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1.
Mol Med ; 26(1): 24, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32143573

RESUMO

BACKGROUND: TFAP2D is a transcription factor important for modulating gene expression in embryogenesis. Its expression and prognostic role in prostate cancer has not been evaluated. METHODS: Therefore, a tissue microarray containing 17,747 prostate cancer specimens with associated pathological, clinical, and molecular data was analyzed by immunohistochemistry to assess the role of TFAP2D. RESULTS: TFAP2D expression was typically increased in prostate cancer as compared to adjacent non-neoplastic glands. TFAP2D staining was considered negative in 24.3% and positive in 75.7% of 13,545 interpretable cancers. TFAP2D staining was significantly linked to advanced tumor stage, high classical and quantitative Gleason grade, lymph node metastasis, and a positive surgical margin (p ≤ 0.0045). TFAP2D positivity was more common in ERG fusion positive (88.7%) than in ERG negative cancers (66.8%; p < 0.0001). Subset analyses in 3776 cancers with and 4722 cancers without TMPRSS2:ERG fusion revealed that associations with tumor phenotype and patient outcome were largely driven by the subset of ERG negative tumors. Multivariate analysis did not identify TFAP2D protein expression levels as a robust independent prognostic parameter. Positive TFAP2D immunostaining was significantly associated with 10 of 11 previously analyzed chromosomal deletions in ERG negative cancers (p ≤ 0.0244 each) indicating that elevated TFAP2D expression parallels genomic instability in prostate cancer. CONCLUSION: These data demonstrate that TFAP2D protein overexpression is linked to prostate cancer progression and genomic instability in ERG negative prostate cancers.

2.
Int J Cancer ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32150281

RESUMO

Altered expression of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been linked to adverse tumor features in various cancer types. To better understand the role of CEACAM1 in prostate cancer, we analyzed a tissue microarray containing tumor spots from 17,747 prostate cancer patients by means of immunohistochemistry. Normal prostate glands showed intense membranous CEACAM1 positivity. Immunostaining was interpretable in 13,625 cancers and was considered high in 28%, low in 43% and absent in 29% of tumors. Low and lost CEACAM1 expression was strongly linked to adverse tumor features including high classical and quantitative Gleason grade, lymph node metastasis, advanced tumor stage, positive surgical margin, a high number of genomic deletions and early biochemical recurrence (p < 0.0001 each). Subset analysis of molecularly defined cancer subsets revealed that these associations were strongest in V-ets avian erythroblastosis virus E26 oncogene homolog (ERG) fusion-positive cancers and that CEACAM1 loss was prognostic even in tumors harboring genomic deletions of the phosphatase and tensin homolog tumor suppressor (p < 0.0001). Multivariate analysis suggested that CEACAM1 analysis can provide independent prognostic information beyond established prognosis parameters at the stage of the initial biopsy when therapy decisions must be taken. In conclusion, loss of CEACAM1 expression predicts poor prognosis in prostate cancer and might provide clinically useful prognostic information particularly in cancers harboring the TMPRSS2:ERG fusion.

3.
Biomolecules ; 10(3)2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32183314

RESUMO

From a root bark of Lespedeza bicolor Turch we isolated two new (7 and 8) and six previously known compounds (1-6) belonging to the group of prenylated polyphenols. Their structures were elucidated using mass spectrometry, nuclear magnetic resonance and circular dichroism spectroscopy. These natural compounds selectively inhibited human drug-resistant prostate cancer in vitro. Prenylated pterocarpans 1-3 prevented the cell cycle progression of human cancer cells in S-phase. This was accompanied by a reduced expression of mRNA corresponding to several human cyclin-dependent kinases (CDKs). In contrast, compounds 4-8 induced a G1-phase cell cycle arrest without any pronounced effect on CDKs mRNA expression. Interestingly, a non-substituted hydroxy group at C-8 of ring D of the pterocarpan skeleton of compounds 1-3 seems to be important for the CDKs inhibitory activity.

