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We retrospectively analyzed real-world data from the ARON-1 project for patients with papillary renal cell carcinoma who received first-line immune-based combinations or tyrosine kinase inhibitors. Immune-based combinations were associated with better 1-yr and 2-yr overall survival rates, better median progression-free survival, and a better objective response rate. Immune-based combinations are the preferable option for first-line treatment in this setting.

Background: Currently, several therapies are available for metastatic castration-resistant prostate cancer (mCRPC) but no specific clinical factors to personalize treatment. We first sought the prognostic value of duration on androgen-deprivation therapy (ADT) for hormone-sensitive prostate cancer (HSPC) in patients receiving androgen-receptor-signaling inhibitors (ARSI) for mCRPC. Methods: A multicenter cohort of mCRPC patients who started ARSI between July 2011 and October 2021 was identified. Based on their initial disease burden and duration on ADT for HSPC, primary progressive (PP) men were classified into four groups: low/intermediate-risk localized disease (LOC) and high-risk localized/locally advanced disease (LAD) and short-term (ST) < 24 vs. long-term (LT) ADT ≥ 24 months, whereas de novo (DN) mHSPC were subdivided into short-time vs. long-time to CRPC. Results: We included 919 mCRPC patients with a median age of 77 years [interquartile range (IQR) = 71–82)]. Median ADT duration in HSPC was 24 months (IQR = 14–40). Median follow-up was 91 months (IQR = 62–138), median OS and PFS from ARSI start were 20 (IQR 10–32) and 10 months (IQR = 5–19), respectively. In PP developing metastatic disease (n= 655, 71.3%), LOC and LAD with ST ADT had a greater than almost double-risk of death compared to LT ADT (LOC/ST: hazard ratio [HR] = 2.01; 95% CI 1.54–2.64; LAD/ST: HR = 1.73; 95% CI 1.34–2.24; p< 0.001). In the multivariate analysis including age, prognostic cohort, Gleason, ECOG, radical radiotherapy and prostatectomy, groups with ST ADT were associated with worse OS compared to LT ADT (LOC/ST: HR = 1.84; 95% CI 1.38–2.45; p< 0.001; LAD/ST: HR = 1.59; 95% CI 1.21–2.10; p< 0.001), along with ECOG > 2 (HR = 1.55; 95% CI 1.06–2.26; p= 0.03). There were also similar results of PFS. Moreover, long-time to CRPC in patients with history of DN mHSPC (n= 264, 28.7%) resulted in a better OS/PFS (HR = 0.76, 95% CI 0.56–1.02, p= 0.064 and HR = 0.74, 95% CI 0.55–0.99, p= 0.042, respectively). Conclusions: Our study showed that duration on ADT for mHSPC was significantly associated with survival in mCRPC undergoing ARSI. These findings suggest a possible connection between initial management of prostate tumour and a better prognostication in mCRPC. Prospective trials are warranted.

Carotid stenosis due to severely calcified plaque can pose a significant therapeutic challenge. Extremely calcified scars/stenosis plaques can be challenging from an endovascular treatment perspective as severely calcified lesions are prone to technical failure, stent re-coil and restenosis. Intravascular lithotripsy, approved for treatment of severely calcified coronary lesions, can be used for breaking up the calcium build up in the intimal and medial layers of the vessel wall prior to stenting. This was designated as a breakthrough device innovation by the Food and Drug Administration. This new technique addresses the challenge of the disease without compromising patient safety during the procedure. We here report procedural set-up, execution and early patient follow up from our first use of this emerging technology in a neurointerventional practice setting.

Obesity has been associated with improved response to immunotherapy in cancer patients. We investigated the role of body mass index (BMI) in patients from the ARON-1 study (NCT05287464) treated by dual immuno-oncology agents (IO+IO) or a combination of immuno-oncology drug and a tyrosine kinase inhibitors (TKI) as first-line therapy for metastatic renal cell carcinoma (mRCC).

