Validating the association of adverse pathology with distant metastasis and prostate cancer mortality 20-years after radical prostatectomy

PurposeTo assess the association of adverse pathology (AP), defined as high-grade (≥ Gleason Grade Group 3) and/or non-organ confined disease, with long-term oncologic outcomes after radical prostatectomy (RP).Materials and MethodsUsing a stratified cohort sampling design, we evaluated the association of AP with the risk of distant metastasis (DM) and prostate cancer-specific mortality (PCSM) up to 20 years after RP in 428 patients treated between 1987 to 2004. Cox regression of cause-specific hazards was used to estimate the absolute risk of both endpoints, with death from other causes treated as a competing risk. Additionally, subgroup analysis in patients with low and/or intermediate-risk disease, who are potentially eligible for active surveillance (AS), was performed.ResultsWithin the cohort sample, 53% of men exhibited AP at time of RP, with median follow up of 15.5 years (IQR 14.6-16.6 years) thereafter. Adverse pathology was highly associated with DM and PCSM in the overall cohort (HR 12.30, 95% confidence interval [CI] 5.30-28.55, and HR 10.03, 95% CI 3.42-29.47, respectively, both P < 0.001). Adverse pathology was also highly associated with DM and PCSM in the low/intermediate-risk subgroup (HR 10.48, 95% CI 4.18-26.28, and 8.60, 95% CI 2.40-30.48, respectively, both P < 0.001).ConclusionsAdverse pathology at the time of RP is highly associated with future development of DM and PCSM. Accurate prediction of AP may thus be useful for individualizing risk-based surveillance and treatment strategies.     

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.     

Association of 5-alpha-reductase inhibitor and prostate cancer incidence and mortality: a meta-analysis

Background5-Alpha-reductase inhibitors (5-ARIs) have been suggested as potential chemopreventive agents for prostate cancer (PCa). This study was conducted to evaluate the effect of 5-ARIs on the incidence and mortality of PCa.MethodsThe PubMed, Embase and Cochrane Library databases were searched comprehensively from database inception to October 2019. The clinical outcomes included the incidence of overall PCa, high-grade (Gleason8-10) PCa, metastatic PCa, overall survival (OS), and cancer-specific survival (CSS).ResultsOverall, 23 studies were included in the present study, representing 11 cohort studies, 5 case-control studies, and 8 randomized controlled trials. The use of 5-ARIs was associated with a decreased risk of overall PCa [relative risk (RR) =0.77; 95% CI: 0.67–0.88; P<0.001] and increased risk of Gleason 8–10 PCa (RR=1.19; 95% CI: 1.01–1.40; P=0.036). In terms of metastatic PCa, there were no significant between-group differences (RR=1.23; 95% CI: 0.69–2.18; P=0.487). Furthermore, we found that prediagnostic 5-ARI usage was not associated with an increased risk of overall or prostate cancer mortality, with HRs of 1.00 (95% CI: 0.92–1.08; P=0.938) and 0.98 (95% CI: 0.80–1.21; P=0.881), respectively.ConclusionsIn conclusion, while male 5-ARI users were associated with a decreased risk of overall prostate cancer and increased risk of high-grade prostate cancer (Gleason 8–10), they were not associated with an increased risk of overall or prostate cancer mortality. 5-ARIs should be recommended carefully for use as chemopreventive agents.     

Impact of percent positive biopsy cores on cancer-specific mortality for patients with high-risk prostate cancer

ObjectiveA high percent positive biopsy cores (PBC), typically dichotomized at ≥50% is prognostic of worse cancer-specific outcomes for patients with low- and intermediate-risk prostate cancer (CaP). The clinical significance of ≥50% PBC for patients with high-risk disease is poorly understood. We examined the association between ≥50% PBC, compared to <50% PBC, and prostate cancer-specific mortality (PCSM) for patients with high-risk disease.Materials and methodsWe identified 7,569 men from the Surveillance, Epidemiology, and End Results program who were diagnosed with high-risk CaP (Gleason score of 8–10, prostate-specific antigen >20 ng/mL, or cT3-T4 stage) in 2010–2011 and had 6 to 24 cores sampled at biopsy. Multivariable Fine and Gray competing risks regression was utilized to examine the association between ≥50% PBC and PCSM.ResultsMedian follow-up was 3.8 years. 56.2% of patients (4,253) had ≥50% PBC. On competing risks regression, ≥50% PBC was associated with a significantly higher risk of PCSM compared to <50% PBC (adjusted hazard ratio [AHR] 2.00, 95% confidence interval [CI] 1.48–2.70, P < 0.001). On subgroup analyses, ≥50% PBC was associated with a significantly higher risk of PCSM only for cT1–T2 disease (AHR 2.23, 95% CI 1.62–3.07) but not cT3–T4 disease (AHR 0.83, 95% CI 0.39–1.76), with a significant interaction (P_interaction = 0.016). No significant interactions by Gleason score, prostate-specific antigen level, use of definitive therapy, or number of biopsy cores sampled were observed.ConclusionIn this large cohort of patients with high-risk CaP, ≥50% PBC was independently associated with an approximately 2-fold increased risk of PCSM for patients with cT1–T2, but not cT3–T4, tumors. Percent PBC, which is a widely available clinical value, should be routinely used to risk stratify men with high-risk disease and identify patients whom may benefit from treatment intensification.     