4.
Sci Rep ; 10(1): 3250, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32094363

RESUMO

The role of subcellular survivin compartmentalization in the biology and prognosis of prostate cancer is unclear. We therefore investigated subcellular localization of survivin in more than 3000 prostate cancer patients by quantitative immunohistochemistry and performed transcriptomics of 250 prostate cancer patients and healthy donors using publicly available datasets. Survivin (BIRC5) gene expression was increased in primary prostate cancers and metastases, but did not differ in recurrent vs non-recurrent prostate cancers. Survivin immunohistochemistry (IHC) staining was limited exclusively to the nucleus in 900 prostate cancers (40.0%), and accompanied by various levels of cytoplasmic positivity in 1338 tumors (59.4%). 0.5% of prostate cancers did not express survivin. Nuclear and cytoplasmic survivin staining intensities were strongly associated with each other, pT category, and higher Gleason scores. Cytoplasmic but not nuclear survivin staining correlated with high tumor cell proliferation in prostate cancers. Strong cytoplasmic survivin staining, but not nuclear staining predicted an unfavorable outcome in univariate analyses. Multivariate Cox regression analysis showed that survivin is not an independent prognostic marker. In conclusion, we provide evidence that survivin expression is increased in prostate cancers, especially in metastatic disease, resulting in higher aggressiveness and tumor progression. In addition, subcellular compartmentalization is an important aspect of survivin cancer biology, as only cytoplasmic, but not nuclear survivin accumulation is linked to biological aggressiveness and prognosis of prostate cancers.

5.
Cancer Causes Control ; 31(3): 283-290, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32034540

RESUMO

PURPOSE: To test the effect of age on cancer-specific mortality (CSM) in most contemporary prostate cancer (PCa) patients of all stages and across all treatment modalities. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 579,369 PCa patients. Cumulative incidence plots and multivariable competing-risks regression analyses (MCR) were used. Subgroup analyses were performed according to ethnicity (African-Americans), clinical stage (T1-2N0M0, T3-4N0M0, TanyN1M0, and TanyNanyM1), as well as treatment modalities. RESULTS: Patient distribution was as follows: 142,338 (24.6%) < 60 years; 113,064 (19.5%) 60-64 years; 127,158 (21.9%) 65-69 years; 94,782 (16.4%) 70-74 years; and 102,027 (17.6%) ≥ 75 years. Older patients harbored worse tumor characteristics and more frequently received no local treatment. Overall, 10-year CSM rates were 4.8, 5.3, 5.9, 7.6, and 14.6%, respectively, in patients aged < 60, 60-64, 65-69, 70-74 ,and ≥ 75 years (p < 0.001). In MCR focusing on the overall cohort and T1-2N0M0 patients, older age independently predicted higher CSM, but not in T3-4N0-1M0-1 patients. CONCLUSIONS: Older age was associated with higher grade and stage and independently predicted higher CSM in T1-2N0M0 patients, but not in higher stages. Differences in diagnostics and therapeutics seem to affect elderly patients within T1-2N0M0 PCa and should be avoided if possible.

6.
J Urol ; : 101097JU0000000000000800, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32068488

RESUMO

INTRODUCTION: The aim of the study was to compare 11C-Choline and 68Ga-PSMA in men undergoing SLND for nodal recurrent PCa. MATERIALS AND METHODS: The study included 641 patients who experienced PSA rise and nodal recurrence after radical prostatectomy and underwent SLND. Lymph node recurrence was documented by PET/CT scan using either 11C-Choline (n=407; 63%) or 68Ga-PSMA ligand (n=234; 37%). The outcome was underestimation of tumour burden (difference between number of positive nodes on final pathology and number of positive spots at PET/CT). Multivariable analysis tested the association between PET/CT tracer (11C-Choline vs. 68Ga-PSMA) and underestimation of tumour burden. RESULTS: Overall, the extent of underestimation of tumour burden was significantly higher in the 11C-Choline group compared to the 68Ga-PSMA (p<0.0001). This was confirmed on multivariable analysis (p=0.028). Repeating these analyses according to PSA, the underestimation of tumour burden was lower with 68Ga-PSMA only when the PSA was ≤1.5 ng/ml. Conversely, the underestimation of the two tracers became similar when PSA was >1.5 ng/ml. Furthermore, we evaluated the risk of underestimation by number of positive spots on PET/CT scan. The higher the number of positive spots the higher the underestimation of tumour burden regardless of the tracer used (p=0.2). CONCLUSIONS: PET/CT scan significantly underestimates the burden of PCa recurrence, regardless of the tracer used. 68Ga-PSMA was associated with a lower rate of underestimation in patients with a PSA below 1.5 ng/ml and a limited nodal tumour load. In all other men, there was no benefit from 68Ga-PSMA over 11C-Choline in assessing the extent of nodal recurrence.

