Prostate Cancer: Symptoms, Diagnosis & Treatment

Background: In prostate cancer (PC) diagnosis, additional systematic biopsy (SB) is recommended to complement MRI-targeted biopsy (TB) to address the limited sensitivity of TB alone. The combination of TB+SB is beneficial for diagnosing additional significant PC (sPC) but harmful in terms of the additional diagnosis of indolent PC (iPC), morbidity, and resource expenditures. We aimed to investigate the benefit of additional SB and to identify predictors for this outcome. Methods: We analyzed the frequency of upgrading to sPC by additional SB in a retrospective single-center cohort of 1043 men. Regression analysis (RA) was performed to identify predictors for this outcome. Reclassification rates of ISUP grade groups between prostate biopsy and a subsequent radical prostatectomy were assessed. Results: Additional SB led to upgrading to sPC in 98/1043 men (9.4%) and to the additional diagnosis of iPC in 71/1043 (6.8%). In RA, men harboring a PI-RADS 2-4 lesion were more likely to have TB results upgraded by SB (p < 0.01) compared to PI-RADS 5 men. When analyzing reclassification rates, additional SB reduced the upgrading to sPC from 43/214 (20.1%) to 8/214 (3.7%). In the PI-RADS 5 subgroup, this difference decreased: 4/87 (4.7%) with TB only vs. 1/87 (1.2%) with TB+SB. Conclusion: Men with a PI-RADS 5 lesion may obviate additional SB. Full article

Prostate-specific antigen (PSA) bounce is common in patients undergoing ¹²⁵I brachytherapy (BT), and our study investigated its clinical features. A total of 100 patients who underwent BT were analyzed. PSA bounce and large bounce were defined as an increase of ≥0.2 and ≥2.0 ng/mL above the initial PSA nadir, respectively, with a subsequent decline without treatment. Biochemical failure was defined using the Phoenix definition (nadir +2 ng/mL), except for a large bounce. With a median follow-up of 49 months, 45% and 7% of the patients experienced bounce and large bounce, respectively. The median time to bounce was 24 months, and the median PSA value at the bounce spike was 1.62 ng/mL, a median raise of 0.44 ng/mL compared to the pre-bounce nadir. The median time to bounce recovery was 4 months. The post-bounce nadir was obtained at a median of 36 months after low-dose-rate BT. On univariate analysis, age, the PSA nadir value at 2 years, and prostate volume were significant factors for PSA bounce. The PSA nadir value at 2 years remained significant in multivariate analysis. We should carefully monitor young patients with high prostate volume having a >0.5 PSA nadir value at 2 years for PSA bounce. Full article

Background: Treatment strategies have changed dramatically in recent years with the development of a variety of agents for metastatic hormone-naïve prostate cancer (mHNPC). There is a need to identify prognostic factors for the appropriate choice of treatment for patients with mHNPC, and we retrospectively examined these factors. Methods: Patients with mHNPC treated at our institution from 2000 to 2019 were included in this study. Overall survival (OS) was estimated retrospectively using the Kaplan–Meier method, and factors associated with OS were identified using univariate and multivariate analyses. A prognostic model was then developed based on the factors identified. Follow-up was terminated on 24 October 2021. Results: The median follow-up duration was 44.2 months, whereas the median OS was 85.2 months, with 88 patients succumbing to their disease. Multivariate analysis identified Gleason pattern (GP) 5 content, bone scan index (BSI) ≥ 1.5, and lactate dehydrogenase (LDH) levels ≥ 300 IU/L as prognostic factors associated with OS. We also developed a prognostic model that classified patients with mHNPC as low risk with no factor, intermediate risk with one factor, and high risk with two or three factors. Conclusions: Three prognostic factors for OS were identified in patients with mHNPC, namely GP5 inclusion, BSI ≥ 1.5, and LDH ≥ 300. Using these three factors, we developed a new prognostic model for OS that can more objectively predict patient prognosis. Full article