Nomogram predicting survival to assist decision-making of radical prostatectomy in patients with metastatic prostate cancer

BackgroundRadical prostatectomy (RP) has heterogeneous effects on survival of patients with metastatic prostate cancer (mPCa). A reliable model to predict risk of cancer-specific mortality (CSM) and the potential benefit derived from RP is needed.MethodsPatients diagnosed with mPCa were identified using the Surveillance, Epidemiology, and End Results database (2004–2015) and categorized in RP versus nonlocal treatment (NLT). Based on the Fine and Gray competing risks model in 8,463 NLT patients, a nomogram was created to predict CSM in mPCa patients. Decision tree analysis was then utilized for patient stratification. The effect of RP was evaluated among 3 different subgroups.ResultsA total of 8,863 patients were identified for analysis. Four hundred (4.5%) patients received RP. The 5-year cumulative incidence of CSM was 52.4% for the entire patients. Based on nomogram scores, patients were sorted into three risk groups using decision tree analysis. In the low- and intermediate-risk group, RP was found to be significantly correlated with a 21.7% risk reduction of 5-year CSM, and 25.0% risk reduction of 5-year CSM, respectively, whereas RP was not associated with CSM in high-risk group (hazard ratio =0.748, 95% confidence interval 0.485–1.150; P=0.190).ConclusionsWe developed a novel nomogram and corresponding patient stratification predicting CSM in mPCa patients. A newly identified patient subgroup with low-, and intermediate-risk of CSM might benefit more from RP. These results should be further validated and improved by ongoing prospective trials.     

Inflammatory bowel disease and risk of urinary cancers: a systematic review and pooled analysis of population-based studies

BackgroundThe aim of this study is to elucidate the risk of urologic cancers in patients with Crohn’s disease (CD) and ulcerative colitis (UC).MethodsElectronic databases including PubMed, the Cochrane Library, Embase and Web of Science, and manual retrieval were conducted from inception to June 2020. Two reviewers independently searched the above databases and selected the studies using prespecified standardized criteria. The Newcastle-Ottawa Scale was used to assess the risk of bias in the included studies, and this meta-analysis was completed by STATA version 14.2.ResultsA total of 12 cohort studies and 4 case-control studies were included in this meta-analysis. Overall, patients with inflammatory bowel disease (IBD) were at significantly increased risk of renal cancer (RCa) [standardized incidence ratio (SIR): 1.53; 95% confidence interval (CI): 1.25–1.80; I²=42.4%], but not at increased risk of prostate cancer (PCa), bladder cancer (BCa) and male genital cancer. In the subgroup analysis, CD patients had a significantly higher RCa risk (SIR: 1.95; 95% CI: 1.45–2.44; I²=39.9%). Besides, CD patients seemed to be at borderline significantly increased risks of PCa (SIR: 1.07; 95% CI: 0.93–1.20; I²=15.1%) and BCa (SIR:1.19; 95% CI: 0.94–1.44; I²=0%), and UC patients seemed to be at borderline significantly increased risks of RCa (SIR:1.31; 95% CI: 0.94–1.67; I²=48.0%) and PCa (SIR: 1.13; 95% CI: 0.93–1.33; I²=73.5%). Notably, we observed that IBD patients in Eastern countries have significantly increased PCa risk (SIR: 2.66; 95% CI: 1.52–3.81; I²=13.6%), especially for UC patients (SIR: 3.01; 95% CI: 1.75–4.27; I²=0.0%).ConclusionsOur findings indicate that IBD patients with special reference to CD patients increase the risk of RCa. Besides, IBD patients in Asian countries have significantly increased risk of PCa, especially for UC patients. Further studies are warranted to elucidate the potential mechanism of RCa associated with IBD and the differences of the risk of urinary cancers between Eastern and Western countries.     