•Adjuvant systemic treatment with sunitinib for patients with renal cell carcinoma (RCC) is controversial.•Systemic adjuvant treatment with Sunitinib improves disease-free survival, however with considerable toxicity.•Adjuvant systemic treatment with immune checkpoint inhibitors (ICI) is associated with lower risk of toxicity, however with conflicting clinical benefit.•This meta-analysis, with the available high-level data of adjuvant systemic treatment with ICI for RCC patients, was not able to demonstrate survival benefit in the overall population.

ABSTRACTIntroductionSignificant advances have been made in the first-line therapy of metastatic renal cell carcinoma (mRCC) since the approval of immune-based combinations, including nivolumab plus ipilimumab or cabozantinib, and pembrolizumab plus axitinib or lenvatinib.Areas coveredThe aim of this review is to compare the different safety profiles of first-line immune-based combinations versus sunitinib across the four respective pivotal trials (CheckMate 214, CheckMate 9ER, KEYNOTE-426, and CLEAR), with a particular attention to patients’ health-related quality of life (HRQoL) assessment.Expert opinionThe concurrent use of an immune-checkpoint inhibitor (ICI) with a tyrosine kinase inhibitor (TKI) as a first-line treatment strategy for mRCC has highlighted the unmet clinical need for prompt detection and consequently proper management of adverse events (AEs), both immune-related and TKI-induced. Overlapping AEs, such as hypertransaminasemia, are most challenging to manage, and evidence is still outlined from clinical practice. The specific patterns of toxicities of the approved first-line immune-based combinations, along with the impact of these interventions on patients’ HRQoL, demand a deeper consideration by physicians while choosing the appropriate treatment for each individual mRCC patient. Both safety profile and HRQoL evaluation could be exploited to guide the first-line treatment selection in this setting.

The treatment of castration-sensitive prostate cancer (CSPC) has been revolutionized by the advent of apalutamide and enzalutamide in this setting; however, a direct comparison between these agents is still missing. In the current paper, we performed both Number Needed to Treat (NNT) and Number Needed to Harm (NNH) analyses aimed to compare clinical outcomes in CSPC patients treated with apalutamide or enzalutamide; data from 3323 CSPC patients enrolled in the ARCHES, ENZAMET and TITAN phase III studies were included. According to our results, apalutamide showed better results in terms of overall survival (OS) and safety in patients with CSPC, while better outcomes were observed with enzalutamide in the low-volume subgroup.

BackgroundSuper large-bore aspiration (SLBA) has shown high rates of complete clot ingestion.ObjectiveTo report the initial clinical feasibility, safety, and efficacy of this novel SLBA insert combination—super large-bore ingestion of clot (SLIC) technique for stroke.MethodsWe performed a retrospective review of three comprehensive stroke center databases. The SLIC technique entails a triaxial assembly of an 8 Fr 0.106″ Base Camp catheter, 0.088″ catheter extender (HiPoint), and an insert catheter (Tenzing 8) that completely consumes the inner diameter of the 0.088″ SLBA catheter. The HiPoint catheter is delivered over the Tenzing 8 to the face of the embolus, which is withdrawn, while aspirating through the Base Camp and HiPoint catheters as a single assembly.ResultsThirty-three consecutive patients with large vessel occlusion were treated with SLIC. The median age was 70 years (30–91) and 17 were male (51.5%). The median presenting National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT score was 21 (1–34) and 8 (5–10), respectively. There was 100% success in delivering the 0.088″ catheter to the site of the occlusion. The successful revascularization rate (modified Thrombolysis in Cerebral Infarction (mTICI) score ≥2B) was 100% within a single pass in most cases (82%). Final mTICI ≥2C was achieved in 94.1% of occlusions, with 73.5% mTICI 3 recanalization. The rate of first pass effect in achieving excellent reperfusion (mTICI ≥2C) was 70.5%. There were no adverse events or postprocedural symptomatic hemorrhages.ConclusionsOur initial experience with the SLIC technique resulted in achieving a first pass effect (mTICI ≥2C) in 70.5%. Navigation of the SLBA catheter extender over the Tenzing insert was successful and safe in this early experience.

