797 Background: ARIES trial evaluated avelumab monotherapy in PD-L1+ve aUC patients (pts) not eligible to cisplatin-based chemotherapy, reaching its primary endpoint (Iacovelli R et al. ASCO-GU 2022). Treatment landscape for aUC has changed since enfortumab-vedotin and pembrolizumab (EV+P) has become the new standard for platinum-eligible pts reporting also a mPFS of 10.6 mos and 1-y OS rate of about 80% in cisplatin ineligible (carboplatin-eligible) pts. Unfortunately, up to 20% of pts are not eligible to platinum-based chemotherapy (PBC) and guidelines continue to recommend immunotherapy alone. Methods: Pts with PDL1+ve aUC and not eligible for cisplatin-based chemotherapy were enrolled and treated with avelumab until progression of disease. Here we reported the final OS, and we evaluated the baseline differences between pts with longer PFS compared to those who immediately progressed. Baseline characteristic included in this analysis were sites of metastases, performance status, body mass index (BMI), haematological values and the Neutrophils-to-Lymphocytes Ratio (NLR). Results: 71 pts were enrolled, the median age was 75 years (range 38 – 88); bladder cancer was the primary tumour in 73.2% of cases, 25.3% had liver metastases, 31% had ECOG=2 and 31% had renal function <50ml/min. After a median FU of 52 mos, the median OS was 10.3 mos (95%CI 5.3 – 15.3) and the median PFS was 2.1 mos (95%CI 1.8 – 2.4). 26 pts (37%) received subsequent therapies, with gem+carbo as most frequently used (15 pts, 21%). A total of 18 pts (25%) had a PFS ≥9 mos while 44 (62%) had a PFS ≤3 mos. Significant differences between these two groups were the presence of liver mets (11% vs. 36%; p=0.047), the presence of node only disease (39% vs 5%; p<0.001) and the rate of pts with NLR>4 (22% vs. 61%; p=0.005). At multivariable analysis only NLR>4 and liver mets were confirmed to be independent prognostic factors. The 27 pts (38%) without liver mets and with NLR>4 had significantly (p=0.001) prolonged mPFS (7.7 vs. 1.9 mos), mOS (20.4 vs. 5.7 mos), and 1y OS rate (67% vs. 32%). Conclusions: ARIES trial confirmed the activity of avelumab in cisplatin-ineligible aUC pts including those not eligible to PBC. This analysis also identified the absence of liver mets and low values of NRL as potential markers of significant benefit from immunotherapy alone. This evidence can be used for a personalized approach in the evolving treatment landscape of aUC. Clinical trial information: NCT03891238 .

Importance:Non-clear cell renal cell carcinomas (nccRCCs) present considerable challenges owing to their heterogeneity and limited clinical trial representation. Understanding the benefits of combining immunotherapy and targeted therapy for these subtypes is crucial for improving patient outcomes. Objective:To evaluate the efficacy of various first-line immunotherapy combinations and targeted therapy in treating metastatic nccRCC. Data Sources:A systematic literature search was conducted across PubMed, Embase, and Cochrane Library databases from inception until December 31, 2024, using relevant keywords and medical subject headings terms. Study Selection:Studies were included if they involved patients with nccRCC, reported on immune checkpoint inhibitor (ICI)-based therapies, and provided data on objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and disease control rate (DCR). Data extraction and Synthesis:Two independent reviewers extracted data, with discrepancies resolved by a third expert. Observational study quality was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed, and heterogeneity was evaluated using the I2 statistic. Main Outcome and Measures:The primary outcomes of interest were ORR, PFS, OS, and DCR. Results:The analysis included 23 studies encompassing various subtypes of nccRCC. Pooled results indicated an ORR of 26.6% and a DCR of 57.8% for nccRCC treatments. Median PFS was 6.59 months, and the median OS was 21.11 months. ICIs demonstrated significant efficacy in nccRCC, exhibiting marked clinical activity across different subtypes. Although monotherapy with ICIs showed effectiveness, combination therapies yielded superior clinical outcomes. Conclusions and Relevance:This systematic review and meta-analysis found that ICIs, particularly when combined with targeted therapies, showed promising efficacy in treating metastatic nccRCC. These findings support their integration into treatment guidelines and emphasize the importance of personalized treatment strategies. Future research should focus on long-term outcomes, safety profiles, and the identification of biomarkers to optimize patient selection and improve outcomes.

