Search Results (735)

Gamma-tocopherol (γ-tocopherol), a major isoform of vitamin E, exhibits potent antioxidant, anti-inflammatory, and anticancer properties, making it a promising therapeutic candidate for treating oxidative stress-related diseases. Unlike other tocopherol isoforms, γ-tocopherol effectively neutralizes reactive oxygen species (ROS) and reactive nitrogen species (RNS), providing robust cellular protection against oxidative damage and lipid peroxidation. Its anti-inflammatory effects are mediated through the modulation of pathways involving cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-α), reducing chronic inflammation and its associated risks. In cancer therapy, γ-tocopherol demonstrates multifaceted activity, including the inhibition of tumor growth, induction of apoptosis, and suppression of angiogenesis, with significant efficacy observed in cancers such as prostate, lung, and colon. Preclinical and clinical studies support its efficacy in mitigating oxidative stress, inflammation, and cancer progression, with excellent tolerance at physiological levels. However, high doses necessitate careful evaluation to minimize adverse effects. This review consolidates current knowledge on γ-tocopherol’s biological activities and clinical implications, underscoring its importance as a natural compound for managing inflammation, oxidative stress, and cancer. As a perspective, advancements in nanoformulation technology could enhance γ-tocopherol’s bioavailability, stability, and targeted delivery, offering the potential to optimize its therapeutic application in the future. Full article

Background: Tumour mutational burden (TMB) is an emerging biomarker for predicting the efficacy of immune checkpoint inhibitors (ICIs) in cancer therapy. While its role is well established in lung cancer and melanoma, its predictive value for breast and prostate cancers remains unclear. Objective: This systematic review aimed to assess the predictive value of TMB for ICI therapy across four major cancer types—lung, melanoma, breast, and prostate—and to explore factors contributing to the variability in its effectiveness as a biomarker. Methods: A systematic search and a review of the literature were conducted in accordance with PRISMA guidelines. Studies examining the relationship between TMB levels and clinical outcomes following ICI therapy in the specified cancers were analyzed. The data were synthesized to evaluate TMB’s predictive value and identify gaps in the current research. Results: High TMB consistently correlated with improved outcomes in lung cancer and melanoma, confirming its predictive utility in these cancers. Conversely, the findings for breast and prostate cancers were inconclusive. The variability in TMB’s predictive value for these cancers suggests the need for complementary biomarkers or refined criteria to enhance its reliability. Methodological inconsistencies in TMB evaluation were also noted as a significant limitation. Conclusions: TMB serves as a robust biomarker for predicting ICI response in lung cancer and melanoma, but demonstrates limited predictive utility in breast and prostate cancers. Future research should prioritize standardizing TMB assessment protocols and investigating additional biomarkers to improve treatment personalization for these cancer types. Full article

Background/Objectives: Laser ablation is a promising technique for tissue-debulking in patients with symptomatic benign prostatic hyperplasia (BPH). This study evaluated the effects of focused laser ablation of the prostate (FLA) on urinary symptoms for patients with BPH. Methods: Since 2018, 62 patients had bilateral prostate FLA for prostate cancer and/or symptomatic BPH, defined as an international prostate symptom score (IPSS) ≥11, and have 6-month follow-up data. Urinary and sexual health were scored with standardized surveys while imaging defined prostate anatomy. FLA was performed as an outpatient procedure with either transrectal MRI-guided (n = 24) or transperineal ultrasound-guided (n = 38) laser fiber placement to debulk the prostate and/or ablate cancer foci plus margins. Enhanced prostate MRI was performed immediately or up to 2 days later to assess the treatment zones. Follow-up then consisted of PSA levels every 6 months and MRI at 6–12 months and then yearly combined with patient sexual/urinary surveys and clinical assessments. Results: All patients had technically successful FLA and 6-month clinical and imaging follow-up. At 6-month follow-up, mean IPSS was reduced by 43% relative to baseline (10.4 vs. 18.4), mean prostate volume was reduced by 30% (42.2 vs. 60.5 mL), and mean PSA was reduced by 58% (4.3 vs. 10.2 ng/mL). All of these changes were statistically significant (p ≤ 0.008). Compared with baseline, there was no significant change in the SHIM score at 6 months (16.0 vs. 16.8; p = 0.59). In a subset of patients for whom 12-month data were available, there were significant reductions in PSA (61%; 4.1 vs. 10.5 ng/mL; p < 0.002) and IPSS (45%; 9.9 vs. 17.9; p < 0.002), while the 12-month SHIM score was not significantly different from baseline (15.2 vs. 16.0; p = 0.27). Mean laser irradiation time was 19 min with a mean energy deposition of 13,562 J. The most frequent adverse events were prolonged urinary catheterization in 10 patients (16%) and urinary tract infection in 8 (13%). Conclusions: FLA is a safe and effective tissue-debulking technique for patients with symptomatic BPH. This outpatient procedure requires minimal procedure time and can be performed without the need for operating rooms or cystoscopy. Our results are consistent with those of previous studies indicating that FLA preserves sexual function. Full article