7.
Eur Urol Focus ; 6(2): 255-258, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32033909

RESUMO

The five-tier grade group (GG) classification for prostate cancer (PCa) does not differentiate between primary (5+4) or secondary (4+5) histological Gleason 5 pattern in GG 5. We addressed the prognostic value of primary versus secondary biopsy Gleason 5 for GG 5 among 18 555 PCa patients treated with radical prostatectomy (RP) between 1992 and 2014. Of these, 922 patients had GG 5 PCa with primary (n=295) or secondary (n=627) Gleason 5 on biopsy. Prediction of biochemical recurrence (BCR), metastasis, and cancer-specific mortality (CSM) was assessed using Kaplan-Meier curves and univariable/multivariable Cox regression controlling for known prognosticators. Median follow-up was 74.8 mo (interquartile range [IQR] 49.2-120.2). BCR developed in 24.3% of patients (n=4508) at a median of 23.6 mo (IQR 7.1-48.6). Metastasis developed in 4.5% (n=827) and 2.0% (n=370) died of PCa. When stratifying GG 5 by primary versus secondary Gleason 5, the estimated 5-yr metastasis-free survival was 80.4% (95% confidence interval [CI] 76.1-85.0%) versus 86.9% (95% CI 84.2-89.7%; p= 0.002) and cancer-specific survival was 90.9% (95% CI 87.5-94.4%) versus 96.3% (95% CI 94.7-98.0%; p< 0.001). On multivariable analysis, the negative impact of primary biopsy Gleason 5 among GG 5 patients remained significant for metastasis (hazard ratio [HR] 1.58; p< 0.001) and CSM (HR 2.44; p< 0.001). Therefore, stratifying GG 5 into primary (5 + 4, 5 + 5) and secondary (4 + 5) Gleason 5 may be warranted. PATIENT SUMMARY: We recorded worse oncological outcomes for patients with a primary histological Gleason 5 pattern on prostate biopsy compared to patients with a secondary biopsy Gleason 5 pattern.

8.
Urol Oncol ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32001198

RESUMO

BACKGROUND: To analyze oncological outcomes of very high-risk patients with initial PSA 50-99.9 and ≥100 ng/ml who underwent radical prostatectomy (RP) for clinically localized prostate cancer. METHODS: Overall, 2,811 RP patients (1992-2018) with negative preoperative CT-scan and bone scintigraphy were included. The impact of preoperative PSA level, categorized as 20-49.9 (n = 2,195) vs. 50-99.9 (n = 454) vs. ≥100 ng/ml (n = 162) on biochemical recurrence (BCR)-free survival, metastasis-free survival (MFS) and cancer-specific survival (CSS) was assessed using Kaplan-Meier and multivariable Cox regression models. RESULTS: Median follow-up was 47.5 months. Ten-year BCR-free survival rates were 46.9 vs. 32.1 vs. 29.0% within PSA-categories 20-49.9 vs. 50-99.9 vs. ≥100 ng/ml, respectively (P < 0.001). Ten-year MFS rates were 78.4 vs. 67.2 vs. 37.3% within PSA-categories 20-49.9 vs. 50-99.9 vs. ≥100 ng/ml (P < 0.001). 10-year CSS rates were 93.7 vs. 85.5 vs. 66.7% within PSA-categories 20-49.9 vs. 50-99.9 vs. ≥100 ng/ml (P < 0.001). In multivariable analyses, PSA-categories 50-99.9 ng/ml and ≥100 ng/ml were independently predicting higher risk of BCR (hazard ratio [HR]: 1.3 and 1.4), metastatic progression (HR: 1.4 and 2.3), and cancer-specific mortality (CSM, HR: 1.9 and 3.4) compared with PSA-category 20-49.9 ng/ml. CONCLUSION: Initial PSA levels ≥50 ng/ml are associated with higher risk of BCR, metastatic progression, and CSM compared with high-risk patients with PSA of 20-49.9 ng/ml. In consequence, these patients may be counseled about a potentially increased risk of undetected metastases prior to RP possibly necessitating intensified multimodal treatments in the future.

