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Among men with high-risk, nonmetastatic, castration-resistant prostate cancer, the addition of enzalutamide to androgen-deprivation therapy improved overall survival by nearly a year as compared with ADT alone: median survival was 67 months with enzalutamide plus ADT and 56 months with ADT alone.

Inhibitors of fibroblast growth factor receptor (FGFR) represent an outstanding treatment approach for selected patients with urothelial cancer (UC). These agents are changing the clinical approach to a subgroup of UC, the luminal-papillary subtype, characterized by FGFR mutations, fusions, or amplification. In this review, we provide an overview of the results of recent clinical trials on FGFR tyrosine kinase inhibitors (TKIs) currently in clinical development for the treatment of UC: erdafitinib, rogaratinib, infigratinib, and the monoclonal antibody vofatamab. The Food and Drug Administration recently granted accelerated approval to erdafitinib for patients with advanced UC with alterations of FGFR2 or FGFR3 after progression on platinum-based chemotherapy. We also look at future therapeutic options of combination regimens with immune-checkpoint inhibitors as strategies for improving the antitumor effects of this class of drug, and for preventing or delaying the development of resistance.

Background The prognostic value of the Geriatric 8 (G8) screening score in metastatic renal cell carcinoma (mRCC) patients receiving first-line immunotherapy remains unclear. This study aimed to evaluate the prognostic role of G8 within the context of the Meet-URO classification in mRCC patients treated with first-line ipilimumab-nivolumab. Methods This retrospective multicentre study analysed 106 mRCC patients treated with first-line ipilimumab-nivolumab. G8 and Meet-URO scores were calculated before treatment initiation. Primary endpoint was overall survival (OS), defined as duration from first administration of Nivolumab to death. OS was analysed in relation to age groups, G8 scores, and Meet-URO score categories, with data censored for patients still alive at the last follow-up. The secondary endpoint, progression-free survival (PFS), was measured from initiating Nivolumab to the earliest instance of disease progression or death. OS and PFS were assessed using Kaplan-Meier methods and Cox regression analyses. The reporting of this study conforms to the REMARK guidelines. Results Patients with G8 > 14 had more favorable IMDC and Meet-URO risk classifications and lower neutrophil-to-lymphocyte ratios. While PFS did not differ significantly between G8 ≤ 14 and >14 groups (1-year 29.3% vs 46.2%, p = 0.2), OS was significantly longer in G8 > 14 group (1-year 76.1% vs 58.6%, p = 0.006). In multivariable analysis, G8 ≤ 14 was independently associated with worse OS (HR 2.36, 95% CI 1.06-5.08, p = 0.03) but not PFS. The Meet-URO score was prognostic for both PFS and OS. In patients ≥70 years, G8 lost its prognostic value, while Meet-URO remained prognostic for OS. Conclusions The G8 score is an independent prognostic factor for OS but not PFS in mRCC patients receiving first-line ipilimumab-nivolumab. The Meet-URO score shows consistent prognostic ability for PFS and OS across age groups. These findings suggest that while G8 may be useful for individual patient-level OS prediction, the Meet-URO score may be superior for guiding treatment decisions in clinical practice.

Background: We retrospectively evaluated the correlation between a baseline measurement of circulating tumor cells (CTCs) and inflammation-based scores in patients with metastatic breast cancer (MBC). Methods: The optimal value of inflammation-based scores as the neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR) and systemic immune-inflammation index (SII) to predict survival was determined and compared with CTC <5 or ⩾5 per 7.5 ml of blood. Results: In the overall population of 516 women with MBC, CTCs correlated with peripheral blood monocytes (p = 0.008) and neutrophils (p = 0.038). In triple-negative tumors, CTCs correlated with monocyte count (p = 0.009); in HER2+ tumors, CTCs correlated with neutrophil count (p = 0.009), with a trend versus monocyte count (p = 0.061), whereas no correlation was found in HER2– estrogen receptor-positive (ER+) tumors. In multivariate analysis only monocytes were associated with ⩾5 CTCs (OR = 2.72, 95% CI 1.09–6.80, p = 0.033). In multivariable analysis for predictors of overall survival, CTC (⩾5 versus <5), number of metastatic sites (>1 versus 1), tumor subtypes (triple-negative versus HER2– ER+ tumors) and MLR only remained significant. Conclusions: CTC and MLR are predictors of overall survival in MBC. CTC correlates with monocytes, in particular in triple-negative tumors.

