Prostate最新文献

Background: Prostate-specific antigen (PSA) kinetics has been investigated as a prognostic marker in post hoc analyses of clinical trials. This study validated the prognostic value of rapid and deep PSA decline in metastatic hormone-sensitive prostate cancer (mHSPC) using real-world data.

Methods: In total, 1296 patients with mHSPC were retrospectively reviewed. We assessed the prognostic value of a PSA decline to ≤ 0.2 ng/mL after 12 weeks of treatment and investigated several potential risk factors for a poor PSA response.

Results: Of 1296 patients, 714 (cohort 1: 55.1%) were treated with conventional hormonal therapy, while 582 (cohort 2: 44.9%) received androgen signaling inhibitors. There were significant differences in progression-free survival and overall survival between patients with PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment and others (p < 0.001 for each). In addition, patients with an initial PSA ≥ 200 ng/mL, Clinical T4 and Grade Group 5 were less likely to achieve PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment, with odds ratios of 0.31 (p < 0.001), 0.67 (p = 0.039) and 0.70 (p = 0.043), respectively.

Conclusion: Our findings suggested that PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment may be a useful prognostic biomarker for mHSPC in the real-world setting. The prognostic value of this should be further investigated in a prospective cohort, and identification of an optimal cutoff value is necessary for its application in clinical trial design or clinical practice.

Background: Robotic-assisted radical prostatectomy (RARP) is widely used as the main surgical approach to treat prostate cancer in the United States. Prostate size is often described as a factor affecting the outcomes of RARP as shown by many studies. However, these studies are limited to a small number of patients.

Objective: To evaluate the functional and oncologic outcomes of RARP in very large prostate sizes.

Methods: Three hundred and seventy-five RARP patients were divided into two groups according to prostate size: Group 1 had prostates larger than 150 g and Group 2 smaller than 50 g. Perioperative variables were matched with propensity score matching 1:3 and postoperative variables were analyzed for significant differences in outcomes between groups. Variables analyzed included estimated blood loss (EBL), operative time, catheter time, hospitalization time, postoperative complications, pathological staging, positive surgical margins (PSM) rates, biochemical recurrence (BCR), potency, and continence rates.

Results: The two groups exhibited similar preoperative characteristics. Patients with larger prostates (Group 1) were more likely to have higher blood loss (EBL), longer console time, and more days with catheter. However, we could not find significant difference in the overall postoperative complications (Clavien-Dindo). Pathological outcomes were also statistically different as patients with larger prostates had (69.7%) more pT2 disease and (12.1%) lower rates of PSM. Finally, we could not find significant difference in the functional outcomes between the groups.

Conclusion: The results demonstrate that prostate size impacts multiple outcomes. Larger prostates had lower-grade disease, reduced EPE and PSM rates, with no significant differences in BCR or functional outcomes. Perioperative differences, such as increased blood loss and console time, were also observed.

Objectives: To evaluate the association of the negative confirmatory and follow-up biopsy with prostate cancer reclassification in active surveillance protocol.

Materials and methods: A systematic search was performed in databases, including Scopus, PubMed, Embase, and Web of Science, on June 25th, 2024, to identify relevant studies regarding negative biopsy and reclassification of prostate cancer among men on AS. The patient data including, sample sizes, follow-up duration, the status of performing the confirmatory biopsy, hazard ratio (HR), and 95% confidence intervals (CI) of each reported HR were evaluated in each study. The relationships between negative biopsies and reclassification were assessed using a forest plot. A random-effect meta-analysis was used when high heterogeneity existed among the studies. Otherwise, a fixed-effect meta-analysis was utilized. A p value of less than 0.05 was considered statistically significant. All statistical analyses were performed by using STATA statistical software, version 16.