9.
Urology ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32084412

RESUMO

OBJECTIVE: To assess the effects of robot-assisted radical prostatectomy in the Trendelenburg position on postoperative neurocognitive outcomes this study compared cognitive function between patients who underwent robot-assisted radical prostatectomy and those who underwent open retropubic radical prostatectomy. METHODS: Objective evaluations of pre- and postoperative cognitive function were performed upon admission and before hospital discharge, by using a neuropsychological test battery. We collected self-reported data on cognitive failures at 3 months postoperatively. Binary logistic regression analysis was used to assess the effects of surgical technique on postoperative cognitive performance. RESULTS: The pre- and postoperative neuropsychological assessments were completed by 367 patients with a median age of 64 years (range 44-76). The incidence of postoperative cognitive dysfunction was 23.9% after robot-assisted (39/165) and 22.3% after open radical prostatectomy (45/202). There was no significant difference in postoperative cognitive function during the early postoperative period (P = 0.758) and self-reported cognitive failures at 3 months (P = 0.303) between robot-assisted and open surgery. Surgical technique was not associated with early postoperative cognitive dysfunction in multivariable analysis (OR 1.012, 95%CI: 0.608-1.685, P = 0.962). CONCLUSION: Compared with open surgery in supine position postoperative neurocognitive disorders do not occur more frequently after robot-assisted radical prostatectomy in the extreme Trendelenburg position. Based on these findings potential adverse effects on cognitive function do not have to be considered in the choice of surgical approach for radical prostatectomy.

10.
Int J Med Robot ; : e2094, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32073227

RESUMO

BACKGROUND: The aim of this study was to compare the incidence of early postoperative delirium in the postanesthesia care unit (PACU) between robot-assisted radical prostatectomy (RARP) in the extreme Trendelenburg position and open retropubic radical prostatectomy (ORP) in supine position. METHODS: Patients were screened for delirium signs 15, 30, 45, and 60 minutes following extubation. RESULTS: PACU delirium was present in 39.3% of RARP (64/163) patients and 41.8% of ORP (77/184) patients. Higher age (OR 1.072, 95%CI: 1.034-1.111, P < .001), total intravenous anesthesia (OR 2.001, 95%CI: 1.243-3.221, P = .004), and anesthesia duration (OR 1.255, 95%CI: 1.067-1.476, P = .006) were associated with PACU delirium, but no association was found between surgical technique and PACU delirium. CONCLUSION: Compared with inhalational anesthesia, total intravenous anesthesia using propofol-sufentanil, higher age, and longer duration of anesthesia were associated with PACU delirium. Based on these findings, adverse effects on postoperative recovery and delirium signs do not have to be considered in the choice of surgical approach for radical prostatectomy. TRIAL REGISTRATION: https://www.drks.de/, identifier: DRKS00010014.