Body composition parameters (BCp) have been associated with outcome in different tumor types. However, their prognostic value in patients with HER2-positive metastatic breast cancer (BC) receiving first line treatment with dual anti-HER2 antibody blockade is unknown. Preclinical evidences suggest that adipocytes adjacent to BC cells can influence response to anti-HER2 treatments. We retrospectively analyzed Computed Tomography (CT)-based BCp from 43 patients with HER2-positive metastatic BC who received first line pertuzumab/trastuzumab-based treatment between May 2009 and March 2020. The impact of baseline CT-based BCp on progression-free survival (PFS) was tested using Kaplan–Meier estimates and univariate and multivariate Cox regression models. We found a significantly worse PFS for patients with high baseline subcutaneous fat index (median 7.9 vs 16.1 months, p = 0.047, HR = 2.04, 95%CI 1–4.17) and for those with high total abdominal fat index (8.1 vs 18.8 months, p = 0.030, HR = 2.17, 95%CI 1.06–4.46). Patients with baseline sarcopenia did not show shorter PFS compared to those without sarcopenia (10.4 vs 9.2 months, p = 0.960, HR = 0.98, 95%CI 0.47–2.03). Total abdominal fat index remained a significant predictor of PFS at multivariate analysis. Our findings suggest that a high quantity of total abdominal fat tissue is a poor prognostic factor in patients receiving trastuzumab/pertuzumab-based first-line treatment for HER2-positive metastatic BC.

Bladder cancer (BCa) patients are diagnosed by cytology and cystoscopy. However, these diagnostic tests bear some limitations. We sought for reliable biomarkers to better determine BCa extension. Prostate-specific membrane antigen (PSMA) appears to fulfill this requirement in prostate cancer but its role in BCa has not been established yet. We then analyzed 87 bladder tissue samples from 74 patients assessing PSMA expression by immunohistochemistry. The median PSMA expression, exclusively found in tumor neovasculature, in terms of H-score significantly differed between non-tumor samples and tumor samples ( p  = 0.00288) showing a higher neovasculature-related PSMA expression. No differences were observed in relation to tumor type, grade and stage. BCa neovasculature-related PSMA overexpression may be useful in defining the degree of extension of the neoplasm. In addition, testing PSMA expression by immunohistochemistry may hold theranostic implications both considering anti-angiogenesis agents and radio-labelled PSMA ligands for intracavitary radionuclide therapy. In our opinion, BCa neovasculature-related PSMA overexpression may be considered an apt target for anti-angiogenesis and radionuclide treatment in BCa, once the evaluation of tumor-retention time for the appropriateness of long half-life therapeutic PSMA ligands as radionuclide treatment will be performed.

Over the years, an increasing proportion of metastatic prostate cancer patients has been found to experience an initial bone flare phenomenon under both standard therapies (androgen deprivation therapy, chemotherapy, radiotherapy, abiraterone, enzalutamide) and novel agents (immunotherapy, bone-targeting radioisotopes). The underlying biological mechanisms of the flare phenomenon are still elusive and need further clarification, particularly in relation to different types of treatment and their treatment response assessment. Flare phenomenon is often underestimated and, in some cases, can negatively affect clinical outcome. In cases with suspected bone flare, the treatment should be continued for a minimum of 12 more weeks before further decisions about efficacy can be taken. Physicians and patients should be aware of this effect to avoid unwarranted anxiety and inadequate early discontinuation of treatment. This review aims at highlighting new evidence on flare phenomenon arising after the introduction of new drugs extending across the biochemical, radiographic and clinical spectrum of the disease.

