Pre-treatment red blood cell distribution width as a predictor of clinically significant prostate cancer.

OBJECTIVE: The present study aims to assess the relationship between red blood cell distribution width (RDW) and clinically significant prostate cancer (csPCa). METHODS: A total of 458 patients with prostate-specific antigen (PSA) ≤ 10 ng/ml, who subsequently underwent 11-core transperineal template-guided prostate biopsy from June 15, 2015 to November 24, 2020, were included in the present study. Receiver-operating characteristic (ROC)-derived area under the curve analysis was performed to evaluate the predictive accuracy. In addition, univariate and multivariate logistic regression analysis was carried out to determine the association between RDW and csPCa detection. RESULTS: A total of 89 patients were diagnosed with csPCa, and these patients presented with higher median RDW. The optimal RDW cut-off was set at 12.35%, which gained the maximal Yuden's index. In addition to csPCa, RDW demonstrated a positive correlation with age (r = 0.210, P < 0.001). It was observed that RDW was independent of prostate-specific antigen density for csPCa detection. Compared with the low-RDW group, patients in the high-RDW group had a 1.586-fold increased risk of being diagnosed with csPCa (OR = 2.586, P = 0.007). In the ROC analysis, the accuracy level increased by 3.1% for the prediction of csPCa, when RDW was added to the multivariate logistic model. CONCLUSION: A high-RDW value is an independent risk factor for csPCa detection. However, more large-scale studies are needed to confirm these findings. If validated, RDW can become an inexpensive, non-invasive, and convenient indicator for csPCa prediction.

Impact of Radiotherapy on Prognosis in Patients Diagnosed with Metastatic Prostate Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: It has been reported that compared with no local therapy (NLT), patients treated with local therapy (LT) using radiotherapy (RT) possess higher survival rate in metastatic prostate cancer (mPCa). The aim of this meta-analysis was to evaluate the impact of RT on prognosis in patients with mPCa. METHODS: We retrieved the literature in PubMed, Embase, and Cochrane Library databases until June 2019 using structured search terms. Several studies were included, which evaluated patients with mPCa who received RT versus NLT. RESULTS: A total of 14,542 patients were analyzed in 7 included papers (2 randomized controlled trials [RCTs] and 5 cohort retrospective studies [CRS]), and 2,232 mPCa patients were treated with RT and 12,310 with NLT. The data of RCTs and CRS were analyzed separately. In RCTs, RT was associated with no significant difference in overall survival (OS) (pooled hazard ratio [HR] = 0.96; 95% confidence interval [CI]: 0.85-1.09; p = 0.55; I2 = 42%) relative to NLT, while survival benefit was observed in the low-metastatic burden group (pooled HR = 0.68; 95% CI: 0.54-0.86; p = 0.001; I2 = 0%), and no survival benefit was observed in the high-metastatic burden group (pooled HR = 1.07; 95% CI: 0.92-1.24; p = 0.39; I2 = 0%). In CRS, RT results in lower cancer-specific mortality (CSM) (pooled HR = 0.49; 95% CI: 0.34-0.75; p < 0.00001; I2 = 0%) and higher OS (pooled HR = 0.61; 95% CI: 0.55-0.68; p < 0.00001; I2 = 0%) relative to NLT. Subsequent analysis demonstrated that high level of M-stage or N-stage was associated with increased CSM (pooled HR = 2.08; 95% CI: 1.69-2.55; p < 0.00001; I2 = 0% and pooled HR = 1.16; 95% CI: 1.03-1.30; p < 0.00001; I2 = 0%; respectively). CONCLUSIONS: Our observations in aggregate indicated that RT at least does not appear to be harmful and may be beneficial for low-metastatic burden patients and better condition patients. More prospective and randomized studies evaluating RT for mPCa are warranted.

Risk factors for infection complications after transrectal ultrasound-guided transperineal prostate biopsy.

BACKGROUND: To investigate the influence factors of infection complications of transrectal ultrasound-guided transperineal prostate biopsy. METHODS: A total of 2192 patients who underwent prostate biopsy under transperineal prostate biopsy were analyzed retrospectively from December 2010 to May 2020.We collected the clinical characteristics and the incidence of complications, and used univariate and multivariate logistic regression analyses to analyze independent risk factors for infection complications after transperineal prostate biopsy. RESULTS: Univariate analysis showed that the following factors were associated with the infection complications: diabetes, bacterial prostatitis, history of urinary retention, history of urinary infection, and number of cores. Furthermore, multivariate logistic analysis revealed that diabetes (OR 2.037, 95% CI 1.143-3.572, P = 0.021) and history of urinary retention (OR 2.563, 95% CI 1.284-3.901, P = 0.013) were independent risk factors for infection complications after transperineal prostate biopsy. CONCLUSIONS: Patients with diabetes and history of urinary retention were more likely to have infection complications after transperineal prostate biopsy.

