Nowadays, the management of prostate cancer has become more and more challenging due to the increasing number of available treatment options, therapeutic agents, and our understanding of its carcinogenesis and disease progression. Moreover, currently available risk stratification systems used to facilitate clinical decision-making have limitations, particularly in providing a personalized and patient-centered management strategy. Although prognosis and prostate cancer-specific survival have improved in recent years, the heterogenous behavior of the disease among patients included in the same risk prognostic group negatively impacts not only our clinical decision-making but also oncological outcomes, irrespective of the treatment strategy. Several biomarkers, along with available tests, have been developed to help clinicians in difficult decision-making scenarios and guide management strategies. In this review article, we focus on the scientific evidence that supports the clinical use of several biomarkers considered by professional urological societies (and included in uro-oncological guidelines) in the diagnosis process and specific difficult management strategies for clinically localized or advanced prostate cancer.

Antibody-mediated rejection (AMR) is a leading cause of kidney graft failure. Complement activation is involved in the AMR process. Our aim is to provide the current understanding of the pathophysiology related to complement-mediated injury in AMR, to present the current evidence regarding complement blockade in AMR management, and to point out emerging therapies and future directions in this area. The complement system plays an important role in the onset and progression of AMR. There is a balance between complement-dependent and -independent mechanisms in the development of rejection lesions. Classic and leptin pathways are involved in this process. C4d positivity is no longer a mandatory feature for AMR diagnosis but remains an independent predictor of negative outcomes. The current evidence regarding AMR treatment is limited. Terminal and proximal complement blockade has gained recognition in clinical practice. Eculizumab and C1 inhibitors are effective in the treatment of AMR as adjuvant therapies to the standard of care. The availability of novel complement inhibitors will lead to more effective and tailored treatment strategies.

Background/Objectives: Penile squamous cell carcinoma (PSCC) is a rare malignancy with a potential major impact on survival. Prognostic assessment remains challenging, particularly in underrepresented eastern European populations, where region-specific evidence is lacking. This paper aimed to identify independent predictors of overall survival in surgically treated patients with PSCC from a Romanian high-volume tertiary center. Methods: This retrospective cohort study analyzed 60 patients who were surgically treated for PSCC between October 2020 and December 2024. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify independent prognostic factors. Results: The mean patient age was 62 ± 12 years. T-stage distribution showed 30% pT1, 35% pT2, 31.67% pT3, and 3.33% pT4, with 55% of patients presenting with nodal metastases. Univariate analyses demonstrated significant associations between lymphovascular invasion (p < 0.001), perineural invasion (p = 0.022), and positive surgical margins (p = 0.030) and risk of death. Multivariate analysis identified three independent prognostic factors: absence of histologically documented urethral invasion (HR 0.32; p = 0.027), T3–T4 disease (HR 8.26; p = 0.005 vs. T1), and N3 stage (HR 3.53; p = 0.030 vs. N0–N1). Patients without urethral invasion demonstrated significantly longer median overall survival (63 months vs. 11 months). The final three-variable prognostic model demonstrated good discrimination (C-index 0.78), providing a potential practical risk stratification tool. Conclusions: Urethral invasion, advanced T-stage, and N3 disease independently predict poor survival in surgically treated PSCC. The identification of urethral invasion as an independent prognostic factor warrants consideration in clinical practice. This is the first study of a Romanian cohort to provide critical data for risk-adapted treatment strategies in underrepresented eastern European populations.

Background: Oncocytoma and angiomyolipoma (AML) are benign renal tumors that may mimic malignant lesions on imaging. With the increasing use of partial nephrectomy (PN) for renal masses, accurate preoperative characterization of these lesions is essential. This study highlights the role of partial nephrectomy as a valuable diagnostic tool in situations where imaging is inconclusive or raises concern for malignancy without definitive confirmation. In the absence of a reliable preoperative diagnosis, partial nephrectomy provides direct histologic verification with minimal perioperative morbidity. Moreover, it offers curative potential when malignancy is present. By achieving both diagnostic certainty and renal preservation, this approach is well-suited for clinical scenarios in which imaging ambiguity might otherwise result in overtreatment through radical surgery or undertreatment Material and methods: in this retrospective study, we reviewed our 5-year experience (2019–2024), 188 partial nephrectomies—including bilateral procedures and operations on solitary kidneys—using robotic and open approaches. All of these 30 tumors were solid renal masses with indeterminate imaging features or suspicious characteristics suggestive of malignancy, further underscoring the limitations of current preoperative diagnostic modalities. Results: Histopathological evaluation confirmed benign renal tumors in 30 cases, with oncocytoma diagnosed in 18 cases (16 robotic, 2 open) and AML in 12 cases (9 robotic, 3 open). Conclusions: Even when imaging raises suspicion of malignancy or remains inconclusive, many small renal masses are ultimately confirmed as benign upon histopathological examination. This study underscores the diagnostic uncertainty associated with small renal tumors and highlights the value of partial nephrectomy as a decisive diagnostic intervention. In situations where non-invasive modalities fail to provide definitive answers, partial nephrectomy offers tissue confirmation with minimal morbidity. Furthermore, when malignancy is present, this approach ensures appropriate oncologic management while preserving renal function. Our findings support the integration of this strategy into routine clinical practice, particularly when diagnostic clarity is essential for guiding safe and effective treatment.

