Prostate cancer represents a major global health challenge, necessitating efficacious therapeutic strategies. Androgen receptor pathway inhibitors (ARPIs) have become central to prostate cancer treatment, demonstrating significant effectiveness in both metastatic and non-metastatic contexts. Abiraterone acetate, by inhibiting androgen synthesis, deprives cancer cells androgens necessary for growth, while second-generation androgen receptor (AR) antagonists disrupt AR signaling by blocking AR binding, thereby impeding tumor progression. Given the predominance of prostate cancer in the elderly, who often present with multiple comorbidities requiring complex pharmacological regimens, the potential for drug-drug interactions with ARPIs is a critical concern. These interactions, particularly through pathways like CYP2D6 inhibition by abiraterone and CYP3A4 induction by enzalutamide and apalutamide, necessitate a thorough understanding to optimize therapeutic outcomes and minimize adverse effects. This review aims to delineate the efficacy of ARPIs in prostate cancer management and elucidate their interaction with common medications, highlighting the importance of vigilant drug management to optimize patient care.

Purpose: Immunotherapy efficacy in elderly patients with comorbidities and poor performance status is not well understood. More knowledge on this topic is needed to identify subgroups that will benefit from immunotherapy. We aimed to evaluate the effect of comorbidity burden in patients receiving immunotherapy. Methods/patients: Patients older than 18 years of age and diagnosed with various malignancies, followed up in our tertiary cancer center were screened. Patients treated with immunotherapy were included in this study. We used to Charlson Comorbidity Index (CCI) to evaluate patients’ comorbidity burden. The primary outcome was overall survival (OS). Hazard ratio (HR) with confidence interval (CI) was evaluated in multivariable analysis. Results: A total number of 197 patients were included. The median age was 62 years. Patients were grouped based on CCI scores: CCI-low (≤ 8) and CCI-high (> 8). One-hundred and seven patients (54.9%) had metastatic disease at the time of diagnosis. Most frequently used immunotherapy agent was nivolumab (n = 124, 62.9%), followed by pembrolizumab (n = 36, 18.3%). The median OS was shorter in the CCI-high group than in the CCI-low group (10.6 vs. 21.2 months, p = 0.002) In multivariable analysis, treatment with anti-CTLA4 (HR: 1.85, 95% CI 1.07–3.20, p = 0.028), ECOG performance status (2–4 vs. 0–1) (HR: 2.17; 95% CI 1.25–3.75; p = 0.005), and higher CCI scores (CCI-high vs. CCI-low) (HR: 1.97; 95% CI 1.3–3.0; p = 0.001) were independently associated with worse OS. Conclusions: Comorbidity burden and performance status independently predict survival outcomes in immunotherapy-treated cancer patients. Comprehensive comorbidity assessment is essential for optimizing treatment and improving patient outcomes.

PURPOSE: Sarcomatoid renal cell carcinoma (sRCC) represents a kidney malignancy with a sarcomatoid component associated with poor prognosis. Immunotherapy (IO)-based combinations demonstrated promising activity in sRCC, yet real-world evidence (RWE) remains limited. We aimed to characterize the clinicopathologic features and outcomes of patients with metastatic sRCC treated with first-line immune-based combinations. PATIENTS AND METHODS: This retrospective analysis from the ARON-1 study included 350 patients with histologically confirmed metastatic sRCC treated with first-line IO + IO, or IO + tyrosine kinase inhibitor across 66 centers in 21 countries (2016-2024). Overall survival (OS) was analyzed using Kaplan-Meier and Cox regression methods. Correlations between 2-year OS and clinical variables were assessed using Pearson's coefficient. RESULTS: After a median follow-up of 19.1 months, median OS was 26.9 months (95% CI, 21.6 to 43.3). OS was longer in males (43.3 v 15.3 months in females; P < .001), in whom underwent nephrectomy (32.3 v 20.7 months; P = .002), and in patients without hepatic (32.3 v 15.3 months; P < .001), without skeletal (41.0 v 20.0 months; P = .007), or without lymph node metastases (43.3 v 24.6 months; P = .037). Median OS varied by International Metastatic RCC Database Consortium (IMDC) risk group: 66.5, 29.4, and 11.7 months in favorable-, intermediate-, and poor-risk patients, respectively ( P < .001). Different IO regimens showed variable outcomes by risk subgroup. Limitations include retrospective design and lack of central pathology review. CONCLUSION: First-line IO-based combinations provide clinically meaningful survival in sRCC, with outcomes affected by sex, metastatic sites, and IMDC risk. This RWE may support a tailored therapeutic approach on the basis of baseline prognostic factors.