Increased diagnoses of silent prostate cancer (PCa) have led to overtreatment and consequent functional side effects. Focal therapy (FT) applies energy to a prostatic index lesion treating only the clinically significant PCa focus. We analysed the potential predictive factors of FT failure. We collected data from patients who underwent robot-assisted radical prostatectomy (RARP) in two high-volume hospitals from January 2017 to January 2020. The inclusion criteria were: one MRI-detected lesion with a Gleason Score (GS) of ≤7, ≤cT2a, PSA of ≤10 ng/mL, and GS 6 on a random biopsy with ≤2 positive foci out of 12. Potential oncological safety of FT was defined as the respect of clinicopathological inclusion criteria on histology specimens, no extracapsular extension, and no biochemical, local, or metastatic recurrence within 12 months. To predict FT failure, we performed uni- and multivariate logistic regression. Sixty-seven patients were enrolled. The MRI index lesion median size was 11 mm; target lesions were ISUP grade 1 in 27 patients and ISUP grade 2 in 40. Potential FT failure occurred in 32 patients, and only the PSA value resulted as a predictive parameter (p < 0.05). The main issue for FT is patient selection, mainly because of multifocal csPCa foci. Nevertheless, FT could represent a therapeutic alternative for highly selected low-risk PCa patients. Full article

This study investigates whether the application of Hemopatch, a novel hemostatic patch, could prevent lymphatic leak after robotic-assisted radical prostatectomy (RARP) and bilateral pelvic lymph node dissection (BPLND). This is a prospective, single-center, phase III randomized controlled trial investigating the efficacy of Hemopatch in preventing lymphatic leak after RARP and BPLND. Participants were randomized to receive RARP and BPLND, with or without the use of Hemopatch, with an allocation ratio of 1:1. The primary outcome is the total drain output volume. The secondary outcomes include blood loss, operative time, lymph node yield, duration of drainage, drain output per day, hospital stay, transfusion and 30-day complications. A total of 32 patients were recruited in the study. The Hemopatch group had a significantly lower median total drain output than the control group (35 mL vs. 180 mL, p = 0.022) and a significantly lower drain output volume per day compared to the control group (35 mL/day vs. 89 mL/day, p = 0.038). There was no significant difference in the other secondary outcomes. In conclusion, the application of Hemopatch in RARP and BPLND could reduce the total drain output volume and the drain output volume per day. The use of Hemopatch should be considered to prevent lymphatic leakage after RARP and BPLND. Full article

To explore the diagnostic value of the Prostate Imaging–Reporting and Data System version 2.1 (PI-RADS v2.1) for clinically significant prostate cancer (CSPCa) in patients with a history of transurethral resection of the prostate (TURP), we conducted a retrospective study of 102 patients who underwent systematic prostate biopsies with TURP history. ROC analyses and logistic regression analyses were performed to demonstrate the diagnostic value of PI-RADS v2.1 and other clinical characteristics, including PSA and free/total PSA (F/T PSA). Of 102 patients, 43 were diagnosed with CSPCa. In ROC analysis, PSA, F/T PSA, and PI-RADS v2.1 demonstrated significant diagnostic value in detecting CSPCa in our cohort (AUC 0.710 (95%CI 0.608–0.812), AUC 0.768 (95%CI 0.676–0.860), AUC 0.777 (95%CI 0.688–0.867), respectively). Further, PI-RADS v2.1 scores of the peripheral and transitional zones were analyzed separately. In ROC analysis, PI-RADS v2.1 remained valuable in identifying peripheral-zone CSPCa (AUC 0.780 (95%CI 0.665–0.854; p < 0.001)) while having limited capability in distinguishing transitional zone lesions (AUC 0.533 (95%CI 0.410–0.557; p = 0.594)). PSA and F/T PSA retain significant diagnostic value for CSPCa in patients with TURP history. PI-RADS v2.1 is reliable for detecting peripheral-zone CSPCa but has limited diagnostic value when assessing transitional zone lesions. Full article

