The prognostic value of the previous nephrectomy in pretreated metastatic renal cell carcinoma receiving immunotherapy: a sub-analysis of the Meet-URO 15 study.

Background: Nephrectomy is considered the backbone of managing patients with localized and selected metastatic renal cell carcinoma (mRCC). The prognostic role of nephrectomy has been widely investigated with cytokines and targeted therapy, but it is still unclear in the immunotherapy era.

Methods: We investigated the Meet-URO-15 study dataset of 571 pretreated mRCC patients receiving nivolumab as second or further lines about the prognostic role of the previous nephrectomy (received in either the localized or metastatic setting) in the overall population and according to the Meet-URO score groups.

Nivolumab in Combination with Stereotactic Body Radiotherapy in Pretreated Patients with Metastatic Renal Cell Carcinoma. Results of the Phase II NIVES Study.

Background: Nivolumab showed an overall survival (OS) benefit in pretreated metastatic renal cell carcinoma (mRCC). The role of stereotactic body radiotherapy (SBRT) in mRCC remains to be defined.

Objective: Our aim was to evaluate the efficacy and safety of SBRT in combination with nivolumab in second- and third-line mRCC patients.

Exceptional response to immunotherapy in association with radiotherapy in patient with breast metastasis from urothelial carcinoma: .

Most common sites of metastasis of urothelial carcinoma (UC) are lungs, liver, lymph nodes and bone. Pembrolizumab, a humanized monoclonal antibody directed against programmed cell death protein-1 (PD-1), represents an effective second-line therapy for advanced UC. Radiotherapy has been shown to induce a mechanism of immunogenic cell death (ICD) resulting in immune memory and advantageous systemic effects.

PD-L1 Expression in De Novo Metastatic Castration-sensitive Prostate Cancer.

De novo metastatic castration-sensitive prostate cancer (mCSPC) is small subgroup of prostate cancer associated with poor prognosis. The aim of our study was to assess the expression of programmed death-ligand 1 (PD-L1) in tumor cells of de novo mCSPC patients. Patients referred to our institution from January 2007 to October 2017 with de novo mCSPC and available diagnostic tissue were included.

Cabozantinib-related cardiotoxicity: a prospective analysis in a real-world cohort of metastatic renal cell carcinoma patients.

Aims: Data regarding the cardiac toxicity of cabozantinib lacks. The aim of our study was to assess the risk of cabozantinib-related cardiotoxicity in mRCC patients.

Methods: We performed a multicentre prospective study on mRCC patients treated with cabozantinib between October 2016 and November 2017.

Second-line therapy for metastatic urothelial carcinoma: Defining the best treatment option among immunotherapy, chemotherapy, and antiangiogenic targeted therapies. A systematic review and meta-analysis.

There is no second-line standard of care universally accepted for platinum-refractory metastatic urothelial carcinoma. Immunotherapy and anti-VEGF(R) targeted therapies are 2 emerging strategies with promising though inconclusive results. We perform a systematic meta-analysis to assess the available options.

Predictive role of changes in the tumor burden and International Metastatic Renal Cell Carcinoma Database Consortium class during active surveillance for metastatic renal cell carcinoma.

Background: Despite important results achieved for metastatic renal cell carcinoma, some patients could benefit from local treatments or an initial active surveillance (AS) period for recurrent disease. We aim to analyze: changes in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk class, the number of metastases and the disease burden from the start of AS to the beginning of systemic therapy; and if these changes influenced patient outcomes.

Patients And Methods: Patients who started AS at our institution from January 2007 to April 2016 were included.

Comparison Between Prognostic Classifications in De Novo Metastatic Hormone Sensitive Prostate Cancer.

Background: The CHAARTED and LATITUDE trials demonstrated improved outcomes with docetaxel or abiraterone plus androgen deprivation therapy in metastatic hormone sensitive prostate cancer (mHSPC) using two different prognostic scores.

Objective: The aim of our study was to assess the concordance between the two scores and if these retained their prognostic value exclusively in de novo mHSPC.

Patients And Methods: De novo mHSPC patients referring to our institution were retrospectively stratified according to the CHAARTED and LATITUDE classifications: high volume/high risk (HV/HR), low-volume/low-risk (LV/LR), and HVorHR (HV/LR and LV/HR).

Immunotherapy versus standard of care in metastatic renal cell carcinoma. A systematic review and meta-analysis.

Background: Recently, immune checkpoint inhibitors against PD-1/PD-L1 or CTLA4 have emerged as new treatments for metastatic renal cell carcinoma (mRCC), despite discrepancy between their effects on OS and PFS. We performed a meta-analysis of randomized trials comparing immunotherapy to standard of care (SOC) in mRCC.

Methods: Searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts prospective studies were identified.

De novo metastatic castration sensitive prostate cancer: State of art and future perspectives.

De novo metastatic castration sensitive prostate cancer (mCSPC) accounts for about 4% of all prostate tumors in Western Countries. This condition has a heterogeneous biological e clinical behavior, ranging from indolent to aggressive and rapidly fatal forms. Recently, the therapeutic landscape for mCSPC has been broadly enriched; indeed robust evidence supports the addiction of chemotherapy (docetaxel) or abiraterone acetate to androgen deprivation therapy (ADT), the latter considered for long the unique standard of care.

