NCI-funded researchers are working to advance our understanding of how to prevent, detect, and treat prostate cancer. Most men diagnosed with prostate cancer will live a long time, but challenges remain in choosing the best treatments for individuals at all stages of the disease.

This page highlights some of the latest research in prostate cancer, including clinical advances that may soon translate into improved care, NCI-supported programs that are fueling progress, and research findings from recent studies.

Men with certain inherited genetic traits are at increased risk for developing prostate cancer. Examples of such traits include inherited BRCA gene mutations and Lynch syndrome. No clear guidelines exist for when or how—or if—to screen men at high genetic risk for prostate cancer.

NCI researchers are using magnetic resonance imaging (MRI) of the prostate in men at high risk to learn more about how often and how early these cancers occur. They’re also testing whether regular scans in such men can detect cancers early, before they spread elsewhere in the body (metastasize).

Traditionally, prostate cancer has been diagnosed using needles inserted into the prostate gland in several places under the guidance of transrectal ultrasound (TRUS) imaging to collect samples of tissue. This approach is called systematic biopsy.

However, ultrasound does not generally show the location of cancer within the prostate. It is mainly used to make sure the biopsy needles go into the gland safely. Therefore, biopsy samples using ultrasound guidance can miss cancer altogether. Or they may identify low-grade cancer while missing areas of high-grade, potentially more aggressive cancer.

Some doctors, concerned that a systematic biopsy showing only low-grade cancer could have missed a high-grade cancer, may suggest surgery or radiation. However, in some cases these treatments will be for a cancer that may have never caused a problem, which is considered overtreatment.

Using MRI and ultrasound. Scientists at NCI have developed a procedure that combines magnetic resonance imaging (MRI) with TRUS for more accurate prostate biopsies. MRI can locate potential areas of cancer within the gland but is not practical for real-time imaging to guide a prostate biopsy. The procedure, known as MRI-targeted biopsy, uses computers to fuse an MRI image with an ultrasound image. This lets doctors use ultrasound guidance to take biopsy samples of areas of possible cancer seen on MRI.

NCI researchers have found that combining MRI-targeted biopsy with systematic biopsy can increase the detection of high-grade prostate cancers while decreasing detection of low-grade cancers that are unlikely to progress.

Testing machine learning. Researchers are testing the use of machine learning, also called artificial intelligence (AI), to better recognize suspicious areas in a prostate MRI that should be biopsied. AI is also being developed to help pathologists who aren't prostate cancer experts accurately assess prostate cancer grade. Cancer grade is the most important factor in determining the need for treatment versus active surveillance.

Standard treatments for prostate cancer that has not spread elsewhere in the body are surgery or radiation therapy (RT), with or without hormone therapy.

Active surveillance is also an option for men who have a low risk of their cancer spreading. This means monitoring the cancer with regular biopsies and holding off on treatment unless there is evidence of progression. Rates of active surveillance more than doubled between 2014 and 2021, to almost 60% of US men diagnosed with low-risk prostate cancer.

Hormone therapy for prostate cancer

Over the last decade, several new approaches to hormone therapy for advanced or metastatic prostate cancer have been approved for clinical use.

Many prostate cancers that originally respond to treatment with standard hormone therapy become resistant over time, resulting in castrate-resistant prostate cancer (CRPC). Four newer drugs have been shown to extend survival in some groups of men with CRPC. All inhibit the action of hormones that drive CRPC:

• enzalutamide (Xtandi)
• abiraterone (Zytiga)
• darolutamide (Nubeqa)
• apalutamide (Erleada)

These drugs are now also used in some people whose prostate cancer still responds to standard hormone therapies but has spread elsewhere in the body (metastasized).

Scientists are continuing to study novel treatments and drugs, along with new combinations of existing treatments, in men with metastatic and castration-resistant prostate cancer.

PARP inhibitors for prostate cancer

A PARP inhibitor is a substance that blocks an enzyme in cells called PARP. PARP helps repair DNA when it becomes damaged. Some prostate tumors have genetic defects that limit their ability to repair DNA damage. Such tumors may be sensitive to PARP inhibitors.

Two PARP inhibitors, olaparib (Lynparza) and rucaparib (Rubraca), have been approved for some men whose prostate cancer has such genetic defects and has metastasized, and whose disease has stopped responding to standard hormone treatments. Ongoing studies are looking at combing PARP inhibitors with hormone therapies.

Immunotherapy: vaccines for prostate cancer

Immunotherapies are treatments that harness the power of the immune system to fight cancer. These treatments can either help the immune system attack the cancer directly or stimulate the immune system in a more general way.