Effect on survival of local treatment in patients with low prostate-specific antigen, high Gleason score prostate cancer: a population-based propensity score-matched analysis.

BACKGROUND: Emerging data suggest that in patients with low prostate-specific antigen (PSA) and high Gleason score, prostate cancer (PCa) is more aggressive and more likely to be related to genomic characteristics of neuroendocrinology. However, the evidence for the advantages of local treatment (LT) for these men is lacking. Hence, we investigated survival in men with low-PSA values and high-grade (Gleason score 8-10) PCa according to the treatment of the primary tumor. METHODS: Kaplan-Meier survival analysis was applied to analyze the effects on overall survival (OS) and cancer-specific survival (CSS) according to the different treatments of the primary tumor. Multivariable Cox proportional hazards survival regression analysis calculated the CSS after propensity score matching (PSM) in 2 cohorts according to treatment type. The treatment types included the following: (I) LT versus non-LT (NLT) and (II) radical prostatectomy (RP) versus radiotherapy (RT). RESULTS: In the Surveillance, Epidemiology, and End Results (SEER) database [2004-2014], we identified 14,208 patients newly diagnosed with low PSA values (10 ng/mL or less), with a Gleason score 8-10, and cT1-4N0M0 prostate adenocarcinoma. After the first PSM, of the 3,512 PCa patients, 1,576 underwent LT and 1,576 underwent NLT. After the second PSM, of the 792 PCa patients, 396 underwent RP, and 396 underwent RT. The 5- and 10-year OS rates for LT vs. NLT patients were 90% and 73% versus 69% and 39%, respectively, while the 5- and 10-year CSS rates for LT vs. NLT patients were 98% and 94% versus 89% and 79%, respectively. Subsequent multivariate survival analysis showed that LT was associated with lower likelihood of PCa mortality relative to NLT [hazard ratio (HR), 0.19; 95% confidence interval (CI), 0.14-0.26, P<0.001], also in RP versus RT (HR, 0.26; 95% CI, 0.12-0.54, P<0.001). CONCLUSIONS: In patients with low PSA values, Gleason score 8-10, and localized PCa, LT resulted in higher survival compared with NLT. Within LT, RP provided the most benefit relative to RT.

Conditionally replicative adenovirus carrying shRNA targeting EZH2 inhibits prostate cancer growth and invasion.

The present study aimed to construct conditionally replicative adenovirus (CRAds) carrying small hairpin (sh)RNA targeting enhancer of zeste homolog 2 (EZH2), in order to study its effect on inhibiting prostate cancer (PCa) cell growth and invasion. Immunohistochemical analyses of EZH2 was performed in tumor tissue samples from PCa and benign prostate hyperplasia (BPH). The human telomerase reverse transcriptase (hTERT) promoter was chosen to transcriptionally control EZH2 gene expression to obtain adenoviral replication (Ad­hTERT­EZH2shRNA) in human PCa cell lines. The inhibitory effect of Ad­hTERT­EZH2shRNA on EZH2 expression was evaluated by reverse transcription­-quantitative polymerase chain reaction and western blot analyses. Cell Counting Kit­8 assays were used to examine the effects of the Ad­hTERT­EZH2shRNA on cell proliferation. Transwell Matrigel invasion assays were used to detected cell invasion. Immunohistochemistry showed that EZH2 staining was stronger in castration­resistant prostate cancer (CRPC) samples, compared with androgen­dependent prostate cancer (ADPC) samples, and was absent in BPH. Furthermore, EZH2 expression knockdown suppressed PCa cell proliferation and invasion. In addition, it was found that Ad­hTERT­EZH2shRNA selectively replicated and significantly reduced the expression of EZH2 in PCa cells lines. The growth ability and invasion of DU145 and PC3 cells in vitro was effectively inhibited by Ad­hTERT­EZH2shRNA. Silencing the expression of EZH2 led to decreased expression of CCND1 and Ki67 and increased expression of E­cadherin, as determined by western blot analysis. Thus, it was shown that CRAds armed with EZH2 shRNA exhibited significant antitumor effects in human PCa cells. Ad­hTERT­EZH2shRNA may be developed as a treatment for hormone­refractory PCa.

