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.

Pancreatic cancer is one of the leading causes of cancer death worldwide. Its high mortality rate has remained unchanged for years. Radiotherapy and surgery are considered standard treatments in early and locally advanced stages. Chemotherapy is the only option for metastatic patients. Two treatment regimens, i. e. the association of 5-fluorouracil-irinotecan-oxaliplatin (FOLFIRINOX) and the association of nabpaclitaxel with gemcitabine, have been shown to improve outcomes for metastatic pancreatic adenocarcinoma patients. However, there are not standardized predictive biomarkers able to identify patients who benefit most from treatments. CA19-9 is the most studied prognostic biomarker, its predictive role remains unclear. Other clinical, histological and molecular biomarkers are emerging in prognostic and predictive settings. The aim of this review is to provide an overview of prognostic and predictive markers used in clinical practice and to explore the most promising fields of research in terms of treatment selection and tailored therapy in pancreatic cancer.

Prostate cancer (PCa) is one of the main causes of cancer-related death in men. In the present immunotherapy era, several immunotherapeutic agents have been evaluated in PCa with poor results, possibly due to its low mutational burden. The recent development of chimeric antigen receptor (CAR)-T cell therapy redirected against cancer-specific antigens would seem to provide the means for bypassing immune tolerance mechanisms. CAR-T cell therapy has proven effective in eradicating hematologic malignancies and the challenge now is to obtain the same degree of in solid tumors, including PCa. In this study we review the principles that have guided the engineering of CAR-T cells and the specific prostatic antigens identified as possible targets for immunological and non-immunological therapies. We also provide a state-of-the-art overview of CAR-T cell therapy in PCa, defining the key obstacles to its development and underlining the mechanisms used to overcome these barriers. At present, although there are still many unanswered questions regarding CAR-T cell therapy, there is no doubt that it has the potential to become an important treatment option for urological malignancies.

Testicular germ cell tumors (TGCTs) represent the most common solid tumor in young men and is a model of curable cancer. The effectiveness of cisplatin-based chemotherapy secures more than 95% of patients' 5-years survival rate. However, some high-risk patients with a very advanced disease develop choriocarcinoma syndrome (CS) connected with acute respiratory failure with poor prognosis and high mortality rate shortly after beginning systemic chemotherapy. CS was first described as a syndrome with hemorrhage from metastatic sites in patients with TGCTs with significantly high choriogonadotropin level. Acute hemorrhage to lung metastases is typical, but hemorrhage can occur from any metastatic site. Patognomic of choriocarcinoma cells is an invasion of small blood vessels within CS. The incidence of CS in patients with TGCTs are not well-defined and can vary across the world. To date, there are a few case reports and small retrospective series reporting a connection between systemic chemotherapy and the development of CS in metastatic TGCTs. CS is known to be triggered by massive tumor cell lysis as a result of chemotherapy and cytokine release, aggravated with alveolar hemorrhage. This can lead to a consecutive superinfection, furthered with neutropenia after chemotherapy, acute respiratory distress syndrome, rising to systemic inflammatory response, resulting in multiorgan failure and death. A reasonably effective approach in patients with extensive disease could be a shortened course of chemotherapy as well as a reduction of dosage in induction chemotherapy before full-dose chemotherapeutical regimen; however, current data regarding optimal treatment approach are limited. Patients' referral to tertiary centers and the administration of induction chemotherapy in an intensive care unit setting could further improve the treatment outcome.

No abstract

No abstract

Currently, renal cell carcinoma is characterized by encouraging benefits from immunotherapy that have led to significant results in treatment outcome. The approval of nivolumab primarily as second-line monotherapy and, more recently, the approval of new combination therapies as first-line treatment have confirmed the importance of immunotherapy in this type of tumor. In this context, the chimeric antigen receptor (CAR)-T represents a further step forward in the field of immunotherapy. Initially tested on hematological malignancies, this new therapeutic approach is also becoming a topic of great interest for solid tumors. Although the treatment has several advantages over previous T-cell receptor-dependent immunotherapy, it is facing some obstacles in solid tumors such as a hostile tumor microenvironment and on-tumor/off-tumor toxicities. Several strategies are under investigation to overcome these problems, but the approval of CART cell therapy is still some way off. In renal cancer, the significant advantages obtained from immune checkpoint inhibitors represent a good starting point, but the potential nephrological toxicity of CART cell therapy represents an important risk. In this review, we provide the rationale and preliminary results of CART cell therapy in renal cell malignancies.

No abstract