Current Options for Second-Line Systemic Therapy in Metastatic Renal Cell Carcinoma

Standard systemic therapy of advanced renal cell carcinoma (RCC) involves targeting angiogenesis, mainly through tyrosine kinase inhibitors (TKI) against the vascular endothelial growth factor receptor (VEGFR) pathway and targeting the immune checkpoints, namely, programmed death-1 (PD-1) or its ligand (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4). With current strategies of combining these two approaches in the front-line setting, less is known about optimal selection of therapy upon development of resistance in the second and later lines of treatment for progressive disease. This review discusses currently available therapeutic options in patients who have progressive RCC after prior treatment with double immune check-point inhibitors (ICIs) or ICI-TKI combinations

Lower urinary tract symptoms and bladder cancer in children: The hidden scenario

Bladder cancer is extremely rare in children. We report a case series of two children with transitional cell bladder cancer who presented with lower urinary tract symptoms. Pathology revealed a low risk for recurrence and progression tumor. In such a case, early diagnosis is crucial and surgical treatment is usually the only treatment needed

Biomarkers in Prostate-Specific Membrane Antigen Theranostics

Theranostics of prostate cancer (PC) represents a growing area of development of imaging agents and targeted radionuclide therapeutics against a major target, prostate specific membrane antigen (PSMA). In view of the encouraging efficacy from the use of 177Lu and other radionuclides in metastatic castration-resistant prostate cancer (mCRPC), it is becoming increasingly important to identify surrogate markers that can help predict which patients are more likely to respond and experience improved survival. This review discusses potential predictors of efficacy of PSMA-targeted radionuclide therapies (TRT) segregated in three major categories: imaging, clinical and molecular

Granular cell tumors of the urethra

Granular cell tumors (GCTs) are a rare type of mesenchymal tumors that are histologically derived by Schwann cells and rise within soft tissues such as skin and mucosal surfaces. Differentiation between benign and malignant GCTs is often difficult and relies on their biological behavior and metastatic potential. While there are no standard guidelines for management, upfront surgical resection, whenever feasible, is key as a definitive measure. Systemic therapy is often limited by poor chemosensitivity of these tumors; however, accumulating knowledge of their underlying genomic landscape has opened some opportunities for targeted approaches, for example, the vascular endothelial growth factor tyrosine kinase inhibitor pazopanib, which is already in clinical use for the treatment of many types of advanced soft tissue sarcomas

Expression of Fibroblast Activation Protein Is Enriched in Neuroendocrine Prostate Cancer and Predicts Worse Survival

Background: Advanced prostate cancer (PC) may accumulate genomic alterations that hallmark lineage plasticity and transdifferentiation to a neuroendocrine (NE) phenotype. Fibroblast activation protein (FAP) is a key player in epithelial-to-mesenchymal transition (EMT). However, its clinical value and role in NE differentiation in advanced PC has not been fully investigated. Methods: Two hundred and eight patients from a multicenter, prospective cohort of patients with metastatic castration-resistant prostate cancer (CRPC) with available RNA sequencing data were analyzed for tumor FAP mRNA expression, and its association with overall survival (OS) and NE tumor features was investigated. Results: Twenty-one patients (10%) were found to have high FAP mRNA expression. Compared to the rest, this subset had a proportionally higher exposure to taxanes and AR signaling inhibitors (abiraterone or enzalutamide) and was characterized by active NE signaling, evidenced by high NEPC- and low AR-gene expression scores. These patients with high tumor mRNA FAP expression had a more aggressive clinical course and significantly shorter survival (12 months) compared to those without altered FAP expression (28 months, log-rank p = 0.016). Conclusions: FAP expression may serve as a valuable NE marker indicating a worse prognosis in patients with metastatic CRPC

Primitive neuroectodermal tumor transformation of testicular teratoma

Malignant transformation of teratoma develops in a small subset of testis cancer patients. Primitive neuroectodermal tumor represents a highly malignant component of testicular germ cell tumors. It is a rare clinical entity which is characterized by a high risk of disease progression and death. Surgical resection plus chemotherapy appears to be the therapy of choice

