Survival outcomes in prostate cancer patients with a prior cancer

BackgroundTo shed light on the survival outcomes of prostate cancer (PCa) patients diagnosed after a prior cancer and identify prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in PCa patients.MethodsIn the primary group, a total of 1,778 PCa patients with a prior cancer were identified in the Surveillance, Epidemiology, and End Results (SEER) database from 2005 to 2015, retrospectively. Baseline characteristics and causes of death (COD) of these patients were collected and compared. In the second group, a total of 10,296 PCa patients [5,148 patients with PCa as the only malignancy and 5,148 patients with PCa as their second primary malignancy (SPM)] diagnosed between 2010 and 2011 were extracted to investigate the impact of prior cancers on survival outcomes.ResultsIn PCa patients with a prior cancer, the most common type of prior cancer was from gastrointestinal system (29.92%), followed by urinary system (21.37%). Patients were more likely to die of the prior caner, and those with prior cancer from respiratory system had the worst survival outcomes. Moreover, the overall ratios in patients with stage (PCa) I–II and III–IV diseases were 0.21 and 1.65, indicating that patients with higher stage diseases were more likely to die of PCa. In the second group, patients with PCa as the SPM had worse OS than those with PCa as the first primary cancer. Lastly, prognostic factors for OS and CSS in PCa patients were explored.ConclusionsPCa remains to be an important COD for patients with a prior malignancy, especially for those with high-stage diseases. PCa patients with a prior cancer had worse survival outcomes than those without.     

基于SEER数据库建立小肝癌患者远处转移预测模型

目的 建立可有效预测小肝癌患者远处转移风险的列线图。方法 从SEER（Surveillance,Epidemiology,and End Results）数据库提取2010年1月至2016年12月诊断的5 595例小肝癌患者的临床病理资料,采用随机数字法按7:3分为训练组（n=3 915）和验证组（n=1 680）。对训练组采用单因素及多因素Logistic回归分析筛选影响远处转移的独立危险因素并构建小肝癌患者远处转移预测模型。采用受试者工作特征（ROC）曲线及校正曲线评估模型的预测准确性,采用决策曲线评价列线图的临床效用。结果 训练组多因素Logistic分析显示婚姻状况（HR 1.541,95%CI 1.182~2.010,P=0.001）、癌结节数目（HR 2.005,95%CI 1.483~2.710,P<0.001）、T分期（HR 2.076,95%CI 1.176~3.664,P=0.012）、N分期（HR 7.753,95%CI 5.349~11.238,P<0.001）、病理分化程度（HR 1.706,95%CI 1.098~2.652,P=0.018）、甲胎蛋白（HR 1.830,95%CI 1.313~2.550,P<0.001）是小肝癌远处转移的独立危险因素。训练组、验证组中ROC曲线下面积（AUC值）分别为0.805（95%CI 0.778~0.832）和0.829（95%CI 0.791~0.868）,校准曲线表明预测值与实际值有良好的一致性,决策曲线显示模型有良好的临床效用。结论 基于SEER数据库建立小肝癌患者远处转移的预测模型具有良好的预测准度,有助于外科医师评估患者远处转移风险,从而为患者提供个体化的诊疗。     

Effects of radical cystectomy,radiotherapy, and chemotherapy on the risk of long-term heart-specific death in bladder cancer patients