ImportanceNon-clear cell renal cell carcinomas (nccRCCs) present considerable challenges owing to their heterogeneity and limited clinical trial representation. Understanding the benefits of combining immunotherapy and targeted therapy for these subtypes is crucial for improving patient outcomes.ObjectiveTo evaluate the efficacy of various first-line immunotherapy combinations and targeted therapy in treating metastatic nccRCC.Data SourcesA systematic literature search was conducted across PubMed, Embase, and Cochrane Library databases from inception until December 31, 2024, using relevant keywords and medical subject headings terms.Study SelectionStudies were included if they involved patients with nccRCC, reported on immune checkpoint inhibitor (ICI)-based therapies, and provided data on objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and disease control rate (DCR).Data extraction and SynthesisTwo independent reviewers extracted data, with discrepancies resolved by a third expert. Observational study quality was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed, and heterogeneity was evaluated using the I2 statistic.Main Outcome and MeasuresThe primary outcomes of interest were ORR, PFS, OS, and DCR.ResultsThe analysis included 23 studies encompassing various subtypes of nccRCC. Pooled results indicated an ORR of 26.6% and a DCR of 57.8% for nccRCC treatments. Median PFS was 6.59 months, and the median OS was 21.11 months. ICIs demonstrated significant efficacy in nccRCC, exhibiting marked clinical activity across different subtypes. Although monotherapy with ICIs showed effectiveness, combination therapies yielded superior clinical outcomes.Conclusions and RelevanceThis systematic review and meta-analysis found that ICIs, particularly when combined with targeted therapies, showed promising efficacy in treating metastatic nccRCC. These findings support their integration into treatment guidelines and emphasize the importance of personalized treatment strategies. Future research should focus on long-term outcomes, safety profiles, and the identification of biomarkers to optimize patient selection and improve outcomes.

Renal cell carcinoma (RCC) is one of the most frequently diagnosed tumors and a leading cause of death. The high risk of local recurrence and distant metastases represent a significant clinical issue. Different image-guided ablation techniques can be applied for their treatment as an alternative to surgery, radiotherapy or systemic treatments. A retrospective analysis was conducted at our institution, including a total number of 34 RCC patients and 44 recurrent RCC tumors in different locations (kidney, lung, adrenal gland, liver, pancreas, pararenal and other) using microwave ablation, radiofrequency ablation, cryoablation and laser ablation. The estimated time to local and distant tumor progression after treatment were 22.53 ± 5.61 months and 24.23 ± 4.47 months, respectively. Systemic treatment was initiated in 10/34 (29%) treated patients with a mean time-to-systemic-therapy of 40.92 ± 23.98 months. Primary technical success was achieved in all cases and patients while the primary efficacy rate was achieved in 43/44 (98%) cases and 33/34 (97%) patients, respectively, with a secondary technical success and efficacy rate of 100%. At a mean follow-up of 57.52 months ± 27.86 months, local tumor progression occurred in 3/44 (7%) cases and distant progression in 25/34 (74%) patients. No significant complications occurred. Image-guided ablations can play a role in helping to better control recurrent disease, avoiding or delaying the administration of systemic therapies and their significant adverse effects.

We tested the feasibility and oncological outcomes after penile-sparing surgery (PSS) for local recurrent penile cancer after a previous glansectomy/partial penectomy. We retrospectively analysed 13 patients (1997–2022) with local recurrence of penile cancer after a previous glansectomy or partial penectomy. All patients underwent PSS: circumcision, excision, or laser ablation. First, technical feasibility, treatment setting, and complications (Clavien–Dindo) were recorded. Second, Kaplan–Meier plots depicted overall and local recurrences over time. Overall, 11 (84.5%) vs. 2 (15.5%) patients were previously treated with glansectomy vs. partial penectomy. The median (IQR) time to disease recurrence was 56 (13–88) months. Six (46%) vs. two (15.5%) vs. five (38.5%) patients were treated with, respectively, local excision vs. local excision + circumcision vs. laser ablation. All procedures, except one, were performed in an outpatient setting. Only one Clavien–Dindo 2 complication was recorded. The median follow-up time was 41 months. Overall, three (23%) vs. four (30.5%) patients experienced local vs. overall recurrence, respectively. All local recurrences were safely treated with salvage surgery. In conclusion, we reported the results of a preliminary analysis testing safety, feasibility, and early oncological outcomes of PSS procedures for patients with local recurrence after previous glansectomy or partial penectomy. Stronger oncological outcomes should be tested in other series to optimise patient selection.

