Alessandro Rizzo

Background: Homologous recombination repair (HRR) testing is increasingly relevant in prostate cancer because it identifies patients who may benefit from biomarker‐guided treatment strategies, including poly(ADP‐ribose) polymerase inhibitors (PARPi). However, real‐world implementation of HRR testing remains variable across countries and clinical settings, and the extent to which current testing pathways capture actionable alterations is not well defined. Methods: ARON‐3 is a multinational, multicentre, retrospective real‐world study of patients with prostate cancer. In this subanalysis, we assessed genomic testing uptake within the overall ARON‐3 cohort and characterised HRR testing pathways and detected pathogenic alterations among patients with available genomic results. Genomic testing included germline, somatic tumour, and/or circulating tumour DNA (ctDNA) assays performed in routine practice across participating centres. Multivariable logistic regression was used to identify clinicopathologic factors associated with undergoing genomic HRR testing. Results: Among 2,192 patients included in ARON‐3, genomic testing results were available for 719 (33%). Among tested patients, 660 (92%) underwent germline testing and 610 (85%) somatic testing; 549 (77%) underwent both, whereas 109 (15%) had germline‐only and 61 (8%) somatic‐only testing. In multivariable analysis, metastatic castration‐resistant prostate cancer, high‐volume disease, and Gleason score > 8 were independently associated with higher odds of testing, while age ≥ 70 years was associated with lower odds of testing. Overall, 238 tested patients (33%) harboured pathogenic HRR alterations, corresponding to 11% of the entire ARON‐3 cohort. Somatic pathogenic alterations were more frequent than germline alterations. BRCA2 was the most frequently altered gene, while non‐BRCA1/2 alterations were also detected, particularly in centres using broader multigene panels. Most centres relied on BRCA1/2 ‐focused assays, and the use of liquid biopsy remained limited. Conclusions: This multinational real‐world analysis demonstrates substantial heterogeneity in HRR testing uptake and testing pathways across participating ARON‐3 centres. Testing was more commonly performed in patients with more advanced disease features, suggesting that clinically relevant subgroups may still be differentially selected for genomic assessment. Broader and more standardised implementation of comprehensive HRR profiling may improve the identification of actionable alterations and strengthen precision medicine in prostate cancer.

1. Trop-2 is a trans-membrane glycoprotein involved in calcium signaling, cell growth and differentiation. Although the physiological function of Trop-2 is not fully elucidated, it is implicated in...

1. Urothelial carcinoma (UC) represents one of the most frequent malignancies of the urinary tract and remains associated with a substantial global burden. According to recent epidemiological estim...

Background: Renal Cell Carcinoma (RCC) represents a growing global health burden, with rising incidence and mortality worldwide. Despite major therapeutic advances, access to novel systemic treatments remains uneven across countries and regions. Methods: We conducted a cross-sectional, web-based international survey to assess the availability and reimbursement status of 20 innovative systemic therapies for RCC. Responses were collected from 144 clinicians, including medical oncologists, radiation oncologists, urologists, and nuclear medicine specialists, across 58 countries. Analyses examined associations between national income level, gross domestic product (GDP), and treatment availability. Findings: Thirty-six percent of the countries analyzed had at least 15 of the 20 therapies available. Full reimbursement for at least 15 of the selected innovative therapies was reported in six countries (10%), while 21 countries (36%) fully reimbursed 10-14 therapies and 13 countries (23%) reimbursed 1-9 therapies. In contrast, no full reimbursement for any of the assessed therapies was reported in 18 countries (31%). Higher national income level was significantly associated with greater availability of innovative therapies (Kruskal–Wallis test, P < .0001). Armenia (0.709), Greece (0.685), and Israel (0.666) exhibited the highest GDP-adjusted Drug Availability Index (DAI), whereas India (5.195), Nigeria (4.612), and Morocco (3.794) demonstrated the greatest number of available therapies per US$1000 of GDP per capita. Interpretation: Access to innovative systemic therapies for RCC remains highly unequal at the global level, with reimbursement posing a major barrier even where drugs are available. Internationally coordinated efforts addressing health policy, infrastructure, and equitable pricing are urgently required to ensure that advances in RCC treatment translate into improved outcomes for patients across diverse economic settings.