Results: A total of 13 articles were included in the study. These articles were published between 2008 and 2023, with the majority being published in recent years (2020-2023). The included articles evaluated a total of 17,900 patients. Our results regarding reclassification and upgrading are represented according to the confirmatory biopsy and subsequent follow-up biopsies. After a negative confirmatory biopsy, the pooled HR for reclassification was 0.46 (95% CI: 0.38-0.55, p < 0.01). Secondly, the study demonstrated that a decreased chance of cancer upgrading was also connected with negative confirmatory biopsies with a pooled HR of 0.57 (95% CI: 0.45-0.72, p < 0.01). Negative follow-up biopsies were linked to a 55% decrease in the risk of reclassification, according to the pooled HR for reclassification in patients with negative biopsies compared to those with positive biopsies of 0.45 (95% CI: 0.42-0.48, p < 0.01). Also, patients with negative follow-up biopsies had a pooled HR for upgrading of 0.57 (95% CI: 0.48-0.67, p < 0.01), indicating a 43% lower chance of upgrading than in patients with positive biopsies.

Conclusion: In active surveillance of PCa patients, a negative confirmatory biopsy decreased the chance of cancer reclassification and upgrading, with the pooled OR 0.46 and 0.57 [p < 0.01], respectively. Also, negative follow-up biopsies were linked to a decreased chance of cancer reclassification and upgrading. Our review recommends extend the follow-up evaluations in PCa patients with negative findings in surveillance biopsy who scheduled for active surveillance.

Background: Targeted and systematic transperineal biopsy of lesions guided by magnetic resonance imaging (MRI) and transrectal ultrasonography (TRUS) fusion technique may optimize the biopsy procedure and enhance the detection of prostate cancer. We described the transperineal biopsy guided by an automatic MRI-TRUS fusion technique, and evaluated the accuracy and feasibility of this method in a prospective single-center study.

Methods: The proposed method focuses on automating the delineation of prostate contours in both the MRI and TRUS images, the registration and fusion of MRI and TRUS images, the generation and visualiztion of the systematic biopsy cores in their corresponding locations within the 2D and the 3D views, as well as the computation and visualiztion of needle trajectories from preoperative planning to intraoperative navigation. A total of 76 patients with clinically suspected prostate cancer underwent systematic (SBx) and targeted (TBx) biopsies, all performed by a single urologist with more than 10 years of experience. The detection rates of prostate cancer (PCa) and clinically significant prostate cancer (csPCa) were recorded. We also measured preoperative registration time, duration of the overall surgical procedure, and postoperative complication rates within the first week following the surgery. Descriptive analyses were presented in this study.

Results: PCa was identified in 73.7% (56/76) of the subjects, while csPCa was identified in 61.8% (47/76). The preoperative registration time was 5.0 min (IQR: 4.4-6.0), while the overall surgery duration was 24.8 min (IQR: 23.2-27.2). Postoperatively, 12 patients experienced immediate hematuria, and one patient reported dysuria 1 day following surgery.

Conclusions: The automatic MRI-TRUS fusion technique for transperineal biopsy is feasible and safe, with preoperative planning to intraoperative navigation it offering convenient and efficient preoperative preparation and surgical procedure.

Background: Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in the current Prostate Imaging-Reporting and Data System version 2.1 (PI-RADS v2.1) is considered optional, with primary scoring based on T2-weighted imaging (T2WI) and diffusion weighted imaging (DWI). Our study is designed to assess the relative contribution of DCE MRI in a patient-cohort with whole mount prostate histopathology and spatially-mapped prostate adenocarcinoma (PCa) for reference.

Methods: We performed a partially-blinded retrospective review of 47 prostatectomy patients with recent multi-parametric MRI (mpMRI). Scans included T2WI, DWI with apparent diffusion coefficient (ADC) mapping, and DCE imaging. Lesion conspicuity was scored on a 10-point scale with ≥ 6 considered "positive," and image quality was assessed on a 4-point scale for each sequence. The diagnostic contribution of DCE images was evaluated on a 4-point scale. The mpMRI studies were assigned PI-RADS scores and tumor, node, metastasis (TNM) T-stage with blinded comparison to spatially-mapped whole-mount pathology. Results were compared to the prospective clinical reports, which used standardized PI-RADS templates that emphasize T2WI, DWI and ADC.

