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Importance: Prostate magnetic resonance imaging (MRI) is increasingly integrated within the prostate cancer (PCa) early detection pathway., Objective: To systematically evaluate the existing evidence regarding screening pathways incorporating MRI with targeted biopsy and assess their diagnostic value compared with prostate-specific antigen (PSA)-based screening with systematic biopsy strategies., Data Sources: PubMed/MEDLINE, Embase, Cochrane/Central, Scopus, and Web of Science (through May 2023)., Study Selection: Randomized clinical trials and prospective cohort studies were eligible if they reported data on the diagnostic utility of prostate MRI in the setting of PCa screening., Data Extraction: Number of screened individuals, biopsy indications, biopsies performed, clinically significant PCa (csPCa) defined as International Society of Urological Pathology (ISUP) grade 2 or higher, and insignificant (ISUP1) PCas detected were extracted., Main Outcomes and Measures: The primary outcome was csPCa detection rate. Secondary outcomes included clinical insignificant PCa detection rate, biopsy indication rates, and the positive predictive value for the detection of csPCa., Data Synthesis: The generalized mixed-effect approach with pooled odds ratios (ORs) and random-effect models was used to compare the MRI-based and PSA-only screening strategies. Separate analyses were performed based on the timing of MRI (primary/sequential after a PSA test) and cutoff (Prostate Imaging Reporting and Data System [PI-RADS] score ≥3 or ≥4) for biopsy indication., Results: Data were synthesized from 80 114 men from 12 studies. Compared with standard PSA-based screening, the MRI pathway (sequential screening, PI-RADS score ≥3 cutoff for biopsy) was associated with higher odds of csPCa when tests results were positive (OR, 4.15; 95% CI, 2.93-5.88; P ≤ .001), decreased odds of biopsies (OR, 0.28; 95% CI, 0.22-0.36; P ≤ .001), and insignificant cancers detected (OR, 0.34; 95% CI, 0.23-0.49; P = .002) without significant differences in the detection of csPCa (OR, 1.02; 95% CI, 0.75-1.37; P = .86). Implementing a PI-RADS score of 4 or greater threshold for biopsy selection was associated with a further reduction in the odds of detecting insignificant PCa (OR, 0.23; 95% CI, 0.05-0.97; P = .048) and biopsies performed (OR, 0.19; 95% CI, 0.09-0.38; P = .01) without differences in csPCa detection (OR, 0.85; 95% CI, 0.49-1.45; P = .22)., Conclusion and Relevance: The results of this systematic review and meta-analysis suggest that integrating MRI in PCa screening pathways is associated with a reduced number of unnecessary biopsies and overdiagnosis of insignificant PCa while maintaining csPCa detection as compared with PSA-only screening.

Genetic testing for prostate cancer (PC) is becoming more widely used in the clinical routine, primarily due to the introduction of PARP inhibitors targeting genetically affected patients in their BRCA1/2 and other homologous recombination repair (HRR) genes. Simultaneously, the number of available therapies that are specifically targeting genetically defined PC subgroups is steadily increasing. As a result, the selection of treatment for PC patients is likely to require testing of multiple genes to enable more specific treatment sequences that consider the genetic characteristics of the tumor. Some of the mutations discovered by genetic testing may be hereditary, necessitating the use of germline testing from normal tissue, which is only permitted within the framework of clinical counseling. This change in PC care requires the collaboration by multiple specialists, including experts in molecular pathology, bioinformatics, biology, and genetic counseling. In this review, we aim to provide an overview on the currently relevant genetic alterations in PC for therapeutic purposes and their implications for familial testing.

Prostate cancer is one of the most significant cancers among men. In addition to epidemiological and etiological data, this summary provides a description of the most important features of prostate specific antigen, used most, and other markers that can make easier to diagnose the disease. It presents the major international and Hungarian studies dealing with prostate cancer screening, including the economic aspects. Genetic tests, DNA- and RNAbased biomarkers are gaining more and more space, they can even help us in screening and avoiding overdiagnosis. The main goal of the future researches should be to develop methods that can be used to detect prostate cancer at an early, curable stage.