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine carcinoma in which Merkel cell polyomavirus (MCPyV) oncoproteins and ultraviolet-induced mutations provide distinct sources of tumor immunogenicity. This narrative review examines the biological determinants, immunohistochemical assessment, and prognostic and therapeutic relevance of programmed death ligand 1 (PD-L1) in MCC, linking tumor immunobiology to pathological interpretation. PD-L1 expression on tumor and immune cells is often concentrated at tumor–immune interfaces, consistent with interferon-γ-driven adaptive immune resistance. Reported associations with survival and treatment response vary across studies, partly reflecting differences in tissue sampling, assays, scoring compartments, and treatment context. Immune checkpoint blockade can produce durable responses in both PD-L1-positive and PD-L1-negative tumors, while baseline PD-L1 expression alone is not a validated criterion for treatment selection. Resistance mechanisms and emerging biomarkers are discussed alongside viral status, T-cell architecture, antigen-presentation defects, and alternative immune checkpoints. A reporting framework should emphasize specimen characteristics, assay documentation, separate assessment of PD-L1 expression in tumor and immune cells, and spatial heterogeneity. Interpreting PD-L1 within this biological and pathological context supports informative reporting and highlights the potential of integrated spatial biomarkers to improve understanding of immune responsiveness in MCC.

BACKGROUND Cancer remains a leading cause of morbidity and mortality worldwide. Given its substantial burden, quality of life has become a key outcome in cancer care and research. Patient-reported outcome measures (PROMs) are commonly used to assess quality of life. Although qualitative research is essential for establishing PROM content validity, patient narratives are less often collected and analysed systematically once PROMs are implemented. Adding open-ended responses to quantitative PROM data may provide policy-relevant insights into what patients themselves prioritise. OBJECTIVE This study has aimed to identify the factors that people living with or beyond cancer across Europe perceive as having the greatest impact on their quality of life. METHODS Following a pan-European validation study of the newly developed EUonQoL-Kit – a set of questionnaires designed to assess the quality of life of people living with or beyond cancer in Europe – the responses to the final open-ended question “Having completed the questionnaire, what do you feel most impacts your quality of life?” were collected. Responses underwent qualitative thematic analysis using a coding framework iteratively developed and interpreted by researchers and people with lived experience of cancer involved as ‘co-researchers’. RESULTS Of the 4,284 cancer patients and survivors participating in the EUonQoL-Kit validation study, 3,350 (78.2%) provided a response to the final open-ended question. Factors perceived as having the greatest impact on quality of life were categorised into 23 distinct themes, covering six overarching domains: Physical health, Psychological wellbeing, Social health, Overall health, Healthcare experience and Environment. The most frequently reported factors included physical symptoms, overall health, relationships and connectivity, emotions and feelings, and impact of care pathway. CONCLUSIONS This study provides a comprehensive overview of the factors that impact quality of life most in people living with or beyond cancer across Europe. Combining structured PROMs with open-ended patient input may support more patient-centred quality of life measurement and interpretation and help align care and policy priorities with what matters most to patients.

1. Myositis may present as an immune-related adverse event (irAE) during immune checkpoint inhibitor (ICI) therapy [1]. Although ICIs have improved cancer treatment by boosting anticancer immune re...

The addition of immunotherapy to chemotherapy has improved prognosis of metastatic biliary tract cancer (BTC). The present systematic review aimed to assess frequency of treatment-emergent adverse events (TEAEs) among metastatic BTC patients receiving first-line immune checkpoint inhibitors (ICIs) plus chemotherapy in the two practice-changing TOPAZ-1 and KEYNOTE-966 clinical trials. The present systematic review and meta-analysis was recorded in the PROSPERO register with no. CRD420251137398. Incidence of TEAEs in patients receiving ICIs plus chemotherapy and in patients treated with placebo plus chemotherapy was collected. A total of two studies were included in these analyses including 1754 patients, comprising 1743 observations and 193 events for Grade 1/2 and 650 events for Grade ≥ 3. The risk of several TEAEs did not significantly differ between patients receiving chemoimmunotherapy versus those treated with chemotherapy alone. The present meta-analysis further confirms the tolerable safety profile of TOPAZ-1 and KEYNOTE-966 regimens as first-line therapy in advanced BTC. Future research should focus on identifying risk factors for TEAEs and develop prophylactic strategies to mitigate this risk without blunting antitumor efficacy. By improving our understanding and management of TEAEs, we might maximize the clinical benefits of ICIs and minimize harm, ultimately enhance clinical outcomes for BTC patients.

Enfortumab vedotin (EV) is approved for the treatment of metastatic urothelial carcinoma (mUC), as monotherapy or in combination with immune checkpoint inh