Background and Objectives: Paraneoplastic hypercalcemia represents a rare but clinically significant complication of penile squamous cell carcinoma (PSCC), with limited evidence available. This systematic review aimed to comprehensively evaluate the pathophysiological mechanisms, clinical presentation, therapeutic strategies and prognostic outcomes of tumor-induced hypercalcemia in PSCC. Methods: A comprehensive literature search was conducted across PubMed/MEDLINE and Scopus databases from inception to December 2024. Cases were included if they documented histopathologically confirmed PSCC with biochemically verified hypercalcemia and objective evidence of paraneoplastic etiology. Data extraction encompassed tumor characteristics, hypercalcemia severity, mechanistic classification, therapeutic interventions and survival outcomes. Analysis followed PRISMA 2020 guidelines adapted for descriptive synthesis. Results: Twelve published cases spanning six decades (1965-2024) met inclusion criteria. The median age at presentation was 56 years, with 91.6% of patients presenting with advanced disease. Severe hypercalcemia (≥14 mg/dL) occurred in 66.7% of cases, with a median calcium level of 15.45 mg/dL. Three distinct pathophysiological mechanisms were identified: PTHrP-mediated humoral hypercalcemia, bone metastasis-associated hypercalcemia and tumor burden-mediated hypercalcemia. Despite biochemical correction, median overall survival was 9 weeks following hypercalcemia diagnosis. Conclusions: Paraneoplastic hypercalcemia in PSCC represents a rare metabolic emergency. While aggressive management can achieve biochemical correction, the occurrence of hypercalcemia uniformly indicates advanced tumor biology with limited survival benefit. Early recognition and prompt multidisciplinary intervention remain essential for symptomatic relief and quality of life preservation. Future prospective studies are needed to better characterize optimal management strategies and refine prognostic models.

Background and Objectives: Paraneoplastic hypercalcemia represents a rare but clinically significant complication of penile squamous cell carcinoma (PSCC); however, limited information is available for this condition. Therefore, this systematically conducted narrative review aimed to comprehensively evaluate the pathophysiological mechanisms, clinical presentation, therapeutic strategies and prognostic outcomes of tumor-induced hypercalcemia in PSCC. Methods: A comprehensive literature search was conducted across PubMed/MEDLINE and Scopus databases from their inception to December 2024. Cases were included if they documented histopathologically confirmed PSCC with biochemically verified hypercalcemia and objective evidence of paraneoplastic etiology. Data extraction included tumor characteristics, severity of hypercalcemia, mechanistic classification, therapeutic interventions and survival outcomes. The search methodology followed PRISMA 2020 guidelines adapted for narrative synthesis. Given the absence of comparative studies for this rare condition, all study types were eligible for inclusion, resulting in an evidence base that consisted exclusively of case reports and case series. Results: Twelve published cases spanning six decades (1965–2024) met the inclusion criteria. The median age at presentation was 56 years, with 91.6% of patients presenting with advanced disease. Severe hypercalcemia (≥14 mg/dL) occurred in 66.7% of cases, with a median calcium level of 15.45 mg/dL. Two established pathophysiological mechanisms were identified: PTHrP-mediated humoral hypercalcemia and bone metastasis-associated hypercalcemia. By contrast, three cases with unmeasured PTHrP levels had an undetermined mechanism. Despite biochemical correction, median overall survival was 9 weeks following diagnosis of hypercalcemia. Conclusions: Paraneoplastic hypercalcemia in PSCC represents a rare metabolic emergency. While aggressive management can achieve biochemical correction, the occurrence of hypercalcemia uniformly indicates advanced tumor biology with limited survival benefit. Early recognition and prompt multidisciplinary intervention remain essential for symptomatic relief and preserving quality of life. Reporting future cases and collaborating with international registries will be necessary to improve understanding of this rare paraneoplastic entity.