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We attempted to assess the performance of an ethnic-specific polygenic risk score (PRS) designed from a Korean population to predict aggressive prostate cancer (PCa) and early-onset (age < 60). A PRS score comprised of 22 SNPs was computed in 3695 patients gathered from one of 4 tertiary centers in Korea. Males with biopsy or radical prostatectomy-proven PCa were included for analysis, collecting additional clinical parameters such as age, BMI, PSA, Gleason Group (GG), and staging. Patients were divided into 4 groups of PRS quartiles. Intergroup differences were assessed, as well as risk ratio and predictive performance based on GG using logistic regression analysis and AUC. No significant intergroup differences were observed for BMI, PSA, and rate of ≥ T3a tumors on pathology. Rate of GG ≥ 2, GG ≥ 3, and GG ≥ 4 showed a significant pattern of increase by PRS quartile (p < 0.001, < 0.001, and 0.039, respectively). With the lowest PRS quartile as reference, higher PRS groups showed sequentially escalating risk for GG ≥ 2 and GG ≥ 3 pathology, with a 4.6-fold rise in GG ≥ 2 (p < 0.001) and 2.0-fold rise in GG ≥ 3 (p < 0.001) for the highest PRS quartiles. Combining PRS with PSA improved prediction of early onset csPCa (AUC 0.759) compared to PRS (AUC 0.627) and PSA alone (AUC 0.736). To conclude, an ethnic-specific PRS was found to predict susceptibility of aggressive PCa in addition to improving detection of csPCa when combined with PSA in early onset populations. PRS may have a role as a risk-stratification model in actual practice. Large scale, multi-ethnic trials are required to validate our results. [ABSTRACT FROM AUTHOR]

Objective: Despite efforts to improve screening and early detection of prostate cancer (PC), no available biomarker has shown acceptable performance in patients with prostate-specific antigen (PSA) gray zones. We aimed to develop a deep learning-based prediction model with minimized parameters and missing value handling algorithms for PC and clinically significant PC (CSPC).Materials and Methods: We retrospectively analyzed data from 18 824 prostate biopsies collected between March 2003 and December 2020 from 2 databases, resulting in 12 739 cases in the PSA gray zone of 2.0-10.0 ng/mL. Dense neural network (DNN) and extreme gradient boosting (XGBoost) models for PC and CSPC were developed with 5-fold cross-validation. The area under the curve of the receiver operating characteristic (AUROC) was compared with that of serum PSA, PSA density, free PSA (fPSA) portion, and prostate health index (PHI).Results: The AUROC values in the DNN model with the imputation of missing values were 0.739 and 0.708 (PC) and 0.769 and 0.742 (CSPC) in internal and external validation, whereas those of the non-imputed dataset were 0.740 and 0.771 (PC) and 0.807 and 0.771 (CSPC), respectively. The performance of the DNN model was like that of the XGBoost model, but better than all tested clinical biomarkers for both PC and CSPC. The developed DNN model outperformed PHI, serum PSA, and percent-fPSA with or without missing value imputation.Discussion: DNN models for missing value imputation can be used to predict PC and CSPC. Further validation in real-life scenarios are need to recommend for actual implementation, but the results from our study support the increasing role of deep learning analytics in the clinical setting.Conclusions: A deep learning model for PC and CSPC in PSA gray zones using minimal, routinely used clinical parameter variables and data imputation of missing values was successfully developed and validated. [ABSTRACT FROM AUTHOR]

Aims: The purpose of this study is to evaluate an aggregate influence of prostate cancer (PCa) susceptibility variants on the development of PCa in Korean men by using the polygenic risk score (PRS) approach. Methods: An analysis of 1,001 cases of PCa and 2,641 controls was performed to: (i) identify potential PCa-related risk loci in Koreans and (ii) validate the cumulative association between these loci and PCa using the PRS. Subgroup analyses based on risk stratification were conducted to better characterize the potential correlation to key PCa-related clinical outcomes (e.g., Gleason score, prostate-specific antigen levels). The results were replicated using 514 cases of PCa and 548 controls from an independent