Transplant oncology: how liver transplant is changing cancer care

The field of transplant oncology is expanding, with liver transplantation now becoming an effective treatment option for more patients with cancer. At Penn Medicine, transplant specialists recently performed a liver transplant in a patient with colorectal cancer that had metastasized to the liver—the first liver transplant in the region for metastatic colorectal cancer, marking an important milestone in a field that is poised to grow.

“The goal of transplant oncology is to offer a treatment that can cure cancer and allow people to live a longer life,” says Maarouf A. Hoteit, MD, director of the Liver Tumor Clinic, medical director of Liver Transplant, and professor of Clinical Medicine (Gastroenterology) at Penn Medicine. “At Penn Medicine, we are trying to push the envelope for transplant oncology to offer a possible cure to more patients.”

Building the field of transplant oncology

Liver transplantation for liver cancer was explored as early as the 1960s, but early long-term outcomes were poor. With donated organs in short supply, it made little sense to transplant livers into cancer patients whose lifespans were limited. The initial breakthrough for the successful use of transplantation in cancer occurred in the 1990s, when criteria were developed to better select patients with hepatocellular carcinoma (HCC), the most common form of primary liver cancer, who have a low risk of cancer recurrence after transplant, Dr. Hoteit says.

As a result, liver transplantation emerged as a successful treatment for HCC that could not be safely removed with surgery because of either the extent of the tumor or because of impaired liver function. The criteria recommended transplant only for patients with tumors below a certain size (a single lesion less than 5 cm, or 3 lesions each measuring less than 3 cm) with no evidence of macrovascular invasion.

“Research at Penn Medicine, part of a national multicenter effort, helped demonstrate that if we can shrink a large tumor exceeding the standard size criteria using cancer therapy first, we can still have good outcomes from transplant,” Dr. Hoteit says. “This can result in a high likelihood of cancer cure not offered by any other treatment.” Such advances helped make more patients with HCC eligible for transplant.

Now, a new frontier in HCC is offering curative therapy to patients with aggressive tumors, including some of the tumors that invade veins in the liver but have not spread outside the liver itself. “These tend to be more aggressive cancers, and historically, they have a high risk of spread,” Dr Hoteit says. “But now we’re looking at whether we can use multimodality treatments, including immunotherapy, to hold the cancer in place and prevent spread to allow for a successful transplant. Clearly, we are not successful in reaching transplant every time when we have an aggressive tumor, but we are certainly pushing hard to achieve that goal.”

Hilar cholangiocarcinoma (bile duct cancer) presents different challenges. These tumors tend to present late and have often spread beyond the liver by the time they are diagnosed. Careful tumor staging and effective pre-transplant cancer therapy may offer a cure with transplantation in carefully selected patients with this difficult-to-treat cancer. To prevent tumor spread, a procedure comprising a multi-step protocol requiring chemotherapy and radiation is performed prior to transplant. This protocol requires a close collaboration between medical oncologists, radiation oncologists, interventional radiologists, GI endoscopists, and the transplant team.

In November 2017, a clinical team from the Divisions of Gastroenterology and Liver Transplantation at Penn Medicine performed the region's first liver transplant for a patient with perihilar cholangiocarcinoma. With an experienced team of transplant oncology specialists, Penn Medicine is one of only a few centers in the Northeast that offers this complex treatment.

“To drive these advances, you need a subgroup of transplant specialists that really understand oncology,” Dr. Hoteit says. “There were multiple steps along this evolution, and Penn Medicine was part of developing the science that led to the adoption of these treatment strategies.”

Liver transplant for metastatic colorectal cancer

In addition, liver transplant is currently an option for some patients with colorectal cancer that has metastasized to the liver. “The liver is the most common place that colon cancer spreads to, and in many cases it doesn’t go to other organs,” says Dr. Hoteit. “Liver resection surgery has been a standard treatment for colorectal cancer patients with liver metastases if contained within the liver.”

But what if the tumor in the liver is not removable?

TransMet, a European randomized controlled trial described in a 2024 Lancet article, helped to answer that question. The study explored liver transplant as a treatment for patients with unresectable colorectal liver metastases, and found that transplant offered significantly higher survival than chemotherapy alone.

Now Penn Medicine has begun treating such patients. To be considered for transplant, a patient must have disease contained exclusively within the liver for one year, with no growth of the tumor for at least three to six months. Advances in colon cancer treatment are making it easier to achieve that control—and may help to expand the number of candidates eligible for transplant.

At the same time, rates of colon cancer are rising in younger patients, potentially adding to the value of liver transplantation in this population. “Younger people are better candidates for transplant, because they are often otherwise healthy enough to go through this major surgery,” Dr. Hoteit says. “This indication for transplant is relatively new, but I suspect it will become increasingly important over time.”

The living donor liver transplant program

Although liver transplantation produces excellent outcomes in many cancer patients, the limited supply of donor organs remains a barrier. The lengthy waiting time on the transplant list is often detrimental as it adds to the challenge of maintaining tumor control until transplant.

“In most patients, cancer treatment works well to control the disease for a period of time on the wait list, but we know that at some point it will stop working. We have a limited time window to get patients transplanted before the tumor starts growing again,” notes Dr. Hoteit.

For some transplant oncology patients, living donation can play a critical role by shortening the path to transplant and reducing reliance on the deceased donor wait list.

“Living donation creates additional opportunities for patients who may otherwise lose their chance at transplant while waiting for a deceased donor organ. For carefully selected oncology patients, it can provide access to transplant during a critical period when the cancer remains controlled,” says Dempsey Hughes, MD, medical director of the Living Donor Liver Transplant Program at Penn Medicine.

Penn Medicine has a robust living donor program and offers resources to help patients connect with suitable donors. “Cancer doesn’t just sit and wait for us,” Dr. Hoteit says. “Having an active and effective living donor program allows us to move quickly to transplant for eligible patients in the transplant oncology program.”

Referrals and consultations

The transplant oncology team at Penn Medicine includes expert transplant specialists, medical oncologists, radiation oncologists, and interventional radiologists who meet weekly to review cases and discuss strategies. Those strategies include treating patients who are suitable for transplant oncology and developing new approaches to extend eligibility in the future. “A big part of the work we’re doing at Penn Medicine is finding ways to offer transplant to more cancer patients than was initially envisioned,” Dr. Hoteit says.

To learn more about Liver Transplant at Penn Medicine, refer a patient, or receive consultation from a transplant specialist, please call 877-937-7366, or submit a referral through our secure online referral form.