In the treatment of uveal melanoma liver metastases, adding two immunotherapy drugs to percutaneous hepatic perfusion (PHP), which bathes only the liver in high-dose chemotherapy, raised the share of patients free of progression at one year to 54.7%, more than three times the 15.8% seen with PHP alone. The result comes from CHOPIN, a randomized phase 2 trial of 76 patients at Leiden University Medical Center in the Netherlands, published in The Lancet Oncology in 2026.
Tumors shrank in 76.3% of patients who received the combination. PHP was approved by the US FDA in 2023 as the HEPZATO KIT and is performed in Europe with the CHEMOSAT device. This article explains how the procedure works, the latest study numbers, where it is offered and what to check before a consultation.
Treatment status · PHP alone is an FDA-approved treatment (August 2023) and a CE-marked class III device in Europe. The immunotherapy combination showed benefit in a phase 2 trial and is moving toward larger multicenter trials. This is general information, not a recommendation for any procedure.
Why uveal melanoma spreads to the liver
Uveal melanoma arises in the uvea of the eye: the iris, ciliary body and choroid. It is the most common cancer inside the eye in adults and accounts for about 3–5% of all melanomas in the United States. It shares a name with skin melanoma but differs in its genetic changes and in how it spreads.
The FOCUS phase 3 paper, from 23 centers in the US and Europe, notes that up to half of patients eventually develop metastases, and about 90% of those involve the liver. Controlling liver tumors is therefore the core of treatment, which is why interventional radiology (IVR) procedures that deliver therapy directly to the liver matter so much in this cancer.
| Treatment | How it works | Key point |
|---|---|---|
| Percutaneous hepatic perfusion (PHP) | Melphalan flows through the whole liver, then blood is filtered outside the body and returned | Treats many tumors across the liver at once; FDA-approved |
| Embolization (TACE, immunoembolization) | Drugs and blocking particles are given through the hepatic artery | Targets the vessels feeding tumors |
| Radioembolization (Y-90) | Radioactive beads are placed in the hepatic artery | Often treats one side of the liver at a time |
| Surgery, ablation | Tumors are removed or destroyed with a needle | For few, small tumors |
Based on the FOCUS paper (Ann Surg Oncol 2024) and a 2026 CVIR commentary. The choice depends on tumor number, location and spread outside the liver.
How percutaneous hepatic perfusion (PHP) works
PHP is a catheter procedure performed through blood vessels in the groin. Under general anesthesia, a catheter is placed in the hepatic artery, and a double-balloon catheter in the inferior vena cava collects blood leaving the liver.
Melphalan (3 mg/kg ideal body weight, maximum 220 mg) is infused into the hepatic artery over 30 minutes, followed by 30 more minutes of filtration outside the body. Filtered blood returns through a neck vein. The liver receives a high dose while exposure for the rest of the body is greatly reduced.
| Step | What happens |
|---|---|
| Preparation | General anesthesia and anticoagulation |
| Isolating liver blood flow | Double-balloon catheter in the inferior vena cava collects liver outflow |
| Drug infusion | Melphalan into the hepatic artery over 30 minutes |
| Filtration | 30 more minutes of extracorporeal filtration before blood returns |
| Repeat | Every 6–8 weeks, up to 6 cycles (median 4 in FOCUS) |
Based on the procedure description in the FOCUS paper (Zager JS, et al. Ann Surg Oncol 2024).
In FOCUS, every patient received G-CSF, an injection that boosts white blood cells, within 72 hours of each procedure to protect blood counts. For catheter-based treatments in general, see our IVR overview; another way to give chemotherapy through the hepatic artery is covered in hepatic arterial infusion chemotherapy.