The recent approval of ¹⁷⁷Lu PSMA-617 (Pluvicto^®) by the United States Food and Drug Administration (FDA) is the culmination of decades of work in advancing the field of targeted radionuclide therapy for metastatic prostate cancer. ¹⁷⁷Lu PSMA-617, along with the bone specific radiotherapeutic agent, ²²³RaCl₂ (Xofigo^®), are now commonly used in routine clinical care as a tertiary line of therapy for men with metastatic castrate resistant prostate cancer and for osseus metastatic disease respectively. While these radiopharmaceuticals are changing how metastatic prostate cancer is classified and treated, there is relatively little guidance to the practitioner and patient as to how best utilize these therapies, especially in conjunction with other more well-established regimens including hormonal, immunologic, and chemotherapeutic agents. This review article will go into detail about the mechanism and effectiveness of these radiopharmaceuticals and less well-known classes of targeted radionuclide radiopharmaceuticals including alpha emitting prostate specific membrane antigen (PSMA)-, gastrin-releasing peptide receptor (GRPR)-, and somatostatin targeted radionuclide therapeutics. Additionally, a thorough discussion of the clinical approach of these agents is included and required futures studies. Full article

The personality trait of neuroticism is associated with adverse health outcomes after cancer treatment, but few studies concern men treated for prostate cancer. We examined men with high and low neuroticism treated with radical prostatectomy for curable prostate cancer without relapse. We compared overall problems and domain summary scores (DSSs) between these groups, and if high neuroticism at pre-treatment was a significant predictor of overall problems and DSSs at follow-up. A sample of 462 relapse-free Norwegian men self-rated neuroticism, overall problems, and DSSs by the EPIC-26 before surgery and at three years’ follow-up. Twenty-one percent of the sample had high neuroticism. Patients with high neuroticism reported significantly more overall problems and DSSs at pre-treatment. At follow-up, only overall bowel problems and urinary irritation/obstruction and bowel DSSs were different. High neuroticism was a significant predictor of overall bowel problems and bowel and irritation/obstruction DSSs at follow-up. High neuroticism at pre-treatment was significantly associated with a higher rate of overall problems both at pre-treatment and follow-up and had some significant predictions concerning bowel problems and urinary obstruction at follow-up. Screening for neuroticism at pre-treatment could identify patients in need of more counseling concerning later adverse health outcomes. Full article

DNA damage repair (DDR) defects are common in different cancer types, and these alterations can be exploited therapeutically. Epithelial ovarian cancer (EOC) is among the tumours with the highest percentage of hereditary cases. BRCA1 and BRCA2 predisposing pathogenic variants (PVs) were the first to be associated with EOC, whereas additional genes comprising the homologous recombination (HR) pathway have been discovered with DNA sequencing technologies. The incidence of DDR alterations among patients with metastatic prostate cancer is much higher compared to those with localized disease. Genetic testing is playing an increasingly important role in the treatment of patients with ovarian and prostate cancer. The development of poly (ADP-ribose) polymerase (PARP) inhibitors offers a therapeutic strategy for patients with EOC. One of the mechanisms of PARP inhibitors exploits the concept of synthetic lethality. Tumours with BRCA1 or BRCA2 mutations are highly sensitive to PARP inhibitors. Moreover, the synthetic lethal interaction may be exploited beyond germline BRCA mutations in the context of HR deficiency, and this is an area of ongoing research. PARP inhibitors are in advanced stages of development as a treatment for metastatic castration-resistant prostate cancer. However, there is a major concern regarding the need to identify reliable biomarkers predictive of treatment response. In this review, we explore the mechanisms of DDR, the potential for genomic analysis of ovarian and prostate cancer, and therapeutics of PARP inhibitors, along with predictive biomarkers. Full article

Although appreciable attempts in screening and diagnostic approaches have been achieved, prostate cancer (PCa) remains a widespread malignancy, representing the second leading cause of cancer-related death in men. Drugs currently used in PCa therapy initially show a potent anti-tumor effect, but frequently induce resistance and PCa progresses toward metastatic castration-resistant forms (mCRPC), virtually incurable. Liquid biopsy has emerged as an attractive and promising strategy complementary to invasive tissue biopsy to guide PCa diagnosis and treatment. Liquid biopsy shows the ability to represent the tumor microenvironment, allow comprehensive information and follow-up the progression of the tumor, enabling the development of different treatment strategies as well as permitting the monitoring of therapy response. Liquid biopsy, indeed, is endowed with a significant potential to modify PCa management. Several blood biomarkers could be analyzed for diagnostic, prognostic and predictive purposes, including circulating tumor cells (CTCs), extracellular vesicles (EVs), circulating tumor DNA (ctDNA) and RNA (ctRNA). In addition, several other body fluids may be adopted (i.e., urine, sperm, etc.) beyond blood. This review dissects recent advancements and future perspectives of liquid biopsies, highlighting their strength and weaknesses in PCa management. Full article