Összefoglaló. A sérült BRCA1/2 gént hordozó prosztatadaganatok klinikai szempontból elkülönülő, agresszív altípust képviselnek. Ugyanakkor a BRCA1/2 gén sérülése a DNS-támadáspontú kemoterápiákkal szemben érzékennyé teszi a daganatot, ami terápiás szempontból kihasználható. A platinaalapú kemoterápia hatékonysága prosztatarákban klinikai vizsgálatokkal nincs alátámasztva, ezért annak alkalmazására igen ritkán kerül sor. Közleményünkben egy előrehaladott stádiumú, agresszív prosztata adenocarcinomával diagnosztizált beteg esetét mutatjuk be, akinél a BRCA2-gén patogén mutációját találtuk, és akinél az előzőleg alkalmazott androgénmegvonásos, valamint docetaxelkezelések sikertelensége miatt karboplatinkezelést alkalmaztunk - ez a beteg állapotának, valamint radiológiai és biokémiai paramétereinek látványos javulásához vezetett. Ez az eset rámutat a DNS-hiba-javító mechanizmusban szerepet játszó gének terápiás szempontból történő felhasználásának potenciális előnyeire prosztatarákban. Orv Hetil. 2021; 162(25): 1004-1008. Summary. BRCA1/2 deficient prostate cancers represent a clinically distinct aggressive subtype. However, the presence of BRCA1/2 alterations enhance the sensitivity to platinum-based chemotherapies. The efficacy of platinum-based chemotherapies in prostate cancer has not been proven in prospective clinical studies and therefore these treatments are rarely used in prostate adenocarcinomas. Here we present a case of BRCA2 mutant prostate cancer, which was diagnosed at a metastatic stage and showed no or only little response to androgen deprivation and docetaxel therapies. Therefore, we started carboplatin chemotherapy which resulted in an exceptional response regarding biochemical, radiographic parameters accompanied by significant improvement of patients' physical condition. This case underlines the potential therapeutic benefits of testing for genes involved in the DNA repair mechanism. Orv Hetil. 2021; 162(25): 1004-1008.

Introduction: The past decade has seen some major changes in the diagnostics of prostate cancer. Progress in MR imaging has allowed us to better visualise prostate cancer and thus perform targeted biopsies of tumour suspect lesions. mpMRI-ultrasound fusion-guided prostate biopsy is a precise and cost-effective method to diagnose prostate cancer. Objective: The purpose of this study was to summarise our results in mpMRI-ultrasound fusion biopsy between 2017 and 2019 and compare them with the findings in the current literature. Method: Between 2017 and 2019, fully 40, mpMRI-ultrasound fusion biopsies were performed transperineally using the BioJet fusion system at Semmelweis University Urology Clinic. The MRI evaluations were done in line with the PI-RADS v2 guidelines. It was analysed whether the PI-RADS score, the location of the tumour, lesion size, the signs of extraprostatic extension, PSA/PSAD density and prostate volume have an influence on the outcome of mpMRI-ultrasound fusion biopsy. Results: Prostate cancer was diagnosed in 80% of the cases during targeted biopsies. The detection rate was 91%, 85%, and 20% for PI-RADS 5, 4 and 3 lesions, respectively. The detection rate was significantly higher for lesions located at the peripheral zone compared to the ones in the transitional zone (khi2(1) = 6.555, p = 0.010, Fisher-exact p = 0.017, V = 0.355). Signs of extraprostatic extension and higher PSAD correlated with better detection rate (khi2(1)= 7.704, p = 0.006, Fisher-exact p = 0.004, V = 0.355; and 0.47 ± 0.50 ng/ml2 vs. 0.18 ± 0.17 ng/ml2; Z = 3.447, p<0.001, respectively). The size of the lesions did not influence the outcome. The analysis showed a significant correlation between large prostate volumes and negative biopsies (50.9 ± 18.8 ml vs. 119.6 ± 91.6 ml; Z= –3.505, p<0.001). Conclusions: The detection rate of prostate cancer with targeted biopsies was higher than the data found in the international literature. The PI-RADS score, the location of the tumour, MRI signs of extraprostatic extension, PSAD and prostate volume had an influence on the detection rate. Our findings may promote a better selection of the best candidates for targeted biopsies in the future.