Permanent 125 I prostate brachytherapy for castration-resistant prostate cancer.

OBJECTIVE: To evaluate the clinical significance of permanent 125 I prostate brachytherapy in patients with castration-resistant prostate cancer. METHODS: A retrospective study of 45 patients with castration-resistant prostate cancer from the Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China was carried out. Patients were divided into two groups according to different treatments: 21 patients received endocrine therapy alone (control group), and 24 patients underwent brachytherapy combined with endocrine therapy (treatment group). Prostate-specific antigen progression-free survival, cancer-specific survival, overall survival and quality of life of the two groups were compared. RESULTS: The median prostate-specific antigen progression-free survival and cancer-specific survival of the treatment group were 29 months (interquartile range 25-37 months) and 37 months (interquartile range 30-50 months), respectively. These were significantly longer than those of the control group (both P < 0.05). Prostate-specific antigen (before androgen deprivation therapy and before brachytherapy), prostate volume, Gleason score, clinical stage and brachytherapy were associated with prostate-specific antigen progression-free survival and cancer-specific survival on univariate analysis. For the quality of life after treatment, urinary symptoms/problems at 1 month after brachytherapy compared with the control group had a statistically significant difference and clinically relevant deterioration, but after 6 months there were no statistically significant differences and clinically relevant deterioration. Compared with the control group, the physical functioning, social functioning, global health and general physical discomfort of the treatment group were significantly improved. CONCLUSIONS: Brachytherapy with 125 I seed implantation can effectively prolong survival of patients with castration-resistant prostate cancer and, to a certain extent, improve patients' quality of life.

Marital status independently predicts prostate cancer survival in men who underwent radical prostatectomy: An analysis of 95,846 individuals.

Marital status is an independent prognostic factor for survival in several types of cancer, but has not been fully studied in prostate cancer (PCa). A total of 95,846 men diagnosed with PCa were treated with radical prostatectomy (RP) between 2004 and 2009 within 18 Surveillance, Epidemiology and End Results registries. Survival curves were generated using Kaplan-Meier estimates and differences in survival were assessed using the log-rank test. Cox regression models were used to assess the impact of marital status on survival outcomes. The results demonstrated that the 8-year cancer-cause specific survival (CSS) rate of married men was higher than unmarried individuals. Further analyses revealed that divorced/separated men had a higher proportion of high Gleason scores (GS) PCa at diagnosis [hazard ratio (HR), 1.12; P=0.007] and those patients had the worst survival outcomes independent of age, ethnicity, grade, stage and sequence number [HR, 1.61; 95% confidence interval (CI), 1.34-1.93]. Interestingly, it was observed that CSS among divorced/separated men decreased as the GS increased (GS≤6: HR, 2.5; GS=7: HR, 1.71; GS≥8: HR, 1.50; all P<0.05). Apart from that, no significant differences in CSS were observed in those who had never been married (HR, 1.20) or were widowed (HR, 1.13) relative to the married group. The results of the present study support the hypothesis that marital status is an independent prognostic factor among men with PCa who underwent RP. It was demonstrated that the mortality rates of divorced or separated men with PCa were significantly greater compared with the other groups. A further understanding of the potential associations among marital status, psychosocial factors and survival outcomes may help in developing novel, more effective methods of treating different groups of patients with PCa.

A potential panel of four-long noncoding RNA signature in prostate cancer predicts biochemical recurrence-free survival and disease-free survival.

PURPOSES: Growing evidences showed that lncRNAs abnormally expressed in cancer tissues and played irreplaceable roles in tumorigenesis, progression and metastasis. In present study, we aimed to identify lncRNA expression signature that can predict biochemical recurrence-free (BCR-free) survival of prostate cancer (PCa) patients. METHODS: A total of 291 patients with pathologic confirmed PCa in The Cancer Genome Atlas dataset were recruited and included. With the specific risk score formula, patients were further classified into high-risk group and low-risk group. Kaplan-Meier survival analyses and Cox regression analyses were performed to determine the association between lncRNA signature and survival outcomes. Gene Set Enrichment Analysis (GSEA) was carried out to identify the potentially associated biological processes and signaling pathway. RESULTS: Overall, 126 differentially expressed lncRNAs were found with more than twofold changes and p value of FDR <0.01. Among which, four lncRNAs were identified to be significantly associated with BCR-free survival. Then, using a risk score based on the signature of these four lncRNAs, we divided the patients into low-risk and high-risk groups with significantly different BCR-free survival and disease-free survival. Further multivariate Cox regression analyses revealed that the four-lncRNA signature was independent of age, AJCC T stage, lymphonodus status, Gleason score, margin and adjuvant postoperative radiotherapy. GSEA suggested that this signature was involved in cell proliferation. CONCLUSIONS: In present study, a novel four-lncRNA signature that is useful in survival prediction in PCa patients was developed. If validated, this lncRNA signature might assist in selecting high-risk subpopulation who need more aggressive therapeutic intervention. The clinical implications and the mechanism of these four lncRNAs deserve further investigation in future studies.