It is possible to obtain diagnostically relevant data on the changes in biochemical elements brought on by cancer via the use of multivariate analysis of vibrational spectra recorded on biological fluids. Prostate cancer and control groups included in this research generated almost similar SERS spectra, which means that the values of peak intensities present in SERS spectra can only give unspecific and limited information for distinguishing between the two groups. Our diagnostic algorithm for prostate cancer (PCa) differentiation was built using principal component analysis and linear discriminant analysis (PCA-LDA) analysis of spectral data, which has been widely used in spectral data management in many studies and has shown promising results so far. In order to fully utilize the entire SERS spectrum and automatically determine the most meaningful spectral features that can be used to differentiate PCa from healthy patients, we perform a multivariate analysis on both the entire and specific spectral intervals. Using the PCA-LDA model, the prostate cancer and control groups are clearly distinguished in our investigation. The separability of the following two data sets is also evaluated using two alternative discrimination techniques: principal least squares discriminant analysis (PLS-DA) and principal component analysis—support vector machine (PCA-SVM). Full article

The peritoneal carcinomatosis of prostate cancer without bone or other visceral organ involvement is extremely rare. We report a case of an isolated peritoneal metastasis of prostate cancer in a patient without other metastatic sites and a history of prostate surgery. A 63-year-old male with locally advanced prostate cancer without known distant metastasis on androgen deprivation therapy presented with abdominal distension that had persisted for a month. Abdominopelvic computed tomography (CT) showed gastric wall thickening and a moderate amount of ascites. The gastroscopy showed hyperemic mucosal patches on the antrum body. A cytological examination of the ascites fluid was negative for malignant cells. Diagnostic laparoscopy showed multiple nodules in the peritoneum. A biopsy was performed. Histological findings were compatible with metastatic carcinoma of the prostate, which was immunohistochemically positive for pan-cytokeratin, the androgen receptor, and prostate-specific antigen (PSA). The patient was then treated with abiraterone acetate. After 1 month of treatment, both ascites and the PSA value decreased. We describe an extremely rare case of isolated peritoneal carcinomatosis from prostate cancer without any organ metastasis or history of surgery. Clinicians should be aware of these very rare metastases of prostate cancer. Hormonal therapy may be helpful for such cases. Full article

Prostate cancer (PCa), which is among the most prevalent types of cancer in men, is a prominent topic in imaging research. The primary aim of PCa imaging is to acquire more accurate characterizations of the disease. More precise imaging of the local stage progression, early discovery of metastatic cancers, reliable diagnosis of oligometastatic cancer, and optimum treatment response evaluation are areas in which contemporary imaging is quickly improving and developing. Imaging techniques, such as magnetic resonance imaging (MRI) for the whole body and molecular imaging with combined positron emission tomography (PET), computed tomography (CT), and MRI, enable imaging to support and enhance treatment lines in patients with local and advanced PCa. With the availability of multiple imaging modalities for the management of PCa, we aim in this review to offer a multidisciplinary viewpoint on the appropriate function of contemporary imaging in the identification of PCa. Full article