When to biopsy Prostate Imaging and Data Reporting System version 2 (PI-RADSv2) assessment category 3 lesions? Use of clinical and imaging variables to predict cancer diagnosis at targeted biopsy

IntroductionWe aimed to determine if clinical and imaging features can stratify men at higher risk for clinically significant (CS, International Society of Urological Pathology [ISUP] grade group ≥2) prostate cancer (PCa) in equivocal Prostate Imaging and Data Reporting System (PI-RADS) category 3 lesions on magnetic resonance imaging (MRI).MethodsApproved by the institutional review board, this retrospective study involved 184 men with 198 lesions who underwent 3T-MRI and MRI-directed transrectal ultrasound biopsy for PI-RADS 3 lesions. Men were evaluated including clinical stage, prostate-specific antigen density (PSAD), indication, and MRI lesion size. Diagnoses for all men and by indication (no cancer, any PCa, CSPCa) were compared using multivariate logistic regression, including stage, PSAD, and lesion size.ResultsWe found an overall PCa rate of 31.8% (63/198) and 10.1% (20/198) CSPCa (13 grade group 2, five group 3, and two group 4). Higher stage (p=0.001), PSAD (p=0.007), and lesion size (p=0.015) were associated with CSPCa, with no association between CSPCa and age, PSA, or prostate volume (p>0.05). PSAD modestly predicted CSPCa area under the curve (AUC) 0.66 (95% confidence interval [CI] 0.518–0.794) in all men and 0.64 (0.487–0.799) for those on active surveillance (AS). Model combining clinical stage, PSAD, and lesion size improved accuracy for all men and AS (AUC 0.82 [0.736–0.910], p<0.001 and 0.785 [0.666–0.904], p<0.001). In men with prior negative biopsy and persistent suspicion, PSAD (0.90 [0.767–1.000]) was not different from the model (p>0.05), with optimal cutpoint of ≥0.215 ng/mL/cc achieving sensitivity/specificity of 85.7/84.4%.ConclusionsPI-RADSv2 category 3 lesions are often not CSPCa. PSAD predicted CSPCa in men with a prior negative biopsy; however, PSAD alone had limited value, and accuracy improved when using a model incorporating PSAD with clinical stage and MRI lesion size.     

Predicting Prostate Cancer Death with Different Pretreatment Risk Stratification Tools: A Head-to-head Comparison in a Nationwide Cohort Study

BackgroundNumerous pretreatment risk classification tools are available for prostate cancer. Which tool is best in predicting prostate cancer death is unclear.ObjectiveTo systematically compare the prognostic performance of the most commonly used pretreatment risk stratification tools for prostate cancer.Design, setting, and participantsA nationwide cohort study was conducted, including 154 811 men in Prostate Cancer data Base Sweden (PCBaSe) 4.0 diagnosed with nonmetastatic prostate cancer during 1998–2016 and followed through 2016.Outcome measurements and statistical analysisWe compared the D’Amico, National Institute for Health and Care Excellence (NICE), European Association of Urology (EAU), Genito-Urinary Radiation Oncologists of Canada (GUROC), American Urological Association (AUA), National Comprehensive Cancer Network (NCCN), and Cambridge Prognostic Groups (CPG) risk group systems; the Cancer of the Prostate Risk Assessment (CAPRA) score; and the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram in predicting prostate cancer death by estimating the concordance index (C-index) and the observed versus predicted cumulative incidences at different follow-up times.Results and limitationsA total of 139 515 men were included in the main analysis, of whom 15 961 died from prostate cancer during follow-up. The C-index at 10 yr of follow-up ranged from 0.73 (95% confidence interval [CI]: 0.72–0.73) to 0.81 (95% CI: 0.80–0.81) across the compared tools. The MSKCC nomogram (C-index: 0.81, 95% CI: 0.80–0.81), CAPRA score (C-index: 0.80, 95% CI: 0.79–0.81), and CPG system (C-index: 0.78, 95% CI: 0.78–0.79) performed the best. The order of performance between the tools remained in analyses stratified by primary treatment and year of diagnosis. The predicted cumulative incidences were close to the observed ones, with some underestimation at 5 yr. It is a limitation that the study was conducted solely in a Swedish setting (ie, case mix).ConclusionsThe MSKCC nomogram, CAPRA score, and CPG risk grouping system performed better in discriminating prostate cancer death than the D’Amico and D’Amico-derived systems (NICE, GUROC, EAU, AUA, and NCCN). Use of these tools may improve clinical decision making.Patient summaryThere are numerous pretreatment risk classification tools that can aid treatment decision for prostate cancer. We systematically compared the prognostic performance of the most commonly used tools in a large cohort of Swedish men with prostate cancer. The Memorial Sloan Kettering Cancer Center nomogram, Cancer of the Prostate Risk Assessment score, and Cambridge Prognostic Groups performed best in predicting prostate cancer death. The use of these tools may improve treatment decisions.     