Renal cell carcinoma in one year: Going inside the news of 2017 - A report of the main advances in RCC cancer research.

Very interesting issues regarding RCC treatment have been raised during 2017. We analysed the main news that may potentially modified clinical practice. Conflicting data came from trials testing targeted therapies in the adjuvant setting, supporting the necessity of further investigations.

The Cardiovascular Toxicity of Abiraterone and Enzalutamide in Prostate Cancer.

Introduction: The cardiovascular toxicity related to abiraterone and enzalutamide has been previously studied by our group. In this analysis, we aim to update our previous findings related to abiraterone and enzalutamide, including the new available evidence, both in castration-resistant and hormone-sensitive prostate cancer. PATIENTS AND METHODS: Prospective studies were identified by searching the MEDLINE/PubMed, Cochrane Library, and ASCO Meeting abstracts.

Addressing the best treatment for non-clear cell renal cell carcinoma: A meta-analysis of randomised clinical trials comparing VEGFR-TKis versus mTORi-targeted therapies.

Aim: Non-clear cell renal cell carcinoma (nccRCC) tumours include a heterogeneous group of malignancies that profoundly differ in terms of morphology, genetic profile, clinical behaviour and prognosis. The optimal treatment algorithm for nccRCC is still unknown and derived mainly from evidence available for ccRCC, being therefore represented by targeted agents against vascular endothelial growth factor and mammalian target of rapamycin (mTOR) pathways. We aimed to compare the efficacy of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKis) and mTOR inhibitors (mTORi) for the treatment of nccRCC patients.

The incidence and relative risk of pulmonary toxicity in patients treated with anti-PD1/PD-L1 therapy for solid tumors: a meta-analysis of current studies.

Aim: Monoclonal antibodies (mAbs) directed against PD-1/PD-L1 have recently entered the therapeutic algorithm of several solid tumors. Among treatment-related adverse events pulmonary toxicity (PT) is of particular interest. We assess the incidence and relative risk (RR) of PT in patients treated with anti-PD1/PD-L1 mAbs.

Acquired hemophagocytic syndrome in a patient with synovial sarcoma: a case report.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome characterized by severe hyperinflammation due to an overwhelming ineffective immune response to different triggers. Most important symptoms are fever, hepatosplenomegaly and cytopenias. Biochemical signs include elevated ferritin, hypertriglyceridemia and low fibrinogen.

Investigating BRCA Mutations: A Breakthrough in Precision Medicine of Castration-Resistant Prostate Cancer.

Despite the development of novel effective therapeutic strategies, metastatic castration-resistant prostate cancer (mCRPC) remains a disease with a lethal course and a high biological and molecular heterogeneity. To date, germline mutations in the BRCA gene represent one of the main risk factors for developing prostate cancer, with a strong association with aggressive phenotype and poor clinical outcomes. A better understanding of the genomic landscape of prostate cancer has strengthened the idea that "synthetic lethality" of this disease might be useful in cancer-drug discovery, focusing on agents such as platinum compounds and poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi).

Metabolic alterations in renal cell carcinoma.

Renal cell carcinoma (RCC) is a metabolic disease, being characterized by the dysregulation of metabolic pathways involved in oxygen sensing (VHL/HIF pathway alterations and the subsequent up-regulation of HIF-responsive genes such as VEGF, PDGF, EGF, and glucose transporters GLUT1 and GLUT4, which justify the RCC reliance on aerobic glycolysis), energy sensing (fumarate hydratase-deficient, succinate dehydrogenase-deficient RCC, mutations of HGF/MET pathway resulting in the metabolic Warburg shift marked by RCC increased dependence on aerobic glycolysis and the pentose phosphate shunt, augmented lipogenesis, and reduced AMPK and Krebs cycle activity) and/or nutrient sensing cascade (deregulation of AMPK-TSC1/2-mTOR and PI3K-Akt-mTOR pathways). We analyzed the key metabolic abnormalities underlying RCC carcinogenesis, highlighting those altered pathways that may represent potential targets for the development of more effective therapeutic strategies.

Metastatic castration-resistant prostate cancer: targeting the mechanisms of resistance to abiraterone acetate and enzalutamide.

Persistent androgen receptor (AR) axis is a functionally important pathway for prostate cancer cells and it is currently regarded as a critical therapeutic target. Although the impressive clinical activity of new hormonal agents, such as the second-generation AR antagonist enzalutamide (formerly MDV3100) and the selective inhibitor of cytochrome P450 17A1 (CYP17A1) abiraterone acetate (AA), in patients with metastatic castration-resistant prostate cancer (mCRPC), innate or acquired resistance invariably arises. To date, emerging hypotheses are different, but the mechanisms of resistance to these drugs have not yet been clarified.

Complete remission with sunitinib in a poor-risk patient with metastatic renal cell carcinoma: the fine balance between toxicity and efficacy.

Sunitinib represents a reasonable therapeutic option for first-line treatment of poor-risk metastatic renal cell carcinoma and the treatment should aim at the delicate balance between managing side effects to improve the toxicity profile and patient compliance to treatment while maintaining anticancer efficacy. Achievement of a complete response, although rare, is possible, even in poor-risk patients. Treatment discontinuation represents a viable alternative for both tumour biology and patients' quality of life.