Sexual dysfunction in newly diagnosed multiple sclerosis women

Objectives The aim of the study was to evaluate female sexuality in a selective population of newly diagnosed multiple sclerosis (MS) women. Materials and methods In this clinic-based study, 63 newly diagnosed consecutive women affected by definite MS were admitted. Disability and depression were evaluated with the expanded disability status scale (EDSS) and Beck depression inventory, respectively. Sexual function was evaluated with the female sexual function index (FSFI). A group of 61 healthy female volunteers with the same baseline characteristics were used as controls. Postmenopausal women and patients with other major concomitant neurological, endocrinological, vascular, gynecological, psychiatric disorders, use of medicines that can cause female sexual dysfunction (FSD) and disease-modifying drugs were excluded from the study. Results All the evaluated patients were ambulant with no major neurological impairment (mean EDSS score 2.5, range 0-3.5). None of the patients were considered clinically depressed, but some of them were sad or worried. According to the sexual history and FSFI scores, sexual dysfunction was diagnosed in 22 (34.9%) out of the 63 patients and in 13 (21.31%) out of the 61 healthy females (P > 0.05). Conclusions In the newly diagnosed MS patients, FSD represent an important issue even though disability and other concomitant disorders affecting sexual function were excluded

Medical Expulsive Therapy for Distal Ureteral Stones

Although minimally invasive treatments for ureteral stones are efficacious, they are not free of complications and are associated with high cost. Medical expulsive therapy (MET) has recently emerged as an alternative strategy for the initial management of small distal ureteral stories. A MEDLINE search was undertaken to evaluate all currently available data on efficacy and safety of MET therapy in such patients. The specific mechanism of action on the ureteral smooth muscle and the emerging evidence of the efficacy (defined as either an increase in expulsion rate or a decrease in time to expulsion) and low-risk profile suggest that alpha-adrenergic receptor antagonists (alpha-blockers) and calcium channel antagonists should be the initial medical treatment in patients amenable to conservative therapy. NSAIDs and anticholinergics have not shown efficacy as single agents or in combination with alpha-blockers or nifedipine. Corticosteroids may provide a small additive effect when combined with either alpha-blockers or nifedipin

Hypoxia-Inducible Factor-2-Altered Urothelial Carcinoma: Clinical and Genomic Features

Background: Hypoxia is recognized as a key feature of cancer growth and is involved in various cellular processes, including proliferation, angiogenesis, and immune surveillance. Besides hypoxia-inducible factor 1-alpha (HIF-1α), which is the main mediator of hypoxia effects and can also be activated under normoxic conditions, little is known about its counterpart, HIF-2. This study focused on investigating the clinical and molecular landscape of HIF-2-altered urothelial carcinoma (UC). Methods: Publicly available next-generation sequencing (NGS) data from muscle-invasive UC cell lines and patient tumor samples from the MSK/TCGA 2020 cohort (n = 476) were interrogated for the level of expression (mRNA, protein) and presence of mutations, copy number variations, structural variants in the EPAS1 gene encoding HIF-2, and findings among various clinical (stage, grade, progression-free and overall survival) and molecular (tumor mutational burden, enriched gene expression) parameters were compared between altered and unaltered tumors. Results: 19% (7/37) of UC cell lines and 7% (27/380) of patients with muscle-invasive UC display high EPAS1 mRNA and protein expression or/and EPAS1 alterations. EPAS1-altered tumors are associated with higher stage, grade, and lymph node metastasis as well as with shorter PFS (14 vs. 51 months, q = 0.01) and OS (15 vs. 55 months, q = 0.01). EPAS1 mRNA expression is directly correlated with that of its target-genes, including VEGF, FLT1, KDR, DLL4, CDH5, ANGPT1 (q EPAS1-altered tumors (9.9 vs. 4.9 mut/Mb), they are enriched in and associated with genes promoting immune evasion, including ARID5B, SPINT1, AAK1, CLIC3, SORT1, SASH1, and FGFR3, respectively (q Conclusions: HIF-2-altered UC has an aggressive clinical and a distinct genomic and immunogenomic profile enriched in angiogenesis- and immune evasion-promoting genes