Vaccines and checkpoint inhibitors are two types of immunotherapy being tested in prostate cancer. Treatment vaccines are injections that stimulate the immune system to recognize and attack a tumor.

One type of treatment vaccine called sipuleucel-T (Provenge) is approved for men with few or no symptoms from metastatic CRPC.

Immunotherapy: checkpoint inhibitors for prostate cancer

An immune checkpoint inhibitor is a type of drug that blocks proteins on immune cells, making the immune system more effective at killing cancer cells.

Two checkpoint inhibitors, pembrolizumab (Keytruda) and dostarlimab (Jemperli) have been approved for the treatment of tumors, including prostate cancers, that have specific genetic features. Pembrolizumab has also been approved for any tumor that has metastasized and has a high number of genetic mutations.

But relatively few prostate cancers have these features, and prostate cancer in general has largely been resistant to treatment with checkpoint inhibitors and other immunotherapies, such as CAR T-cell therapy.

Research is ongoing to find ways to help the immune system recognize prostate tumors and help immune cells penetrate prostate tumor tissue. Studies are looking at whether combinations of immunotherapy drugs, or immunotherapy drugs given with other types of treatment, may be more effective in treating prostate cancer than single immunotherapies alone.

Targeted radiation therapy and PSMA

Scientists have developed targeted therapies based on PSMA, the same protein that is being tested for imaging prostate cancer. For treatment, the molecule that targets PSMA is chemically linked to a radioactive compound. This new compound can potentially find, bind to, and kill prostate cancer cells throughout the body.

In a recent clinical trial, men with a type of advanced prostate cancer who received a PSMA-targeting drug lived longer than those who received standard therapies. This trial led to FDA approval of the drug, Lu177-PSMA-617 (Pluvicto), to treat some people with metastatic prostate cancer. Ongoing and planned clinical trials are testing PSMA-targeting drugs in patients with earlier stages of prostate cancer, and in combination with other treatments, including targeted therapies like PARP inhibitors and immunotherapy.

Personalized clinical trials for prostate cancer

Research is uncovering more information about the genetic changes that happen as prostate cancers develop and progress. Although early-stage prostate cancer has relatively few genetic changes compared with other types of cancer, researchers have learned that metastatic prostate cancers usually accumulate more mutations as they spread through the body.

These mutations may make men with metastatic prostate cancers candidates for what are called “basket” clinical trials of new drugs. Such trials enroll participants based on the mutations found in their cancer, not where in the body the cancer arose. In the NCI-MATCH trial, a high percentage of enrolled men with advanced prostate cancer had mutations that could potentially be targeted with investigational drugs.

PARP Inhibitors - Poly(ADP-ribose) Polymerase Inhibitors

A substance that blocks an enzyme in cells called PARP. PARP helps repair DNA when it becomes damaged. DNA damage may be caused by many things, including exposure to UV light, radiation, certain anticancer drugs, or other substances in the environment. In cancer treatment, blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Also called poly (ADP-ribose) polymerase inhibitor.

At a Glance

• Men with cancer confined to the prostate experienced different long-term side effects depending on the type of treatment received.
• Understanding the pros and cons of different treatments may help men and their health care teams make more informed treatment decisions.

Although prostate cancer is the most common cancer in men in the United States, it comes with a relatively good prognosis. Most men with prostate cancer will still be alive 15 years after their diagnosis.

Currently, men with prostate cancer that hasn’t spread outside the gland have several treatment choices. Because most men with prostate cancer are expected to live a long time, weighing the long-term side effects of different treatments is important. Side effects can include bladder and bowel problems, and difficulty with sexual functioning.

Men with prostate cancer at low risk of spreading may undergo surgery to remove the whole prostate or radiation therapy. Some may instead choose active surveillance: observing the cancer over time with imaging and tissue biopsies, and only starting treatment if it grows. Men with cancer at higher risk of spreading may have surgery, or radiation plus therapy to suppress hormones that fuel prostate cancer growth.

Studies have shown that how long men live is similar regardless of the chosen treatment. Whether the long-term side effects differ substantially between these treatments hasn’t been clear.

A research team led by Drs. Bashir Al Hussein Al Awamlh and Daniel Barocas from Vanderbilt University Medical Center decided to look more closely at this issue. They recruited almost 2,500 men, 80 years old or younger, from diverse racial backgrounds and geographic areas across the country for a new study, funded in part by NIH. All the men were treated for prostate cancer between 2011-2012 and followed for side effects for 10 years after treatment. The results were published on January 23, 2024, in JAMA.

