cardiovascular outcomes in the future (blue).
Follow-up on patients with initial negative mpMRI target and systematic biopsy for PI-RADS ≥ 3 lesions - an EAU-YAU study enhancing prostate cancer detection.
Prostate Cancer and Prostatic DiseasesTo investigate the detection and predictors of prostate cancer (PCA) and clinically significant prostate cancer (csPCA) in patients with positive multiparametric MRI (mpMRI) followed by a negative MRI - guided target biopsy (TB) and systematic biopsy (SB).
This retrospective multicenter study included 694 patients from 10 tertiary referral centers with an initial positive mpMRI (PI-RADS ≥ 3) and negative results on both MRI-TB and SB. Patients were classified into three groups based on follow-up: Group 1 (prostate re-biopsy without new mpMRI), Group 2 (standardized second prostate mpMRI and subsequent re-biopsy), and Group 3 (follow-up with mpMRIs and biopsy based on clinical and radiological triggers). The primary outcomes were the detection of any PCA and csPCA during follow up. Study groups were compared according to their probability of PCA and csPCA assessed with the ERSPC-MRI risk calculator. Statistical analysis included Kaplan - Meier analysis, Cox regression, and multivariable analysis for the detection of (cs)PCa.
The overall detection of PCA and csPCA was 26.8% and 19.3%, respectively, with varying rates in different PI-RADS groups. Group 3 had the highest 2-year and 5-year PCA-free survival (94 and 84%) and csPCA - free survival (96 and 86%). Multivariable analysis revealed a significantly higher risk of PCA and csPCA in Group 1 and 2 compared to Group 3 (p < 0.01). Clinical and radiological predictors for PCA and csPCA included higher age, prostate volume, PI-RADS score, the presence of atypical small acinar proliferation (ASAP), and a smaller number of TB and SB performed during the initial biopsy. Study limitations, include the retrospective design and reliance on clinical and radiological triggers for follow-up decisions.
Patients with positive mpMRI but negative TB and SB results exhibit varying rates of PCA and csPCA depending on the follow up scheme. Tailored follow-up strategies are essential for optimal management in this clinical scenario.
Significant Effect of Carbon-Ion Radiation Therapy Combined With Androgen Deprivation on Biochemical Recurrence Rates in High-Risk Prostate Cancer Patients: A Two-Center Controlled Trial Compare With X-Ray External Beam Radiation Therapy.
ProstateTo compare the effects of carbon-ion radiation therapy (CIRT) and external beam radiotherapy (EBRT) on the prognosis of patients with prostate cancer.
The effects of initial prostate-specific antigen (iPSA), clinical Tumor (cT) stage, radiotherapy method, and other clinical factors on the prognosis of 577 patients with radiotherapy were analyzed.
Cox regression analysis showed that CIRT (RR: 0.49, p = 0.0215), cT stage ≥ 3 (RR: 2.72, p = 0.0003), and iPSA ≥ 16 ng/mL (RR: 1.74, p = 0.0347) were independent predictors of biochemical recurrence (BCR). After propensity score matching (PSM), CIRT (RR: 0.42, p = 0.0147), cT stage ≥ 3 (RR: 2.55, p = 0.0092), and iPSA ≥ 16 ng/mL (RR: 2.12, p = 0.0366) were still the predictors of univariate analysis. In multivariate analysis, CIRT (RR: 0.42, p = 0.015) and cT stage≥ 3 (RR:2.21, p = 0.0332) were independent predictors of BCR. Among them, we used iPSA and cT stages to establish a new radiotherapy selection model based on BCR risk. Patients who met more than one factor (score ≥ 1) and underwent CIRT had significantly better BCR progression-free survival (PFS) than those who received EBRT (p ≤ 0.01). This was also confirmed by Kaplan-Meier analysis after PSM.
CIRT patients exhibited lower 5-year BCR rates compared to the EBRT group. Patients with a risk score of our model ≥ 1 undergoing CIRT were more likely to experience BCR benefits compared to those receiving EBRT.
