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Objectives: Within the tertiary-case database, the authors tested for differences in long-term continence rates (≥ 12 months) between prostate cancer patients with extraprostatic vs. organ-confined disease who underwent Robotic-Assisted Radical Prostatectomy (RARP).
Method: In the institutional tertiary-care database the authors identified prostate cancer patients who underwent RARP between 01/2014 and 01/2021. The cohort was divided into two groups based on tumor extension in the final RARP specimen: patients with extraprostatic (pT3/4) vs. organ-confined (pT2) disease. Additionally, the authors conducted subgroup analyses within both the extraprostatic and organ-confined disease groups to compare continence rates before and after the implementation of the new surgical technique, which included Full Functional-Length Urethra preservation (FFLU) and Neurovascular Structure-Adjacent Frozen-Section Examination (NeuroSAFE). Multivariable logistic regression models addressing long-term continence were used.
Results: Overall, the authors identified 201 study patients of whom 75 (37 %) exhibited extraprostatic and 126 (63 %) organ-confined disease. There was no significant difference in long-term continence rates between patients with extraprostatic and organ-confined disease (77 vs. 83 %; p = 0.3). Following the implementation of FFLU+ NeuroSAFE, there was an overall improvement in continence from 67 % to 89 % (Δ = 22 %; p < 0.001). No difference in the magnitude of improved continence rates between extraprostatic vs. organ-confined disease was observed (Δ = 22 % vs. Δ = 20 %). In multivariable logistic regression models, no difference between extraprostatic vs. organ-confined disease in long-term continence was observed (Odds Ratio: 0.91; p = 0.85).
Conclusion: In this tertiary-based institutional study, patients with extraprostatic and organ-confined prostate cancer exhibited comparable long-term continence rates.
Non-organ confined stage and upgrading rates in exclusive PSA high-risk prostate cancer patients
(2022)
Background: The pathological stage of prostate cancer with high-risk prostate-specific antigen (PSA) levels, but otherwise favorable and/or intermediate risk characteristics (clinical T-stage, Gleason Grade group at biopsy [B-GGG]) is unknown. We hypothesized that a considerable proportion of such patients will exhibit clinically meaningful GGG upgrading or non-organ confined (NOC) stage at radical prostatectomy (RP).
Materials and methods: Within the Surveillance, Epidemiology, and End Results database (2010–2015) we identified RP-patients with cT1c-stage and B-GGG1, B-GGG2, or B-GGG3 and PSA 20–50 ng/ml. Rates of GGG4 or GGG5 and/or rates of NOC stage (≥ pT3 and/or pN1) were analyzed. Subsequently, separate univariable and multivariable logistic regression models tested for predictors of NOC stage and upgrading at RP.
Results: Of 486 assessable patients, 134 (28%) exhibited B-GGG1, 209 (43%) B-GGG2, and 143 (29%) B-GGG3, respectively. The overall upgrading and NOC rates were 11% and 51% for a combined rate of upgrading and/or NOC stage of 53%. In multivariable logistic regression models predicting upgrading, only B-GGG3 was an independent predictor (odds ratio [OR]: 5.29; 95% confidence interval [CI]: 2.21–14.19; p < 0.001). Conversely, 33%–66% (OR: 2.36; 95% CI: 1.42–3.95; p = 0.001) and >66% of positive biopsy cores (OR: 4.85; 95% CI: 2.84–8.42; p < 0.001), as well as B-GGG2 and B-GGG3 were independent predictors for NOC stage (all p ≤ 0.001).
Conclusions: In cT1c-stage patients with high-risk PSA baseline, but low- to intermediate risk B-GGG, the rate of upgrading to GGG4 or GGG5 is low (11%). However, NOC stage is found in the majority (51%) and can be independently predicted with percentage of positive cores at biopsy and B-GGG.
Despite recent advances in the treatment of metastatic prostate cancer (PCa), resistance development after taxane treatments is inevitable, necessitating effective options to combat drug resistance. Previous studies indicated antitumoral properties of the natural compound amygdalin. However, whether amygdalin acts on drug-resistant tumor cells remains questionable. An in vitro study was performed to investigate the influence of amygdalin (10 mg/mL) on the growth of a panel of therapy-naïve and docetaxel- or cabazitaxel-resistant PCa cell lines (PC3, DU145, and LNCaP cells). Tumor growth, proliferation, clonal growth, and cell cycle progression were investigated. The cell cycle regulating proteins (phospho)cdk1, (phospho)cdk2, cyclin A, cyclin B, p21, and p27 and the mammalian target of rapamycin (mTOR) pathway proteins (phospho)Akt, (phospho)Raptor, and (phospho)Rictor as well as integrin β1 and the cytoskeletal proteins vimentin, ezrin, talin, and cytokeratin 8/18 were assessed. Furthermore, chemotactic activity and adhesion to extracellular matrix components were analyzed. Amygdalin dose-dependently inhibited tumor growth and reduced tumor clones in all (parental and resistant) PCa cell lines, accompanied by a G0/G1 phase accumulation. Cell cycle regulating proteins were significantly altered by amygdalin. A moderate influence of amygdalin on tumor cell adhesion and chemotaxis was observed as well, paralleled by modifications of cytoskeletal proteins and the integrin β1 expression level. Amygdalin may, therefore, block tumor growth and disseminative characteristics of taxane-resistant PCa cells. Further studies are warranted to determine amygdalin’s value as an antitumor drug.