As seen previously, survival rates were similar between men in the two groups, regardless of treatment received. Overall, 0.4% of men with low-risk cancer and 5% of men with high-risk cancer died of their disease over the following 10 years.

Participants reported similar levels of overall physical and mental health regardless of treatment choice. But the researchers did observe differences in some specific side effects between treatments. Men with low-risk cancer who underwent surgery were more likely to report problems with sexual functioning up to 5 years after treatment than men who had radiation or who initially chose surveillance. However, the differences between groups was no longer significant by the 10-year mark.

Among men with low-risk cancer, 14% who had surgery had trouble with leaking urine 10 years after treatment, compared with 4% of those who had radiation therapy and 10% of those who initially chose active surveillance. But 8% of men who had radiation reported serious bowel problems after 10 years compared with 3% of those who had surgery.

For men with high-risk cancer, no differences in sexual functioning were seen between surgery or radiation therapy plus hormone therapy at any time point. About a quarter of those who had surgery reported urinary leakage after 10 years, compared with 11% who had radiation therapy. Seven percent of men who had radiation plus hormone therapy reported serious bowel problems, compared with 2% to 5% of men who had surgery.

“Many men with localized prostate cancer survive for 15 years or more, with minimal differences in survival among various treatment strategies,” says Al Hussein Al Awamlh. “Given this long-time horizon and similar survival rates, the choice of treatment for patients may be influenced by the adverse effects of the treatments.”

—by Sharon Reynolds

The following are some of our latest news articles on prostate cancer research:

January 5, 2024, by Carmen Phillips

The number of treatment options for prostate cancer has exploded over the last decade. That trend is showing no signs of letting up, with the Food and Drug Administration’s (FDA) recent decision to expand the approved uses of enzalutamide (Xtandi) to treat people with prostate cancer that hasn’t spread, or metastasized, to other parts of the body.

Under this new approval, announced on November 16, enzalutamide can now be used alone, or in combination with leuprolide, to treat nonmetastatic prostate cancer that is castration sensitive.

The new approval also requires that the patient have had an increase in their blood PSA levels after earlier surgery or radiation, known as a biochemical recurrence. However, the approval only applies to those considered to be at high-risk of their cancer spreading.

FDA’s decision was based on the results of a large clinical trial called EMBARK. In the trial, patients treated with the combination of enzalutamide and leuprolide had better metastasis-free survival than those treated with leuprolide (and a placebo). Metastasis-free survival is a measure of how long people live after starting treatment without their cancer spreading or without dying from any cause.

Trial participants treated only with enzalutamide also had better metastasis-free survival than those treated with leuprolide alone.

But the extent to which this new approval and the EMBARK results will, or should, change patient care is still unclear, explained Fatima Karzai, M.D., of NCI’s Center for Cancer Research, who specializes in treating prostate cancer but was not involved in the trial.

For example, Dr. Karzai said, more time is needed to know whether trial participants treated with enzalutamide alone or in combination with leuprolide live longer overall. As a result, this new approval “will garner different treatment approaches” that oncologists recommend to their patients.

Other experts believe the approval will have a substantial impact on patient care. One of the trial’s lead researchers, Stephen Freedland, M.D., of Cedars-Sinai in Los Angeles, said many patients with these high-risk biochemical recurrences will now be treated with the enzalutamide and leuprolide combination.

Dr. Freedland acknowledged that side effects are a concern. “But there are a lot of benefits” to using both drugs together, he added, including “delaying metastasis.” The development of metastases not only requires immediate treatment but also can cause significant pain, particularly when the cancer has spread to the bones.

In addition, Dr. Freedland noted that other analyses from the trial suggests that, overall, treatment with both drugs doesn’t harm people’s quality of life.

From castration-resistant to castration-sensitive localized prostate cancer

Enzalutamide works by disrupting testosterone’s interaction with cancer cells. It's already approved by FDA to treat nonmetastatic and metastatic prostate cancer, including when the cancer can no longer be controlled with drugs that block testosterone production (like leuprolide), known as castration-resistant disease.

In up to half of people with castration-sensitive localized prostate cancer who previously had surgery or radiation to eliminate the tumor, their PSA levels start to creep up, sometimes rapidly, within 10 years. When any such uptick happens, it may mean that the cancer is starting to grow again in the prostate or that there are small tumors somewhere else in the body.

A key measure that oncologists use to judge whether rising PSA levels are a concern is how long it takes for the levels to double from the time they became detectable again.