Background/Objectives: The prognostic value of baseline clinical parameters in predicting the survival prolonging effect of Radium-223-dichloride (²²³RaCl₂) for metastatic castration resistant prostate cancer (mCRPC) patients has been the object of intensive research and remains an open issue. This national multicenter study aimed to corroborate the evidence of ten years of clinical experience with ²²³RaCl₂ by collecting data from eight Italian Nuclear Medicine Units. Methods: Data from 581 consecutive mCRPC patients treated with ²²³RaCl₂ were retrospectively analyzed. Several baseline variables relevant to the overall survival (OS) analysis were considered, including age, previous radical prostatectomy/radiotherapy, number of previous treatment lines, prior chemotherapy, Gleason score, presence of lymphoadenopaties, number of bone metastases, concomitant use of bisphosphonates/Denosumab, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), as well as baseline values of hemoglobin (Hb), platelets, Total Alkaline Phosphatase (tALP), Lactate Dehydrogenase (LDH), and Prostate-Specific Antigen (PSA). Data were summarized using descriptive statistics, univariate analysis and multivariate analysis with the Cox model. Results: The median OS time was 14 months (95%CI 12–17 months). At univariate analysis age, the number of previous treatment lines, number of bone metastases, ECOG-PS, presence of lymphadenopathies at the time of enrollment, as well as baseline tALP, PSA, and Hb, were independently associated with OS. After multivariate analysis, the number of previous treatment lines (HR = 1.1670, CI = 1.0095–1.3491, p = 0.0368), the prior chemotherapy (HR = 0.6461, CI = 0.4372–0.9549, p = 0.0284), the presence of lymphadenopathies (HR = 1.5083, CI = 1.1210–2.0296, p = 0.0066), the number of bone metastases (HR = 0.6990, CI = 0.5416–0.9020, p = 0.0059), ECOG-PS (HR = 1.3551, CI = 1.1238–1.6339, p = 0.0015), and baseline values of tALP (HR = 1.0008, CI = 1.0003–1.0013, p = 0.0016) and PSA (HR = 1.0004, CI = 1.0002–1.0006, p = 0.0005) remained statistically significant. Conclusions: In the era of precision medicine and in the landscape of novel therapies for mCRPC, the prognostic stratification of patients undergoing ²²³RaCl₂ has a fundamental role for clinical decision-making, ranging from treatment choice to optimal sequencing and potential associations. This large Italian multicenter study corroborated the prognostic value of several variables, emerging from ten years of clinical experience with ²²³RaCl₂. Full article

Background: The growing role of multiparametric MRI (mpMRI) and MRI-targeted biopsy (MRI-TBx) suggests they may replace random systematic biopsy (SBx), specifically detection and subsequent treatment of clinically significant prostate cancer (csPCa). Objectives: To perform a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the detection rates (DR) of csPCa using MRI-TBx alone, SBx alone, or their combination in biopsy naïve patients suspected of having prostate cancer (PCa). Methods: PubMed, MEDLINE, Embase, and the Cochrane Library were searched up to 23 March 2023, for RCTs comparing PCa DR between biopsy strategies in patients with suspected prostate cancer. Detection rates were pooled using random/fixed effect models, and the study quality was assessed using the Cochrane risk of bias revised tool. Results: Ten RCTs (involving 3646 patients) were analysed, revealing that the combined biopsy method achieved higher overall csPCa DR compared to the SBx method alone (RR = 1.40 [95% CI = 1.15–1.71] and 1.47 [95% CI = 1.13–1.92], respectively). However, there was no significant difference in DR for clinically insignificant prostate cancer (ciPCa) between the two methods. Conclusions: This review concludes that MRI-TBx and SBx detect overall and clinically significant prostate cancer (csPCa) better than SBx alone. The variety of factors requires cautious interpretation, yet these findings are the strongest evidence. The combination technique is recommended for biopsy-naïve groups, but more study is needed to optimise execution and overcome uncertainties. Full article