cohort. Results: Genome-wide association analysis from our discovery cohort revealed 11 candidate single-nucleotide polymorphisms (SNPs) associated with PCa showing statistical significance of p < 5.0 × 10–5. Seven variants were located at 8q24.21 (rs1016343, rs16901979, and rs13252298 in PRNCR1 ; rs4242384, rs7837688, and rs1447295 in CASC8 ; and rs1512268 in NKX3). Two variants located within HNF1B (rs7501939 and rs4430796) had a significant negative association with PCa risk [odds ratio (OR) = 0.717 and 0.747, p = 6.42 × 10–7 and 3.67 × 10–6, respectively]. Of the six independent SNPs that remained after linkage disequilibrium (LD) pruning, the top four SNPs best predicted PCa risk with an area under the receiver operating characteristic curve (AUC) of 0.637 (95% CI: 0.582–0.692). Those with top 25% polygenic risk had a 4.2-fold increased risk of developing PCa compared with those with low risk. Conclusion: Eleven PCa risk variants in Korean men were identified; PRSs of a subset of these variants could help predict PCa susceptibility. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the effect of 5 alpha-reductase inhibitor (5-ARI) treatment on prostate cancer (PCa) and clinically significant PCa (csPCa) detection in patients undergoing transrectal ultrasound (TRUS)/magnetic resonance imaging (MRI) fusion biopsy in the current era of multi-parametric MRI (mpMRI). We retrospectively reviewed our TRUS/MRI fusion biopsy database (n = 706). Eighty (11.3%) patients who had used 5-ARI for more than one year at the time of biopsy were stratified as 5-ARI group. Subsequently, we performed comparative analyses of 5-ARI and non-5-ARI groups. csPCa was defined by a Gleason score ≥3 + 4 in a single biopsy core. Chi-squared test was used to evaluate the performance of mpMRI in predicting PCa/csPCa between the two groups. Multivariate logistic regression analyses were performed to evaluate the significant variables associated with PCa detection. There were no significant differences in PCa/csPCa detection rates between 5-ARI and non-5-ARI groups (all, P > 0.05). In multivariate logistic regression analyses for the evaluation of variables associated with csPCa detection, age (odds ratio [OR], 1.062; 95% confidence interval [CI], 1.035–1.090; P < 0.001), pre-biopsy PSA (OR, 1.062; 95% CI, 1.034–1.090; P < 0.001), prostate volume on TRUS (OR, 0.956; 95% CI, 0.943–0.970, P < 0.001), and PI-RADsV2 category (OR, 5.528; 95% CI, 3.017–10.131; P < 0.001) were found to be significant predictors. However, 5-ARI had no significant association with PCa detection (P = 0.384). Conclusively, 5-ARI therapy did not adversely affect PCa/csPCa detection after TRUS/MRI fusion biopsy, which suggests that exposure to 5-ARI may not impair the performance of mpMRI. [ABSTRACT FROM AUTHOR]

Purpose: There have been conflicting reports regarding the association of perioperative blood transfusion (PBT) with oncologic outcomes including recurrence rates and survival outcomes in prostate cancer. We aimed to evaluate whether perioperative blood transfusion (PBT) affects biochemical recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS) following radical prostatectomy (RP) for patients with prostate cancer. Materials and Methods: A total of 2,713 patients who underwent RP for clinically localized prostate cancer between 1993 and 2014 were retrospectively analyzed. We performed a comparative analysis based on receipt of transfusion (PBT group vs. no-PBT group) and transfusion type (autologous PBT vs. allogeneic PBT). Univariate and multivariate Cox-proportional hazard regression analysis were performed to evaluate variables associated with BRFS, CSS, and OS. The Kaplan-Meier method was used to calculate survival estimates for BRFS, CSS, and OS, and log-rank test was used to conduct comparisons between the groups. Results: The number of patients who received PBT was 440 (16.5%). Among these patients, 350 (79.5%) received allogeneic transfusion and the other 90 (20.5%) received autologous transfusion. In a multivariate analysis, allogeneic PBT was found to be statistically significant predictors of BRFS, CSS, and OS; conversely, autologous PBT was not. The Kaplan-Meier survival analysis showed significantly decreased 5-year BRFS (79.2% vs. 70.1%, log-rank, p = 0.001), CSS (98.5% vs. 96.7%, log-rank, p = 0.012), and OS (95.5% vs. 90.6%, log-rank, p < 0.001) in the allogeneic PBT group compared to the no-allogeneic PBT group. In the autologous PBT group, however, none of these were statistically significant compared to the no-autologous PBT group. Conclusions: We found that allogeneic PBT was significantly associated with decreased BRFS, CSS, and OS. This provides further support for the immunomodulation hypothesis for allogeneic PBT. [ABSTRACT FROM AUTHOR]