When the PSA doubling time is rapid, around 9 months or less, studies have suggested it means those patients are at high-risk of having their cancer spread to other organs.

But how to best address biochemical recurrences—even those with rapid PSA doubling times—has been “a gray zone,” Dr. Karzai explained.

Should treatment begin immediately to prevent the cancer from gaining steam? Or should treatment wait until the patient is experiencing symptoms or for confirmation from imaging scans that the cancer has spread?

Currently, many people with a biochemical recurrence with a PSA doubling time of 9 months or less are started on leuprolide or similar drugs, she said.

The EMBARK trial was designed to try to bring some clarity to the question.

In large clinical trials, enzalutamide improved how long men with castration-sensitive prostate cancer that has already spread live overall. So, with the EMBARK trial, researchers wanted to see if enzalutamide might also improve outcomes in people with prostate cancer that hasn’t spread but that—based on rising PSA levels—may be poised to.

Better metastasis-free survival, time with no treatment

Funded by Pfizer and Astellas Pharma, the manufacturers of enzalutamide, the trial enrolled nearly 1,100 participants who had been treated for localized prostate cancer. All participants had PSA levels that had returned and doubled within 9 months, but with no signs that their cancer had spread.

EMBARK participants were randomly assigned to treatment with both enzalutamide and leuprolide or with either drug alone.

After starting treatment, participants had full-body CT scans and bone scans every 6 months to look for signs that their cancer had returned. Participants whose PSA levels decreased to undetectable levels within 37 weeks could pause treatment. Such breaks are often called “treatment holidays.” Treatment resumed if their PSA levels started to rise again.

Darolutamide Extends Survival in Metastatic Prostate Cancer

Adding darolutamide to standard therapy helped patients live longer without increasing side effects.

Five years after starting treatment, Dr. Freedland and his colleagues reported, about 87% of participants treated with enzalutamide and leuprolide were still alive with no evidence of metastasis, compared with 80% of people treated with only enzalutamide and 71% with only leuprolide. The findings were published in October in The New England Journal of Medicine.

Dr. Freedland noted that, to date, there is a strong statistical trend suggesting that people treated with both drugs also will live longer overall than those treated with leuprolide alone. But participants will have to be followed longer before it’s known for sure.

About 91% of people in the combination treatment group were able to pause treatment because of undetectable PSA levels, compared with 86% in the enzalutamide-only group and 68% in the leuprolide group.

Many patients in all three groups were able to pause treatment for 2 years or more, although the median length of treatment suspension was longest in the combination treatment group (20 months versus 17 and 11 months, respectively).

Side effects and quality of life

There were no surprises in terms of the side effects seen in the trial in people treated with enzalutamide alone or with leuprolide. That said, side effects were common and sometimes serious in all three treatment groups.

In the enzalutamide–leuprolide group, the most common side effects were hot flashes, fatigue, and muscle aches, although many of these were also common in the leuprolide alone group. In the enzalutamide–alone group, the most common side effects include hot flashes, fatigue, and enlarged breasts. Severe side effects were not frequent in any of the groups and were generally higher in those treated with enzalutamide.

In an editorial that accompanied the trial results, Ana Aparicio, M.D., who specializes in treating prostate cancer at the University of Texas M.D. Anderson Cancer Center, noted that of the trial participants who died, potentially up to 60% were from causes other than prostate cancer.

The large number of noncancer deaths can point to a problem called overtreatment—that is, treatment that was not likely to extend or improve a person’s life.

“The extent to which the cancer treatments contributed to these deaths is unknown,” Dr. Aparicio wrote. “But even if there was no association, their frequency arguably diminishes [the treatments’] potential benefit.”

Nevertheless, she concluded, the results show that, at least for some patients, the upside of “early cancer control” with enzalutamide alone or combined with leuprolide “outweigh[s] its risks.”

According to a separate analysis from EMBARK published in October in NEJM Evidence, treatment with enzalutamide and leuprolide did not appear to decrease EMBARK participants’ quality of life, Dr. Freedland noted.

The prospect of a prolonged treatment holiday is also an important consideration, he continued.

“After 8 or 9 months of therapy, if you do really well, we stop [treatment],” he said. “It’s not years and years of treatment. We’re going to be very aggressive for a period, and if you do well, chances are really high you’ll reach that [suspension] threshold.”

Treatment decisions in the era of PSMA-PET

The first participants in EMBARK were enrolled more than 8 years ago. Since that time, an imaging technology used specifically in people with prostate cancer, called PSMA PET, has emerged. This form of PET imaging can detect tumors missed by conventional PET imaging, which was used in the EMBARK trial.