Background: In recent years, the role of prostate-specific membrane antigen (PSMA) in the imaging and treatment of prostate cancer (PCa) has been extensively investigated. However, despite its name, PSMA is not exclusively specific to PCa. It has been found to be expressed in the neo-vasculature of various solid tumors, including breast cancer (BC), in which it is associated with tumor angiogenesis. Methods: This review aims to assess the potential of PSMA-based radiopharmaceuticals for BC diagnosis and treatment. It explores the current landscape by analyzing preclinical and clinical studies, as well as ongoing clinical trials, to provide insights into the PSMA-targeted approaches in BC management. Results: Early studies suggest PSMA-based imaging could improve BC lesion detection, especially in TNBC. The available data remains too preliminary to conclusively assess whether PSMA-based imaging or therapy will offer a significant advantage in BC. However, some preclinical findings suggest that this approach may hold promise as a novel strategy for managing this widespread malignancy. Conclusions: PSMA-based strategies show potential for BC diagnosis and treatment, but further research is needed. Ongoing and future clinical trials are expected to provide deeper insights into the potential utility of this approach. Full article

Introduction: Prostate cancer, notably prostate adenocarcinoma (PARD), has high incidence and mortality rates. Although typically resistant to immunotherapy, recent studies have found immune targets for prostate cancer. Stratifying patients by molecular subtypes may identify those who could benefit from immunotherapy. Methods: We used single-cell and bulk RNA sequencing data from GEO and TCGA databases. We characterized the tumor microenvironment at the single-cell level, analyzing cell interactions and identifying fibroblasts linked to mitophagy. Target genes were narrowed down at the bulk transcriptome level to construct a PARD prognosis prediction nomogram. Unsupervised consensus clustering classified PARD into subtypes, analyzing differences in clinical features, immune infiltration, and immunotherapy. Furthermore, the cellular functions of the genes of interest were verified in vitro. Results: We identified ten cell types and 160 mitophagy-related single-cell differentially expressed genes (MR-scDEGs). Strong interactions were observed between fibroblasts, endothelial cells, CD8⁺ T cells, and NK cells. Fibroblasts linked to mitophagy were divided into six subtypes. Intersection of DEGs from three bulk datasets with MR-scDEGs identified 26 key genes clustered into two subgroups. COX regression analysis identified seven prognostic key genes, enabling a prognostic nomogram model. High and low-risk groups showed significant differences in clinical features, immune infiltration, immunotherapy, and drug sensitivity. In prostate cancer cell lines, CAV1, PALLD, and ITGB8 are upregulated, while CLDN7 is downregulated. Knockdown of PALLD significantly inhibits the proliferation and colony-forming ability of PC3 and DU145 cells, suggesting the important roles of this gene in prostate cancer progression. Conclusions: This study analyzed mitophagy-related genes in PARD, predicting prognosis and aiding in subtype identification and immunotherapy response analysis. This approach offers new strategies for treating prostate cancer with specific molecular subtypes and helps develop potential biomarkers for personalized medicine strategies. Full article

