Pembrolizumab plus Lenvatinib for Synchronous Triple Primary Malignancies of the Kidney, Bladder, and Liver: Clinical Implications of Conflict of Drug Doses and Dominant Tumor Biology.

Introduction: Synchronous triple primary malignancies are extremely rare, particularly those involving renal cell carcinoma (RCC), bladder cancer, and hepatocellular carcinoma (HCC). Case Presentation: We describe a 74-year-old man in whom RCC, bladder cancer, and HCC were diagnosed simultaneously. Although surgical resection was recommended, the patient declined and elected to receive systemic therapy. Based on the biological rationale that pembrolizumab plus lenvatinib may show activity across RCC, urothelial carcinoma, and HCC, this regimen was initiated. The RCC and bladder cancer were well controlled; however, the HCC ruptured early during treatment, requiring transcatheter arterial embolization. Lenvatinib was subsequently reduced because the initial dose, appropriate for RCC, was excessive for HCC. Despite dose adjustment, the hepatic lesions progressed, and the patient ultimately underwent hepatectomy and nephrectomy. Early postoperative recurrence of HCC was observed. Conclusion: This case highlights the clinical challenges of systemic therapy for synchronous triple primary malignancies, particularly the need to address drug-dose conflict among multiple tumors, identify the dominant tumor, and consider the tumor immune microenvironment when selecting a single regimen for multiple cancers.