11.
Urol Oncol ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31928867

RESUMO

BACKGROUND: To examine the impact of different pretreatment definitions on biochemical recurrence (BCR)-free survival, metastasis-free survival, and cancer-specific survival after radical prostatectomy. METHODS: Overall, 26,364 patients with clinically localized disease who underwent radical prostatectomy at a single institution (1992-2017) were retrospectively analyzed. Seven pretreatment definitions of high-risk CaP (prostate-specific antigen [PSA] ≥20 ng/ml, clinical stage ≥T2c, clinical stage T3 [cT3], biopsy Gleason score [GS] 8-10 [Grade Group {GG} IV-V], biopsy GS 9 to 10 [GG V], D'Amico risk definition, National Comprehensive Cancer Network risk definition) were evaluated. Kaplan-Meier, as well as multivariable Cox regression analyses were used. RESULTS: Depending on the definition, patients with high-risk CaP comprised between 0.9% (cT3) and 20.3% (D'Amico high-risk) of the population. Ten-year BCR-free survival rates varied from 36.0% (≥cT2c) to 47.4% (National Comprehensive Cancer Network high-risk). Ten-year metastasis-free survival rates varied from 56.6% (GS 9-10/GG V) to 77.5% (PSA ≥ 20 ng/ml). Ten-year cancer-specific survival rates varied from 86.6% (cT3) to 94.5% (PSA ≥ 20 ng/ml). In multivariable analysis, all high-risk definitions were associated with significantly higher risk of BCR (hazard ratio [HR]: 3.4-3.9), metastatic progression (HR: 3.9-8.8), and cancer-specific mortality (HR: 2.8-11.2). CONCLUSIONS: Variety in outcomes exists, depending on the pretreatment definition of high-risk CaP. Among the tested, GS 9 to 10 (GG V), cT2c, and cT3 were the strongest predictor for higher BCR risk, cT3 was the strongest predictor for higher metastatic progression risk and GS 9 to 10 (GG V) was the strongest predictor for higher cancer-specific mortality risk in multivariable analyses.

12.
Cancer Med ; 9(4): 1409-1418, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31893572

RESUMO

Survivin is an inhibitor of apoptosis. Aberrant survivin expression occurs in malignant tumors and has often been linked to unfavorable patient outcome. Here we analyzed 12 432 prostate cancers by immunohistochemistry. Survivin immunostaining was regularly expressed at high levels in normal prostate epithelium but expression was often reduced in prostate cancers. Among 9492 evaluable prostate cancers, 9% expressed survivin strongly, 19% moderately, 28% weakly, and 44% lacked it. Loss of cytoplasmic survivin was seen in advanced tumor stage, higher Gleason score, preoperative PSA levels, and Ki-67 labeling index, and associated with earlier PSA recurrence (P < .0001). Survivin loss was significantly more common in cancers carrying TMPRSS2:ERG fusions (61% survivin negative) than in ERG wild-type cancers (32% survivin negative; P < .0001). Multivariate analysis revealed that reduced cytoplasmic survivin expression predicted poor prognosis independent from Gleason score, pT, pN, and serum PSA level. This was valid for ERG-positive and ERG-negative cancers. Survivin expression loss even retained its prognostic impact in 1020 PTEN deleted cancers, a group that is already characterized by dismal patient prognosis. In conclusion, reduced survivin expression is associated with more aggressive tumors and inferior prognosis in prostate cancer.

13.
Urology ; 136: 127-132, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31705945

RESUMO

OBJECTIVE: To assess the prevalence of fluoroquinolone resistant (QR) bacteria, multidrug resistant (MDR) bacteria and Enterococcus faecalis (E. faecalis) in rectal swabs of patients undergoing transrectal prostate biopsy and for evaluating if risk factor assessment is reliable for prediction of QR bacteria, MDR bacteria, or E. faecalis. PATIENTS AND METHODS: Two hundred consecutive patients received a rectal swab examination prior to transrectal magnetic resonance imaging-guided fusion biopsy, for evaluating the prevalence of QR bacteria, MDR bacteria, and E. faecalis. The results of a standardized risk factor questionnaire, assessing known prognosticators for higher prevalence of resistant bacteria in rectal flora were correlated with the occurrence of QR bacteria, MDR bacteria, and E. faecalis in rectal swabs. RESULTS: QR E. coli was detected in 12 patients (6%). Regarding MDR bacteria, extended spectrum ß- lactamase- producing E. coli occurred in 8 patients (4%). E. faecalis was found in 15 patients (7.5%). A total of 193 patients completed the risk factor questionnaire. Of those, 107 (53.2%) patients harbored no risk factors, while 86 (42.8%) had at least 1 risk factor, of which the most common was repeat biopsy. No association was found between any risk factor and occurrence of QR bacteria, MDR bacteria, or E. faecalis (P >.05). CONCLUSION: The prevalence of resistant germs in our cohort was lower compared to other series. Moreover, the rate of QR bacteria, MDR bacteria, or E. faecalis in rectal swabs was not reliably associated with risk factor assessment.