FOCUS phase 3: PHP alone
The FDA approval was based on the FOCUS phase 3 trial. Between February 2016 and October 2020, patients with unresectable metastatic uveal melanoma enrolled at 23 centers in the US and Europe, and results for the 91 treated patients were assessed by an independent review committee.
| Measure | Result (91 patients) |
|---|---|
| Objective response rate | 36.3% (complete 7.7%, partial 28.6%) |
| Disease control rate | 73.6% |
| Median duration of response | 14.0 months |
| Median progression-free survival | 9.0 months |
| Median overall survival | 20.5 months (80% at 1 year, 43% at 2 years) |
Zager JS, et al. Ann Surg Oncol 2024;31:5340–5351. Independent review, RECIST 1.1.
The paper describes median survival for uveal melanoma with liver metastases as about one year historically. In FOCUS, 80% of treated patients were alive at one year, and about 74 in 100 saw their tumors shrink or stop growing. The 36.3% response rate compared with a pooled historical rate of 5.5%.
CHOPIN: adding immunotherapy
Professor Ellen Kapiteijn and colleagues at Leiden University Medical Center randomized 76 previously untreated patients with liver-only or liver-dominant metastases between December 2020 and November 2024, 38 per arm. One group received PHP alone in weeks 1 and 7. The other received the same PHP plus ipilimumab and nivolumab every 3 weeks for four doses, with no maintenance therapy.
| Measure | PHP + ipilimumab/nivolumab | PHP alone |
|---|---|---|
| 1-year progression-free survival | 54.7% | 15.8% |
| Median progression-free survival | 12.8 months | 8.3 months |
| Objective response rate | 76.3% | 39.5% |
| Complete response | 13% | 3% |
| 2-year survival (exploratory) | 49.6% | 22.1% |
Median follow-up 24.9 months. PFS hazard ratio 0.34 (95% CI 0.19–0.60). From The Lancet Oncology 2026, The ASCO Post (March 12, 2026) and Delcath materials.
The risk of progression was 66% lower with the combination, and the survival hazard ratio of 0.39 also favored it. Because the trial was not designed to prove a survival difference, the investigators called for confirmation in larger multicenter trials.
In a 2026 commentary in CardioVascular and Interventional Radiology, radiologists from Charité Berlin and KU Leuven praised the study for showing that liver-directed therapy can do more than control local tumors: it may create conditions in which immunotherapy works better.
Side effects and how they are managed
The main side effect of PHP is a drop in blood counts. In FOCUS the most common events were low platelets (65.3%) and anemia (63.2%), followed by nausea and fatigue. Regular blood tests detect these early, and they are managed with white-cell-boosting injections and transfusion when needed. There were no treatment-related deaths in FOCUS.
| Grade 3–4 adverse event | Combination | PHP alone |
|---|---|---|
| Any treatment-related | 82% | 41% |
| Low platelets | 34% | 14% |
| Low white cells | 26% | 14% |
| Immunotherapy-related | 16% | Not applicable |
CHOPIN (The Lancet Oncology 2026). Grade 3–4 means events that need treatment or hospital care.
Side effects were more frequent with the combination, and one patient died of immune-related myocarditis, myositis and myasthenia gravis. The combination is best given at centers experienced in managing immunotherapy side effects, with regular checks for heart and muscle symptoms.
Who is eligible
The FDA label covers adults with metastatic uveal melanoma and unresectable liver metastases affecting less than 50% of the liver, with no disease outside the liver, or limited disease in bone, lymph nodes, subcutaneous tissue or lung that can be treated with surgery or radiation.
- Whether liver function and blood counts can tolerate the procedure
- Whether heart and lung health allow general anesthesia and anticoagulation
- Whether any disease outside the liver can be controlled with surgery or radiation
- If immunotherapy is considered, whether there are risk factors such as autoimmune disease
This list reflects general conditions from the FOCUS paper and CHOPIN eligibility. The treating team decides based on imaging and blood tests.