Development and validation of a novel nomogram to predict overall survival of patients with moderate to severe chronic kidney disease

IntroductionThe risk of death significantly increased from stage 3 chronic kidney disease (CKD) onward. We aimed to construct a novel nomogram to predict the overall survival (OS) of patients afflicted with CKD from stage 3–5.MethodsA total of 882 patients with stage 3–5 CKD were enrolled from the NHANES 2001–2004 survey. Data sets from the 2003–2004 survey population were used to develop a nomogram that would predict the risk of OS. The 2001–2002 survey population was used to validate the nomogram. Least absolute shrinkage and selection operator (Lasso) regression was conducted to screen the significant predictors relative to all-cause death. The multivariate Cox regression based on the screened factors was applied to effectively construct the nomogram. The performance of the nomogram was evaluated according to the C-index, the area under the receiver operating characteristic curve (AUC), and the calibration curve with 1000 bootstraps resample. Kaplan–Meier’s curves were used for testing the discrimination of the prediction model.ResultsFive variables (age, urinary albumin-to-creatinine ratio (UACR), potassium, cystatin C (Cys C), and homocysteine) were screened by the Lasso regression. The nomogram was constructed using these factors, as well as the CKD stage. The included factors (age, CKD stage, UACR, potassium, Cys C, and homocysteine) were all significantly related to the death of CKD patients, according to the multivariate Cox regression analysis. The internal validation showed that this nomogram demonstrates good discrimination and calibration (adjusted C-index: 0.70; AUC of 3-, 5-, and 10-year OS were 0.75, 0.78, and 0.77, respectively). External validation also demonstrated exceedingly similar results (C-index: 0.72, 95% CI: 0.69–0.76; AUC of 3-, 5-, and 10-year OS were 0.76, 0.79, and 0.80, respectively).ConclusionsThis study effectively constructed a novel nomogram that incorporates CKD stage, age, UACR, potassium, Cys C, and homocysteine, which can be conveniently used to facilitate the individualized prediction of survival probability in patients with stage 3–5 CKD. It displays valuable potential for clinical application.     

Cancer-specific Survival After Metastasis Following Primary Radical Prostatectomy Compared with Radiation Therapy in Prostate Cancer Patients: Results of a Population-based,Propensity Score–Matched Analysis

BackgroundData regarding the difference in the clinical course from metastasis to prostate cancer–specific mortality (PCSM) following radical prostatectomy (RP) compared with radiation therapy (RT) are lacking.ObjectiveTo examine the association between primary treatment modality and prostate cancer–specific survival (PCSS) after metastasis.Design, setting, and participantsWe used the Surveillance Epidemiology and End Results–Medicare linked database from 1994 to 2007 for patients diagnosed with localized prostate cancer (PCa). We used cancer stage and Gleason score to stratify patients into low and intermediate–high risks.InterventionRadical prostatectomy or radiation therapy.Outcome measurements and statistical analysisOur outcome is time from onset of metastases to PCSM. Propensity score matching and Cox regression were used to analyze the PCSM hazard for the RP group compared with the RT group.Results and limitationsOur study consisted of 66 492 men diagnosed with PCa, 51 337 men receiving RT, and 15 155 men undergoing RP within 1 yr of cancer diagnosis. During the study period, 2802 men were diagnosed as having metastatic disease. A total of 916 men with metastases were included in the propensity-matched cohort; of these men, 186 died from PCa. During the follow-up, for the low-risk patients, the adjusted PCSS after metastasis was 86.2% and 79.3% in the RP and RT groups, respectively; for the intermediate–high-risk patients, the PCSS after metastasis was 76.3% and 63.3% in the RP and RT groups, respectively. The hazard ratios estimating the risk of PCSM between the RP and RT groups were 0.64 (95% confidence interval [CI], 0.36–1.16) and 0.55 (95% CI, 0.39–0.77) for the low- and intermediate–high-risk groups, respectively. Because of the nature of observational studies, the results may be affected by residual confounders and treatment indication.ConclusionsFollowing the development of metastases, men who received primary RP have a longer PCSS than men who received primary RT. Our results may have implications for the timing and nature of local PCa treatment.     