In this study, we have evaluated whether 57 genome-wide association studies (GWAS)-identified common variants for type 2 diabetes (T2D) influence the risk of developing prostate cancer (PCa) in a population of 304 Caucasian PCa patients and 686 controls. The association of selected single nucleotide polymorphisms (SNPs) with the risk of PCa was validated through meta-analysis of our data with those from the UKBiobank and FinnGen cohorts, but also previously published genetic studies. We also evaluated whether T2D SNPs associated with PCa risk could influence host immune responses by analysing their correlation with absolute numbers of 91 blood-derived cell populations and circulating levels of 103 immunological proteins and 7 steroid hormones. We also investigated the correlation of the most interesting SNPs with cytokine levels after in vitro stimulation of whole blood, peripheral mononuclear cells (PBMCs), and monocyte-derived macrophages with LPS, PHA, Pam3Cys, and Staphylococcus Aureus. The meta-analysis of our data with those from six large cohorts confirmed that each copy of the FTO_rs9939609A, HNF1B_rs7501939T, HNF1B_rs757210T, HNF1B_rs4430796G, and JAZF1_rs10486567A alleles significantly decreased risk of developing PCa (p = 3.70 × 10⁻⁵, p = 9.39 × 10⁻⁵⁴, p = 5.04 × 10⁻⁵⁴, p = 1.19 × 10⁻⁷¹, and p = 1.66 × 10⁻¹⁸, respectively). Although it was not statistically significant after correction for multiple testing, we also found that the NOTCH2_rs10923931T and RBMS1_rs7593730 SNPs associated with the risk of developing PCa (p = 8.49 × 10⁻⁴ and 0.004). Interestingly, we found that the protective effect attributed to the HFN1B locus could be mediated by the SULT1A1 protein (p = 0.00030), an arylsulfotransferase that catalyzes the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. In addition to these results, eQTL analysis revealed that the HNF1B_rs7501939, HNF1B_rs757210, HNF1B_rs4430796, NOTCH2_rs10923931, and RBMS1_rs7593730 SNPs influence the risk of PCa through the modulation of mRNA levels of their respective genes in whole blood and/or liver. These results confirm that functional TD2-related variants influence the risk of developing PCa, but also highlight the need of additional experiments to validate our functional results in a tumoral tissue context. Full article

In recent years, stereotactic body radiation therapy (SBRT) has gained popularity among clinical methods for the treatment of medium and low risk prostate cancer (PCa), mainly as an alternative to surgery. The hypo-fractionated regimen allows the administration of high doses of radiation in a small number of fractions; such a fractionation is possible by exploiting the different intrinsic prostate radiosensitivity compared with the surrounding healthy tissues. In addition, SBRT treatment guaranteed a better quality of life compared with surgery, avoiding risks, aftermaths, and possible complications. At present, most stereotactic prostate treatments are performed with the CyberKnife (CK) system, which is an accelerator exclusively dedicated for stereotaxis and it is not widely spread in every radiotherapy centre like a classic linear accelerator (LINAC). To be fair, a stereotactic treatment is achievable also by using a LINAC through Volumetric Modulated Arc Therapy (VMAT), but some precautions must be taken. The aim of this work is to carry out a dosimetric comparison between these two methodologies. In order to pursue such a goal, two groups of patients were selected at Instituto Nazionale Tumori—IRCCS Fondazione G. Pascale: the first group consisting of ten patients previously treated with a SBRT performed with CK; the second one was composed of ten patients who received a hypo-fractionated VMAT treatment and replanned in VMAT-SBRT flattening filter free mode (FFF). The two SBRT techniques were rescaled at the same target coverage and compared by normal tissue sparing, dose distribution parameters and delivery time. All organs at risk (OAR) constraints were achieved by both platforms. CK exhibits higher performances in terms of dose delivery; nevertheless, the general satisfying dosimetric results and the significantly shorter delivery time make VMAT-FFF an attractive and reasonable alternative SBRT technique for the treatment of localized prostate cancer. Full article