Study Type - Prognosis (cohort series) Level of Evidence 2b What's known on the subject? and What does the study add? This study reports that patients aged 70 years or older have a higher possibility of locally advanced cancer than younger patients. Instead of conservative management, radical eradication of clinically localized prostate cancer should be actively considered in well-selected healthy patients older than 70 years. OBJECTIVE To analyse the differences in the clinicopathological results between two groups of Korean patients aged younger or older than 70 years with clinically localized prostate cancer., METHODS A cohort of consecutive male patients who underwent radical prostatectomy was retrospectively analysed. In total, 995 patients (74.6%) were younger than 70 years, and 338 patients (25.4%) were 70 years or older., Biochemical recurrence (BCR) -free survival was evaluated in the patients, who were followed up for more than 24 months., The Kaplan-Meier method was used to calculate survival estimates for BCR-free survival. Multivariate Cox proportional hazard regression analysis was performed to predict non-organ-confined status and BCR., RESULTS Mean preoperative prostate-specific antigen (PSA) levels and biopsy or pathological Gleason scores showed no differences between the two age groups., Older patients, aged more than 70 years, displayed significantly higher risk of locally advanced prostate cancer and BCR than younger patients., Subgroup analysis showed that the risk of the presence of locally advanced disease was significantly increased in patients of 70 years or older when we compared the proportion of locally advanced disease only in patients with PSA <4 ng/mL., Multivariate analysis showed that old age, high PSA and high Gleason score were significantly associated with non-organ confined status and BCR., CONCLUSIONS Patients aged 70 years or older had a higher possibility of locally advanced cancer than younger patients., Radical eradication of clinically localized prostate cancer should be actively considered in well-selected healthy patients older than 70 years. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the risk of concordant cancers in patients with prostate cancer (CaP) and examine whether this risk differed according to family history of CaP.Materials and Methods: We examined 1,102 patients with CaP , having prospectively acquired pedigrees, and analyzed information regarding multiple primary cancers. The prevalence of concordant cancers was assessed with respect to the family history of CaP . First-degree familial CaP was defined as a positive history of CaP in first-degree relatives (parents, siblings, and offspring). Odds ratios for each concordant cancer in men with first-degree familial CaP were estimated. Clinical characteristics were compared between men with and without concordant cancers.Results: The prevalence of multiple primary cancers in sporadic PCa was 12.0%, similar to that of first-degree familial CaP (13.5%, P = 0.698). Gastrointestinal cancer was the most common concordant cancer (3.6%), followed by colorectal (2.9%), lung (1.5%), urothelial (1.3%), kidney (1.1%), and other cancers. Colorectal cancer was more frequent in first-degree familial CaP than in sporadic disease (6.8 vs. 2.7%, P = 0.045). However, the rates of other concordant cancers were similar between the 2 groups (P range, 0.242-0.963). Compared with sporadic disease, the age-adjusted odds ratio for concordant colorectal cancer in first-degree familial CaP was 2.930 (95% confidence interval, 1.082-7.929). Patients with concordant colorectal cancer had fewer (2.8 vs. 3.9 cores, P = 0.041) and a lower percentage of (23.5 vs. 33.1%, P = 0.030) positive biopsy cores than CaP only patients.Conclusions: A family history of CaP was significantly associated with a risk of concordant colorectal cancer. These findings imply that some CaP shares a genetic pathogenesis with colorectal cancer. [ABSTRACT FROM AUTHOR]