BackgroundAt present, the low risk of bladder cancer (BCa)-specific death has allowed for investigation into treatment-related cardiotoxicity. To aid clinicians in selecting appropriate cardiovascular disease screening strategies and interventions, this study explored the heart-specific mortality and prognostic factors of patients with BCa after radical cystectomy (RC), radiotherapy (RT), or chemotherapy (CT), and compared their long-term heart-specific mortality with that of the general male population.MethodsWe identified three different treatments for BCa patients from the Surveillance, Epidemiology, and End Results (SEER) database: RC, RT, and CT. Patients were included from 2000 to 2012 and followed through 2015. A cumulative mortality curve and competitive risk regression model were applied to evaluate the prognostic factors of heart-specific mortality, and standardized mortality ratios (SMRs) were calculated.ResultsOf 39,500 men, 30.3%, 18.8%, and 50.9% received RC, RT, and CT, respectively. For patients with a survival period of less than 50 months, tumor-specific death exhibited a rapidly increasing trend, which subsequently flatlined. However, the rates heart-specific mortality and other causes exhibited a tendency to increase stably. The heart-specific and all-cause mortality rates of patients in any age group treated with the three abovementioned strategies were higher than those of the general population. The heart-specific mortality of patients with carcinoma in situ treated with RC and CT exceeded their all-cause mortality, while that of other tumor stages did not. The risks of heart-specific [sub-distribution hazard ratio (SHR) =1.38; 95% confidence interval (CI): 1.22–1.57] and tumor-specific (SHR =1.68; 95% CI: 1.60–1.77) deaths in patients who received RT were higher than those of patients who underwent CT.ConclusionsThe risks of heart-specific and tumor-specific deaths in patients who received RT were higher than those of the RC and CT groups, especially in patients over 65 years of age who received RT.     

Development and validation of a nomogram for predicting the overall survival of prostate cancer patients: a large population-based cohort study

BackgroundProstate cancer (PC) is the second most common malignant tumor, and its survival is of great concern. However, the assessment of survival risk in current studies is limited. This study is to develop and validate a nomogram for the prediction of survival in PC patients using data from the Surveillance, Epidemiology, and End Results (SEER) database.MethodsA total of 153,796 PC patients were included in this cohort study. Patients were divided into a training set (n=107,657) and a testing set (n=46,139). The 3-, 5- and 10-year survival of the PC patients were regarded as the outcomes. Predictors based on the demographic and pathological data for survival were identified by multivariate Cox regression analysis to develop the predictive nomogram. Internal and subgroup validations were performed to assess the predictive performance of the nomogram. The C-index, time-dependent receiver operating characteristic (ROC) curves, and corresponding areas under the ROC curves (AUCs) were used to estimate the predictive performance of the nomogram.ResultsAge at diagnosis, race, marital status, tumor node metastasis (TNM) stage, prostate specific antigen (PSA) status, Gleason score, and pathological stage were identified as significantly associated with the survival of PC patients (P<0.05). The C-index of the nomogram indicated a moderate predictive ability [training set: C-index =0.782, 95% confidence interval (CI): 0.779–0.785; testing set: C-index =0.782, 95% CI: 0.777–0.787]. The AUCs of this nomogram for the 3-, 5-, and 10-year survival were 0.757 (95% CI: 0.756–0.758), 0.741 (95% CI: 0.740–0.742), and 0.716 (95% CI: 0.715–0.717), respectively. The results of subgroup validation showed that all the AUCs for the nomogram at 3, 5, and 10 years were more than 0.70, regardless of marital status and race.ConclusionsWe developed a nomogram with the moderate predictive ability for the long-term survival (3-, 5-, and 10-year survival) of patients with PC.     

老年前列腺癌伴骨转移患者的临床特征及治疗策略

为确定老年前列腺癌伴骨转移患者的临床特征及预后的独立预测因子。本研究回顾性分析了205例老年性前列腺癌伴骨转移患者的临床资料,运用生存曲线分析生存率,运行Cox回归模型进行多因素分析。同时,我们对比了197例年轻的前列腺癌伴骨转移的患者,运用卡方检验比较了上述得到的预测因子。结果显示,所有患者均得到完整随访,其1、2、3和5年生存率分别为95．5％,77．5％,68．5％和33．7％。Gleason评分,原发肿瘤放疗、骨转移数目、ALP、器官和区域淋巴结转移数目均与生存率密切相关。多因素回归分析表明Gleason评分是独立预测因子。相较于年轻患者,老年患者生存率更好,但是接受放疗的老年患者生存率却显著低于年轻患者。以上结果为今后前列腺癌伴骨转移生存预测模型的建立提供了数据支持。     