Where the treatment is available
| Region | Status | Basis |
|---|---|---|
| United States | FDA-approved August 2023 (HEPZATO KIT); offered at designated specialist centers | FOCUS phase 3, FDA approval |
| Europe | CHEMOSAT (class III device) used at centers such as Leiden University Medical Center and University Hospital Southampton | CHOPIN, ESMO 2026 data |
| UK NICE | Procedure guidance IPG691 issued 2021; update focused on uveal melanoma liver metastases in progress | NICE |
Centers and costs change, so confirm directly with the hospital before a consultation.
At ESMO 2026 in Madrid in October, results were reported for 12 patients treated with PHP at University Hospital Southampton between 2019 and 2026: response rate 66.7%, median hepatic progression-free survival 18.4 months and median overall survival 28 months, with no treatment-related deaths. A Dutch registry comparison of PHP plus immunotherapy with the systemic drug tebentafusp, and phase 2 trials extending PHP to breast and colorectal cancer liver metastases (DELUMA, Del-Liver), were also presented.
Patients treated in Japan can first ask their care team whether the procedure is available locally. For an overseas consultation, prepare recent contrast CT or liver MRI, blood tests, pathology results and a record of previous treatments. Foreign patients usually are not covered by the host country's public insurance, so confirm costs and waiting times with the hospital. Other liver-directed options are covered in Y-90 radioembolization and TACE (transarterial chemoembolization), and needle ablation in our RFA overview.
Questions to ask your doctor
- What percentage of my liver is involved, and am I a candidate for PHP?
- Which suits me best: PHP, embolization or radioembolization?
- If immunotherapy is added, which side effects will you monitor and how?
- How many sessions, how far apart, and how many days in hospital?
- How much experience does this hospital have with PHP?
For consultation preparation, see also five questions before an RFA consultation.
Frequently asked questions
What is usually the first treatment for uveal melanoma liver metastases?
When disease is limited to or dominant in the liver, liver-directed therapies such as PHP, embolization and radioembolization are central. Systemic drugs are also considered depending on HLA-A*02:01 test results. Doctors decide the order based on tumor number, location and spread outside the liver.
How many PHP sessions are given?
FOCUS planned up to six sessions every 6–8 weeks, and patients received a median of four. In CHOPIN, PHP was given twice, in weeks 1 and 7.
Is adding immunotherapy better?
In CHOPIN, 1-year progression-free survival was 54.7% with the combination versus 15.8% with PHP alone, and the response rate was 76.3%. Grade 3–4 side effects were 82% versus 41%. Larger trials will follow this phase 2 result; for now, the decision is made with doctors by weighing benefits and risks.
How is PHP different from embolization?
Embolization targets the vessels feeding visible tumors with drugs and blocking particles. PHP bathes the entire liver in chemotherapy and filters the outflowing blood, so the whole liver, including small tumors not seen on scans, is treated at once.
This article summarizes official overseas sources and published studies as general information. It is not medical advice. Please discuss treatment choices with the doctors who examine you.
Sources (checked November 2, 2026)
- Kapiteijn E, et al. Percutaneous hepatic perfusion combined with ipilimumab and nivolumab for metastatic uveal melanoma (CHOPIN). The Lancet Oncology. 2026.
- The ASCO Post. Metastatic Uveal Melanoma: Nivolumab and Ipilimumab Plus Percutaneous Hepatic Perfusion. March 12, 2026.
- Zager JS, Orloff M, et al. Efficacy and Safety of the Melphalan/Hepatic Delivery System in Patients with Unresectable Metastatic Uveal Melanoma: Results from an Open-Label, Single-Arm, Multicenter Phase 3 Study. Annals of Surgical Oncology. 2024;31:5340–5351.
- Collettini F, Maleux G. Liver-Directed Therapies Can Be More Than "Local Tumor Control". CardioVascular and Interventional Radiology. 2026.
- NICE. Melphalan chemosaturation with percutaneous hepatic artery perfusion and hepatic vein isolation for primary or metastatic cancer in the liver (update of IPG691).
- Delcath Systems. ESMO Congress 2026 presentations and independent PHP data in liver-dominant metastatic uveal melanoma. October 19, 2026.