The post-transcriptional messenger RNA (mRNA) decay and turnover rate of the template-independent poly(A) tail, localized at the 3′-untranslated region (3′UTR) of mRNA, have been documented among subtle mechanisms of uncontrolled cancer tissue growth. The activity of Poly(A) deadenylase and the expression pattern of RNASEL have been examined. A total of 138 prostate tissue specimens from 46 PC patients (cancer specimens, corresponding adjacent surgically healthy tissues, and in their normal counterparts, at least 2 cm from carcinoma) were used. For the stratification prediction of healthy tissue transition into malignant phenotype, the enzyme activity of tumor-adjacent tissue was considered in relation to the presence of microfocal carcinoma. More than a four-times increase in specific enzyme activity (U/L g.prot) was registered in PC on account of both the dissociation of its inhibitor and genome reprogramming. The obtained ROC curve and Youden index showed that Poly(A) deadenylase identified PC with a sensitivity of 93.5% and a specificity of 94.6%. The RNASEL expression profile was raised significantly in PC, but the sensitivity was 40.5% and specificity was 86.9%. A significantly negative correlation between PC and control tissue counterparts with a higher expression pattern in lymphocyte-infiltrated samples were reported. In conclusion, significantly upregulated Poly(A) deadenylase activity may be a checkpoint for the transition of precancerous lesion to malignancy, while RNASEL may predict chronic inflammation. Full article

(1) Background: In literature, approximately 20% of mCRPC present somatic DNA damage repair (DDR) gene mutations, and their relationship with response to standard therapies in mCRPC is not well understood. The objective was to evaluate outcomes of mCRPC patients treated with standard therapies according to somatic DDR status. (2) Methods: Eighty-three patients were recruited at Caen Cancer Center (France). Progression-free survival (PFS) after first-line treatment was analyzed according to somatic DDR mutation as primary endpoint. PFS according to first exposure to taxane chemotherapy and PFS2 (time to second event of disease progression) depending on therapeutic sequences were also analyzed. (3) Results: Median first-line PFS was 9.7 months in 33 mutated patients and 8.4 months in 50 non-mutated patients (p = 0.9). PFS of first exposure to taxanes was 8.1 months in mutated patients and 5.7 months in non-mutated patients (p = 0.32) and significantly longer among patients with ATM/BRCA1/BRCA2 mutations compared to the others (10.6 months vs. 5.5 months, p = 0.04). PFS2 was 16.5 months in mutated patients, whatever the sequence, and 11.7 months in non-mutated patients (p = 0.07). The mutated patients treated with chemotherapy followed by NHT had a long median PFS2 (49.8 months). (4) Conclusions: mCRPC patients with BRCA1/2 and ATM benefit from standard therapies, with a long response to taxanes. Full article

To identify new protein targets for PCa detection, first, a shotgun discovery experiment was performed to characterize the urinary proteome of PCa patients. This revealed 18 differentially abundant urinary proteins in PCa patients. Second, selected targets were clinically tested by immunoblot, and the soluble E-cadherin fragment was detected for the first time in the urine of PCa patients. Third, the proteogenome landscape of these PCa patients was characterized, revealing 1665 mutant protein isoforms. Statistical analysis revealed 6 differentially abundant mutant protein isoforms in PCa patients. Analysis of the likely effects of mutations on protein function and PPIs involving the dysregulated mutant protein isoforms suggests a protective role of mutations HSPG2*Q1062H and VASN*R161Q and an adverse role of AMBP*A286G and CD55*S162L in PCa patients. This work originally characterized the urinary proteome, focusing on the proteogenome profile of PCa patients, which is usually overlooked in the analysis of PCa and body fluids. Combined analysis of mass spectrometry data using two different software packages was performed for the first time in the context of PCa, which increased the robustness of the data analysis. The application of proteogenomics to urine proteomic analysis can be very enriching in mutation-related diseases such as cancer. Full article

Advanced prostate cancers have a poor survival rate and a lack of effective treatment options. In order to broaden the available treatments, immunotherapies have been investigated. These include cancer vaccines, immune checkpoint inhibitors, chimeric antigen receptor T cells and bispecific antibodies. In addition, combinations of different immunotherapies and with standard therapy have been explored. Despite the success of the Sipuleucel-T vaccine in the metastatic, castrate-resistant prostate cancer setting, other immunotherapies have not shown the same efficacy in this population at large. Some individual patients, however, have shown remarkable responsiveness to these therapies. Therefore, work is underway to identify which populations will respond positively to therapy via the identification of predictive biomarkers. These include biomarkers of the immunologically active tumour microenvironment and biomarkers indicative of high neoantigen expression in the tumour. This review examines the constitution of the prostate tumour immune microenvironment, explores the effectiveness of immunotherapies, and finally investigates how therapy selection can be optimised by the use of biomarkers. Full article