Localized prostate cancer: An analysis of the Centers for Disease Control and Prevention Breast and Prostate Cancer Data Quality and Patterns of Care study (CDC PoC-BP)

IntroductionLimited evidence exists on the comparative effectiveness of local treatments for prostate cancer (PCa) due to the lack of generalizability. Using granular national data, we sought to examine the association between radical prostatectomy (RP) and intensity-modulated radiation therapy (IMRT) treatment and survival.MethodsRecords were abstracted for localized PCa cases diagnosed in 2004 across seven state registries to identify patients undergoing RP (n=3019) or IMRT (n=667). Comorbidity was assessed by the Adult Comorbidity Evaluation-27 (ACE-27). Propensity score matching (PSM) was used to balance covariates between treatment groups. All-cause and PCa-specific mortality were primary endpoints. A subgroup analysis of patients with high-risk PCa (RP, n=89; IMRT, n=95) was conducted.ResultsFollowing PSM, matched patients (n=502 pairs) treated with either RP or IMRT were well-balanced with respect to covariates. With a median followup of 10.5 years (interquartile range [IQR] 9.9–11.0), the 11-year overall survival (OS) was 71.2% (95% confidence interval [CI] 66.9–75.8) for RP and 62.3% (95% CI 57.4–67.6) for IMRT. IMRT was associated with a 41% increased risk of all-cause mortality (hazard ratio [HR] 1.41, 95% CI 1.13–1.76) but not PCa-specific mortality (HR 1.75, 95% CI 0.84–3.64), as compared to RP. In patients with high-risk PCa, IMRT, as compared to RP, was not associated with a statistically significant difference in all-cause (HR 1.53, 95% CI 0.97–2.42) or PCa-specific mortality (HR 1.92, 95% CI 0.69–5.36).ConclusionsDespite a low mortality rate at 10 years and possible residual confounding, we found a significantly increased risk of all-cause mortality but no PCa-specific mortality associated with IMRT as compared to RP in this population-based study.     

Population-based outcome of muscle-invasive bladder cancer following radical cystectomy: who can benefit from adjuvant chemotherapy?

BackgroundThe benefit of adjuvant chemotherapy remains controversial in muscle-invasive bladder cancer (MIBC) after radical cystectomy. The present study’s primary objective was to construct a predictive tool for the reasonable application of adjuvant chemotherapy.MethodsAll of the patients analyzed in the present study were recruited from the Surveillance Epidemiology and End Results program between 2004 and 2015. Propensity score matching (PSM) was used to reduce inherent selection bias. Cox proportional hazards models were applied to identify the independent prognostic factors of overall survival (OS) and cancer-specific survival (CSS), which were further used to construct prognostic nomogram and risk stratification systems to predict survival outcomes. The prognostic nomogram’s performance was assessed by concordance index (C-index), receiver-operating characteristic (ROC) and calibration curves. Decision curve analysis (DCA) was performed to evaluate the clinical net benefit of the prognostic nomogram.ResultsA total of 6,384 patients with or without adjuvant chemotherapy were included after PSM. Several independent predictors for OS and CSS were identified and further applied to establish a nomogram for 3-, 5- and 10-year, respectively. The nomogram showed favorable discriminative ability for the prediction of OS and CSS, with a C-index of 0.709 [95% confidence interval (CI): 0.699–0.719] for OS and 0.728 (95% CI: 0.718–0.738) for CSS. ROC and calibration curves showed satisfactory consistency. The DCA revealed high clinical positive net benefits of the prognostic nomogram. The different risk stratification systems showed that adjuvant chemotherapy resulted in better OS (P<0.001) and CSS (P<0.001) than without adjuvant chemotherapy for high-risk patients; while the OS (P=0.350) and CSS (P=0.260) for low-risk patients were comparable.ConclusionsWe have constructed a predictive model and different risk stratifications for selecting a population that could benefit from postoperative adjuvant chemotherapy. Adjuvant chemotherapy was found to be beneficial for high-risk patients, while low-risk patients should be carefully monitored.     

