Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic landscape of solid tumors. However, although ICIs are better tolerated than conventional chemotherapy, their use is associated with a peculiar toxicity profile, related to the enhancement of the immune response, affecting several organs. Among immune-related adverse events (irAEs), up to 10% involve the endocrine system. Most of them are represented by thyroid disorders (hypothyroidism and hyperthyroidism), mainly correlated to the use of anti-PD-1 and/or anti-PD-L1 agents. Less common endocrine irAEs include hypophysitis, adrenalitis, and metabolic irAEs. A deeper understanding of endocrine toxicities is a critical goal for both oncologists and endocrinologists. A strict collaboration between these specialists is mandatory for early recognition and proper treatment of these patients. In this review we will provide a comprehensive overview of endocrine and metabolic adverse events of ICIs, with particular interest in the pathogenesis, predisposing factors and clinical presentation of these irAEs, and their impact on clinical outcomes of patients. Furthermore, we will summarize the most recent studies and recommendations on the clinical approach to immune-related endocrinopathies with the purpose to optimize the diagnostic algorithm, and to help both oncologists and endocrinologists to improve the therapeutic management of these unique types of irAEs, in a real-life scenario.

Immunotherapy with immune checkpoint inhibitors (ICI) is increasingly employed in oncology. National and international endocrine and oncologic scientific societies have provided guidelines for the management of endocrine immune-related adverse events. However, guidelines recommendations differ according to the specific filed, particularly pertaining to recommendations for the timing of endocrine testing. In this position paper, a panel of experts of the Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), and Italian Society of Pharmacology (SIF) offers a critical multidisciplinary consensus for a clear, simple, useful, and easily applicable endocrine-metabolic assessment checklist for cancer patients on immunotherapy.

Immunity plays a crucial role in fighting cancer, but tumours can evade the immune system and proliferate and metastasize. Enhancing immune responses is a new challenge in anticancer therapies. In this context, efficacy data are accumulating on immune checkpoint inhibitors and adjuvant therapies for various types of advanced-stage solid tumours. Unfortunately, immune-related adverse events are common. Although infrequent, renal toxicity may occur via several mechanisms and may require temporary or permanent drug suspension, renal biopsy, and/or immunosuppressive treatment. This short review aims to provide a practical approach to the multidisciplinary management of cancer patients with renal toxicity during treatment with immune checkpoint inhibitors.

We present the case of a patient with vaginal mucosal melanoma who underwent complete remission after immunotherapy and ‘0-7-21’ radiotherapy regimen (24 Gy/3 fractions/21 days). An 80-year-old woman had a biopsy of a voluminous vaginal lesion and received a histological diagnosis of melanoma with angiomatoid aspects. The patient underwent immunotherapy with pembrolizumab 2 mg/kg every 3 weeks and was sent to our attention for planning radiotherapy as the extent of the lesion did not make it susceptible to surgery. Considering the concomitant administration of pembrolizumab, we chose to treat this patient with a modulated intensity radiation therapy technique delivering a hypofractionated dose of 24 Gy in 3 fractions delivered on days 0, 7, and 21. We observed a complete clinical remission of the melanoma 12 months after radiotherapy and she has been alive for 18 months with no clinical signs of local recurrence.

Background: Immune checkpoint inhibitors (ICIs) have transformed the management of solid tumors, yet only a subset of patients achieve durable benefit. The gut microbiota is a key modulator of antitumor immunity, and systemic antibiotic therapy (ABT), frequently prescribed—and sometimes overused—in oncology, can profoundly disrupt microbial homeostasis. Observational studies suggest that ABT may impair ICI efficacy, but results remain heterogeneous, warranting an updated synthesis. Methods: We conducted a systematic review and meta-analysis in accordance with the PRISMA 2020 guidelines. PubMed, Scopus, and EMBASE were searched for studies published between 2018 and 2025 evaluating the association between ABT exposure and time-to-event outcomes in patients with solid tumors treated with ICIs. Studies were required to report explicit definition of the ABT exposure window. Random-effects models were considered primary. A sensitivity analysis was performed in non-small cell lung cancer (NSCLC). Results: Fifteen studies encompassing 52,489 patients were included. ABT exposure was associated with significantly worse OS (random-effects HR 1.16, 95% CI 1.03–1.29) and PFS (random-effects HR 1.11, 95% CI 0.95–1.27), indicating an increased risk of death and disease progression compared with no ABT exposure. In the NSCLC sensitivity analysis, ABT was consistently associated with inferior PFS and, when accounting for heterogeneity, with significantly reduced OS, supporting the robustness of the association. Conclusions: ABT administered in temporal proximity to ICIs is associated with clinically meaningful worsening of survival outcomes across solid tumors, consistent with microbiome-mediated impairment of immunotherapy efficacy. These findings support cautious ABT stewardship in patients receiving ICIs and highlight the need for prospective studies integrating microbiome profiling and standardized ABT exposure assessment.

Background: The use of complementary integrative medicine (CIM) by cancer patients is currently very common. The main reasons why patients turn to CIM are to improve quality of life (QoL) and support the immune system. Unfortunately, many patients rely on CIM self-prescription, neglecting the risk of interactions with anticancer treatments (ACTs). The primary objective is to demonstrate the feasibility of combining CIM and ACT in a multidisciplinary approach to improve the QoL of cancer patients and to reduce ACT’s adverse events. Methods: Cancer patients were treated with CIM by expert physicians. CIM mainly consisted of vitamins C and D, the medicinal mushrooms blend U-CARE, and probiotics administered alone or in combination. The patients were followed-up by physicians and data were recorded in a detailed shared file. Results: A total of 54 cancer patients were treated with an integrative approach, especially during ACTs. The combination showed a good safety profile. No adverse events occurred in 92.6% of patients, whereas only 7.4% of patients experienced gastrointestinal or liver toxicity from the CIM approach. The main benefit of the CIM approach was improved fatigue and QoL, and this was mainly achieved by the concomitant use of polytherapy-based complementary medicine (PCM) and U-CARE. The toxicity improvement was mainly associated with the use of solely U-CARE. Conclusions: These results highlight the feasibility of the CIM approach in cancer patients addressed by a multidisciplinary team of experts in the field. The patient-centered and evidence-based approach of CIM is an example of the comprehensive and coordinated strategy pursued by the EU in its programmatic document against cancer aiming to focus on the QoL of patients and to avoid potentially harmful CIM self-prescription.