Metastatic prostate cancer is a major health burden worldwide, necessitating the continuous development of effective treatment strategies. Androgen deprivation therapy remains the cornerstone of prostate cancer treatment, but novel approaches are needed for metastatic castration-resistant prostate cancer (mCRPC). Recent studies have highlighted the prevalence of mutations in DNA repair genes, including BRCA1 and BRCA2, in mCRPC patients, rendering them more susceptible to platinum-based chemotherapy and Poly (ADP-ribose) polymerase (PARP) inhibitors. Platinum-based chemotherapy, particularly in combination with taxanes, has demonstrated encouraging activity in mCRPC, as well as homologous recombination gene alterations have shown increased sensitivity to platinum compounds in these patients. The combination of platinum-based chemotherapy with PARP inhibitors represents a novel and potentially effective therapeutic strategy for this subgroup of patients. However, the optimal sequence of administering these agents and the potential for cross-resistance and cross-toxicities remain areas requiring further investigation. Prospective randomized studies are essential to elucidate the most effective treatment approach for this challenging patient population. This review aims to explore the potential of platinum-based chemotherapy in the context of prostate cancer, and more in detail in homologous recombination repair (HRR) mutated patients. We discuss the synergistic effects of combining platinum compounds with PARP inhibitors and the potential benefits of adopting specific therapeutic sequences.

Neutrophil-to-eosinophil ratio (NER) has been described to be associated with outcomes to immune checkpoint inhibitors (ICI) in several tumor types, but less is known about its role of in the response to avelumab in advanced urothelial cancer (aUC). Thus, we reported outcomes by NER of aUC patients treated with avelumab as maintenance after initial response to platinum-based chemotherapy and enrolled in the Maintenance with AVeLumAb ([MALVA] in advanced urothelial neoplasms in response to first-line chemotherapy: an observational retrospective study) study (Meet-URO 25). Median NER at baseline and after 3 cycles of avelumab were calculated. Progression-free survival (PFS) and overall survival (OS) by NER were reported. At the cutoff date (April 15, 2023), a total of 109 patients were included. The median NER was 28.05 at baseline and 24.46 after 3 cycles of avelumab, respectively. Median PFS was not reached for patients with baseline NER less than the median (<median) compared to 5.1 months for patients with baseline NER greater than the median (≥median) (P = .0005). Median OS was significantly longer for patients with baseline NER <median compared with patients with baseline NER ≥median (not reached vs. 11.7 months, respectively; P = .0016). Significantly better PFS and OS were confirmed for NER after 3 cycles of avelumab <median compared with NER ≥median at the same timepoint. NER <median may be predictive of PFS in aUC patients treated with avelumab, and prognostic for OS regardless of treatment. Prospective studies are warranted to validate NER as a readily available and reproducible laboratory-biomarker for efficacy outcomes of avelumab in aUC.

Ulcerative colitis (UC) is associated with an increased risk of developing colitis-associated colorectal cancer (caCRC), a major complication of long-standing disease. In this review, we examined the pathogenic association between UC and caCRC, highlighting the risk factors, molecular mechanisms, and current strategies for prevention and management. Compared to sporadic colorectal cancer, caCRC tends to occur at a younger age and is more frequently characterized by mucinous or signet-ring cell histology, proximal colonic involvement, and a higher incidence of synchronous lesions. The risk of caCRC increases 8-10 years after UC diagnosis and is influenced by disease duration, extent of colonic involvement, inflammatory burden, family history of colorectal cancer, and coexisting primary sclerosing cholangitis. The inflammation-to-cancer progression follows a multistep pathway of genetic alterations, advancing from low-grade to high-grade dysplasia, and ultimately to carcinoma. While chemopreventive agents such as 5-aminosalicylates may offer some benefit, surveillance colonoscopy remains the primary strategy for risk reduction. Early detection and individualized prevention strategies are critical for improving long-term outcomes in patients with UC.

Importance: Avelumab maintenance therapy improves survival in patients with advanced urothelial carcinoma who respond to first-line platinum-based chemotherapy. However, real-world evidence on its effectiveness and on the prognostic value of baseline clinical factors remains limited. Objective: To evaluate the real-world effectiveness of Avelumab maintenance therapy and to identify baseline prognostic factors associated with clinical outcomes. Design: Multicenter prospective observational study including a retrospective cohort of patients treated before study initiation. Setting: Several Italian oncology centers participating between 2021 and 2023. Participants: A total of 251 patients with advanced or metastatic urothelial carcinoma who received Avelumab maintenance therapy after achieving disease control with first-line platinum-based chemotherapy. Intervention(s) or Exposure(s): Avelumab maintenance therapy administered according to clinical practice. Baseline clinical variables, including ECOG performance status, metastatic sites, and corticosteroid use, were assessed for prognostic significance. Main Outcome(s) and Measure(s): Primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes included overall response rate (ORR) and disease control rate (DCR). Prognostic factors were evaluated using multivariate Cox regression. Results: Median OS was 22.4 months, and median PFS was 7 months. The ORR and DCR were 26.75% and 69.30%, respectively. Independent predictors of worse OS were ECOG ≥1 (HR 1.57), bone metastases (HR 1.88), brain metastases (HR 7.02), and baseline corticosteroid use (HR 2.42). An exploratory prognostic score integrating ECOG status, bone metastases, and steroid use stratified patients into three groups with significantly different outcomes: median OS was 39.9 months (no adverse factors), 14.1 months (one factor), and 8.4 months (two or more factors), with corresponding ORRs of 33.6%, 28.0%, and 6.9%. Conclusions and Relevance: In this large real-world cohort, Avelumab maintenance confirmed its effectiveness and safety in advanced urothelial carcinoma. A simple exploratory prognostic score based on ECOG performance status, bone metastases, and baseline corticosteroid use successfully stratified patients by survival outcomes and may support personalized treatment strategies in clinical practice.

Immune checkpoint inhibitor-related pneumonitis (CIP) is an uncommon but clinically relevant toxicity in renal cell carcinoma (RCC), where immune checkpoint inhibitors are frequently used either as dual immunotherapy or in combination with VEGF-targeted tyrosine kinase inhibitors. In RCC, CIP poses specific diagnostic challenges because respiratory symptoms and computed tomography findings may overlap with pulmonary metastases, infections, thromboembolic events, heart failure, and TKI-related lung toxicity. This review summarizes the incidence of CIP across pivotal RCC trials and real-world cohorts, compares its epidemiology with non-small cell lung cancer, and discusses clinical presentation, radiological patterns, differential diagnosis, and current management strategies. Particular attention is given to RCC-specific mechanisms, including immune-mediated alveolar injury, T cell activation, cytokine dysregulation, macrophage activation, GSDME-mediated pyroptosis, and the potential contribution of VEGF pathway inhibition to pulmonary inflammation. We also review risk factors, steroid-refractory disease, second-line immunosuppression, and the unresolved issue of ICI rechallenge after pneumonitis. A better understanding of these mechanisms and clinical features may improve early recognition, guide multidisciplinary management, and support safer use of immunotherapy-based combinations in patients with RCC.