Background
Hepatocellular carcinoma, or HCC, is the most common primary liver cancer. When HCC grows into the portal vein and forms tumoral portal vein thrombosis, or PVTT, treatment becomes much more difficult. The portal vein carries blood from the intestines to the liver, so invasion of this vessel usually signals advanced disease, worse liver function, and a higher risk of spread. Because of this, PVTT has traditionally been considered a contraindication to liver transplantation in many transplant programs.
However, there is growing interest in using locoregional treatments to control the tumor, especially in carefully selected patients. Transarterial radioembolization, also called TARE or Y90 radioembolization, delivers radioactive microspheres directly into the arteries feeding the tumor. This approach can shrink liver tumors and, in some cases, cause regression of PVTT. If the disease remains controlled for long enough and the tumor burden falls within transplant criteria, some patients may become eligible for liver transplantation. This process is called downstaging.
The study summarized here evaluated whether Y90 radioembolization could successfully downstage patients with HCC and PVTT to liver transplant eligibility, and what happened after transplantation in terms of cancer recurrence and survival.
Study design and patient selection
This was a multicenter Italian study involving five liver transplant centers and consecutive patients treated between 2010 and 2023. The investigators included 240 patients with HCC and PVTT who underwent TARE. The key question was not only whether the tumor responded radiologically, but whether the response was durable and clinically meaningful enough to permit transplantation.
To be considered successfully downstaged, patients needed several conditions to be met. First, the PVTT had to show a complete or partial radiological response that persisted for at least 6 months. Second, patients also had to meet each center’s specific morphologic transplant criteria, which generally relate to tumor size, number of lesions, and extent of liver involvement. Third, alpha-fetoprotein, or AFP, had to remain below center-specific thresholds. AFP is a blood marker often elevated in HCC and is used as an additional indicator of tumor activity.
The study assessed outcomes for the overall TARE-treated population as well as for the subset who ultimately underwent liver transplantation. Among those who were downstaged, the researchers also compared cancer-related death according to whether or not transplantation occurred, using a competing-risk method that better reflects real-world clinical outcomes.
Key findings
Out of 240 treated patients, 61 patients, or 25.4%, achieved sustained downstaging after TARE. This means roughly one in four patients with HCC and PVTT had a durable enough response to move closer to transplant eligibility. Ultimately, 37 patients, or 15.4% of the total cohort, went on to receive liver transplantation.
The median interval from TARE to transplant was 17 months, showing that successful downstaging is not immediate. It requires prolonged observation to confirm stable disease control and to ensure the biology of the tumor is favorable. This waiting period also functions as a practical test of tumor aggressiveness: cancers that remain quiet over many months are more likely to behave well after transplant.
In competing-risk analysis among the downstaged patients, transplantation was linked to a substantially lower risk of cancer-related death. At 60 months, the cumulative incidence of cancer-related death was 15.8% in transplanted patients compared with 45.2% in those who were downstaged but not transplanted. The subdistribution hazard ratio was 0.221, with a 95% confidence interval of 0.071 to 0.683, and the result was statistically significant (p=0.0087). In practical terms, this suggests that once a patient with PVTT has been successfully downstaged, liver transplantation can offer a major oncologic advantage over continued non-transplant management.
Outcomes after transplantation
Among the 37 patients who underwent liver transplantation, post-transplant survival outcomes were encouraging. The 3-year and 5-year overall survival rates were 67.2% and 61.6%, respectively. Disease-free survival, also called recurrence-free survival, was 79.3% at both 3 and 5 years. These results are notable because patients with PVTT are generally considered high-risk, and historically have been excluded from transplant candidacy in many centers.
Pathological examination of the removed livers showed complete tumor necrosis in 56.7% of explants. This means more than half of transplanted patients had no viable tumor left in the liver specimen, suggesting a strong treatment effect from radioembolization and/or prolonged tumor control before surgery. Complete necrosis is often considered a favorable sign because it may reflect both effective local therapy and less aggressive tumor biology.
Why these results matter
This study adds important evidence to a difficult area of liver cancer care. Patients with HCC and PVTT are often limited to palliative or non-curative options because portal vein invasion is associated with poor outcomes after surgery. Y90 radioembolization, however, may change the treatment pathway for a small but meaningful subset of patients.
The findings support several clinically important ideas. First, TARE can produce sustained control of tumor thrombus in the portal vein. Second, response needs to be durable, not just early and temporary, before transplant is considered. Third, in patients who meet downstaging criteria, liver transplantation appears to provide the best chance for long-term cancer control.
The study also highlights the importance of multidisciplinary decision-making. Patients with advanced HCC require coordination among hepatologists, interventional radiologists, transplant surgeons, oncologists, and radiologists. Careful patient selection is essential, because not every person with PVTT will benefit from this strategy. Liver function reserve, tumor extent, AFP level, response durability, and overall clinical condition all matter.
Clinical interpretation
From a practical standpoint, the study suggests that Y90 radioembolization may serve as a bridge to transplant in select patients with PVTT, rather than being viewed only as a palliative treatment. The fact that transplantation was associated with markedly lower cancer-related mortality after successful downstaging strengthens the argument for considering transplant-oriented pathways in specialized centers.
At the same time, the data should be interpreted cautiously. This was not a randomized trial, and only a minority of the full cohort ultimately received transplantation. Patients who are able to reach transplant after prolonged response are likely a highly selected group with more favorable tumor biology. That selection effect is part of what makes the outcomes look strong, but it is also clinically meaningful: it identifies a population that can truly benefit from aggressive curative-intent treatment.
Another important point is timing. The median 17-month interval from TARE to transplant suggests that patience and surveillance are crucial. Immediate transplantation after an early response would not capture the stability needed to judge long-term behavior. In many transplant programs, sustained observation after downstaging is used to reduce the risk of post-transplant recurrence.
Limitations
As with all observational studies, there are limitations. Treatment decisions were made across multiple centers, which may introduce variability in downstaging criteria and transplant practices. The study also reflects real-world selection, so the transplanted patients may not represent the full spectrum of patients with HCC and PVTT.
In addition, the analysis does not prove that TARE alone is responsible for the excellent outcomes; rather, it shows that TARE can identify a group of patients who achieve sufficient disease control to proceed to transplantation, where survival is much better. The results are promising, but broader validation in larger prospective cohorts would help define which patients are the best candidates.
Bottom line
In patients with hepatocellular carcinoma and tumoral portal vein thrombosis, Y90 radioembolization successfully downstaged about one-quarter of patients to transplant eligibility. Among those who reached transplantation, cancer-related outcomes were substantially better, with favorable survival and low recurrence rates. More than half of explanted livers showed complete tumor necrosis.
Overall, the study supports radioembolization as a meaningful transplant-oriented strategy for carefully selected PVTT patients. While still specialized and not applicable to everyone, this approach may open a curative path for patients who would otherwise be considered beyond transplant options.