Prostate cancer is one of the most commonly diagnosed malignant neoplasms. In Hungary, 4000-4500 men are diagnosed annually, which is below the European incidence. In contrast, the Hungarian prostate cancer mortality clearly exceeds the EU average. This is probably due to the lack of awareness and early recognition of prostate cancer. At an early stage, prostate cancer can be cured, 5-year survival is almost 100%, while in metastatic form it is only 28%. There are several treatment options available for prostate cancer. Since it is multiplex within the organ and the cancer foci are histopathologically heterogeneous, only the treatment of the whole prostate is curative. Radical prostatectomy is the only curative treatment that can provide a complete healing and increased life expectancy in men with prostate cancer. It is recommended to be performed in men with a life expectancy of at least 10 years. During surgery, the prostate is removed, along with its capsule, seminal vesicles on both sides and pelvic lymph nodes. During surgery, the urinary continence and, if possible, erectile function should be preserved.

In the last few years, the emergence of new high throughput molecular technologies allowed a never-before-seen insight into the genetic, epigenetic, transcriptomic and proteomic background of cancers. These studies have been performed in a large number of patients' samples and provided a great amount of data. Current efforts to translate these new findings into therapeutic strategies are ongoing, but already provided significant information which may change clinical practice in the near future. As a result of this development, the most frequent molecular alterations and affected pathways responsible for the formation and progression of prostate cancer have been identified. In this review, we provide an overview on the current progress in primary and metastatic prostate cancer research focusing on the molecular subtype classification and the most frequently dysregulated pathways, such as androgen signaling, PI3K pathway, cell cycle and DNA repair regulation. In this context, we highlight therapies already approved or are currently under clinical investigation for prostate cancer. Orv Hetil. 2019; 160(7): 252-263.

Vitamin D 3 supplementation has a beneficial effect on cancerous patients, although it can influence the redox- and metal homeostasis. The aim of our investigation was to demonstrate the effect of vitamin D 3 consumption on the redox- and metal homeostasis in prostate cancer, because of the recommended daily dose increased from 200 IU to 2000 IU in recent years in Hungary. Forty-three volunteers were involved in the study. The grouping was applied according to the clinical routine laboratory parameters (vitamin D 3 ) and the tumor markers (PSA, fPFA). Patients were divided into 5 groups: (A) patient control (N = 8), (B) patient control with vitamin D 3 treatment (N = 9), (C) high-risk prostate cancer group (N = 6), (D) high-risk prostate cancer group with vitamin D 3 treatment (N = 8) and (E) vitamin D 3 treated cancerous group with androgen deprivation therapy (N = 11). The element concentrations were determined with ICP-OES. Among the redox parameters, free radical scavenging capacity and H-donating ability were determined with luminometry and spectrometry. Vitamin D 3 treatment caused differences in the metal- and redox homeostasis in either patient control and cancerous groups. The concentration of Fe, Cr, and Pb significantly increased in the erythrocytes of prostate cancer patients. According to the higher scavenging capacity by vitamin D 3 treatment, it seems that vitamin D 3 helps to equilibrate the redox homeostasis that could affect the outcome of cancer positively. However, the tendency in the metal element status does not give a clear explanation of cancer's outcome, but the accumulation of Pb by vitamin D 3 supplementation needs to be taken into more serious consideration in set terms of occupational diseases., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Purpose: There is a rising interest in measuring the societal burden of malignancies including prostate cancer. However, population-based studies reporting incidence costs of prostate cancer in the long term are lacking in Europe. The objectives of the study are to analyse the long-term costs and survival of prostate cancer patients treated by radical prostatectomy (RP) or conservative management (nRP)., Methods: A retrospective claims data analysis of the National Health Insurance Found Administration of Hungary between 01.01.2002 and 31.10.2013 was carried out. Annual incidence costs related to prostate cancer and overall survival were calculated for a cohort of patients diagnosed between 2002 and 2005., Results: Altogether 17,642 patients were selected; 2185 (12%) of them have undergone RP. The annual incidence rate ranged between 4177 and 4736 cases. Mean age of RP and nRP patients was 59.4 (SD 5.9) and 71.0 (8.4) years, respectively. The mean survival time of the RP patients was significantly longer compared to nRP patients both in the total sample (11.2 vs. 7.4 years; p < 0.001) and in the subgroup <70 years (11.3 vs. 8.8 years; p < 0.001). At the end of the 12-year follow-up, RP patients had a higher (0.83 vs. 0.68), while nRP patients had a slightly lower (0.35 vs. 38) probability of being alive compared with the age-matched general male population. The long-term cumulative costs of the RP and nRP patients amounted to €4448 and €8616. The main driver of the cost difference was the high drug costs in the nRP group., Conclusions: To our knowledge, this study applied the longest time-window in reporting population-based incidence costs in Europe. We found that not only RP patients lived longer but they had significantly lower total long-term costs than nRP patients. Therefore, radical prostatectomy is a cost-effective strategy in prostate cancer.