Downregulation of PARVA promotes metastasis by modulating integrin-linked kinase activity and regulating MAPK/ERK and MLC2 signaling in prostate cancer

BackgroundMetastasis is the predominant cause of mortality in prostate cancer (PCa); however, the underlying mechanisms are largely uncharted. Here, we found that Parvin alpha (PARVA) is downregulated in PCa and its loss is associated with clinical metastasis. We further explored the mechanistic basis of this finding.MethodsThe mRNA expression of PARVA was identified by analysis of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data sets. Immunohistochemistry (IHC) analysis was performed to evaluate the PARVA expression pattern in 198 PCa tissues, and 36 metastatic lymph node tissues. The function and molecular mechanism by which PARVA affects PCa were investigated in vitro using knockdown and overexpression cell lines. The effect of PARVA in cell proliferation, migration, and invasion in PCa cells was detected by MTS assay and Transwell assay. Real-time polymerase chain reaction (PCR) and Western blot analysis were used to assess the gene expression in mRNA and protein level.ResultsThe microarray data analysis indicated that PARVA was drastically downregulated in primary and metastatic PCa compared with normal and primary samples, respectively (all P<0.001). Multivariate Cox regression analysis suggested that downregulation of PARVA in PCa was an independent prognostic factor for poor biochemical recurrence (BCR)-free survival (P<0.01). IHC analysis confirmed that PARVA was frequently downregulated in metastatic and primary PCa tissues (All P<0.001). Furthermore, PARVA expression was found to be associated with Gleason score, pathological stage, extracapsular extension, and lymph node invasion (All P<0.05). Knockdown of PARVA triggered cell migration and invasion in vitro, whereas overexpression of PARVA reverted the invasive phenotypes. Mechanistic investigations identified that overexpression of PARVA repressed the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) phosphorylation via inhibiting the integrin-linked kinase (ILK) biological function. With knockdown of ILK, the downregulated MAPK/ERK phosphorylation and Myosin Light Chain 2 (MLC2) expression by PARVA overexpression were abolished, indicating that the PARVA effect on PCa is ILK/MAPK/ERK pathway dependent.ConclusionsOur study revealed that loss of PARVA expression in PCa promotes metastasis by releasing the inhibition of ILK activity, followed by the activation of MAPK/ERK and MLC2 signaling.     

Secondary bladder cancer after upper tract urothelial carcinoma in the US population

Study Type – Prognosis (cohort) Level of Evidence 2a What's known on the subject? and What does the study add? It is known that a certain percentage of patients treated for upper tract urothelial carcinoma (UTUC) will go on to develop a secondary bladder cancer; however, the risk factors for developing a secondary bladder tumour have not been studied in a population‐based setting. Given the large changes in how UTUC has been diagnosed and managed in recent years, this study aimed to evaluate the natural history of UTUC in the US population over a 30‐year period, with a particular emphasis on the development of secondary bladder cancer.

OBJECTIVE

• ? To assess the natural history of upper tract urothelial carcinoma (UTUC) and the development of lower tract secondary cancer.

PATIENTS AND METHODS

• ? Patients diagnosed with UTUC between 1975 and 2005 were identified within nine Surveillance, Epidemiology and End Results registries.
• ? Baseline characteristics of patients with and without secondary bladder cancer were compared.
• ? A multivariate logistic regression model was fitted to test if the year of diagnosis predicted the likelihood of developing a secondary bladder cancer.

RESULTS

• ? Of the 5212 patients with UTUC, 242 (4.6%) had a secondary bladder cancer (range: 1.7–8.2%).
• ? There was a mean interval of 26.5 (95% CI: 22.2–30.8) months between cancer diagnoses.
• ? Compared with those without secondary tumours, patients with secondary bladder malignancy were more likely to present with larger tumours (4.2 vs 3.1 cm, P < 0.001) and with tumours located in the ureter (P < 0.001).
• ? Year of diagnosis was not a predictor of the likelihood of having a secondary bladder malignancy in a multivariate analysis controlling for demographic and tumour characteristics (odds ratio: 0.99; 95% CI: 0.95–1.03)

CONCLUSIONS

• ? Patients with larger urothelial tumours located in the ureter were those most likely to develop a secondary lower tract tumour.
• ? No longitudinal changes in the rate of secondary bladder cancer were noted among patients with UTUC over the 30‐year study period.