Assuntos
Bactérias/isolamento & purificação , Farmacorresistência Bacteriana Múltipla , Biópsia Guiada por Imagem/métodos , Próstata/patologia , Reto/microbiologia , Humanos , Masculino , Cuidados Pré-Operatórios , Estudos Prospectivos , Medição de Risco , Fatores de Risco
14.
Urol Oncol ; 38(3): 79.e9-79.e14, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31653563

RESUMO

PURPOSE: Gleason Score (GS) 9-10 prostate cancer is associated with particularly adverse oncological outcomes and the optimal treatment is unknown. Therefore, cancer-specific mortality (CSM) rates after radical prostatectomy (RP) ± adjuvant radiation therapy (aRT) vs. external beam radiation therapy (EBRT) were tested. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2015), 17,897 clinically localized prostate cancer patients with biopsy GS 9-10 were identified who either received RP ± aRT or EBRT. Temporal trends, cumulative incidence plots and multivariable competing-risks regression analyses were used after propensity score matching. Sensitivity analyses were performed according to primary treatment type (RP only vs. EBRT). RESULTS: Of all, 8,890 (49.7%) underwent EBRT vs. 9,007 (50.3%) underwent RP. Of those, 2,584 (28.7%) received aRT. No significant change in treatment assignment was recorded over time. In cumulative incidence smoothed plots, 10 year CSM rates were 19.9% vs. 19.6% (P = 0.3) and 10 year other-cause mortalityrates were 11.5% vs. 31.2%, respectively, in RP vs. EBRT patients (P < 0.001). In multivariable competing-risks regression analyses, RP did not reach independent predictor status of lower CSM (hazard ratio (HR): 0.93, P = 0.2). In sensitivity analyses within RP only vs. EBRT patients, RP represented an independent predictor of lower CSM (HR: 0.76, P < 0.001). CONCLUSIONS: In biopsy GS 9-10 patients, no CSM differences were observed after RP ± aRT vs. EBRT. However, in patients in whom RP did not have to be combined with aRT, RP seems to be associated with a minor improvement in cancer-specific survival compared to EBRT. This applied to the majority of GS 9-10 RP patients.

15.
Acta Oncol ; 59(3): 268-273, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31687881

RESUMO

Background: Remodelling and spacing factor 1 (RSF1) is involved in the regulation of chromatin remodelling and represents a potential therapeutic target. High RSF1 expression has been linked to adverse tumour features in many cancer types, but its role in prostate cancer is uncertain.Methods: In this study, RSF1 expression was analysed by immunohistochemistry on a tissue microarray with 17,747 prostate cancers.Results: Nuclear RSF1 staining of 16,456 interpetable cancers was considered strong, moderate, weak and negative in 25.2%, 48.7%, 5.3% and 20.8% of cancers respectively. Positive RSF1 expression was associated with advanced tumour stage, high Gleason grade, lymph node metastasis (p < .0001 each), early biochemical recurrence (p < .0003) and more frequent in the ERG positive than in the ERG negative subset (88% versus 71%; p < .0001). Subset analysis revealed, that associations between RSF1 expression and unfavourable tumour phenotype and PSA recurrence were present in both subgroups but stronger in the ERG negative than in the ERG positive subset. The univariate Cox proportional hazard ratio for PSA recurrence-free survival for strong versus negative RSF1 expression was a weak 1.60 compared with 5.91 for the biopsy Gleason grade ≥4 + 4 versus ≤3 + 3. The positive association of RSF1 protein detection with deletion of 3p13, 10q23 (PTEN), 12p13, 16q23, and 17p13 (p < .0001 each) suggest a role of high RSF1 expression in the development of genomic instability.Conclusion: In summary, the results of our study identify RSF1 as an independent prognostic marker in prostate cancer with a particularly strong role in ERG negative cases.