The standard of care for locoregional renal cell carcinoma is surgery, but many patients experience recurrence. The objective of the current study was to determine if adjuvant atezolizumab (vsplacebo) delayed recurrence in patients with an increased risk of recurrence after resection.

Upper tract urothelial carcinomas (UTUCs) arise in the renal pelvis or the ureter, accounting for approximately 5% of all urothelial carcinomas. Recent years have witnessed the publication of several studies aimed at assessing the molecular, biologic, and clinical features of UTUC, reporting that FGFR3mutations are the most observed genetic aberrations; however, several knowledge gaps persist in the understanding of the genomic landscape of this genitourinary malignancy with few treatment options.

Immune checkpoint inhibitor (ICI)-based combinations have become the first-line standard of care in metastatic renal cell carcinoma (mRCC), but their activity on the primary tumor is still one of the most debated issues.

ABSTRACTIntroductionWhile sorafenib monotherapy represented the mainstay of medical treatment for advanced hepatocellular carcinoma (HCC) patients for more than a decade, novel agents and combination therapies have recently produced unprecedented paradigm shifts. The combination of lenvatinib plus pembrolizumab is now being evaluated as a front-line treatment in advanced HCC patients; early phase clinical trials have already reported promising results.Areas coveredThis paper reviews the combination of lenvatinib plus pembrolizumab for the treatment of advanced HCC. The preclinical rationale and completed and ongoing trials are examined and later, the authors reflect on biomarkers of predictive of response to immune-based combinations and future treatment decision-making on the basis of tolerability and clinical benefits provided by these novel therapeutics. A literature search was conducted in April 2021 of Pubmed/Medline, Cochrane library and Scopus databases; moreover, abstracts of international cancer meetings were reviewed.Expert opinionThe landscape of new agents and combinations continues to expand. Recently, immune-based combinations have reported important results in advanced HCC, as witnessed by the landmark IMbrave150 trial. Based on the promising results of early phase clinical trials, lenvatinib plus pembrolizumab has the potential to represent a novel treatment option in this setting.

ABSTRACTBackgroundPARP inhibitors (PARPi) have recently emerged as a new treatment option for several solid tumors, including metastatic castration-resistant prostate cancer (mCRPC). However, several grade 3–4 adverse events have been reported during PARPi administration, leading to limitations in treatment adherence.MethodsHerein, we conducted a meta-analysis aimed at analyzing the incidence rate of commonly reported grade 3–4 adverse events, dose reduction, and treatment discontinuation in mCRPC patients treated with PARPi monotherapy.ResultsIncidence rate with 95% confidence intervals (CIs) of grade 3–4 toxicities, dose reduction, and treatment discontinuation were calculated. Six trials involving 752 mCRPC patients were available for the meta-analysis. According to our results, anemia was the most frequently observed grade 3–4 toxicity (24.1%), and dose reduction (26.9%) and treatment discontinuation (14.1%) were common events during PARPi treatment.ConclusionsClinicians should carefully consider these risks, especially taking into account that the use of PARPi in mCRPC patients is expected to rise in the near future.