Better prognostication of clinically localized prostate cancer (PCA) is urgently needed. Former studies using different study end-points provided controversial results regarding the prognostic value of serum chromogranin A (CGA) in clinically localized PCA. However, serum CGA was not tested for correlation with the most significant study end-point of long-term disease-specific survival (DSS). CGA and matrix metalloproteinase-7 (MMP7) levels were measured by the BRAHMS KRYPTOR in two independent patient groups with 127 serum and 110 plasma samples. CGA and MMP7 concentrations were correlated with clinicopathological and survival data. In addition, we tested the combinations of CGA with PSA and with a currently identified prognostic factor, MMP7, for their prognostic value. CGA concentrations were significantly elevated in advanced compared to clinically localized cases both in serum and plasma samples (45 vs. 23 ng/ml, p < 0.001 and; 41 vs. 22 ng/ml; p = 0.002 respectively). In accordance, high CGA levels were correlated with poor DSS. In clinically localized cases, CGA levels alone were not prognostic, but its dichotomized combinations with PSA or MMP7 were independently associated with DSS (HR: 4.88, 95% CI: 1.35-17.71, p = 0.016, HR: 7.46, 1.65-33.63, p = 0.009, respectively). Elevated serum CGA levels in progressed PCA and its prognostic value suggest a potential for CGA in disease monitoring. Our results revealed no independent prognostic value for CGA as a single serum marker in clinically localized cases. However, when combining with PSA or MMP7, CGA may improve both marker's performance in distinguishing between clinically significant and indolent PCAs.

Objective: The majority of prostate cancers require androgen hormones for growth, and androgen ablation is an important part of the systemic treatment of advanced prostate cancer. Nevertheless, most of these cancers eventually relapse as they become less sensitive to androgen ablation and anti-androgen treatment. Elucidating the molecular events that are responsible for the conversion of androgen-sensitive cancers to androgen-refractory tumors may reveal new therapeutic opportunities., Methods: In the present study, we investigated nine androgen-sensitive and nine androgen-refractory prostate cancer samples to evaluate the expression levels of 10 selected proteins that have been implicated in oncogenesis and cancer progression., Results: Our immunohistochemical data show that three of the investigated proteins (i.e., minichromosome maintenance-2, methylguanine-DNA methyltransferase, and androgen receptor) are expressed at significantly different levels in the androgen-refractory cancer samples than in the androgen-sensitive tumors, whereas the expression levels of the seven other studied proteins (i.e., β-catenin, p27, p21, p16, Ki67, hypoxia-inducible factor 1 alpha, and geminin) are not significantly different regarding the two groups., Conclusions: Our data suggest that the increased expression of minichromosome maintenance-2 and decreased expression of methylguanine-DNA methyltransferase related to androgen receptor are indicative of the androgen-refractory stage in prostate cancer. Further studies are required to determine whether these expression changes play a causative role in the transition of androgen-sensitive to androgen-refractory prostate cancer.