16.
Mol Oncol ; 14(1): 129-138, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31736271

RESUMO

The chromatin-organizing factor CCCTC-binding factor (CTCF) is involved in transcriptional regulation, DNA-loop formation, and telomere maintenance. To evaluate the clinical impact of CTCF in prostate cancer, we analyzed CTCF expression by immunohistochemistry on a tissue microarray containing 17 747 prostate cancers. Normal prostate tissue showed negative to low CTCF expression, while in prostate cancers, CTCF expression was seen in 7726 of our 12 555 (61.5%) tumors and was considered low in 44.6% and high in 17% of cancers. Particularly, high CTCF expression was significantly associated with the presence of the transmembrane protease, serine 2:ETS-related gene fusion: Only 10% of ERG-negative cancers, but 30% of ERG-positive cancers had high-level CTCF expression (P < 0.0001). CTCF expression was significantly associated with advanced pathological tumor stage, high Gleason grade (P < 0.0001 each), nodal metastasis (P = 0.0122), and early biochemical recurrence (P < 0.0001). Multivariable modeling revealed that the prognostic impact of CTCF was independent from established presurgical parameters such as clinical stage and Gleason grade of the biopsy. Comparison with key molecular alterations showed strong associations with the expression of the Ki-67 proliferation marker and presence of phosphatase and tensin homolog deletions (P < 0.0001 each). The results of our study identify CTCF expression as a candidate biomarker for prognosis assessment in prostate cancer.

17.
Int Urol Nephrol ; 52(1): 59-66, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31542882

RESUMO

PURPOSE: There is no contemporary proof of cancer-control benefits in octogenarian clinically localized prostate cancer (PCa) patients with life expectancy (LE) < 10 years. Therefore, cancer-specific mortality (CSM) rates after external beam radiation therapy (EBRT) vs. no local treatment (NLT) were tested in octogenarian PCa patients with LE < 10 years. METHODS: Within the surveillance, epidemiology, and end results database (2004-2015), we identified 22,361 octogenarian clinically localized PCa patients who either received EBRT or NLT. Temporal trends, cumulative incidence plots and multivariable competing-risks regression analyses (MCR) were used after propensity score matching. Sensitivity analyses were performed according to D'Amico risk groups and LE > 5 years. RESULTS: Of all, 7325 (32.8%) received EBRT vs. 15,036 (67.2%) received NLT. Rates of EBRT significantly increased over time (25.0-42.4%). Overall, 10-year CSM rates were 10.6% vs. 17.0% and 10-year other-cause mortality rates were 50.3% vs. 58.1%, in EBRT vs. NLT patients (both p < 0.001). In MCR focusing on the overall cohort, EBRT represented an independent predictor of lower CSM (hazard ratio: 0.5). In sensitivity analyses, hazard ratios of 0.5 (p < 0.001), 0.5 (p < 0.001) and 0.8 (p = 0.5) were, respectively, recorded in D'Amico high-, intermediate- and low-risk patients. In sensitivity analyses addressing patients with LE > 5 years virtually the same results were recorded. CONCLUSIONS: In octogenarian patients with LE < 10 years, EBRT seems to be associated with lower CSM in D'Amico high-risk, as well as in D'Amico intermediate-risk patients relative to their NLT counterparts. Based on these observations, greater consideration for EBRT may be given in octogenarian patients.