Results: Per lesion sensitivity for PCa was 93.5%, 82.6%, 63.0%, and 58.7% on T2WI, DCE, ADC and DWI, respectively. Mean lesion conspicuity was 8.5, 7.9, 6.2, and 6.1, on T2W, DCE, ADC and DWI, respectively. The higher values on T2WI and DCE imaging were not significantly different from each other but were both significantly different from DWI and ADC (p < 0.001). DCE scans were determined to have a marked diagnostic contribution in 83% of patients, with the most common diagnostic yield being detection of contralateral peripheral zone tumor or delineating presence/absence of extra-prostatic extension (EPE), contributing to more accurate PCa staging by PI-RADS or TNM, as compared to histopathology.

Conclusion: We demonstrate that DCE may contribute to lesion detection and local staging as compared to T2WI plus DWI-ADC alone and that lesion conspicuity using DCE is markedly improved as compared to DWI-ADC. These findings support modification of PI-RADS v2.1 to include use of DCE acquisitions and that a TNM staging is feasible on mpMRI as compared to surgical pathology.

Background: The Nectin-4 directed antibody drug conjugate enfortumab vedotin (EV) has emerged as frontline systemic therapy in combination with immune checkpoint blockade for urothelial carcinoma (UC), capitalizing on the ubiquitous expression of this protein in UC. There is limited data available regarding expression of Nectin-4 by immunohistochemistry in prostate cancer, but this is of interest as a substantial number of UC patients likely to receive EV have concomitant prostate cancer.

Methods: Nectin-4 protein expression was evaluated by immunohistochemistry in tissue microarrays encompassing a cohort of 302 prostatic adenocarcinomas spanning Grade Groups 1-5. Intensity of expression was scored from 1 (weak) to 3 (intense staining readily apparent at low magnification). H-scores were calculated by multiplying the percentage of cells staining by the intensity of expression.

Results: Nectin-4 expression was frequently observed in benign prostate tissue (86% of cases, mean H-score of 40, median 20, interquartile range [IQR]: 10-60) and in prostatic adenocarcinoma (91% of cases, mean H-score of 90, median 70, IQR: 20-150). Significant differences in Nectin-4 expression among prostatic adenocarcinoma Grade Groups 1-5 were not observed. Across all prostatic adenocarcinomas evaluated, the mean Nectin-4 H-score of 90 was statistically significantly higher than the mean H-score of 40 observed in benign prostate tissue (p < 0.001). Three of four prostatic ductal adenocarcinomas showed Nectin-4 expression, with a median H-score of 250 (IQR: 152-300).

Conclusions: Nectin-4 protein expression is common in benign prostate tissue and prostatic adenocarcinoma. These findings provide a rationale for future studies investigating potential activity of EV in prostate cancer.

Background: Caffeic acid (CA), a dietary compound, has been studied for its potential impact on inhibiting prostate cancer (PCa) growth. PCa is often associated with heightened expression of glyoxalase-1 (Glo-1), making it a target for potential therapeutic interventions. CA's mechanisms in suppressing Glo-1 expression and its effects on PCa cell proliferation are areas of interest for understanding its potential as an anticancer agent.

Methods: Cellular viability and proliferation were evaluated through MTT and clonogenic assays. The expression levels of particular proteins were assessed using western blot analysis and immunocytochemistry.

Results: Results indicated significant reduction in PCa cell proliferation by CA, accompanied by induction of DNA double-strand breaks, leading to apoptotic cell death through decreased pro-caspases expression. Additionally, CA was found to inhibit Glo-1 expression. To enhance CA's anticancer effect, a novel approach was taken by combining it with methylglyoxal (MG). Exogenous MG treatment, a glycolysis by-product and glyoxalase enzyme substrate, exhibited dose and time-dependent toxicity in PCa cells when combined with CA. This combination treatment showed heightened toxicity against PCa cells, attributed to CA's inhibition of Glo-1 expression and the nontoxic doses of exogenous MG. Consequently, increased levels of endogenous MG were observed, leading to apoptosis and suggesting a promising strategy for targeting glyoxalase oncogenic signaling pathways in PCa with minimal adverse effects.

Conclusion: The study highlights the potential of CA as a therapeutic agent for inhibiting PCa growth through multiple mechanisms, including the induction of apoptotic cell death and inhibition of Glo-1 expression. Combining CA with MG enhances its anticancer effects, offering a promising strategy for targeting glyoxalase oncogenic pathways in PCa.

