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Background and objective: Genetic predisposition is a factor in 40–70% of cases of benign prostatic hyperplasia (BPH) and voiding symptoms. However, informal reviews summarizing genes and variants imparting genetic disposition to BPH are not yet available. Methods: We conducted an informal narrative review of genes and variants associated with BPH or voiding symptoms in candidate gene studies, genome-wide association studies (GWAS), and Mendelian randomization studies. A literature search of PubMed was performed using the terms “BPH heritability”, “LUTS heritability”, “BPH risk variant”, “LUTS genetic risk”, “GWAS BPH”, and “genome-wide BPH”. Key findings and limitations: Candidate gene studies focused on variants related to the vitamin D receptor, steroid metabolism, detoxification, inflammation, cytokines, and growth factors, which were previously found to be associated with prostate cancer. Despite overall limited conclusiveness of candidate gene approaches, some recent studies point to population-dependent contributions of single variants to genetic BPH predisposition. Four GWAS and two Mendelian randomization studies for BPH identified correlation of BPH and voiding symptoms with variants related to testosterone, prostate-specific antigen, progesterone, transcription factors, the cell cycle, neuronal organization, and thyroid-stimulating hormone. Conclusions and clinical implications: The drug targetability of most of the genes identified in the BPH setting is precluded by predictable unbalanced side effects, low efficacy, unknown organ specificity, and a lack of characterization in the prostate. Meta-analyses of GWAS are not yet available for BPH. Unless calculated using quantitative approaches, specific contributions of the risk variants identified to the overall risk of BPH remain uncertain. Patient summary: While age is a risk factor for benign enlargement of the prostate in all affected patients, genetic factors may be involved in 39–72% of patients. Research has identified a number of possible risk genes, but is still at a very early stage. It is unlikely that drugs could be used to target these genes because of expected side effects that would be tolerated for cancer treatment, but not for benign diseases, or low efficacy in previous clinical trials.

PURPOSE: The proPSMA trial at ten Australian centers demonstrated increased sensitivity and specificity for PSMA PET/CT compared to conventional imaging regarding metastatic status in primary high-risk prostate cancer patients. A cost-effectiveness analysis showed benefits of PSMA PET/CT over conventional imaging for the Australian setting. However, comparable data for other countries are lacking. Therefore, we aimed to verify the cost-effectiveness of PSMA PET/CT in several European countries as well as the USA. METHODS: Clinical data on diagnostic accuracy were derived from the proPSMA trial. Costs for PSMA PET/CT and conventional imaging were taken from reimbursements of national health systems and individual billing information of selected centers in Belgium, Germany, Italy, the Netherlands, and the USA. For comparability, scan duration and the decision tree of the analysis were adopted from the Australian cost-effectiveness study. RESULTS: In contrast to the Australian setting, PSMA PET/CT was primarily associated with increased costs in the studied centers in Europe and the USA. Mainly, the scan duration had an impact on the cost-effectiveness. However, costs for an accurate diagnosis using PSMA PET/CT seemed reasonably low compared to the potential consequential costs of an inaccurate diagnosis. CONCLUSION: We assume that the use of PSMA PET/CT is appropriate from a health economic perspective, but this will need to be verified by a prospective evaluation of patients at initial diagnosis.

Purpose: This study aims to address therapy-related toxicities and quality of life in prostate cancer patients undergoing transperineal ultrasound (TPUS) guided radiotherapy (RT). Methods: Acute and late gastrointestinal (GI) and genitourinary (GU) toxicities were assessed by physicians using CTCAE v5.0. Patient-reported quality of life outcomes were evaluated using EORTC QLQ-C30, -PR25 and IPSS. We utilized Volumetric Modulated Arc Therapy (VMAT) or intensity modulated radiation therapy (IMRT) as the RT technique for this study. The assessments were carried out before RT, at RT end, 3 months after RT and subsequently at 1-year intervals. Prostate-specific antigen (PSA) was also evaluated at each follow-up. Results: In this study, a total of 164 patients were enrolled, while among them, 112 patients delivered quality-of-life data in a prospective evaluation. The median pre-treatment PSA was 7.9 ng/mL (range: 1.8–169 ng/ml). At the median follow-up of 19 months (3–82 months), the median PSA decreased to 0.22 ng/ml. Acute grade II GI and GU toxicities occurred in 8.6 % and 21.5 % patients at RT end. Regarding late toxicities, 2.2 % patients experienced grade II GI toxicities at 27 months and only one patient at 51 months, whereas no grade II GU late toxicities were reported at these time points. Quality of life scores also indicated a well-tolerated treatment. Patients mainly experienced acute clinically relevant symptoms of fatigue, pain, as well as deterioration in bowel and urinary symptoms. However, most symptoms normalized at 3 months and remained stable thereafter. Overall functioning showed a similar decline at RT end but improved over time. Conclusion: The outcomes of TPUS-guided RT demonstrated promising results in terms of minimal physician-reported toxicities and satisfactory patient-reported QoL.

Abstract Predictors of rebound after correction of coronal plane deformities using temporary hemiepiphysiodesis (TH) are not well defined. The following research questions were tested: (1) Is the dynamic knee joint load useful to improve rebound prediction accuracy? (2) Does a large initial deformity play a critical role in rebound development? (3) Are BMI and a young age risk factors for rebound? Fifty children and adolescents with idiopathic knee valgus malalignment were included. A deviation of the mechanical femorotibial angle (MFA) of ≥ 3° into valgus between explantation and the one-year follow-up period was chosen to classify a rebound. A rebound was detected in 22 of the 50 patients (44%). Two predictors of rebound were identified: 1. reduced peak lateral knee joint contact force in the first half of the stance phase at the time of explantation (72.7% prediction); 2. minor initial deformity according to the MFA (70.5% prediction). The best prediction (75%) was obtained by including both parameters in the binary logistic regression method. A TH should not be advised in patients with a minor initial deformity of the leg axis. Dynamic knee joint loading using gait analysis and musculoskeletal modeling can be used to determine the optimum time to remove the plates.