The optimal oncological result of radical prostatectomy (RP) is complete removal of the prostate gland and seminal vesicles with negative surgical margins. Preoperative diagnostic biopsies are examined and reported by the pathologist according to standardized rules. Staging of the disease is based on modern preoperative image analysis, most commonly multiparametric MRI. Pathological assessment and reporting of RP specimens is based on the International Society of Uropathology guidelines issued by the 2009 Consensus Conference. Positive surgical margin (PSM) is reported by the pathologist in approximately 1/3rd of RP cases. PSM increases the risk of biochemical, local and systemic progression. Pseudo-whole mount assessment of these specimens is the basis for radio-pathological correlation, thus providing quality control for preoperative MRI as well as assisting preoperative image analysis, sampling and diagnostic workup.

Introduction: Prostate cancer, the most frequent malignant disease in males in Europe, accounts for a great proportion of health expenditures., Aim: A systematic review of registry-based studies about the cost-of-illness and related factors of prostate cancer, published in the last 10 years., Method: A MEDLINE-based literature review was carried out between January 1, 2003 and October 1, 2013., Results: Fifteen peer-reviewed articles met the criteria of interest. In developed countries radiotherapy, surgical treatment and hormone therapy account for the greatest per capita costs. In Europe early stage tumours (4-7000 €, 2006), while in the USA metastatic prostate cancer (19 900-25 500 $, 2004) was associated with highest per capita expenses. In Europe the greatest costs incurred within the initial treatment (6400 €/6 months, 2008), while in the USA within the end-of-life care (depending on age: 62 200-93 400 $, 2010)., Conclusions: Despite public health importance of prostate cancer, the cost-of-illness literature from Europe is relatively small.

Purpose: The main objective of this retrospective study was to evaluate the influence of pathological experience in histological examination of prostate cancer (PCa) on preoperative understaging (UNS), undergrading (UNG), and upgrading (UPG)., Methods: Histopathological data of prostate biopsy (PB) and radical prostatectomy (RP) specimens of patients undergoing subsequent radical prostatectomy (n = 430) in our center were compared. Histological diagnoses of PB were provided either by corresponding academic pathology institute (Group 1: 322 patients) or by external (nonacademic) departments which had a lower number (≤ 100/year) of PCa histopathological evaluations (Group 2 108 patients). The rate of UNG, UPG, and UNS in both groups and also the effects of institutional learning curve were analyzed in terms of grading and staging., Results: Significant difference was detected between Group 1 and Group 2 in average preoperative Gleason score (GS) values and in the rate of well, moderately, and poorly differentiated cancers as well. There was also a significant difference in the rate of UNG (29.1 vs. 56.5 %, p < 0.0001). The mean preoperative and postoperative GS in Group 1 was significantly lower in the first 50 than in the last 50 patients, but the rates of UNG, UPG, and UNS did not differ significantly between the groups., Conclusions: The experience of pathologists has direct influence on grading concordance and on UNG and UPG, between PB and RP specimen; however, it has no significant effect on complete preoperative understaging. The bigger pathological experience improves the sensitivity of the histological diagnostic process.