18.
J Urol ; 203(2): 338-343, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31437119

RESUMO

PURPOSE: Pelvic lymph node dissection represents the gold standard of lymph node staging in patients with prostate cancer. We sought to assess the effect of extended pelvic lymph node dissection on oncologic outcomes in patients with characteristics of D'Amico intermediate or high risk prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: In a multi-institutional database of 4 centers we identified 9,742 patients who underwent radical prostatectomy from 2000 to 2017 with or without pelvic lymph node dissection. Only patients with a greater than 5% probability of lymph node invasion according to the Briganti nomogram were included in study. We performed 2:1 propensity score matching to account for potential differences between the 2 cohorts. Cox regression models were used to test the effect of pelvic lymph node dissection on biochemical recurrence, metastasis and cancer specific mortality. RESULTS: Overall 707 patients (7.3%) did not undergo pelvic lymph node dissection, of whom 520 and 187 harbored D'Amico intermediate and high risk characteristics, respectively. A median of 14 lymph nodes (IQR 8-21) were removed in the pelvic lymph node dissection cohort and 1,714 of these cases (19.0%) harbored lymph node metastasis. After propensity score matching the biochemical recurrence-free, metastasis-free and cancer specific mortality-free survival rates were 60.4% vs 65.6% (p=0.07), 87.0% vs 90.0% (p=0.06) and 95.2% vs 96.4% (p=0.2) for pelvic lymph node dissection vs no pelvic lymph node dissection 120 months after radical prostatectomy. Multivariable Cox regression models adjusted for postoperative and preoperative tumor characteristics revealed that pelvic lymph node dissection performed at radical prostatectomy was no independent predictor of biochemical recurrence, metastasis or cancer specific mortality (all p ≥0.1). CONCLUSIONS: There was no significant difference in oncologic outcomes in patients with D'Amico high or intermediate risk prostate cancer in whom pelvic lymph node dissection was or was not performed at radical prostatectomy. The therapeutic value of pelvic lymph node dissection remains unclear.


Assuntos
Excisão de Linfonodo/métodos , Prostatectomia , Neoplasias da Próstata/cirurgia , Humanos , Metástase Linfática , Masculino , Pelve , Prostatectomia/métodos , Neoplasias da Próstata/classificação , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento
19.
J Urol ; 203(2): 299-303, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31483694

RESUMO

PURPOSE: We analyzed the number of multiparametric magnetic resonance imaging targeted biopsy cores per lesion needed to detect prostate cancer in patients treated with radical prostatectomy. MATERIALS AND METHODS: Analyses focused on targeted biopsy of magnetic resonance imaging lesions suspicious for prostate cancer with a PI-RADS® (Prostate Imaging Reporting and Data System) score of 3 or greater and consecutive radical prostatectomy. Descriptive statistics included the frequency/proportion and IQR. Multivariable logistic regression analyses on the per lesion level were used to predict the number of targeted biopsies with prostate cancer. RESULTS: In the total cohort of 771 radical prostatectomy cases 437 (57%) and 334 (43%) were systematic transrectal ultrasound guided biopsy naïve or had 1 or more prior negative systematic transrectal ultrasound guided biopsies, respectively. A maximum PI-RADS score of 3, 4 and 5 was present in 67 (8.7%), 567 (74%) and 137 patients (18%), respectively. A total of 1,459 multiparametric magnetic resonance imaging lesions suspicious for prostate cancer were identified for analysis. Prostate cancer was detected based on an initial, second, third, or fourth or greater targeted biopsy in 79%, 92%, 98% and 100% of cases, respectively. The rate of prostate cancer detection on the first targeted biopsy core increased with higher PI-RADS scores of 3, 4 and 5 (67%, 79% and 87%, respectively). The number of prior negative systematic transrectal ultrasound guided biopsies and pathological tumor stage emerged as independent predictors on multivariate analysis, addressing the need for 2 or more targeted biopsy cores to detect clinically significant prostate cancer. CONCLUSIONS: Radical prostatectomy based analyses demonstrated that most cancers could be detected by 2 targeted biopsies only while in a minority of cases 3 or more targeted biopsies were necessary. Such findings might indicate that the targeted biopsy procedure and the related technology have improved, especially in patients with intermediate/high risk prostate cancer.


Assuntos
Biópsia Guiada por Imagem/estatística & dados numéricos , Imagem por Ressonância Magnética Intervencionista , Próstata/patologia , Neoplasias da Próstata/patologia , Ultrassonografia de Intervenção , Idoso , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Próstata/diagnóstico por imagem , Prostatectomia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos
20.
J Nucl Med ; 61(1): 6-12, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31732677

RESUMO

Since its introduction to the diagnostic pathway for prostate cancer management, prostate-specific membrane antigen (PSMA)-ligand PET has demonstrated great potential. PSMA-ligand imaging is increasingly influencing therapeutic decision making, although its impact on patient outcomes still needs to be defined. One relatively new application, enabled through chemical and engineering efforts, is PSMA-guided surgery. This review highlights the potential of PSMA-guided surgery and discusses its implications in lymph node dissection in primary and recurrent prostate cancer.

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