Papel de PCA3 y SelectMDx en la optimización de la vigilancia activa en el cáncer de próstata

Introduction and objectivesA not negligible percentage of patients included in active surveillance (AS) for low and very low risk prostate cancer (PCa) are reclassified in the confirmatory biopsy or have disease progression during follow-up. Our aim is to evaluate the role of PCA3 and SelectMDx, in an individual and combined way, in the prediction of pathological progression (PP) in a standard AS program.Materials and methodsProspective and observational study comprised of 86 patients enrolled in an AS program from 2009 to 2019, with results for PCA3 and SelectMDx previous to PCa diagnosis or during their confirmatory period. Univariate and multivariate analysis were performed to correlate PCA3 and SelectMDx scores as well as clinical and pathological variables with PP-free survival (PPFS). The most reliable cut-offs for both biomarkers in the context of AS were defined.ResultsSelectMDx showed statistically significant differences related to PPFS (HR: 1.035; 95% CI: 1.012-1.057) (P = .002) with a C-index of 0.670 (95% CI: 0.529-0.810) and AUC of 0.714 (95% CI: 0.603-0.825) at 5 years. In our series, the most reliable cut-off point for SelectMDx was 5, with a sensitivity and specificity for PP of 69.8% and 67.4%, respectively. Same figure for PCA3 was 65, with a sensitivity and specificity for PP of 51.16% and 74.42%, respectively. The combination of both biomarkers did not improve the prediction of PP, C-index 0.630 (95% CI: 0.455-0.805).ConclusionsIn the context of low or very low risk PCa, SelectMDx > 5 predicted 5 years PP free survival with a moderate discrimination ability outperforming PCA3. The combination of both tests did not improved outcomes.     

The effect of lowering cholesterol through diet on serum prostate-specific antigen levels: A secondary analysis of clinical trials

ImportanceStatins appear to lower serum prostate-specific antigen (PSA) and improve prostate cancer (PCa) outcomes through cholesterol-dependent and independent mechanisms. While dietary modifications have an established role in serum cholesterol reduction, whether diet-driven cholesterol reductions yield similar PCa benefits to that observed with statins is unclear. We aimed to study the effect of dietdriven cholesterol reduction on serum PSA and estimated-PCa risk.MethodsA total of 291 men from six published randomized controlled trials of dietary interventions were included. Men were aged ≥40 years, free of PCa, and had baseline PSA <10.0 ng/mL. Participants received one of four diets (high-fiber, low-glycemic index, low-glycemic load, or cholesterol-lowering) for 8–24 weeks. The primary outcome evaluated the association between change from baseline low-density lipoprotein cholesterol (LDL-C) and PSA. How cholesterol reduction modified PCa risk was estimated using the Prostate Cancer Prevention Trial (PCPT) risk calculator (limited to age ≥55 years, baseline PSA ≥1.0 ng/mL).ResultsBaseline PSA was 0.90 ng/mL (interquartile range [IQR] 0.55–1.60) and LDL-C was 90 mg/dL (IQR 69–125). In multivariate regression, PSA decreased 1.9% (95% confidence interval [CI] 0.55–3.2, p=0.005) per 10% reduction in LDL-C. This regression was greater in men with baseline PSA ≥2.0 ng/mL (−5.4%, 95% CI 2.2–8.6] per 10% LDL-C reduction, p-interaction=0.001). In men with estimable PCPT risk, statin-comparable LDL-C reductions (≥15%) reduced PSA by 12% (p<0.001) and estimated PCa risk by 6.5% (p=0.005).ConclusionsThis is the first study to show that serum cholesterol reduction through dietary interventions significantly lowered serum PSA and estimated PCa risk. Whether cholesterol-lowering diets improve PCa outcomes warrants investigation.     

Identification and validation of a six immune-related gene signature for prediction of biochemical recurrence in localized prostate cancer following radical prostatectomy

BackgroundProstate cancer (PCa) is the second lethal heterogeneous cancer among males worldwide, and approximately 20% of PCa patients following radical prostatectomy (RP) will undergo biochemical recurrence (BCR). This study is aimed to identify the immune-related gene signature that can predict BCR in localized PCa following RP.MethodsExpression profile of genes together with clinical parameters from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus database (GEO) and the immune-related genes from the Molecular Signatures Database v4.0 were applied to construct and validate the gene signature. The Cox regression analyses were conducted to identify the candidate genes and establish the gene signature. To estimate the prognostic power of the risk score, the time-dependent receiver operating characteristic (ROC) analysis and Harrell’s index of concordance (C-index) were utilized. We also established a nomogram to forecast the probability of patients’ survival.ResultsA total of 268 patients from the TCGA and 77 patients from {"type":"entrez-geo","attrs":{"text":"GSE70770","term_id":"70770"}}GSE70770 and six immune-related genes (SCIN, THY1, TBX1, NOTCH4, MAL, BNIP3L) were eventually selected. The Kaplan-Meier analysis demonstrated that patients in the low-risk group had a significantly longer recurrence-free survival (RFS) compared to those in the high-risk group. In the multivariate Cox model, the signature was identified as an independent prognostic factor, which was significantly associated with RFS (TCGA: HR =5.232, 95% CI: 1.762–15.538, P=0.003; {"type":"entrez-geo","attrs":{"text":"GSE70770","term_id":"70770"}}GSE70770: HR =2.158, 95% CI: 1.051–4.432, P=0.036). Moreover, the C-index got improved after incorporating the risk score into original clinicopathological parameters. In addition, the novel nomogram was constructed to better predict the 1-, 3- and 5-year RFS.ConclusionsThis signature could serve as an independent prognostic factor for BCR. Incorporation of our signature into traditional risk classification might further stratify patients with different prognosis, which could assist practitioners in developing clinical decision-making.     