439 Background: Avelumab (ave) was approved as maintenance therapy after platinum-based first line (1L) therapy for patients (pts) with aUC based on ph. 3 Javelin Bladder 100 study (NCT02603432), showing significant overall survival (OS) improvement. Here we tested the activity of ave as 1L of therapy in cis-unfit pts with aUC and PD-L1+ve expression. Methods: ARIES is a single-arm, multi-site, open-label phase II trial. Enrolled pts had aUC, were cis-unfit (at least one of: ECOG-PS = 2, CrCl < 60 mL/min, grade ≥2 peripheral neuropathy/hearing loss, progression within 6-mos before the end of neo/adj chemo), had not previously received chemo for aUC and PD-L1≥5% (SP263) centrally assessed. Pts received ave 10 mg/Kg IV Q2W until progression, unacceptable toxicity and withdrawal, whichever occurred first. The primary endpoint was the 1-year OS. Key secondary endpoints were median-OS, -PFS, ORR and safety. Results: A total of 198 eligible cis-unfit pts have been tested for PD-L1 and 71 (35.6%) have been found positive. Among enrolled patients (N = 71), median age was 75 y, 35 (49.3%) had visceral disease, and 22 (31.0%) had ECOG-PS = 2; 50 (70.4%) had CrCl < 60 mL/min and 9 (12.7%) progressed within 6-mos from the end of neo/adj chemo. At the cut-off data (Oct 7, 2021), median follow up was 9.0 mo and 13 patients are still on treatment. The median OS was 10.0 mos (95% CI, 5.7-14.3), and 40.8% of patients were alive at 1-year. The ORR for all patients was 22.5%; complete response, 1.4% (n = 1); partial response, 21.1% (n = 15). Clinical benefit was 43.6% (n = 31). Median PFS was 2.0 mos (95% CI, 1.4-2.6). Among the 56 pts who received at least 3 cycles (29 days) of therapy the median OS was 16.0 vs 1.0 mos. Five (7.0%) grade 3 ave-related adverse events, and no treatment-related death were reported. Conclusions: Ave is active and safe in pts with cis-unfit, PD-L1+ve aUC and poor baseline characteristics. Clinical trial information: NCT03891238.

Background: Cisplatin-based chemotherapy is the most recommended treatment for metastatic urothelial cancer (mUC). However, about 50% of patients are considered to be cisplatin ineligible. Anti-programmed cell death protein 1/programmed death-ligand 1 (PD-L1) therapies have, nevertheless, increased the options available to clinicians and are especially valuable for treating these patients. This study therefore tested the activity and safety of avelumab as first-line therapy for mUC.Patients and methods: Patients with mUC who were ineligible for cisplatin-based chemotherapy were screened centrally for PD-L1 expression and only those with a tumour proportion score > 5% were enrolled in the trial. The primary endpoint was 1-year overall survival (OS), and the secondary endpoints were median OS, median progression-free survival, overall response rate, duration of the response, safety and tolerability. All the survival rates were estimated with the KaplaneMeier product-limit methodology and compared across groups using the log -rank test.Results: A total of 198 patients were screened, with 71 (35.9%) whose PD-L1 expression was >5% enrolled in the study. The median age was 75 years, bladder cancer was the primary tumour in 73.2% of cases and 25.3% had liver metastases. The main reasons for the cisplatin ineligibility were a low rate of creatinine clearance (<60 ml/min), present in 70.4% of patients, and an Eastern Cooperative Oncology Group performance status of 2, which affected 31%. The median OS was 10.0 months (95% confidence interval 5.5-14.5 months) and 43% of patients were alive at 1 year. A complete response was achieved in 8.5% of cases, and 15.5% had a partial response. Adverse any-grade and high-grade events occurred in 49.3% and 8.5% of patients, respectively. A grade 3 infusion reaction was the only high-grade treatment-related adverse event. No treatment-related deaths were reported.Conclusions: This ARIES trial confirmed the activity and safety of avelumab for treating mUC, adding a new therapy option to the armamentarium of checkpoint inhibitors already approved for platinum-ineligible, locally advanced/mUC.

