Abdul‐Muhsin, Haidar

Abstract Background and Objective Management of von Hippel–Lindau (VHL) disease is challenging due to multisystem involvement and limited systemic treatment options. Belzutifan has shown promising efficacy in clinical trials; however, real-world data remain limited. We aimed to evaluate its effectiveness and safety in a real-world cohort. Methods We conducted a retrospective study of 59 patients with VHL disease treated with belzutifan between August 2021 and January 2026. Objective response rates (ORR) for renal cell carcinoma (RCC), central nervous system hemangioblastomas (CNS HB), and pancreatic neuroendocrine tumors (pNET) were assessed by an independent radiologist. Retinal hemangioblastoma outcomes were evaluated through ophthalmology records by chart review. Results Median follow-up was 29 months. ORR was 27.6%, 39.6%, and 85.7% for RCC, CNS HB, and pNET, respectively. Among 13 patients with retinal hemangioblastomas (20 eyes), 17 eyes (85%) showed improvement. At data cutoff, 47 patients (79.6%) remained on treatment, while 12 (20.3%) discontinued (7 due to adverse events, 3 to disease progression, and 2 to other reasons). The most common adverse event was anemia (86.4%). Grade ≥3 events occurred in 10 patients (16.9%). The procedure rate per patient-year decreased from 0.35 in the 3 years prior to treatment to 0.08 during follow-up (Incidence Rate Ratio, 0.23; 95% CI, 0.12–0.47; P < 0.001) Conclusions Belzutifan demonstrated efficacy across VHL-associated lesions, with favorable safety profile. Most adverse events were grade 1–2. A reduction in procedure rate was observed after treatment initiation.

Objectives To comprehensively review the available literature on prehabilitation and rehabilitation exercise, nutrition, and psychological support interventions for patients with kidney cancer (KC), to summarise the clinically relevant efficacy and cost‐effectiveness of interventions, to expose key knowledge gaps, and to inform future investigations and initiatives. Methods This review was performed according to the per Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) Extension for Scoping Reviews Guidelines. We included randomised controlled trials (RCTs) assessing programmes of prehabilitation or rehabilitation, exercise, psychological support, or nutrition components in patients with KC or KC caregivers from January 2004 to March 2022. Statistically significant positive (SS+) and negative (SS−) results were summarised. Results The systematic search yielded 10 968 records including 18 RCTs, involving 2774 unique subjects, 706 of whom were KC patients/survivors. None included caregivers or assessed cost‐effectiveness. Two interventions were implemented before surgery, one was implemented prior to initiation of systemic therapy, eight were implemented during systemic or radiation therapy, three were implemented after treatment, while implementation time was not specified for four interventions. Conclusion Most (14/18) RCTs involving exercise, nutrition, psychological support, or prehabilitative or rehabilitative programmes for KC performed to date demonstrated SS+ results. The evidence was most robust regarding previously evaluated psychological support, especially mindfulness‐based interventions (9/10 studies demonstrating SS+ improvement in primary outcomes), followed by therapeutically valid exercise with/without psychological support (5/8 RCTs demonstrated efficacy), then nutrition or pharmacological interventions (2/5 demonstrated efficacy). Level 1 evidence supports counselling patients and referral to mindfulness‐based psychological therapy along with physical therapy or physical medicine and rehabilitation, as well as consideration of preoperative carbohydrate drinks. No studies have examined impact on caregivers, or cost‐effectiveness, which are both critical areas for future study.