Prostate cancer (PCa) poses a major public health problem in men. Metastatic PCa is incurable, and ultimately threatens the life of many patients. Mutations in tumor suppressor genes and oncogenes are important for PCa progression, whereas the role of epigenetic factors in prostate carcinogenesis is insufficiently examined. The histone demethylase KDM5C exerts important roles in tumorigenesis. KDM5C has been reported to be highly expressed in various cancer cell types, particularly in primary PCa. Here, we could show that KDM5C is highly upregulated in metastatic PCa. Functionally, in KDM5C knockdown cells migratory and invasion capacity was reduced. Interestingly, modulation of KDM5C expression influences several EMT signaling pathways (e.g., Akt/mTOR), expression of EMT transcription factors, epigenetic modifiers, and miR-205, resulting in increased expression of E-cadherin and reduced expression of N-cadherin. Mouse xenografts of KDM5C knockdown cells showed reduced tumor growth. In addition, the Akt/mTOR pathway is one of the classic signaling pathways to mediate tumor metabolic homeostasis, which is beneficial for tumor growth and metastasis. Taken together, our findings indicate that a combination of a selective KDM5C- and Akt/mTOR-inhibitor might be a new promising therapeutic strategy to reduce metastatic burden in PCa. Full article

A new and externally validated MRI-PM for csPCa was developed in the metropolitan area of Barcelona, and a web-RC designed with the new option of selecting the csPCa probability threshold. The development cohort comprised 1486 men scheduled to undergo a 3-tesla multiparametric MRI (mpMRI) and guided and/or systematic biopsies in one academic institution of Barcelona. The external validation cohort comprised 946 men in whom the same diagnostic approach was carried out as in the development cohort, in two other academic institutions of the same metropolitan area. CsPCa was detected in 36.9% of men in the development cohort and 40.8% in the external validation cohort (p = 0.054). The area under the curve of mpMRI increased from 0.842 to 0.897 in the developed MRI-PM (p < 0.001), and from 0.743 to 0.858 in the external validation cohort (p < 0.001). A selected 15% threshold avoided 40.1% of prostate biopsies and missed 5.4% of the 36.9% csPCa detected in the development cohort. In men with PI-RADS <3, 4.3% would be biopsied and 32.3% of all existing 4.2% of csPCa would be detected. In men with PI-RADS 3, 62% of prostate biopsies would be avoided and 28% of all existing 12.4% of csPCa would be undetected. In men with PI-RADS 4, 4% of prostate biopsies would be avoided and 0.6% of all existing 43.1% of csPCa would be undetected. In men with PI-RADS 5, 0.6% of prostate biopsies would be avoided and none of the existing 42.0% of csPCa would be undetected. The Barcelona MRI-PM presented good performance on the overall population; however, its clinical usefulness varied regarding the PI-RADS category. The selection of csPCa probability thresholds in the designed RC may facilitate external validation and outperformance of MRI-PMs in specific PI-RADS categories. Full article

There are limited and discrepant data on prostate cancer (PCa) and vitamin D. We investigated changes in three vitamin D₃ metabolites in PCa patients after prostatectomy with zoledronic acid (ZA) treatment regarding their metastasis statuses over four years. In 32 patients from the ZEUS trial, 25(OH)D₃, 24,25(OH)₂D₃, and 1,25(OH)₂D₃ were measured with liquid chromatography coupled with tandem mass spectrometry at four time points. All the patients received daily calcium and vitamin D₃. Bone metastases were detected in 7 of the 17 ZA-treated patients and in 5 of the 15 controls (without ZA), without differences between the groups (p = 0.725). While 25(OH)D₃ and 24,25(OH)₂D₃ increased significantly after the study’s start, with following constant values, the 1,25(OH)₂D₃ concentrations remained unchanged. ZA treatment did not change the levels of the three metabolites. 25(OH)D₃ and 24,25(OH)₂D₃ were not associated with the development of bone metastases. In contrast, 1,25(OH)₂D₃ was also higher in patients with bone metastasis before the study’s start. Thus, in high-risk PCa patients after prostatectomy, 25(OH)D₃, 24,25(OH)₂D₃, and 1,25(OH)₂D₃ were not affected by supportive ZA treatment or by the development of metastasis over four years, with the exception of 1,25(OH)₂D₃, which was constantly higher in metastatic patients. There might be potential prognostic value if the results can be confirmed. Full article