Accurate preoperative distinction between in situ and invasive Breast Cancer (BC) is critical for clinical decision-making and treatment planning. Radiomics and Machine Learning (ML) have shown promise in enhancing diagnostic performance from breast MRI, yet their application to this specific task remains underexplored. The aim of this study was to evaluate the performance of several ML classifiers, trained on radiomic features extracted from DCE–MRI and supported by basic clinical information, for the classification of in situ versus invasive BC lesions. In this study, we retrospectively analysed 71 post-contrast DCE–MRI scans (24 in situ, 47 invasive cases). Radiomic features were extracted from manually segmented tumour regions using the PyRadiomics library, and a limited set of basic clinical variables was also included. Several ML classifiers were evaluated in a Leave-One-Out Cross-Validation (LOOCV) scheme. Feature selection was performed using two different strategies: Minimum Redundancy Maximum Relevance (MRMR), mutual information. Axial 3D rotation was used for data augmentation. Support Vector Machine (SVM), K Nearest Neighbors (KNN), Random Forest (RF), and Extreme Gradient Boosting (XGBoost) were the best-performing models, with an Area Under the Curve (AUC) ranging from 0.77 to 0.81. Notably, KNN achieved the best balance between sensitivity and specificity without the need for data augmentation. Our findings confirm that radiomic features extracted from DCE–MRI, combined with well-validated ML models, can effectively support the differentiation of in situ vs. invasive breast cancer. This approach is quite robust even in small datasets and may aid in improving preoperative planning. Further validation on larger cohorts and integration with additional imaging or clinical data are recommended.

Background: The addition of neutrophil-to-lymphocyte ratio (NLR) and bone metastases to the International Metastatic RCC Database Consortium (IMDC) score (by the Meet-URO score) has been shown to better stratify pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab. This study aimed to validate the Meet-URO score in patients receiving cabozantinib to assess its predictivity and prognostic role. Methods: A multicenter retrospective analysis evaluated mRCC patients receiving ⩾second-line cabozantinib. NLR, IMDC score and bone metastases were assessed before the start of cabozantinib. The primary endpoint was overall survival (OS). Harrell’s c-index was calculated to compare the accuracy of the prediction of the two scores. Results: Overall, 174 mRCC patients received cabozantinib as second and third line (51.7% and 48.3%, respectively) with a median follow-up of 6.8 months. A shorter median overall survival (mOS) was observed for the IMDC poor-risk group, NLR ⩾3.2 and the presence of bone metastases, while the IMDC intermediate-risk group had a similar mOS to the favourable-risk one. Applying the Meet-URO score, three risk groups were identified: group 1 (55.2% of patients) with a score of 0–3, group 2 (38.5%) with a score of 4–8 and group 3 (6.3%) with a score of 9. Compared to group 1 (mOS: 39.4 months), a statistically significant worse mOS was observed in group 2 (11.2 months) and group 3 (3.2 months) patients, respectively. The Meet-URO c-index score was 0.640, showing a higher discriminative ability than the IMDC score (c-index: 0.568). Conclusion: This analysis showed that the Meet-URO score provides a more accurate prognostic stratification than the IMDC score in mRCC patients treated with ⩾second-line cabozantinib besides nivolumab. Moreover, it is an easy-to-use tool with no additional costs for clinical practice (web-calculator is available at: https://proviso.shinyapps.io/Meet-URO15_score/). Future investigations will include the application of the Meet-URO score to the first-line immunotherapy-based combination therapies.

BackgroundAngiogenesis has been recognized as the most important factor for tumor invasion, proliferation, and progression in metastatic renal cell carcinoma (mRCC). However, few clinical data are available regarding the efficacy of cabozantinib following immunotherapy.ObjectiveTo describe the outcome of cabozantinib in patients previously treated with immunotherapy.Patients and methodsPatients with mRCC who received cabozantinib immediately after nivolumab were included. The primary endpoint was to assess the outcome in terms of efficacy and activity.ResultsEighty-four mRCC patients met the criteria to be included in the final analysis. After a median follow-up of 9.4 months, median overall survival was 17.3 months. According to the IMDC criteria, the rates of patients alive at 12 months in the good, intermediate, and poor prognostic groups were 100%, 74%, and 33%, respectively (p < 0.001). The median progression-free survival (PFS) was 11.5 months (95% CI 8.3–14.7); no difference was found based on duration of previous first-line therapy or nivolumab PFS. The overall response rate was 52%, stable disease was found as the best response in 25.3% and progressive disease in 22.7% of patients. Among the 35 patients with progressive disease on nivolumab, 26 (74.3%) patients showed complete/partial response or stable disease with cabozantinib as best response after nivolumab. The major limitations of this study are the retrospective nature and the short follow-up.ConclusionsCabozantinib was shown to be effective and active in patients previously receiving immune checkpoint inhibitors. Therefore, cabozantinib can be considered a valid therapeutic option for previously treated mRCC patients, irrespective of the type and duration of prior therapies.