Background/Objectives: Drug prescribing in elderly people with chronic diseases carries certain risks. The desire to treat several different diseases at the same time increases the risk of inadequate drug prescribing. Prostate cancer is a disease of older men and occurs in most men over the age of 65. With age, the risk of prostate cancer increases, but so does the risk of the inadequate prescription of drugs. Our research aimed to highlight the potential inadequate prescription of drugs in patients with prostate cancer, considering that it is mostly a population of older men in whom a greater number of comorbidities is expected, followed by the use of a greater number of drugs. Methods: Our investigation was designed as an observational, cross-sectional study of 334 male patients who presented at the Multidisciplinary Tumor Board (MDT) for urological cancers at the University Clinical Center Kragujevac, Kragujevac, Serbia, from 1 September to 15 December 2023. Our primary outcome was obtaining the MAI score. Results: Our study showed that a significant number of drugs per patient with a prostate cancer diagnosis were prescribed potentially inadequately. The factors associated with greater risk for PIP were the initial level of PSA, ADT meta (intermittent), and several prescribed drugs; on the other hand, secondary hormonal therapy was the reason for less frequent PIP. Conclusions: In conclusion, patients with prostate cancer are under increased risk of inappropriate prescribing when they are prescribed more medication, have high PSA, and have ADT meta (intermittent). To stop the incidence of inappropriate prescribing and its serious economic and health consequences, clinicians should take special care when prescribing new drugs to such patients. Full article

Background: Multiparametric MRI (mpMRI) as a non-invasive imaging tool is important in prostate cancer (PCa) detection and localization. Combined with radiomics analysis, features extracted from mpMRI have been utilized to predict PCa aggressiveness. T2 mapping provides quantitative information in PCa diagnoses but is not routinely available in clinical practice. Previous work from our group developed a deep learning-based method to estimate T2 maps from clinically acquired T1- and T2-weighted images. This study aims to evaluate the added value of the estimated T2 map by combining it with conventional T2-weighted images for detecting clinically significant PCa (csPCa). Methods: An amount of 76 peripheral zone prostate lesions, including clinically significant and insignificant cases, were retrospectively analyzed. Radiomic features were extracted from conventional T2-weighted images and deep learning-estimated T2 maps, followed by feature selection and model development using five-fold cross-validation. Logistic regression and Gaussian Process classifiers were employed to develop the prediction models, with performance evaluated by area under the curve (AUC) and accuracy metrics. Results: The model incorporating features from both T2-weighted images and estimated T2 maps achieved an AUC of 0.803, significantly outperforming the model based solely on T2-weighted image features (AUC of 0.700, p = 0.048). Conclusions: Radiomics features extracted from deep learning-estimated T2 maps provide additional quantitative information that improves the prediction of peripheral zone csPCa aggressiveness, potentially enhancing risk stratification in non-invasive PCa diagnostics. Full article

Background: The relationship between case volume and clinical outcomes is well established for most urological procedures but remains underexplored in prostate ultrasound/MRI fusion biopsy (UMFB). UMFB aims to detect clinically significant prostate cancer (csPCa) by adhering to cancer detection benchmarks for PI-RADS lesions identified via multiparametric MRI (mpMRI). These benchmarks, defined by Ahmed et al., include cumulative cancer detection rate (C-CDR) targets of >80% for PI-RADS 5, >50% for PI-RADS 4, and <20% for PI-RADS 1–3. Methods: This retrospective, single-center study analyzed the case volumes required for two experienced urologists (U1 and U2, each with >15 years of practice) to consistently achieve the Ahmed-defined C-CDR benchmarks for csPCa (ISUP grade ≥ 2) using UMFB. Both transrectal and transperineal approaches were included to enable comprehensive learning curve analysis. Data from 2017 to 2023 were reviewed, encompassing 157 UMFBs performed by U1 and 242 by U2, with a transrectal-to-perineal ratio of 7:3. Results: Both urologists achieved Ahmed-defined C-CDR targets from the outset. Over a median follow-up of 30 months, patients with initial PI-RADS 4 or 5 ratings and negative primary biopsies remained prostate cancer-free in 77% of cases for U1 and 91.2% for U2 (p = 0.152). Conclusions: This study demonstrates that experienced urologists can achieve high diagnostic accuracy and maintain patient safety immediately upon implementing UMFB, meeting established benchmarks without requiring additional procedural learning. Full article