The aim of this study is to investigate the incidental prostate cancer (iPCa) detection rates of different embedding methods in a large, contemporary cohort of patients with bladder outlet obstruction (BOO) treated with transurethral surgery. We relied on an institutional tertiary-care database to identify BOO patients who underwent either transurethral loop resection or laser (Holmium:yttrium–aluminium garnet) enucleation of the prostate (HoLEP) between 01/2012 and 12/2019. Embedding methods differed with regard to the extent of the additional prostate tissue submitted following the first ten cassettes of primary embedding (cohort A: one [additional] cassette/10 g residual tissue vs. cohort B: complete embedding of the residual tissue). Detection rates of iPCa among the different embedding methods were compared. Subsequently, subgroup analyses by embedding protocol were repeated in HoLEP-treated patients only. In the overall cohort, the iPCa detection rate was 11% (46/420). In cohort A (n = 299), tissue embedding resulted in a median of 8 cassettes/patient (range 1–38) vs. a median of 15 (range 2–74) in cohort B (n = 121) (p < .001). The iPCa detection rate was 8% (23/299) and 19% (23/121) in cohort A vs. cohort B, respectively (p < .001). Virtual reduction of the number of tissue cassettes to ten cassettes resulted in a iPCa detection rate of 96% in both cohorts, missing one stage T1a/ISUP grade 1 carcinoma. Increasing the number of cassettes by two and eight cassettes, respectively, resulted in a detection rate of 100% in both cohorts without revealing high-grade carcinomas. Subgroup analyses in HoLEP patients confirmed these findings, demonstrated by a 100 vs. 96% iPCa detection rate following examination of the first ten cassettes, missing one case of T1a/ISUP 1. Examination of 8 additional cassettes resulted in a 100% detection rate. The extent of embedding of material obtained from transurethral prostate resection correlates with the iPCa detection rate. However, the submission of 10 cassettes appears to be a reasonable threshold to reduce resource utilization while maintaining secure cancer detection.
Background: No North-American study tested the survival benefit of chemotherapy in de novo metastatic prostate cancer according to race/ethnicity. We addressed this void.
Methods: We identified de novo metastatic prostate cancer patients within the Surveillance, Epidemiology, and End Results database (2014–2015). Separate and specific Kaplan–Meier plots and Cox regression models tested for overall survival differences between chemotherapy-exposed versus chemotherapy-naïve patients in four race/ethnicity groups: Caucasian versus African-American versus Hispanic/Latino vs Asian. Race/ethnicity specific propensity score matching was applied. Here, additional landmark analysis was performed.
Results: Of 4232 de novo metastatic prostate cancer patients, 2690 (63.3%) were Caucasian versus 783 (18.5%) African-American versus 504 (11.8%) Hispanic/Latino versus 257 (6.1%) Asian. Chemotherapy rates were: 21.3% versus 20.8% versus 21.0% versus 20.2% for Caucasians versus African-Americans versus Hispanic/Latinos versus Asians, respectively. At 30 months of follow-up, overall survival rates between chemotherapy-exposed versus chemotherapy-naïve patients were 61.5 versus 53.2% (multivariable hazard ratio [mHR]: 0.76, 95 confidence interval [CI]: 0.63–0.92, p = 0.004) in Caucasians, 55.2 versus 51.6% (mHR: 0.76, 95 CI: 0.54–1.07, p = 0.11) in African-Americans, 62.8 versus 57.0% (mHR: 1.11, 95 CI: 0.73–1.71, p = 0.61) in Hispanic/Latinos and 77.7 versus 65.0% (mHR: 0.31, 95 CI: 0.11–0.89, p = 0.03) in Asians. Virtually the same findings were recorded after propensity score matching within each race/ethnicity group.
Conclusions: Caucasian and Asian de novo metastatic prostate cancer patients exhibit the greatest overall survival benefit from chemotherapy exposure. Conversely, no overall survival benefit from chemotherapy exposure could be identified in either African-Americans or Hispanic/Latinos. Further studies are clearly needed to address these race/ethnicity specific disparities.