Background: We compared multimodality treatment (MMT, defined as robot-assisted radical prostatectomy (RARP) with androgen deprivation therapy (ADT), with or without adjuvant radiotherapy (RT)) vs. ADT alone in oligometastatic prostate cancer (OPC) patients. Methods: From 2010 to 2018, we identified 74 patients affected by cM1a-b OPC (≤5 metastases). Kaplan–Meier (KM) plots depicted cancer-specific mortality (CSM), disease progression, metastatic castration-resistant PC (mCRPC), and time to second-line systemic therapy rates. Multivariable Cox regression models (MCRMs) focused on disease progression and mCRPC. Results: Forty (54.0%) MMT and thirty-four (46.0%) ADT patients were identified. On KM plots, higher CSM (5.9 vs. 37.1%; p = 0.02), mCRPC (24.0 vs. 62.5%; p < 0.01), and second-line systemic therapy (33.3 vs. 62.5%; p < 0.01) rates were recorded in the ADT group. No statistically significant difference was recorded for disease progression. ForMCRMs adjusted for the metastatic site and PSA, a higher mCRPC rate was recorded in the ADT group. No statistically significant difference was recorded for disease progression. Treatment-related adverse events occurred in 5 (12.5%) MMT vs. 15 (44.1%) ADT patients (p < 0.01). Conclusions: MMT was associated with lower CSM, mCRPC, and second-line therapy rates. A lower rate of treatment-related adverse events was recorded for the MMT group.

Introduction Non-muscle invasive bladder cancer (NMIBC) accounts for 70-75% of all bladder cancers and is a heterogeneous disease characterized by a wide spectrum of recurrences and progression. Adjuvant treatment for intermediate- and high-risk NMIBC is mainly represented by Bacillus Calmette Guerin (BCG). However, 20%-40% of patients develop disease recurrences or persistence following BCG treatment and are classified as "BCG unresponsive' (BCGu), thus representing a therapeutic challenge due to their worse prognosis and unavailability of effective intravesical treatments. Areas covered We provide an overview of completed and ongoing clinical trials assessing the role of innovative immunological and target agents in patients with BCGu and BCG naive (BCGn) NMIBCs. New treatment options are emerging, demonstrating promising clinical activity, namely, pembrolizumab, atezolizumab, oportuzumab monatox, nadofaragene firadenovec, and N-803. Expert opinion The increasing number of newer therapeutic agents for patients with NMIBC poses challenges regarding the choice of the most suited treatment option for each patient and the best treatment sequence, given their diverse mechanisms of action and varying degrees of activity. Tailored treatment approaches are advocated, based on a deeper comprehension of disease features, available therapies, patient's characteristics, and consequently, on the identification and validation of prognostic and predictive biomarkers.

Background: Pre-clinical data suggest that docetaxel and enzalutamide interfere with androgen receptor translocation and signalling. The aim of this study is to assess the efficacy of their concurrent administration in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC). Methods: In this open-label, randomised, phase II trial, previously untreated mCRPC patients were randomised 1:1 to receive eight 21-d courses of docetaxel 75 mg/m(2), oral prednisone 5 mg twice daily and oral enzalutamide 160 mg/d (arm DE), or the same treatment without enzalutamide (arm D). The primary end-point was the percentage of patients without investigator-assessed disease progression 6 months after the first docetaxel administration. Results: The 246 eligible patients were randomly assigned to receive docetaxel, prednisone and enzalutamide (n = 120) or docetaxel and prednisone (n = 126). The 6-month progression rate was 12.5% (95% confidence interval [CI] 8.1-20.6) in arm DE and 27.8% (95% CI 22.8-39.4) in arm D (chi-squared test 10.01; P = 0.002). The most frequent grade III-IV adverse events were fatigue (12.5% in arm DE versus 5.6% in arm D), febrile neutropenia (9.3% versus 4.0%) and neutropenia (7.6% versus 5.6%). Conclusions: The combination of enzalutamide and docetaxel appears to be more clinically beneficial than docetaxel alone in previously untreated mCRPC patients, although serious adverse events were more frequent. Our findings suggest that first-line treatment with this combination could lead to an additional clinical benefit when prompt and prolonged disease control is simultaneously required. Clearly, these results should be considered cautiously because of the study's phase II design and the absence of an overall survival benefit. (C) 2021 Elsevier Ltd. All rights reserved.