Background/Objectives: ACEIs protect against radiation pneumonitis by reducing angiotensin II production, oxidative stress, and inflammation. This study highlights the significance of concurrent angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) use in radiotherapy by evaluating its impact on radiotherapy-related side effects and survival outcomes, addressing the gap in existing research and providing insights to guide clinical practice in oncology. Methods: The literature was retrieved from the MEDLINE, EMBASE, Web of Science, and Scopus databases from January 2000 to October 2024. Studies on adults (≥18 years) with histologically confirmed cancer, receiving ACEIs or ARBs during radiotherapy, were included. Radiotherapy-related side effects and clinical outcomes were analysed using odds ratios (ORs) and 95% confidence intervals (95%CIs), comparing ACEI/ARB users to non-users. Differences in the median survival time, recurrence, and death rates were also calculated. Results: Sixteen studies (14 cohort studies and two randomised trials) were included. ACEI users exhibited a 50% reduction in the risk of ≥grade 2 radiation pneumonitis (OR: 0.50, 95%CI: 0.32–0.77) in lung cancer and significant reductions in the odds of proctitis (80%, OR: 0.20, 95%CI: 0.12–0.33), haematuria (75%, OR: 0.25, 95%CI: 0.16–0.41), and rectal bleeding (61%, OR: 0.39, 95%CI: 0.30–0.51) in prostate cancer. ACEI/ARB users showed reduced symptomatic radiation necrosis in brain metastases and better 6-month functional independence in supratentorial glioblastoma. Among six studies reporting survival, ACEI/ARB users had longer median survival in early-stage non-small-cell lung cancer and glioblastoma but shorter survival in small cell lung cancer and brain metastases. ARB users had inconsistent survival rates for lung cancer. The varying survival outcomes suggest that ACEIs/ARBs have different effects depending on the cancer type and stage, potentially influenced by cancer-specific factors, treatment protocols, or disease progression. Conclusions: ACEI use is associated with a reduction in radiation pneumonitis, but evidence for other radiotherapy-related toxicity and survival outcomes remains inconsistent across cancer types and severities. Further research should carefully control for confounders. Full article

This study aimed to evaluate the diagnostic potential of soluble Programmed Death Ligand 1 (sPD-L1) and Programmed Death 1 (sPD-1) molecules in plasma, along with urinary mRNA biomarkers—Prostate-Specific Membrane Antigen (PSMA), Prostate Cancer Antigen 3 (PCA3), and androgen receptor (AR) genes—for identifying clinically significant prostate cancer (PCa), defined as pathological stage 3. In a cohort of 68 PCa patients, sPD-L1 and sPD-1 levels were quantified using ELISA, while mRNA transcripts were measured by RT-qPCR. Results highlight the potential of integrating these liquid-based biomarkers. In particular, the combination of sPD-L1, sPD-1, and AR demonstrated the most significant improvement in diagnostic performance, increasing the area under the curve (AUC) from 0.65 to 0.81 and sensitivity from 60% to 88%, compared to AR alone. PSMA demonstrated an AUC of 0.82 and a specificity of 52.8%, which improved to an AUC of 0.85 and a specificity of 94.4% with the inclusion of sPD-L1 and sPD-1. Similarly, PCA3 achieved an AUC of 0.75 and a specificity of 53.8%, increasing to an AUC of 0.78 and a specificity of 76.9% when combined with these biomarkers. Incorporating sPD-L1 into a three-gene panel further elevated the AUC from 0.74 to 0.94. These findings underscore the value of multimodal liquid-based diagnostic panels in improving the management of clinically significant PCa. Full article