BackgroundData regarding the safety and efficacy of flow diverting stents (FDS) in the treatment of middle cerebral artery (MCA) bifurcation aneurysms are scarce and limited to small single center series, with particular concern for increased risk of ischemic complications with jailing one of the M2 branches.MethodsProspectively-maintained databases at six North American and European centers were queried for patients harboring MCA bifurcation aneurysms undergoing treatment with FDS (2011–2018). The pertinent clinical and radiographic data were collected and analyzed.Results87 patients (median age 60 years, 69% females) harboring 87 aneurysms were included. The majority of aneurysms were unruptured (79%); 75.9% were saccular with a median maximal diameter of 8.5 mm. Radiographic imaging follow-up was available in 88.5% of cases at a median of 16.3 months post-treatment, showing complete occlusion in 59% and near complete occlusion (90–99%) in 18% of aneurysms. The overall rate of ischemic and hemorrhagic complications was 8% and 1.1%, respectively. Symptomatic and permanent complications were encountered in 5.7% and 2.3% of patients respectively, with retreatment pursued in 2.3% of patients. Jailed branch occlusion was detected in 11.5% of cases, with clinical sequelae in 2.3%. Last follow-up modified Rankin Scale of 0–2 was noted in 96.8% of patients. On multivariate analysis, male sex was the only independent predictor of aneurysmal persistence at last follow-up imaging (p=0.019).ConclusionFDS treatment for MCA bifurcation aneurysms is feasible, with comparable safety and efficacy profiles to other available endovascular options when utilized in carefully selected aneurysms. Jailing of M2 branches was not associated with a higher risk of post-procedural ischemic complications.

ABSTRACTIntroductionTreatment-related neurotoxicity is a common side effect in cancer patients. However, few data are available regarding the risk of several neurotoxicities in patients treated with immune checkpoint inhibitors.Areas coveredThe MOUSEION-02 study is an up-to-date meta-analysis aimed at assessing the risk of peripheral neuropathy, peripheral sensory neuropathy, and headache in cancer patients receiving immunotherapy and immuno-oncology combinations. Patients receiving immunotherapy (as monotherapy or in combination with other anticancer agents) showed lower risk of all-grade peripheral neuropathy (RR, 0.50; 95% CI, 0.35–0.70) and all-grade peripheral sensory neuropathy (RR, 0.49; 95% CI, 0.30–0.79). Similarly, in patients treated with immune checkpoint inhibitor monotherapy, we observed lower risk of all-grade peripheral neuropathy (RR, 0.05; 95% CI, 0.03–0.10) and all-grade peripheral sensory neuropathy (RR, 0.11; 95% CI, 0.05–0.23). No differences were observed in terms of all-grade headache.Expert opinionAlthough the results of this meta-analysis should be interpreted with caution due to several issues, our study draws attention to immunotherapy-related neurotoxicity with the aim of maximizing clinical outcomes of cancer patients experiencing these not uncommon, and yet poorly studied, adverse events.

ABSTRACTIntroduction: In the evolving treatment scenario of metastatic renal cell carcinoma, cabozantinib is gaining increasing attention, presenting as a cornerstone therapy, both as a monotherapy and in combination with immune-checkpoint inhibitors.Areas covered: In this review, the authors explore the role of cabozantinib in the treatment of metastatic clear cell and non-clear cell renal cell carcinoma, presenting data from the most recent clinical trials and investigating ongoing studies. They, furthermore, evaluate the pharmacokinetic, pharmacodynamic, and immunomodulatory effect of cabozantinib, as well as underlining the tolerability profile and patients’ quality of life.Expert opinion: Cabozantinib’s administration as a single agent is restricted to intermediate- and poor-risk patients (according to IMDC criteria). The further advent of anti-VEGF-receptor tyrosine kinase inhibitors combined with immune checkpoint inhibitor regimens (such as pembrolizumab + axitinib) has allowed to expand the use of cabozantinib, leading to its combination with nivolumab. In the next few years, more information is required to look for the application of cabozantinib-based combinations as a later-line approach in metastatic RCC patients, beside their use in the first-line setting.

