What is PD-L1 and Why Should I Be Tested for It?

With the arrival of new cancer drugs that act in specialized ways or target things like the immune system, it’s helpful to know whether your cancer might respond to a certain drug before starting the medication. One category of some of the newer cancer drugs is called immune checkpoint inhibitors. These drugs are usually made of antibodies that release an immune system response onto cancer cells.¹ When evaluating cancer treatments, professionals typically describe improvement as the cancer “responding” to treatment, so we will use that language here as well.

What do immune checkpoint inhibitors do?

Some cancer cells use immune system checkpoint molecules to look like normal cells and go undetected when an immune response tries to kill them. That’s where checkpoint inhibitors come in: they block the protein molecules that prevent T-cells (a type of white blood cell) from recognizing them as cancerous, and they proceed to deploy an immune response against them.¹

What is PD-L1?

PD-L1 is a protein that helps some cells avoid immune system attacks. This protein extends out from the cell surface and communicates with the protein PD-1 that is on some immune cells called T-cells. Taken together, the pairing of PD-L1 and PD-1 is called an immune checkpoint, and this pairing tells the T-cell to leave the tumor cell alone and not attack it.² The immune checkpoint inhibitor drugs prevent this pairing from taking place so the T-cells can attack the tumor cells.

WWhat does a PD-L1 test involve?

The PD-L1 test involves taking a small piece of tumor tissue and sending it to a lab for analysis.² The test itself measures how much PD-L1 a tumor produces, to gauge whether it might be efficient to use immune checkpoint inhibitors in treatment. Testing is not foolproof, though – some tumors that express high amounts of PD-L1 may not be responsive to checkpoint inhibitors, while tumors with low levels of PD-L1 may have a stronger response.²

Immune checkpoint inhibitors that work on the PD-1/PD-L1 checkpoint have been developed and approved by the FDA for various cancers, including bladder cancer, lung cancer, kidney cancers, squamous cell cancer of the head and neck, and Hodgkin lymphoma.² The use of these drugs in other cancers is being studied, as well. Less than 5% of those who took our Bladder Cancer In America survey were tested for PD-L1 expression.

Which treatments are available?

There are several immune checkpoint inhibitors approved for the treatment of metastatic bladder cancer for those whose cancer has progressed despite treatment with cisplatin-based chemotherapy, which is the first-line treatment. Anti-PD-L1 therapies include the drug avelumab (Bavencio); and anti-PD-1 therapies include nivolumab (Opdivo) and pembrolizumab (Keytruda). While biomarker testing like testing for PD-L1 has been helpful for some patients in determining who might benefit from these drugs, the tests are not ideal predictive markers.³ Testing may not always be necessary; some of these drugs are simply used when a tumor does not respond to cisplatin-based chemotherapy. In fact, the standard of care for patients whose cancer progressed after chemotherapy is immunotherapy with checkpoint inhibitors.⁴

How PD-L1 testing can open up new treatment opportunities

Although PD-L1 testing may not be necessary, it may be beneficial for patients with metastatic bladder cancer, since there are still few treatments available for them. Testing may open up the possibility of participating in clinical trials, since there are more and more trials being launched on PD-1/L-1, with fewer patients available to recruit.⁵ Participating in a clinical trial can open up new treatment opportunities that patients wouldn’t otherwise be able to access.

Understanding your tumor pathology

Talk with your doctor about the kind of bladder cancer you have and whether PD-L1 testing might be beneficial. It’s important to keep in mind that the test is not perfect, and doesn’t necessarily accurately predict the kind of response you might have with an immune checkpoint inhibitor. Your doctor can go over your treatment response history and your tumor pathology, and talk with you about which treatments might be most appropriate at the given time.