Background: There is emerging evidence of an inverse association between prostatic inflammation (PI) and prostate cancer (PCa) diagnosis and outcome. The Irani score, a validated system that scores PI according to the grade of stromal infiltration (Irani G) and the aggressiveness of glandular infiltration (Irani A), has indeed been found to be inversely associated with PCa diagnosis and outcome, but the presence of two categories (G and A) makes the performance of this score suboptimal. This study aimed to determine whether a novel prostatic inflammation score (PIS) that combines Irani G and A scores better defined the risk of being diagnosed with PCa at prostate biopsy (PBx). Methods: Between January 2013 and December 2023, the Irani scores were routinely assessed on hematoxylin and eosin-stained PBx cores. The novel PIS was obtained by combining Irani G and A scores by their kernel distribution. PIS 1 included patients who scored G 0–1/A 0–1, PIS 2 those who scored G 2–3/A 0–1, and PIS 3 included those who scored G 0–3/A 2–3. Logistic regression analysis was used to test the association between the novel PIS and the risk of being diagnosed with PCa and clinically significant (cs) PCa at PBx. Results: Among the 4620 eligible patients, PCa and csPCa detection rate was 47% and 25%, respectively. Overall, 3088 (66.8%) had low Irani G and 4041 (87.5%) had low Irani A scores. Using PIS, 2971 (64%) were classified as PIS 1, 1070 (23%) as PIS 2, and 579 (13%) as PIS 3. Notably, almost one-quarter of patients had heterogeneous Irani features. Multivariable analysis pointed out a significant association between PIS and the risk of being diagnosed with PCa and csPCa; the higher the PIS, the lower the likelihood of such diagnoses. Limitations included the absence of external validation. Conclusions: The novel PIS, easily obtained during routine pathology examination, was significantly associated with the risk of being diagnosed with PCa and csPCa at PBx. While PI seems to be overall protective over PCa, the different types (stromal vs. glandular) of inflammation depicted by PIS seem to express a different risk. Full article

Background/Objectives: Multiparametric-Magnetic Resonance Imaging(mp-MRI) presents the ability to detect clinically significant cancer, aiming to avoid biopsy if the results are negative or target an abnormal lesion if a suspected lesion of the prostate is found. Recent guidelines recommend the performance of 12 standard biopsies along with 3 to 5 targeted biopsies in suspected prostate lesions, depending on the size of the prostate lesion. In addition, prostate biopsy can be performed by either the transperineal or the transrectal approach. The aim of this comprehensive review is to highlight the role of both standard and targeted MRI/Ultrasound (US) fusion transperineal biopsy (TPB) in the diagnostic approach of prostate cancer cases, to report its diagnostic efficacy and complication rates and to suggest the promising usage of MRI/US fusion TPB in the future. Methods: A comprehensive review of the existing literature, including systematic reviews, meta-analyses, and clinical guidelines, was conducted to compare the efficacy and safety of transperineal and transrectal approaches in prostate cancer detection. Special emphasis was placed on mp-MRI-guided targeted biopsy and its combination with systematic sampling. Results: Prostate biopsy via the transperineal approach is related to increased detection rates, especially for anterior lesions, and decreased infection risk compared to the transrectal approach, while complication rates (hematuria, hemospermia, etc.) remain similar. Due to lower infection rates via the transperineal route, the performance of prostate biopsy using the transperineal approach is strongly recommended. Finally, transperineal fusion MRI/US biopsy can be valuable for repeat biopsies in patients who had an initial negative biopsy or for the follow-up of patients that undergo active surveillance. Conclusions: MRI/US fusion-guided TPB represents a significant advancement in prostate cancer diagnostics, combining improved precision with reduced infection risks. Although TPB presents higher detection rates for anterior prostatic lesions and lower post-biopsy infection rates, there is no significant difference in cancer detection rates compared to TRB. Targeted training and investment may reduce long-term expenses of TPB by lowering hospitalizations, antibiotic usage, and related costs. Future research should further refine this approach and explore its integration with emerging technologies like artificial intelligence for enhanced lesion targeting and diagnostic accuracy. Full article

Cancer is one of the leading causes of death globally, and is ranked second in the United States. Early detection is crucial for more effective treatment and a higher chance of survival rates, reducing burdens on individuals and societies. Genitourinary cancers, in particular, face significant challenges in early detection. Finding new and cost-effective diagnostic methods is of clinical need. Metabolomic-based approaches, notably volatile organic compound (VOC) analysis, have shown promise in detecting cancer. VOCs are small organic metabolites involved in biological processes and disease development. They can be detected in urine, breath, and blood samples, making them potential candidates for sensitive and non-invasive alternatives for early cancer detection. However, developing robust VOC detection methods remains a hurdle. This review outlines the current landscape of major genitourinary cancers (kidney, prostate, bladder, and testicular), including epidemiology, risk factors, and current diagnostic tools. Furthermore, it explores the applications of using VOCs as cancer biomarkers, various analytical techniques, and comparisons of extraction and detection methods across different biospecimens. The potential use of VOCs in detection, monitoring disease progression, and treatment responses in the field of genitourinary oncology is examined. Full article