Purpose: Following patients after prostatectomy can be expensive and stressful, therefore, a novel and reliable approach to improve stratification is needed both at diagnosis of PCa and following its treatment. We evaluate the association of both ERG and claudin-4, claudin-5, and beta-catenin expression in tumor tissues of patients with organ-confined and advanced prostatic adenocarcinomas., Methods: A total of 30 patients were included in the study. Nine men who underwent radical prostatectomy for organ-confined (pT2N0M0) cancer (OCC), 10 patients with clinically advanced cancer (CAC), and 11 controls with benign prostatic hypertrophy (BPH). Using immunohistochemistry applied to tissue microarrays, each group was evaluated for beta-catenin, claudin-4, claudin-5, and ERG expression., Results: The expression of ERG was higher in the CAC group when compared to OCC and BPH (p = 0.7684, p = 0.0224, respectively). Among these patients, 5 from the CAC (45 %) and 5 from the OCC group (56 %) stained positively for ERG (p = 1.0). The mean staining score for those with ERG+ advanced cancer was greater than that for the ERG+ organ-confined cancer (p = 0.0209). ERG staining correlated with Gleason score (Pearson's correlation: 0.498, p = 0.0051), but not with serum PSA level (Pearson's correlation: 0.404, p = 0.1202). When analyzing outcome data, high ERG expressing tumors have shown a significantly worse overall survival (p = 0.0084)., Conclusions: Our results of presence or absence of claudin-4 and claudin-5 and ERG staining intensities suggest their potential as prognostic factors for prostate cancer.

Unlabelled: Several reports are known about the effects of nutrition supplements in the improvement of quality of life of patients with tumor, however, the physiological background remains largely unknown. Table beet affects numerous biochemical reactions, enzymes and metabolic-synthesis., Methods: Natural table beet product come from commercial service was given twice 10 g daily for 1 month for 24 patients (mean age 68+/-8 years) with hormone-resistant and metastatic prostate cancer treated with taxan chemotherapy, who report themselves first, mean 3,6+/-2,8 years ago with their complains. 18 men's data were amenable after treatment for evaluation. In addition to routine laboratory examination values of HbA1c, 9 cytokines and levels of 3 growth factors, the global parameters of redox-homeostasis, few elements of their metal-ions, Zn- and level of free protoporfirin, trans-metilating processes before and 1 month after treatment were determined., Results: In most of the patients, favorable impact of beet was enforced and significantly high levels of Zn- and free protoporfirin decreased; furthermore, trans-metilating processes fastened., Conclusions: According to results, it seems that moderate and permanent consumption of table beet product affects the life expectancy of patients favorably; however, due to the increasing values of EGF, medical control is necessary for patients with prostate cancer treated by chemotherapy.

Objective: To investigate the patterns of expression of the junctional proteins beta-catenin and claudins in different prognostic groups of patients with prostatic cancer, to determine their value as prognostic markers., Patients and Methods: We evaluated the samples of 30 patients who had a radical prostatectomy for organ-confined cancer (pT2N0M0), men with clinically advanced cancer, and a control group with benign prostatic hyperplasia. Using immunohistochemistry applied to tissue microarrays, each group was evaluated for claudin-1, -2, -3, -4, -5, -7, -8 and -10, and beta-catenin expression., Results: There were differences among the three groups in the expression of claudin-1 (P = 0.001), -2 (P = 0.014), -3 (P = 0.027), -4 (P = 0.001), -8 (P = 0.001) and beta-catenin (P = 0.002), regardless of Gleason score. By contrast, claudin-5, -7 and -10 patterns were not significantly different among the groups. Furthermore, claudin-1 (P = 0.014) and -4 (P = 0.004) could be used to distinguish between those patients who had metastases and those who did not., Conclusions: The pattern of claudin expression could be a novel diagnostic marker in re-classifying adenocarcinomas, and an additional sensitive predictive factor for a clinically poor prognosis. Our results suggest that patients with organ-confined and advanced cancer are subsets with distinct claudin expression profiles, and that claudin-4 is related to cellular differentiation in prostate cancer, which is not only the receptor molecule for the Clostridium perfringens enterotoxin, and thus a theoretical future therapeutic target for prostate cancer, but also a marker of progression.