Renal cell carcinoma (RCC) has traditionally been considered radioresistant with a limited role for conventional fractionation as a local approach. Nevertheless, since the appearance of stereotactic body radiation therapy (SBRT), radiotherapy (RT) has been increasingly employed in the management of metastatic RCC (mRCC). The aim of this study was to evaluate the role of SBRT for synchronous and metachronous oligo metastatic RCC patients in terms of local control, delay of systemic treatment, overall survival and toxicity. A Monocentric single institution retrospective data collection was performed. Inclusion criteria were: (1) oligo-recurrent or oligo-progressive disease (less than 5 metastases) in mRCC patients after radical/partial nephrectomy or during systemic therapy, (2) metastasectomy or other metastasis-directed, rather than SBRT not feasible, (3) any contraindication to receive systemic therapy (such as comorbidities), (4) all the histologies were included, (5) available signed informed consent form for treatment. Tumor response and toxicity were evaluated using the response evaluation criteria in solid tumors and the Common Terminology Criteria for Adverse Events version 4.03, respectively. Progression-free survival in-field and out-field (in-field and out-field PFS) and overall survival (OS) were calculated via the Kaplan–Meier method. The drug treatment-free interval was calculated from the start of SBRT to the beginning of any systemic therapy. From 2010 to December 2018, 61 patients with extracranial and intracranial metastatic RCC underwent SBRT on 83 lesions. Intracranial and extracranial lesions were included. Forty-five (74%) patients were treated for a solitary metastatic lesion. Median RT dose was 25 Gy (range 10–52) in 5–10 fractions. With a median follow-up of 2.3 years (range 0–7.15), 1-year in-field PFS was 70%, 2-year in-field PFS was 55%. One year out-field PFS was 39% and 1-year OS was 78%. Concomitant systemic therapy was employed for only 11 (18%) patients, for the others 50 (82%) the drug treatment-free rate was 70% and 50% at 1 and 2 years, respectively. No > G1 acute and late toxicities were reported. The pattern of failure was pre-dominantly out-of-field, even if the population was negatively selected and the used RT dose could be considered palliative. Therefore, SBRT appears to be a well-tolerated, feasible and safe approach in oligo metastatic RCC patients with an excellent in-field PFS. SBRT might play a role in the management of selected RCC patients allowing for a delay systemic therapy begin (one out of two patients were free from new systemic therapy at 2 years after SBRT). Further research on SBRT dose escalation is warranted.

BACKGROUND:We address novelty regarding metabolomic profiling in renal cell carcinoma (RCC) patients, in an attempt to postulate potential treatment strategies.METHODS:A large-scale literature search in existing scientific websites focusing on the keywords "renal cell carcinoma", "clear cell histology", "papillary histology", "metabolomic profiling", and "therapeutics" was performed. Results: The PI3K/Akt signaling pathway is key in clear cell RCC metabolism and accordingly several drugs are presently available for routine use in clinical practice. Along this line, new treatment combinations against PI3K/Akt family members are currently under clinical investigation. On the other hand, new developed targets such as c-Met tyrosine kinase domain, glutathione (GSH) metabolism, and histone deacetylases enzymes (HDAC), as well as therapeutic strategies targeting them are currently being tested in clinical trials and here discussed.CONCLUSIONS:In RCC patients, the PI3K/Akt signaling is still the most effective targetable pathway. Targeting other metabolic pathways such as c-Met, GSH, and HDAC appears to be a promising approach and deserve further insights.