A risk prediction model for acute kidney injury in patients with pulmonary tuberculosis during anti-tuberculosis treatment

BackgroundAcute kidney injury (AKI) is not a rare complication during anti-tuberculosis treatment in some patients with pulmonary tuberculosis (PTB). We aimed to develop a risk prediction model for early recognition of patients with PTB at high risk for AKI during anti-TB treatment.MethodsThis retrospective cohort study assessed the clinical baseline, and laboratory test data of 315 inpatients with active PTB who were screened for predictive factors from January 2019 to June 2020. The elements were analyzed by logistic regression analysis. A nomogram was established by the results of the logistic regression analysis. The prediction model discrimination and calibration were evaluated by the concordance index (C-index), ROC curve, and Hosmer-Lemeshow analysis.ResultsA total of 315 patients with PTB were enrolled (67 patients with AKI and 248 patients without AKI). Seven factors, including microalbuminuria, hematuria, cystatin-C (CYS-C), albumin (ALB), creatinine-based estimated glomerular filtration rates (eGFRs), body mass index (BMI), and CA-125 were acquired to develop the predictive model. According to the logistic regression, microalbuminuria (OR = 3.038, 95%CI 1.168–7.904), hematuria (OR = 3.656, 95%CI 1.325–10.083), CYS-C (OR = 4.416, 95%CI 2.296–8.491), and CA-125 (OR = 3.93, 95%CI 1.436–10.756) were risk parameter, while ALB (OR = 0.741, 95%CI 0.650–0.844) was protective parameter. The nomogram demonstrated good prediction in estimating AKI (C-index= 0.967, AUC = 0.967, 95%CI (0.941–0.984), sensitivity = 91.04%, specificity = 93.95%, Hosmer-Lemeshow analysis SD = 0.00054, and quantile of absolute error = 0.049).ConclusionsMicroalbuminuria, hematuria, ALB reduction, elevated CYS-C, and CA-125 are predictive factors for the development of AKI in patients with PTB during anti-TB treatments. The predictive nomogram based on five predictive factors is achieved good risk prediction for AKI during anti-TB treatments.     

A first step towards a global nomogram to predict disease progression for men on active surveillance

BackgroundSigns of disease progression (28%) and conversion to active treatment without evidence of disease progression (13%) are the main reasons for discontinuation of active surveillance (AS) in men with localised prostate cancer (PCa). We aimed to develop a nomogram to predict disease progression in these patients.MethodsAs a first step in the development of a nomogram, using data from Movembers’ GAP3 Consortium (n=14,380), we assessed heterogeneity between centres in terms of risk of disease progression. We started with assessment of baseline hazards for disease progression based on grouping of centres according to follow-up protocols [high: yearly; intermediate: ~2 yearly; and low: at year 1, 4 & 7 (i.e., PRIAS)]. We conducted cause-specific random effect Cox proportional hazards regression to estimate risk of disease progression by centre in each group.ResultsDisease progression rates varied substantially between centres [median hazard ratio (MHR): 2.5]. After adjustment for various clinical factors (age, year of diagnosis, Gleason grade group, number of positive cores and PSA), substantial heterogeneity in disease progression remained between centres.ConclusionsWhen combining worldwide data on AS, we noted unexplained differences of disease progression rate even after adjustment for various clinical factors. This suggests that when developing a global nomogram, local adjustments for differences in risk of disease progression and competing outcomes such as conversion to active treatment need to be considered.     