ABSTRACTBackground:With hormonal agents quickly expanding as novel therapeutic options in nonmetastatic castration-resistant prostate cancer (nmCRPC), the toxicity profile of enzalutamide, apalutamide, and darolutamide should be kept in mind.Methods:We performed an updated meta-analysis with the aim to analyze the risk of treatment-related cardiovascular (CV) events, any grade, and grade 3–4 (G3-4) hypertension in nmCRPC patients treated with enzalutamide, apalutamide, and darolutamide plus androgen deprivation therapy (ADT) versus ADT plus placebo in randomized controlled trials (RCTs). Results were compared by calculating Relative Risk (RR) with 95% confidence intervals (CIs); RRs were combined with Mantel-Haenszel method.Results:Three RCTs involving 4110 patients were available for the meta-analysis. According to our results, the addition of novel hormonal agents was associated with a significantly increased risk of CV events (RR = 1.71; 95% CI 1.29–2.27) and G3-4 hypertension (RR = 1.53; 95% CI 1.19–1.97). In addition, a trend toward a higher risk of any grade hypertension was reported in the experimental arm.Conclusions:The use of enzalutamide, apalutamide, and darolutamide in nmCRPC patients implies a careful benefit-risk assessment. Real-world, large-cohort studies are warranted to confirm the findings of our meta-analysis.

•Penile squamous cell (PSCC) carcinoma is a rare tumor with an aggressive behavior.•Meet-URO 23/I-RARE database is a multicentric registry on rare genitourinary tumors.•This retrospective study evaluates clinical outcomes and prognostic factors in PSCC.•Patients with an ORR to I line platinum-based chemotherapy have a better survival.•Poor ECOG PS, lymph node metastases and higher age are poor prognostic factors.

Purpose To report use of distal radial artery (dRA) access for carotid artery stenting (CAS) and to discuss procedural setup and technical considerations for a successful intervention.Methods A retrospective review of our prospective neurointerventional database of CAS was conducted between May 2019 and March 2020. All CAS cases via dRA in the anatomical snuffbox were identified. Patient demographics, clinical information, procedural and radiographic data was collected.Results 22 CAS procedures in 20 patients via dRA were identified. Patients’ mean age was 69.4 years (range 53–87 years). 3 patients were female. Mean radial artery diameter was 2.1 mm (range 1.6–2.8 mm). dRA access was achieved in all cases. Conversion to femoral access was required in 2 cases (9.1%) due to persistent radial artery vasospasm resulting in patient discomfort despite multiple additional doses of intraarterial vasodilators and added intravenous sedation as well as tortuous vessel anatomy and limited support of the catheters in a type 3 aortic arch for left CAS.Conclusion Our preliminary experience with dRA access for CAS suggests this approach to be feasible and safe for patients. Technical considerations are important and preprocedural planning is necessary for a successful intervention. Catheter systems and devices specifically designed for radial access are needed to enable more interventionalists to safely perform neurointerventional procedures via wrist access.

The incidence of kidney cancer is increasing; it could be counteracted with new ways to predict and detect it. We aimed to implement an artificial neural network in order to predict new cases of renal-cell carcinoma (RCC) in the population using population rate, obesity, smoking incidence, uncontrolled hypertension, and life expectancy data in the United States.

Intracranial dural arteriovenous fistulae (dAVFs) with cortical venous drainage (CVD) require treatment because of their aggressive clinical presentation and natural history. Although endovascular treatment is effective for the majority of these lesions in the current endovascular era, surgical management has been required if the lesions are not amenable to or fail endovascular treatments.

ABSTRACTIntroductionSignal transducer and activator of transcription 3 (STAT3) is involved in cancer initiation and resistance to chemo-radiation therapies and targeted agents. The role of STAT3 in inflammation and immunity together with its involvement in a variety of diseases including genitourinary, gastrointestinal, lung, ovarian and brain tumors makes STAT3 an ideal candidate for therapeutic strategies.Areas CoveredThe authors provided an overview on STAT3 inhibitors and examined the most recent results obtained by these agents in cancer patients. The authors discussed the results published since 2015 and the ongoing clinical trials on anti-STAT3 agents in cancer patients. The authors also provide our opinion on the future perspectives of this therapeutic approach in this context. The manuscript includes information from trial databases and scientific literature.Expert OpinionFuture challenges include the development of non-peptide small-molecule inhibitors of STAT3 designed to directly inhibit STAT3 activity. In addition, inhibitors of STAT3/STAT3 nuclear translocation or DNA binding activity are also emerging as novel promising therapeutic approaches A better comprehension of the role of STAT3 in modulating immune response together with advances in understanding the mechanisms of STAT3-induced chemo and/or radio-resistance will also help the design of combined strategies in cancer patients.