     

^99mTc—MDP骨扫描在前列腺癌骨转移诊断中的价值

目的：探讨^99mTc-MDP骨扫描在前列腺痛骨转移诊断中的价值。方法：对明确诊断为前列腺癌的527例患者行^99mTc-MDP骨扫描,骨扫描不能确诊为骨转移者再经MRI、CT和病理检查等最后确诊有无骨转移。结果：在527例前列腺癌^99mTc-MDP骨扫描中,阳性显像331例,阴性显像196例;最后确诊骨转移者318例,占前列腺癌总例数的60．34％（318／527）．无骨转移者209例,占前列腺癌总例数的39．66％（209／527）。^99mTc-MDP骨扫描诊断前列腺癌骨转移的灵敏度为84．59％（269／318）,特异度为70．33％（147／209）,误诊率为29．67％（62／209）．漏诊率为15．4l％（49/318）．阳性预测值为81．27％（269／331）,阴性预测值为75．00％（147／l96）。随着^99mTc-MDP骨扫描诊断前列腺癌骨转移病灶数量级别从I级增至Ⅱ级和Ⅲ级时,其诊断前列腺癌骨转移的准确度越来越高。结论：^99mTc-MDP骨扫描诊断前列腺癌骨转移具有微高的灵敏度、特异性、阳性预测值和阴性预测倩,误诊率和漏诊率低。随骨转移病灶级别的增加,其诊断前列腺癌有无骨转移的价值越来越大。     

Clinical usefulness of bone markers in prostate cancer with bone metastasis

Bone metastases occur in approximately 70% of patients with advanced prostate cancer. Skeletal‐related events have been correlated with reduced survival and quality of life of patients with prostate cancer. Biochemical markers of bone metabolism (e.g. bone formation, bone resorption, osteoclastogenesis) might meet an unmet need for useful, non‐invasive and sensitive surrogate information for following patients' skeletal health. Recently, zoledronic acid and denosumab have been proven to have the potential for preventing skeletal‐related events among prostate cancer patients with bone metastasis. An improved understanding of the mechanisms underlying bone metastasis has also led to the recognition of multiple molecular targets and advances in therapy. However, estimating the efficacy of these agents is difficult. A clinical trial for castration‐resistant prostate cancer is currently underway based on the definition of The Prostate Cancer Clinical Trials Working Group, and bone turnover markers are being used as conventional end‐points for the clinical trial. Bone turnover markers are useful surrogate markers reflecting the effect of new therapeutic drugs and prognosis, as well as assessment of bone metastases. In particular, N‐terminal cross‐linked telopeptide of type 1 collagen and bone‐specific alkaline phosphatase are widely used bone metabolism markers, and offer reliable surrogate markers to detect bone metastatic spread and to predict prognosis for prostate cancer patients with bone metastases.     

Positive association between preoperative lymphocyte-to-monocyte ratio and risk of the status of positive surgical margins by prostate cancer: results in 497 consecutive patients treated only by radical prostatectomy

