Immunotherapy for Prostate Cancer Presents New Treatment Options

There was a time not too long ago when prostate cancer treatment meant one of three things: surgery, chemotherapy or radiation therapy.

Healthcare providers, researchers and specialists continue to refine the ways they use these tools. Nerve-sparing surgery, precisely targeted radiation therapy and carefully calibrated doses and cycles of chemo, have helped countless men enjoy longer and richer lives, including their sex lives.

While those "Big Three" treatments continue to be used all over the world, new techniques and therapies for treating cancer—specifically, prostate cancer—are always under development.

One of the new trends is using immunotherapy to treat various types of prostate cancer.

For prostate cancer that's still localized in the gland, primary treatments such as surgery and radiation are usually the go-to choices. For men whose prostate cancer has metastasized and is resistant to hormone therapy, immunotherapy may be an option.

Immunotherapy is a technique in which the patient's own immune cells are prompted to fight cancer.

Take a look at how immunotherapy for prostate cancer works, find out which men are good candidates for the treatment and learn some of the limitations and hurdles researchers have yet to cross.

What is immunotherapy?

Immunotherapy, as the name suggests, involves getting your body's own immune system activated in the fight against cancer cells. It's been around since the early 1990s, but it's only been approved by the Food and Drug Administration (FDA) for use against prostate cancer for a few years.

The first approved immunotherapy for prostate cancer is a product called sipuleucel-T (sip-T), which is still in use and marketed under the name Provenge.

"That's where you remove cells from the body," said Daniel P. Petrylak, M.D., chief of genitourinary oncology at Yale School of Medicine. "You take the lymphocytes out, you harvest them and then you reinfuse them three days later after exposing them to something called prostatic acid phosphatase."

This process is repeated three times every two weeks and has been shown to make a significant impact in prolonging life for many men whose prostate cancer has metastasized. Interestingly, the treatment doesn't lower prostate-specific antigen (PSA) levels, nor does it shrink the tumor—usually the main indications of successful treatment—but it does help men live longer.

"There was a lot of confusion about it," Petrylak said. "The interesting thing about sip-T, which was approved in 2010, is it gives a survival benefit, but you don't generally see PSA declines, nor do you see improvements in soft tissue lesions, but it does improve survival. It slows the progress of the disease down.

"[Immunotherapy is] for metastatic patients," Petrylak added. "We've found that the lower the volume of the disease, the better the patients do. So bone-only, PSAs of less than 22 and resistant to hormones, those are the patients it's appropriate for."

Immune checkpoint inhibitors

Another type of immunotherapy for prostate cancer is a category called immune checkpoint inhibitor.

Pembrolizumab is the primary drug for this purpose, approved for use by the FDA in 2017. It works by blocking chemical signals that mask the cancer cells and activating immune cells that attack the tumor.

"The best way to think about this is, do you remember the show 'Star Trek'? Think of the cloaking device," Petrylak said. "The cloaking device was a way in which the Klingons hid themselves from the Federation. So the cloaking device is the way the tumor cells shield themselves from the immune system. These drugs, these checkpoint inhibitors, basically block that process. They unmask the tumor cells to the immune system."

One challenge for immunotherapy researchers in treating prostate cancer versus other types of cancer is that the prostate doesn't trigger immune responses as readily as other parts of the body.

"Urine, which is dirty, technically goes through the prostate," said Murugesan Manoharan, M.D., the chief of urologic oncologic surgery at Miami Cancer Institute, part of Baptist Health. "So the way it's designed is the immune environment is a little bit on the lower side. Otherwise, it would respond to everything. Any bacteria in the urine would cause the prostate to get inflamed."

Another roadblock in the use of pembrolizumab and other checkpoint inhibitors is that they show efficacy only in a small percentage of men. In order for the inhibitors to function, the patient's tumor must have a particular genetic marker called microsatellite instability (MSI). The DNA of those who have it makes unstable proteins, which the immune system can recognize and attack if they're given checkpoint inhibitors. It's just not a very common genetic mutation, unfortunately.

"About 2 percent of metastatic prostate cancer makes that marker," Petrylak said. "But when we have administered pembrolizumab to those patients with the MSI phenotype, we have seen dramatic responses. So it's something that every patient who has metastatic disease should be evaluated for because even though it's rare, when it's there, it can be life-changing."

Another exciting area of research was placed on an accelerated approval path by the FDA starting in 2020. It involves the use of a type of monoclonal antibody called bispecific T-cell engager (BiTE). It directs the patient's T-cells—a type of white blood cell vital to the immune system—to tumor cells and prompts them to attack.

"How can I make the T-cell and the enemy fight?" Manoharan said. "Well, we have something called a BiTE, a bispecific T-cell engager. And these things have two hooks. One hook catches the T-cell and holds it, and the other hook pulls the protein and the cancer cell together. So now they are together and they can fight each other. That's known as BiTE therapy."

Conclusions

There is still a long road ahead for the use of immunotherapy in treating prostate cancer, but the good news is tremendous progress is being made. It's helping more and more men live better lives every day.

"When I first started out in the 1990s, survival [in metastatic patients] was about 12 months," Petrylak said. "We've improved that in the hormone-resistant patients to about three years. With all of our new treatments, with the immune therapy, with the chemotherapy agents, the hormonal therapy agents as well, all of those have really come into play and are very important.

"The future looks very, very bright."

Editor's note: Do you have a personal prostate cancer story you’d like to share? Are you a survivor? Did immunotherapy help you? Giddy welcomes first-person accounts that break down stigmas and connect with readers to let them know they're not alone. To share your story, send a message to Mike Werling at mwerling@getmegiddy.com.