The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria have been largely adopted in clinical practice. In a recent retrospective study, we assessed that the addition of the first site of metastatic disease to brain, bone, and liver improves prognostic stratification of patients with metastatic renal cell carcinoma (mRCC). Here, we performed an external validation in patients with mRCC. Our aim was to evaluate if the addition of a new independent variable could improve IMDC prognosis prediction and reduce heterogeneity within risk categories.

Renal cell carcinoma (RCC) scenario has radically changed with the advent of immunotherapy; in this setting, the identification of predictive and prognostic factors represents an urgent clinical need to evaluate which patients are the best candidate for an immunotherapy approach. The aim of our study was to analyze the association between nivolumab in pretreated patients with metastatic RCC and clinicopathological features, metastatic sites, and clinical outcomes. A total of 37 patients treated between January 2017 and April 2020 in our institution were retrospectively evaluated. All patients received nivolumab as second- or later-line of therapy after progression on previous tyrosine kinase inhibitors. The primary outcomes were overall survival (OS) from immunotherapy start and OS from first-line start. Univariate analysis was performed through the log-rank test and a Cox regression proportional hazards model was employed in multivariable analysis. Of the 12 variables analyzed, 4 were significantly associated with prognoses at multivariate analysis. Cox proportional hazard ratio models confirmed that International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) risk group, liver metastases at diagnosis, and central nervous system (CNS) metastases at diagnosis were associated with worse OS with an estimated hazard ratio of 4.76 [95% confidence interval (CI), 2.05–19.8] for liver metastases and 2.27 (95% CI, 1.13–28.9) for CNS metastases. Pancreatic metastases at diagnosis were correlated to a better prognosis with an estimated hazard ratio of 0.15 (95% CI, 0.02–0.38). IMDC risk group, liver metastases at diagnosis, and CNS metastases at diagnosis may identify a population of patients treated with immunotherapy in second- or later-line associated with worse prognosis.

Background: Immune checkpoint inhibitors targeting the programmed death receptor ligand 1 (PD-L1)/programmed death receptor 1 (PD-1) pathway represent a drastic change in the treatment landscape of RCC resulting in a dynamic and evolving scenario. There is an urgent need for predictive biomarkers of response to provide a personalized therapeutic strategy for individual patients. Objective: In this review, we focused on trials that investigated the administration of a PD-1 and PDL1 inhibitor alone or in combination with another agent and compared the different assays applied in each trial to evaluate the role of PD-L1 as a prognostic and predictive biomarker. Conclusion: So far, the use of PD-L1 expression alone is not sufficient to predict treatment response and present many limitations: the lack of consensus between different methodologies on biomarker assessment, the heterogeneity of PD-L1 between primary tumors and metastatic sites, different criteria of response to therapy (RECIST vs. irRECIST), the complex interplay with inflammatory components, previous treatments, administration of antibiotic therapy. Combinations of different biomarkers and biological features, such as gene expression associated with angiogenesis, immune response and myeloid inflammation are promising biological variables that need to be validated in the context of prospective clinical trials.

Background: The management of renal cell carcinoma is rapidly evolving and immunotherapy, mostly consisting of immune checkpoint inhibitors, is revolutionizing the treatment scenario of metastatic patients. Novel fractionation schedules of radiotherapy, consisting of high doses in few fractions, can overcome the radioresistance of this tumor. Localized radiotherapy is associated with a systemic effect, known as the abscopal effect. This effect mediated by the immune system can be enhanced associating radiotherapy with immunotherapy. Objective: In this review, we explore the role of radiotherapy and immunotherapy in RCC, the rationale of combining these strategies and the on-going clinical trials investigating combinations of these two treatment modalities. Conclusion: Combining immunotherapy and radiotherapy has a strong rationale and pre-clinical studies support their association because it can overcome the immunosuppression of the tumor microenvironment and increase the anti-tumor immune response. More clinical evidence, deriving from onclinical trials, are needed to prove the efficacy and safety of these treatments combined.