BackgroundPositive surgical margins (PSM) is one of the most important factors affecting the prognosis of prostate cancer (PCa) patients after radical prostatectomy (RP). Although some studies have found the preoperative systematic inflammation-based scores the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) can predict the incidence and prognosis of PCa, few studies have explored the predictive value of preoperative systematic inflammation-based scores on the PSMs for PCa patients after RP.MethodsFrom June 2014 to September 2020 a total of 497 patients underwent RP at our institution. Blood samples from all patients were collected within one week before surgery. Preoperative clinical characteristics including age, body mass index (BMI), prostate-specific antigen (PSA), and biopsy Gleason sum (BGS) were assessed. Postoperatively pathological specimens were assessed for pathological Gleason sum (PGS), pathological stage, and margin status.ResultsIn the multivariable analysis including preoperative variables, PSA and LMR were the independent predictive factors for PSM (OR: 2.817; 95% CI, 1.836–4.320, P<0.001; OR: 1.124; 95% CI, 1.018–1.240, P=0.021. Considering pre-, intra-, and postoperative variables, BGS, perineural invasion, seminal vesicle invasion (SVI), pathologic Gleason sum (PGS) combined, were associated with increased risk of PSM in the univariable analysis (P<0.001 for all variables). However, in the multivariable analysis, perineural invasion (OR: 2.672; 95% CI, 1.649–4.330; P<0.001), PGS (OR: 2.52; 95% CI, 1.556–4.082; P<0.001) were independent predictive factors for the incidence of PSM. Finally, LMR was shown to be an independent predictive factor (OR: 0.881; 95% CI, 0.779–0.996; P=0.043) for apical PSMs, with increasing LMR predicting the lower incidence of apex location. And we also found that LMR was an independent factor that predicts multifocal positive margins (OR: 1.179; 95% CI, 1.023–1.358; P=0.023).ConclusionsPreoperative LMR could be used as an independent predictor to predict the incidence of PSMs after RP. And Considering pre-, intra-, and postoperative variables, we also found that preoperative LMR could predict the occurrence of apical and multifocal PSMs.     

基于SEER数据库分析联合肝切除术对II期胆囊癌患者预后的影响

目的 拟应用大数据库样本探讨不同手术策略对II期胆囊癌患者预后影响是否有差异.方法 从美国SEER数据库筛选2004年1月1日至2015年12月31日间诊断的529例II期胆囊癌患者,按手术策略分为联合肝脏切除术组、非联合肝脏切除术组,通过Kaplan-Meier生存分析绘制生存曲线并计算中位生存时间,利用Cox风险回...     

Establishment of a novel prognostic prediction model through bioinformatics analysis for prostate cancer based on ferroptosis-related genes and its application in immune cell infiltration

BackgroundFerroptosis-related genes (FRGs) play vital roles in survival and prognosis of prostate cancer (PCa) patients. We establish a ferroptosis-related prediction model through bioinformatics analysis for overall survival (OS) and disease-free survival (DFS), so as to evaluate the clinical survival status through the characteristics of immune cell infiltration (ICI), which could provide information for treatment monitoring.MethodsAt first, 268 FRGs were obtained from previous studies. Differentially expressed FRGs were identified based on The Cancer Genome Atlas (TCGA) database, and FRG enrichment analysis was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We then performed univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses to establish OS- and DFS-related prognostic prediction models. The association of the model and clinicopathological features was further analyzed. Subsequently, unique genomic signatures of immune cell subsets were obtained through the KEGG database. Based on specific genes associated with ferroptosis and their association with ICI, immune infiltration was assessed in patients in different risk groups.ResultsWe constructed an OS- and an DFS-prognostic model through bioinformatics analysis. The predicted values of OS and DFS-related models were higher in T3–4 than in T1–2 (P=0.0057, P<0.001), and the predicted value of the DFS model in N0 stage was higher than that in N1 stage (P=0.0136). Results of Single-sample gene set enrichment analysis (ssGSEA) on the basis of the KEGG dataset showed p53 signaling being the most enriched signal in the high-risk group, while endocytosis was the most enriched signal in the low-risk group. M2 macrophages (P=0.007) and neutrophils (P=0.024) were enriched in the high-risk group, and CD4-activated memory T cells were significantly accumulated in the low-risk group (P=0.017).ConclusionsThe OS- and DFS-related model based on FRGs and ICI create new insights into the disease state assessment of PCa patients., which may aid in the development of individualized and precise treatment in the future.