Systematic sampling during MRI-US fusion prostate biopsy can overcome errors of targeting—prospective single center experience after 300 cases in first biopsy setting

BackgroundMultiparametric magnetic resonance imaging (mpMRI) and targeted biopsy have become an integral part of the diagnosis of prostate cancer (PCa), as recommended by the European Association of Urology Guidelines. The aim of the current study was to evaluate the performance of MRI and MRI-transrectal ultrasound (TRUS) fusion prostate biopsy as first biopsy setting in a tertiary center.MethodsA cohort of 300 patients was included in the current analysis. All patients presented with clinical or biochemical suspicion of PCa and harbored at least one suspect lesion on mpMRI. MRI-TRUS fusion prostate biopsy, followed by 12 core systematic prostate biopsy were performed by the same operator using a rigid registration system.ResultsThe mean age of the patients was 64 years (IQR: 58–68.5 years) and the mean PSA was 6.35 ng/mL (IQR: 4.84–9.46 ng/mL). Overall cancer and csPCa diagnosis rates were 47% and 40.66%. Overall PCa/csPCa detection rates were 20.4%/11.1%, 52%/45% and 68.5%/66.7% for PI-RADS lesions 3, 4 and 5 (P<0.001/P<0.0001). Larger lesion diameter and lesion volume were associated with PCa diagnosis (P=0.006 and P=0.001, respectively). MRI-TRUS fusion biopsy missed PCa diagnosis in 37 cases (of whom 48.6% ISUP 1) in comparison with 9 patients missed by systematic biopsy (of whom 11.1% ISUP 1). In terms of csPCa, systematic biopsy missed 77.7% of the tumors located in the anterior and transitional areas. The rate of csPCa was highest when targeted biopsy was associated with systematic biopsy: 86.52% vs. 68.79% for targeted biopsy vs. 80.14% for systematic biopsy, P=0.0004. In 60.6% of cases, systematic biopsy was positive for PCa at the same site as the targeted lesion. Of these patients, eight harbored csPCa and were diagnosed exclusively on systematic biopsy.ConclusionsMRI-TRUS fusion prostate biopsy improves the diagnosis of csPCa. The main advantage of an MRI-guided approach is the diagnosis of anterior and transitional area tumors. The best results in terms of csPCa diagnosis are obtained by the combination of MRI-TRUS fusion with systematic biopsy. The systematic biopsy performed during MRI-targeted biopsy could have an important role in overcoming errors of MRI-TRUS fusion systems.     

A nomogram to predict residual cavity formation after thoracoscopic decortication in chronic tuberculous empyema

Open in a separate window OBJECTIVESThe goal of this study was to develop and validate a nomogram for predicting residual cavity formation after video-assisted thoracoscopic decortication in patients with chronic tuberculous empyema (CTE).METHODSWe retrospectively analysed patients who were diagnosed and treated for CTE at our hospital from January 2017 to December 2020. We used univariable and binary logistic regression analyses to identify independent risk factors. A predictive nomogram was developed and validated for predicting the risk of residual cavity formation after video-assisted thoracoscopic decortication in patients with CTE. The receiver operating characteristic (ROC) was used to evaluate the nomogram.RESULTSData from 103 patients were analysed. The contact area between the lung and empyema (P = 0.001, odds ratio [OR] 1.017, 95% confidence interval [CI] 1.007–1.028), calcification (P = 0.004, OR 0.12, 95% CI 0.029–0.501) and thickness of the pleura (P = 0.02, OR 1.315, 95% CI 1.045–1.654) were risk factors for residual cavity formation after video-assisted thoracoscopic decortication. A 50% residual cavity formation rate was used as the cut-off to validate the nomogram model. The area under the ROC curve for the nomogram was 0.891 (95% CI, 0.82–0.963). The sensitivity and specificity of the nomogram were 86.67% and 82.19%, respectively. The calibration curve indicated good consistency between the predicted and actual risks.CONCLUSIONSThe preliminary nomogram could contribute to preventing postoperative residual cavity formation and making appropriate surgical decisions.     

The association between metabolic syndrome and advanced prostate cancer in Chinese patients receiving radical prostatectomy

The global incidence of metabolic syndrome (MetS) is dramatically increasing. Considerable interest has been devoted to the relationship between MetS and prostate cancer (PCa) risk. However, few studies have examined the association between MetS and PCa progression. This retrospective study consisted of 1016 patients with PCa who received radical prostatectomy. The association between MetS and pathological features was evaluated using logistic regression analysis. Compared with patients without MetS, those with MetS indicated an increased risk of prostatectomy Gleason score (GS) ≥8 (odds ratio [OR] =1.670, 95% confidence interval (CI) 1.096–2.545, P= 0.017), and a 1.5-fold increased risk of pT3–4 disease (OR = 1.583, 95% CI 1.106–2.266, P= 0.012). The presence of MetS was an independent predictor of lymph node involvement (OR = 1.751, 95% CI 1.038–2.955, P= 0.036). Furthermore, as the number of MetS components accumulated, the risk of a GS ≥ 8 increased. The present study indicates a significant association between MetS and advanced PCa. The results need to be evaluated in large-scale prospective cohorts.