Adenoid cystic carcinoma/basaloid cell carcinoma of the prostate (ACC/BCC) is a very rare variant of prostate cancer with uncertain behavior. Few cases are reported in the literature. Data on treatment options are scarce. The aim of our work was to retrospectively review the published reports. Thirty-three case reports or case series were analyzed (106 patients in total). Pathological features, management, and follow-up information were evaluated. Despite the relatively low level of evidence given the unavoidable lack of prospective trials for such a rare prostate tumor, the following considerations were made: prostate ACC/BCC is an aggressive tumor often presenting with locally advanced disease and incidental diagnosis occurs during transurethral resection of the prostate for urinary obstructive symptoms. Prostate-specific antigen was not a reliable marker for diagnosis nor follow-up. Adequate staging with Computed Tomography (CT) scan and Magnetic Resonance Imaging (MRI) should be performed before treatment and during follow-up, while there is no evidence for the use of Positron Emission Tomography (PET). Radical surgery with negative margins and possibly adjuvant radiotherapy appear to be the treatments of choice. The response to androgen deprivation therapy was poor. Currently, there is no evidence of the use of truly effective systemic therapies. Full article

Previous randomized trials have not provided conclusive evidence about dose escalations and associated toxicities for salvage radiotherapy (SRT) in prostate cancer. Here, we retrospectively analyzed whether dose escalations influenced progression-free survival in 554 patients that received salvage radiotherapy for relapses or persistently elevated prostate cancer antigen (PSA) after a radical prostatectomy. Patients received SRT between 1997 and 2017 at two University Hospitals in Germany. We compared patient groups that received radiation doses <7000 cGy (n = 225) or ≥7000 cGy (n = 329) to analyze the influence of radiation dose on progression-free survival. In a second matched-pair analysis of 216 pairs, we evaluated prognostic factors (pT2 vs. pT3–4, Gleason score [GS] ≤ 7 vs. GS ≥ 8, R0 vs. R1, and pre-SRT PSA <0.5 vs. ≥0.5 ng/mL). After a median follow-up of 6.8 (4.2–9.2) years, we found that escalated doses significantly improved progression-free survival (p = 0.0042). A multivariate analysis indicated that an escalated dose, lower tumor stages (pT2 vs. pT3/4), and lower GSs (≤7 vs. 8–10) were associated with improved progression-free survival. There was no significant effect on overall survival. Our data suggested that escalating the radiation dose to ≥7000 cGy for SRT after a prostatectomy significantly improved progression-free survival. Longer follow-ups are needed for a comprehensive recommendation. Full article

PCa screening is based on the measurements of the serum prostate specific antigen (PSA) to select men with higher risks for tumors and, thus, eligible for prostate biopsy. However, PSA testing has a low specificity, leading to unnecessary biopsies in 50–75% of cases. Therefore, more specific screening opportunities are needed to reduce the number of biopsies performed on healthy men and patients with indolent tumors. Urine samples from 45 patients with elevated PSA were collected prior to prostate biopsy, a mass spectrometry (MS) screening was performed to identify novel biomarkers and the best candidates were validated by ELISA. The urine quantification of PEDF, HPX, CD99, CANX, FCER2, HRNR, and KRT13 showed superior performance compared to PSA. Additionally, the combination of two biomarkers and patient age resulted in an AUC of 0.8196 (PSA = 0.6020) and 0.7801 (PSA = 0.5690) in detecting healthy men and high-grade PCa, respectively. In this study, we identified and validated novel urine biomarkers for the screening of PCa, showing that an upfront urine test, based on quantitative biomarkers and patient age, is a feasible method to reduce the number of unnecessary prostate biopsies and detect both healthy men and clinically significant PCa. Full article