The objective of the study was to test the impact of implementing standard full functional-length urethral sphincter (FFLU) and neurovascular bundle preservation (NVBP) with intraoperative frozen section technique (IFT) on long-term urinary continence in patients undergoing robotic-assisted radical prostatectomy (RARP). We relied on an institutional tertiary-care database to identify patients who underwent RARP between 01/2014 and 09/2019. Until 10/2017, FFLU was not performed and decision for NVBP was taken without IFT. From 11/2017, FFLU and IFT-guided NVBP was routinely performed in all patients undergoing RARP. Long-term continence (≥ 12 months) was defined as the usage of no or one safety- pad. Uni- and multivariable logistic regression models tested the correlation between surgical approach (standard vs FFLU + NVBP) and long-term continence. Covariates consisted of age, body mass index, prostate volume and extraprostatic extension of tumor. The study cohort consisted of 142 patients, with equally sized groups for standard vs FFLU + NVBP RARP (68 vs 74 patients). Routine FFLU + NVBP implementation resulted in a long-term continence rate of 91%, compared to 63% in standard RARP (p < 0.001). Following FFLU + NVBP RARP, 5% needed 1–2, 4% 3–5 pads/24 h and no patient (0%) suffered severe long-term incontinence (> 5 pads/24 h). No significant differences in patient or tumor characteristics were recorded between both groups. In multivariable logistic regression models, FFLU + NVBP was a robust predictor for continence (Odds ratio [OR]: 7.62; 95% CI 2.51–27.36; p < 0.001). Implementation of FFLU and NVBP in patients undergoing RARP results in improved long-term continence rates of 91%.
Bone-seeking 223Radium-dichloride (223Ra) is an established treatment prolonging survival and reducing morbidity in selected patients with metastatic castration-resistant prostate cancer (mCRPC) with skeletal involvement. Radioligand therapy with 177Lutetium-PSMA-617 (177Lu-PSMA-617) has been increasingly implemented in patients with mCRPC failing conventional treatment options. In this study, the safety and efficacy of 177Lu-PSMA-617 in patients with progressive bone involvement under treatment with 223Ra was assessed. Twenty-eight men (median age 73 years, range 63–89 years) with progressive mCRPC, who started 177Lu-PSMA-617 within 8 weeks after the last 223Ra administration, received a median of 4 (IQR 3–6) and a total of 120 cycles of 223Ra and a median of 4 (IQR 2–7) cycles 177Lu-PSMA-617 with a mean treatment activity of 6.5 ± 1.2 GBq per cycle, reaching a mean cumulative activity of 30.7 ± 23.4 GBq. A PSA response (≥50% PSA decline 12 weeks after the first 177Lu-PSMA-617 cycle) was observed in 18/28 (64.3%) patients and imaging-based partial remission (PR) was observed in 11/28 (39.3%) patients. Median imaging-based progression-free survival (PFS) was 10 (95% CI, 6–14) months and median overall survival (OS) was 18 (95% CI, 14–22) months. Patients with low bone tumor burden (2–20 lesions) had a significantly longer OS (28 vs. 14 months, p < 0.045) compared to patients with a high tumor burden (>20 lesions). Grade ≥ 3 hematological toxicity was observed in six patients after their last treatment cycle with anemia, leukopenia and thrombocytopenia in 5/28 (17.9%), 4/28 (14.3%) and 6/28 (21.4%) patients, respectively. In progressive bone-metastatic mCRPC patients, prompt initiation of 177Lu-PSMA-617 after failing 223Ra is effective with an acceptable toxicity profile.
Refers to Clinically Significant Prostate Cancer Diagnosis Without Histological Proof: A Possibility in the Prostate-specific Membrane Antigen Era? European Urology Open Science, Volume 44, October 2022, Pages 30-32. Joris G. Heetman, Lieke Wever, Leonor J. Paulino Pereira, Roderick C.N. van den Bergh https://doi.org/10.1016/j.euros.2022.06.013
Localized prostate cancer exhibits multiple genomic alterations and heterogeneity at the proteomic level. Single-cell technologies capture important cell-to-cell variability responsible for heterogeneity in biomarker expression that may be overlooked when molecular alterations are based on bulk tissue samples. This study aims to identify prognostic biomarkers and describe the heterogeneity of prostate cancer and the associated microenvironment by simultaneously quantifying 36 proteins using single-cell mass cytometry analysis of over 1.6 million cells from 58 men with localized prostate cancer. We perform this task, using a high-dimensional clustering pipeline named Franken to describe subpopulations of immune, stromal, and prostate cells, including changes occurring in tumor tissues and high-grade disease that provide insights into the coordinated progression of prostate cancer. Our results further indicate that men with localized disease already harbor rare subpopulations that typically occur in castration-resistant and metastatic disease.