PURPOSE:To report long-term oncological outcomes after penile-sparing surgery (PSS) for superficial (Ta-Tis) or initially invasive (T1) penile cancer patients. METHODS:We retrospectively analysed 85 patients with Ta/Tis/T1cN0cM0 penile cancer (1996-2018). All patients underwent PSS: circumcision, excision or laser ablation. First, Kaplan-Meier plots and multivariable Cox regression models tested tumor recurrence rates (any local/regional/metastatic). Second, Kaplan-Meier plots depicted progression-free survival (≥T2 or N1-3 or M1 disease). RESULTS:Median (IQR) follow-up time was 64 (48-95) months. Overall, 48 (56%) patients experienced tumor recurrence. Median (IQR) time to tumor recurrence was 34 (7-52) months. Higher recurrence rates were observed for Tis (65%) and T1 (64%), compared to Ta (40%), but these differences were not significant on multivariable Cox regression analyses (HR:2.0 with 95% CI [0.9-5.1] and HR:2.2 with 95% CI [0.9-5.9], respectively). Moreover, higher recurrence rates were observed for G2-3 tumors (74%), compared to G1 (57%), but these differences were not significant on multivariable Cox regression analyses (HR:1.6; 95% CI [0.8-3.2]). During follow-up, 15 (17.5%) vs. 18 (21.2%) vs. 10 (11.5%) patients underwent 1 vs. 2 vs. ≥3 PSS. Moreover, 26 (30.6%) and 4 (4.7%) men were treated with glansectomy and partial/total penile amputation due to local progression, tumor size or patient preference. Additionally, 24 (28%) men underwent invasive nodal staging. Last, 22 (25.9%) patients experienced disease progression. Median (IQR) time to disease progression was 51 (31-82) months. CONCLUSION:Patients treated with PSS for newly diagnosed superficial or initially invasive squamous cell carcinoma of the penis should be informed about the non-negligible risk of tumor recurrence and disease progression over time. In consequence, strict follow-up protocols are needed.

326 Background: Antiangiogenic therapy has been a milestone in the treatment of metastatic renal cell carcinoma (mRCC) for years. The positive results with immune-checkpoint inhibitors (ICI) are changing the frontline standard of care of mRCC patients (pts). To date, prospective data are lacking to determine the efficacy of antiangiogenic therapy in pts progressed to ICI. The multikinase inhibitor Cabozantinib (cabo) has shown prolonged survival in pre-treated mRCC pts. Moreover, by targeting multiple pathways and crucial kinases involved in microenvironment-driven immune-escape, it may represent an ideal agent to be used sequentially after ICI. Methods: This is the first prospective open label, single arm, multicenter, phase II study to evaluate efficacy and safety of Cabo in pts with mRCC pre-treated with adjuvant or first line PD-1/PD-L1-based therapy (as monotherapy or in combination with an TKI or anti CTLA-4). Cabo 60 mg once daily was administered until progressive disease (PD) or unacceptable toxicity. The primary endpoint was progression free survival (PFS), secondary endpoints were overall survival (OS), objective response rate (ORR) and safety. Results: Among 23 patients enrolled, 22 were included in the analysis (one was excluded for screening failure). Median age was 59.5 years (range: 29-74), 69.5% were male. At baseline, Karnofsky performance status was 100 in 59% of pts, 80-90 in 31.8% and 70-80 in 9%. 22.7% of pts had a good Heng score, 50% intermediate and 27.2% poor. Median duration of the previous therapy with anti PD-1 or anti-PD-L1 compounds was 4.3 months. Pts received an average of 4.7 months of Cabo. Among evaluable cases, 6 pts (27.2%) achieved a partial response and 5 pts (22.7%) stable disease. The median follow-up was 7.2 months and the median PFS was 7.2 months. 2 pts discontinued treatment for toxicity, 8 pts for PD, 1 patient discontinued treatment for different reason than PD, 11 pts are still on treatment. Grade (G) 3 adverse events (AEs) occurred in 22.7% of pts; the most common AEs were hand and foot syndrome (HFS) (G1 in 36.3% of pts, G2 18.1%, G3 4.5%), diarrhea (G1 31.8%, G2 18.1%), hypothyroidism (G1 9.09 %, G2 22.7 %), mucositis (G1 36.3%, G2 4,5%), and fatigue (G1 18.1%, G2 18.1%). Transitory withholding of cabo was observed in 63.6% of pts (14/22) and it was due to AEs in the 90% of the cases. For 5/22 pts (22.7 %), dose reduction was needed to manage AEs. The most common AEs leading to temporary drug interruption were HFS G1-3 (13.9%), liver disfunction G1-G2 (13.9%), diarrhea G1-G2 (11.6%), nausea and vomiting G2 (11.6 %) and fatigue G2 (9.3%). Conclusions: So far, the treatment with cabo after a I line anti-PD-1 based immunotherapy resulted active and well tolerated. Clinical trial information: NCT03463681 .