Background: Radiation-induced late fecal incontinence (LFI) is one of the most quality-of-life impairing symptoms in prostate cancer. We aimed to assess the impact of radiotherapy (RT) technique and dose-volume effects on LFI using a robust score.

Methods: We identified 409 patients who underwent curative intent using standard fractionated radiation therapy, 190 of them were finally included and analyzed. The severity of LFI was assessed using the Jorge & Wexner score.

Results: With a median follow-up of 55 months (range 15-96) months, LFI crude rate was 11.5%. In the multivariate analyses, image-guided radiotherapy (IGRT), rectal maximum dose (Dmax) and anal canal minimum dose (Dmin) were significantly associated with LFI risk. The use of IGRT was associated with lower risk of LFI (p = 0.02); higher rectum Dmax (≥ 68.4 Gy; p = 0.02) and anal canal Dmin (≥ 6.4 Gy; p = 0.04) were associated with increased risk.

Conclusion: Our results suggest a significant impact of the total dose delivered to the anorectal volumes and the use of IGRT to spare organs at risk during radiation delivery.

Background: Recent clinical trials have shown that patients with metastatic castration-sensitive prostate cancer in real-world settings have different overall survival (OS) rates after stratifying for tumor burden or visceral metastasis. However, some patients with a low tumor burden and without visceral metastasis still have a poor survival. Androgen receptor signaling is still a main therapeutic target of prostate cancer treatment even after the achievement of castration resistance. In this regard, we hypothesized that time to castration resistance can be a prognostic factor of metastatic castration-sensitive prostate cancer even after achieving castration resistance. The current study aimed to assess the novel prognostic factors, particularly time to castration resistance, of prostate cancer in patients at a real-world single institution.

Methods: The data of 261 patients who were newly diagnosed with metastatic castration-sensitive prostate cancer from January 2007 to December 2023 were retrospectively analyzed.

Results: The median OS was 60.7 months, and the median time to castration resistance was 13.1 months. Among 261 patients, 158 developed castration-resistant prostate cancer. A shorter time to castration resistance, the presence of distant lymph node metastasis, ISUP grade group 5, and older age were associated with a shorter OS in patients who developed castration-resistant prostate cancer. A shorter time to castration resistance was significantly associated with a shorter OS regardless of the tumor burden. Further, it was associated with a shorter OS even after the achievement of castration resistance.

Conclusions: The study results support the presence of persistent androgen receptor signaling even after achieving castration resistance in prostate cancer, and time to castration resistance can be a biomarker for the activation of androgen receptor signaling regardless of tumor burden.

Background: This study aims to assess the relationship between body mass index (BMI) and prostate volume, utilizing pre and postoperative measurements.

Methods: A retrospective, observational study was conducted at a single site using data from an institutional database. Medical records of patients who underwent robot-assisted radical prostatectomy were reviewed. Data included age, BMI, and prostate volumes measured through digital rectal exam (DRE), transrectal ultrasound (TRUS), magnetic resonance imaging (MRI), and surgical specimen weight (SPW).

Results: A total of 168 patients were identified and included in the analysis. Spearman's correlation test revealed a significant association between BMI and prostate volume for all measurement methods, reporting r = 0.146 (p = 0.047) for DRE, r = 0.268 (p < 0.0001) for TRUS, r = 0.177 (p = 0.021) for MRI and r = 0.234 (p = 0.002) for SPW. Linear regression analysis confirmed the significant association between BMI and prostate volume, reporting, respectively, R² = 0.026 (p = 0.036) for DRE, R² = 0.076 (p < 0.0001) for TRUS, R² = 0.038 (p = 0.011) for MRI and R² = 0.040 (p = 0.009) for SPW. Notably, considering the SPW the best way to estimate prostate volume, for every increase in BMI, the predicted increase of prostate volume is 0.865gr.

Conclusions: This study demonstrates a positive linear correlation between BMI and prostate volume, highlighting the importance of considering BMI in prostate volume assessments.