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

Sep 23, 2026

Uploaded by Jasmine

Synchronous triple primary malignancies are exceptionally rare, particularly when renal cell carcinoma (RCC), bladder cancer, and hepatocellular carcinoma (HCC) arise concurrently. A 74-year-old man was diagnosed simultaneously with RCC, invasive urothelial carcinoma, and HCC after hematuria and imaging identified tumors in all three organs. Systemic pembrolizumab plus lenvatinib was chosen after surgery was declined, leading to good control of RCC and bladder cancer but early HCC rupture. Lenvatinib dosing was reduced for HCC, yet hepatic lesions progressed, requiring hepatectomy and nephrectomy, followed by early HCC recurrence.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Introduction

Case Presentation

Case Report

Bladder Tumor

Renal Tumor

Liver Tumor

Discussion and Clinical Implications

Drug-dose conflict and dominant tumor biology

Immune microenvironment considerations

Case Reports in Oncology | Case Rep Oncol 2026;19:805–814 | | | --- | --- | | DOI: 10. 1159/000551772
Received: January 15, 2026
Accepted: March 13, 2026
Published online: March 31, 2026 | © 2026 The Author(s) .
Published by S. Karger AG, Basel [www.karger.com/cro](www.karger.com/cro) | This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC) ([https://karger.com/Services/OpenAccessLicense](https://karger.com/Services/OpenAccessLicense)). Usage and distribution for commercial purposes requires written permission. Case Report 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 Yuichiro Atagi Yusuke Fukatani Reina Kouno Kousuke Seto Katsuyoshi Hashine National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan Keywords Renal cell carcinoma · Bladder cancer · Hepatocellular carcinoma · Triple primary malignancies · Systemic therapy Abstract 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. © 2026 The Author(s) . Published by S. KargerAG, Basel Correspondence to: Yuichiro Atagi, yatagi.170326 [gmail.com](gmail.com) Case Reports in Oncology Case Rep Oncol 2026;19:805–814 806 | DOI: 10. 1159/000551772 | © 2026 The Author(s) . Published by S. Karger AG, Basel [www.karger.com/cro](www.karger.com/cro) | | --- | --- | Atagi et al.: Triple Primary Malignancies and Drug-Dose Conflict Introduction Synchronous triple primary malignancies are extremely rare, with a large singleinstitution analysis reporting an incidence of only 0.082% among patients with cancer [1] . Previous studies have shown that skin, gastrointestinal, and breast cancers are most frequently included in such combinations, although the distribution varies by region, with a relatively high occurrence of bladder and lung cancers described in some reports [1–4] . The management of synchronous triple primary malignancies is particularly challenging because each tumor has a distinct molecular profile and established standard treatments. Additionally, therapeutic prioritization must be determined by evaluating the progression and biological behavior of each malignancy, often requiring multidisciplinary discussion and coordination across multiple specialties. We report a rare case of synchronous triple primary cancers originating in the kidney, bladder, and liver. We describe the considerations involved in treatment selection and the rationale for choosing a regimen combining an immune checkpoint inhibitor with a tyrosine kinase inhibitor as systemic therapy. Case Report A 74-

FAQs

Why is treatment selection difficult in synchronous triple primary malignancies?

Each tumor has a distinct molecular profile and standard therapies, so management requires assessing progression and biological behavior and coordinating decisions across specialties.

What systemic regimen was used after surgery was declined?

The patient received pembrolizumab plus lenvatinib, based on the biological rationale that the combination may have activity across RCC, urothelial carcinoma, and HCC.

How did the drug-dose conflict affect outcomes for HCC?

The initial lenvatinib dose, appropriate for RCC, was excessive for HCC. After early HCC rupture and subsequent dose reduction, hepatic lesions still progressed, leading to hepatectomy and nephrectomy and early postoperative recurrence.

Sep 23, 2026

Uploaded by Jasmine