Over the last few years efficacy of immunotherapy using immune checkpoint inhibitors (ICI) has been investigated in patients with bladder cancer (BC) at all stages. The present article aims to assess new therapeutic options with emerging agents in BC patients, shedding light on ICI-based treatments encompassing all disease stages, from non-muscle invasive (NMIBC) to muscle-invasive (MIBC) BC, concluding with metastatic MIBC. In bacillus Calmette-Guerin (BCG) unresponsive patients with carcinoma in situ, pembrolizumab has been recently approved. In the neoadjuvant setting, results from two clinical trials seem to identify pathological and genomic features of highly responsive tumors. Squamous cells and lymphoepithelioma/like histotypes, programmed cell-death ligand 1 (PD-L1) expression and high levels of activate T cells have been associated with higher response rate. In the metastatic setting, only 30% of patient may respond to ICI. A panel of biomarkers for patient selection is an actual need since the correlation between response and PD-L1 expression seem inconsistent across clinical trials, with some exceptions. Molecular characterization of BC, tumor mutation burden and immune-gene expression profiling might introduce new molecular biomarkers, hopefully transferable into the clinical-pathological practice.

Cancer patients may be at high risk of infection and poor outcomes related to SARS-CoV-2. Analyzing their prognosis, examining the effects of baseline characteristics and systemic anti-cancer active therapy (SACT) are critical to their management through the evolving COVID-19 pandemic. The AIOM-L CORONA was a multicenter, observational, ambispective, cohort study, with the intended participation of 26 centers in the Lombardy region (Italy). A total of 231 cases were included between March and September 2020. The median age was 68 years; 151 patients (62.2%) were receiving SACT, mostly chemotherapy. During a median follow-up of 138 days (range 12–218), 93 events occurred. Age ≥60 years, metastatic dissemination, dyspnea, desaturation, and interstitial pneumonia were all independent mortality predictors. Overall SACT had a neutral effect (Odds Ratio [OR] 0.83, 95%Confidence Interval [95%CI] 0.32–2.15); however, metastatic patients receiving SACT were less likely to die as compared to untreated counterparts, after adjusting for other confounding variables (OR 0.23, 95%CI 0.11–0.51, p < 0.001). Among cancer patients infected by SARS-CoV-2, those with metastases were most at risk of death, especially in the absence of SACT. During the ongoing pandemic, these vulnerable patients should avoid exposure to SARS-CoV-2, while treatment adjustments and prioritizing vaccination are being considered according to international recommendations.

Various definitions are currently in use to describe high-risk prostate cancer. This variety in definitions is important for patient counseling, since predicted outcomes depend on which classification is applied to identify patient's prostate cancer risk category. Historically, strategies for the treatment of localized high-risk prostate cancer comprise local approaches such as surgery and radiotherapy, as well as systemic approaches such as hormonal therapy. Nevertheless, since high-risk prostate cancer patients remain the group with higher-risk of treatment failure and mortality rates, nowadays, novel treatment strategies, comprising hypofractionated-radiotherapy, second-generation antiandrogens, and hadrontherapy, are being explored in order to improve their long-term oncological outcomes. This narrative review aims to report the current management of high-risk prostate cancer and to explore the future perspectives in this clinical setting.

We aimed to assess the incidence of prosthesis-related complications in patients who received a testicular prosthesis at the time of radical orchiectomy for testicular cancer and were then treated with chemotherapy (ChT) or radiotherapy (RT). We reviewed the records of the patients who underwent radical orchiectomy at our Institute since 1999; we also retrieved data from patients who underwent surgery elsewhere and then received ChT or RT at our Institution since 1999. We used the chi-square test to evaluate differences in the incidence of prosthesis-related complications between the groups. We retrieved the records of 587 patients; 393 had a testicular prosthesis implanted. Median follow-up was 57.7 months. One hundred thirty-eight patients (35.11%) received ChT, 129 RT (38.82%) and 10 (2.55%) both ChT and RT; of them, 6 (4.34%), 8 (6.20%) and 0 reported problems respectively. Seven (6.03%) of the 116 patients (29.52%) who had no further treatment had complications. The incidence of complications was not significantly different between patients who had no further treatment versus patients who underwent ChT (p = .75) or RT (p = .83). Testicular prosthesis insertion at the time of radical orchiectomy is safe even in patients subsequently undergoing ChT or RT.