ABSTRACTIntroductionImmune-based combinations, including nivolumab plus ipilimumab, pembrolizumab plus axitinib, and (at a lesser extent) avelumab plus axitinib, should be regarded among the new standards of care for first line therapy of metastatic renal cell carcinoma. Toxicity profiles are different among all these above combinations, as well as between them and targeted agents monotherapies, including sunitinib (i.e. the control arm of all the above studies).Areas coveredWe performed a systematic review and meta-analysis with the aim to compare adverse events from immune-based combinations versus sunitinib monotherapy across four recent randomized controlled trials (CheckMate-214, Keynote-426, IMmotion-151, and JAVELIN Renal 101) of front-line treatment for metastatic renal cell carcinoma, with particular attention to those from the ipilimumab plus nivolumab combination.Expert opinionBeyond efficacy and activity, the ipilimumab plus nivolumab combination appears feasible, being endowed by an acceptable safety profile, in line with that of the other available options for the treatment of metastatic RCC. The different patterns of toxicities emerging from this systematic review and meta-analysis need to be kept in mind while choosing the appropriate treatment for each individual patient. Furthermore, prevention, prompt identification, and treatment of immune-related adverse events remains an area to be improved.

ABSTRACTIntroductionMonoclonal antibodies directed against programmed cell death-1 (anti-PD-1) and its ligand (anti-PD-L1) showed a significant efficacy among different immunogenic metastatic tumors such as melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC). Between immune-related adverse events (irAEs) dependent on immune checkpoint inhibitors (ICPIs), immune-related liver diseases are uncommon and a definitive diagnosis is not always feasible.Areas coveredWe revised data from phase II/III clinical trials and real-world retrospective analyses on liver-related adverse events induced by anti-PD-1 (nivolumab/pembrolizumab) and anti-PD-L1 (atezolizumab) in advanced cancer populations (melanoma, NSCLC and RCC). Furthermore, we described clinical-pathological patterns of immune-related liver diseases in real-life.Expert opinionUse of anti-PD-1 and anti-PD-L1 led to a paradigm shift in the management of patients with melanoma, NSCLC and RCC. IrAEs can occur potentially in any tissue, leading to discontinuation of ICPIs, at least in a small proportion of these patients, and to a negative impact on their prognosis. Hepatobiliary immune-related adverse events are underestimated due to inappropriate monitoring. Development of novel diagnostic and therapeutic strategies for cancer patients receiving ICPIs as well as the identification of predictive biomarkers of liver injury could allow a better patients’ selection and improve clinical outcomes of immune-related liver diseases.

Several models are adopted in clinical practice to estimate prognosis of patients with metastatic renal cell carcinoma (mRCC); however, none of these models have evaluated patients treated by immune-checkpoint inhibitors. The aim of this study was to investigate if the site of initial metastasis could be a parameter able to stratified prognosis among patients with mRCC among different risk groups defined by the International Metastatic Renal Cell Database Consortium (IMDC) model. The site of initial metastasis was defined as the primary tissue or organ in which metastasis was diagnosed in the course of the medical history of the disease.

Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke.

Prostate cancer is the most frequent non-cutaneous malignancy in men in the United States. In the last few years, many recommendations have been made available from the 2014 International Society of Urologic Pathology consensus conference, 2016 World Health Organization blue book and 2018 8th edition of American Joint Committee on Cancer Staging System. Here, we focus on four topics which are considered relevant on the basis of their common appearance in routine practice, clinical importance and ‘need to improve communication between pathology reports and clinicians’: prostate cancer classification, prostate cancer grading, prostate cancer staging, and current definition of clinically significant prostate cancer. Tissue biomarkers that can predict significant disease and/or upgrading and tissue-based genomics for the purpose of diagnosis and prognosis are mentioned briefly.