For decades, doctors treating men with prostate cancer could offer only extreme choices: surgically remove the prostate, target it with radiation that often damaged healthy tissue nearby, or remove the testicles. Treatments commonly caused pain and debilitating side effects such as incontinence and sexual dysfunction.
Today, however, a prostate cancer diagnosis comes with a widening range of options that are more precise, less harmful, less invasive, and more personalized to the patient’s body and life circumstances. Some of the advances in surgery and radiation began taking hold in the mid-1990s and have continued to evolve, while other treatments have emerged in the past 10 to 15 years.
“We no longer have a one-size-fits-all approach,” says Patrick Pilié, MD, assistant professor in the Department of Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center.
When Francis Collins, MD, former director of National Institutes of Health (NIH), revealed in April that he had late-stage prostate cancer, it focused attention on this widespread disease and its treatments. Prostate cancer is the second-most common cancer diagnosed in males in the United States, after skin cancer, according to the American Cancer Society (ACS). According to the most recent data from the Centers for Disease Control and Prevention, 236,659 new prostate cancers were reported in 2021, and cases are rising. The disease killed 33,363 men in 2022.
About 40 percent of men over age 65 have low-grade prostate cancer [a small tumor that’s unlikely to spread], yet “many of them never know it,” Collins wrote in his announcement. The good news: “Very few of them develop advanced disease.”
Collins’ low-grade cancer did advance; he announced that he would undergo robotic surgery to remove his prostate. NIH spokesperson Renate Myles confirmed this week that Dr. Collins had the surgery and is doing well.
The evolution of surgery by robotic arms (controlled by a surgeon) is among an array of technological and procedural advances. 3-D images give doctors precise information about the boundaries of tumors. Genetic analysis helps doctors assess which treatments a patient will respond to best. Certain drugs stop the growth of cancer cells by inhibiting their ability to repair their own DNA or reducing the hormones that they need to survive.
Some of the advances are applied to other cancers as well, but Pilié says they are particularly important for prostate cancer because it is “the most heterogeneous cancer.” That is, it varies greatly in how it presents in examinations, how it spreads, how it affects people, and how it responds to interventions.
Here are several advances, which are sometimes used together or successively.
Perhaps the most expanding response to a prostate cancer diagnosis today is to watch it: that is, to repeatedly assess it and decide if, and how, to intervene. The continuing improvement of diagnostics, coupled with the expansion of treatments for various levels and characteristics of prostate cancer, allow doctors to spare many patients the most invasive procedures.
In the past, “there [were] many patients who got surgery or radiation therapy that they probably didn’t need,” says Lorelei Mucci, MD, director of Strategic Research Partnerships at the ACS. With active surveillance, “the goal is to delay when somebody might need treatment,” and if treatment is needed, to choose an approach that balances effectiveness against harmful side effects.
For a “low-risk prostate cancer” — one that appears unlikely to expand aggressively, or to affect someone’s quality or length of life — Pilié says that active surveillance makes sense, at least at the start. He and Mucci stress the “active” aspect of the surveillance.
“It’s not wiping your hands and saying, ‘You’ll be fine,’” Pilié says. Active surveillance requires blood tests to monitor levels of PSA (prostate-specific antigen, a protein that indicates the possibility of prostate cancer), along with biopsies and MRIs of the tumor when warranted.
The risk is that the cancer can advance under-the-radar to a point where suddenly the condition is severe. “Trying to decide between watching cancer and doing something can be a very fine line,” notes Benjamin Chung, MD, director of robotic surgery at Stanford Health Care in California.
Collins walked that fine line with his doctors. He had been undergoing active surveillance for years, but earlier this year a sharp rise in his PSA level led doctors to take biopsies and MRI scans, which showed that the cancer had grown significantly and become more aggressive.
“When I heard the diagnosis was now a 9 on a cancer-grading scale that goes only to 10, I knew that everything had changed,” Collins wrote.
Some treatments have evolved to reduce the side effects and other burdens that significant medical interventions put on patients. Consider radiation therapy: In the 1980s, radiation was typically delivered through 40 rounds of treatments over several months, says Daniel Spratt, MD, chair of radiation oncology at University Hospitals in Cleveland. At University Hospitals today, the treatment is completed in five rounds within a couple of weeks, with far less damage to the tissue surrounding the prostate.