Predictive value of neutrophil-to-lymphocyte ratio in diagnosis of prostate cancer among men who underwent template-guided prostate biopsy: A STROBE-compliant study.

To evaluate the predictive value of neutrophil-to-lymphocyte ratio (NLR) in diagnosis of prostate cancer (PCa). Data of 662 patients who underwent prostate biopsy from January 2012 to June 2016 were retrospectively reviewed. The receiver operating characteristic-derived area under the curve analyses were performed to assess the predictive accuracy. Simultaneously, Youden's index was calculated to determine the optimal NLR cutoff. Furthermore, univariate and multivariate logistic regression analyses were performed to determine the association between NLR value and PCa detection. On account of an NLR value of 2.44 was shown with the maximal Youden's index on the receiver operating characteristic curve, the cutoff value of NLR was set at 2.44. Accordingly, patients were classified into high-NLR or low-NLR group. The patients in high-NLR group might have significant higher risk to be diagnosed with PCa (HR 1.640; P = 0.031), especially in the subgroup with prostate-specific antigen (PSA) ranged from 4 to 10 ng mL (hazard ratio [HR] 4.364; P = 0.003). The high-NLR was independent of age of diagnosis, PSA, prostate volume, abnormal digital rectal examination, and hypoechoic lesion on transrectal ultrasound for positive prostate biopsy. In the so-called gray area, combination of NLR value could raise 4.6% of the accuracy of the multivariate logistic model in PCa prediction, but not in advanced PCa prediction.The patients with high-NLR value may have significant higher risk to be diagnosed with PCa, especially among the patients with PSA ranged from 4 to 10 ng mL. In this subgroup, the adding of NLR value in the multivariate model can improve the accuracy of PCa prediction in a large degree. If validated, the NLR will become a promising, accessible, inexpensive biomarker for PCa prediction.

Effect of prostate volume on the peripheral nerve block anesthesia in the prostate biopsy: A strobe-compliant study.

OBJECTIVE: The objective of this study was to evaluate the anesthetic efficacy of periprostatic nerve block (PNB) in transrectal ultrasound (TRUS)-guided biopsy on different prostate volume. METHODS: A total of 568 patients received prostate biopsy in our hospital from May 2013 to September 2015 and were retrospectively studied. All patients were divided into local anesthesia group (LAG) and nerve block group (NBG). Then each group was subdivided into 4 subgroups (20-40, 40-60, 60-100, and >100 mL groups) according to different prostate volume range. Visual analogue scale (VAS) and visual numeric scale (VNS) were used to assess the patient's pain and quantify their satisfaction. The scores and complications were compared between the groups. RESULTS: The age and serum prostate-specific antigen (PSA) level before biopsy had no significant differences at intergroup or intragroup level. The VAS scores were significantly lower in the NBG than those in the LAG in terms of prostate volume (1 (1-2) versus 2 (1-3), 2 (1-3) versus 2 (2-4), 2 (2-3) versus 3 (2-5), 4 (3-5) versus 5 (4-7), all P < 0.05). Conversely, the VNS scores were higher in the NBG (4 (3-4) versus 3.5 (3-4), 3 (3-4) versus 3 (3-3), 3 (2-4) versus 3 (2-3), 2 (2-2) versus 1 (1-2), all P < 0.05). Patients with smaller prostate volume undergoing PNB or local anesthesia experienced significantly lower pain and higher satisfaction scores than those with large prostate. Whether in PNB or local anesthesia group, patients with large prostate volume had more chance to have hematuria, hemospermia, urinary retention than smaller one except infection (P < 0.05). Those complications had no significant differences between LAG and NBG (P > 0.05). CONCLUSION: Compared with local anesthesia, ultrasound-guided PNB has superior analgesic effect and equal safety, but for patients with a large prostate volume, the analgesic effect is inefficient.