A major reason for that change is that radiation oncologists are getting more precise images of the cancerous tumor and are better able to target it while causing minimal or no damage to surrounding tissue. In the past, two-dimensional X-ray imaging gave doctors a view only of the bony anatomy.
“We drew on X-ray films, like you would with a pen,” to highlight the area for treatment, Spratt says. Doctors targeted radiation to kill the cancer cells, knowing that they were also hitting surrounding tissue. Rectum damage — such as bleeding — was a common side effect.
More recent 3-D imaging has allowed surgeons to literally get a better picture of the tumor and deliver radiation more precisely to the cancerous tissue, Spratt says. His team also uses spacer gel that goes around the prostate, creating about a centimeter of space away from the rectum, Spratt says.
Before these practices became common, Spratt says, “we were always trying to figure out how much [radiation] the rectum is able to tolerate.” Now his team can actually deliver stronger doses of radiation to the prostate, which reduces the number of treatments needed and also reduces damage to surrounding tissue. Spratt calls the changes “transformative” for doctors and patients.
Advances in genetic testing have enabled doctors to learn about DNA mutations in a patient that might influence how they respond to specific treatments. These mutations can be hereditary or can develop within the tumor itself.
“The shining example,” Pilié says, are PARP inhibitors: oral medications that are often given to patients who have mutations in their BRCA genes. Both men and women have BRCA genes, which are commonly referred to as “breast cancer genes” because people with mutated BRCA genes are more likely to develop that disease, as well as prostate and ovarian cancer.
Cancer cells use PARP, a protein, to repair damage to their DNA and keep growing. By inhibiting PARP, this treatment curtails the ability of the cancer cells to repair damage, which in turn stops the cells from growing and dividing.
This approach is especially valuable for patients whose cancer has been resistant to other therapies, Pilié says. He notes that genetic testing has become more available and less costly in recent years, so that it is now routinely recommended for certain prostate cancer patients, including those with a family history of prostate, breast, and ovarian cancer, and those whose cancer has metastasized.
Because prostate cancer cells depend on androgens (such as testosterone) to grow and survive, lowering androgen levels can stop or slow the growth of the cancer. While surgical castration is one option for aggressive and advanced cancer, the reductions are routinely achieved through the delivery of drugs that suppress testosterone production, a process known as androgen deprivation therapy.
“Androgen pathway inhibitors have been the single biggest improvement in treating advanced prostate cancer in the last 5 to 10 years,” Pilié says. “They have significantly improved survival.”
Antiandrogen therapy is commonly used in conjunction with other treatments, but it can have drawbacks, including bone frailty and reduced sexual function. Sometimes the body develops a resistance to the inhibitors, making them less effective as time goes on.
Robotic surgery for prostate cancer isn’t new, but over the past two decades it has evolved to become the most common way that prostatectomies – surgery to remove part or all of the prostate – are performed in the United States, according to the ACS. Although it is unclear if the long-term outcomes for patients are better with robotic surgery than with open prostatectomy, the robotic process guides the doctors’ movements precisely and smoothly (the robotic arms have a greater range of motion than human hands) and it tends to have fewer side effects, such as blood loss and pain, Chung says.
For the procedure, the surgeon sits at a console near the operating table and controls the robotic arms and a tiny 3-D camera that provides a high-definition view of the prostate and surrounding area. The surgeon makes several incisions through which he or she inserts the robotic arms and camera. One recent advance, Chung says, is robotic surgery using a single incision, which can reduce damage to the body and post-operative pain.
Collectively, these developments have shifted the focus toward a more personalized approach, taking into account the aggressiveness of the cancer, the patient’s other medical conditions and life circumstances, and appropriateness of the treatment along with the harm that it might cause.
“It’s about identifying cancers that have the highest chance of being aggressive, causing symptoms, taking a man’s life,” Spratt says. “You adapt treatment strategies from there.”
“We are far more cognizant [than before] about this balance of cure and quality of life,” he adds. “Not all cancer needs to be cured.”
Patrick Boyle is a senior staff writer for AAMCNews whose areas of focus include medical research, climate change, and artificial intelligence. He can be reached at pboyle@aamc.org.