In Advanced Prostate Cancer, Targeted Radiation Drug Effective

Known as a radiopharmaceutical, the treatment improved how long trial participants lived.

In a study presented in June 2023 at American Society of Clinical Oncology annual meeting, in fact, researchers showed that, based on PSMA-PET findings, many people with biochemical recurrences with rapid PSA doubling times actually had small tumors either in and around the prostate or elsewhere in the body

Use of PSMA-PET has expanded rapidly in the United States, so questions have been raised about how it should alter how people interpret the EMBARK results and—with this new approval—apply its findings in everyday patient care.

Although PSMA-PET scans can find small tumors missed by standard imaging (PET and bone scans), Dr. Karzai said, “it remains unclear whether early identification will alter the course of a patient’s disease.” In other words, a small tumor somewhere in the body may not grow or spread soon, if ever.

More research is needed on how to apply PSMA-PET imaging findings to decisions about treatment, Dr. Freedland said.

But, even in the absence of PSMA-PET results, he added, factors such as patient age, their overall health, and how they weigh the potential benefits of different treatments versus their risk will all come into play.

“While we don’t expect 100% of patients will go on [the combination treatment], it’ll be interesting to see how physicians and patients interpret these data and make decisions in the real world,” Dr. Freedland said.

For the time being at least, Dr. Karzai said, good doctor–patient communication about treatment options will be important.

“Clinicians will need to have balanced conversations with patients about the benefits of treatment when compared to the side effects” of both drugs, she said.

August 4, 2023, by Shana Spindler

The Food and Drug Administration (FDA) has approved the combination of enzalutamide (Xtandi) with talazoparib (Talzenna) as an initial treatment for some people with metastatic castration-resistant prostate cancer. This is a form of prostate cancer that has spread from the prostate to other parts of the body and no longer responds to standard hormone-blocking treatments.

The talazoparib and enzalutamide combination is approved to treat people whose prostate cancer has an alteration in a specific group of genes involved in repairing damaged DNA. Talazoparib works by blocking the DNA repair activities of a protein called PARP, which in combination with altered DNA repair genes, makes it harder for cancer cells to survive. Enzalutamide works by blocking hormones from fueling cancer cell growth.

The approval, announced on June 20, makes talazoparib the third PARP-blocking drug to be cleared by the agency to treat prostate cancer. FDA based the approval on a set of data from a large, randomized phase 3 clinical trial called TALAPRO-2—funded by Pfizer, the maker of talazoparib.

The trial included two separate cohorts of participants, one of which enrolled only men whose tumors had alterations in DNA repair genes.

The new approval was based on findings from this cohort, in which participants treated with the drug combination lived longer without their cancer getting worse than those treated with the standard treatment of enzalutamide alone. At nearly 3 years after starting the talazoparib and enzalutamide treatment, about 50% of patients whose tumors had one of these changes were still alive without their cancer getting worse. For those who received enzalutamide alone, that number was about 20%.

Findings from this part of the trial were presented in June at the 2023 American Society of Clinical Oncology annual meeting.

About a quarter of men with prostate cancer have an alteration in a DNA repair gene, said Neeraj Agarwal, M.D., a medical oncologist at the University of Utah Huntsman Cancer Institute, who co-led the study. Because prostate cancer is so common, he added, many people will be eligible to receive the combination treatment even with approval limited to this subset of patients.

But some experts in prostate cancer treatment cautioned that patients in the trial have not been followed long enough to know if the drug combination improves how long patients live overall.

That’s an important missing piece of information, said Fatima Karzai, M.D., of the Genitourinary Malignancies Branch in NCI’s Center for Cancer Research. The data “need more time so we know how participants who may harbor these alterations will do,” Dr. Karzai explained.

In particular, it’s unclear if the enzalutamide–talazoparib combination provides more benefit to patients than the current practice of using enzalutamide as an initial treatment followed by a PARP inhibitor only after their cancer starts to get worse.

This latter option, she noted, offsets some of the combination’s side effects, which were more severe than those of the standard treatment.

Treatment intensification to prevent progression

In 2020, FDA approved the first PARP inhibitors for the treatment of metastatic castration-resistant prostate cancer with altered DNA repair genes. Both approvals covered use of the drugs as second-line treatments—that is, only for patients whose cancer was no longer responding to an earlier hormone therapy.

Although the initial approvals were promising, Dr. Agarwal said, he wondered whether waiting to offer PARP inhibitors until after the standard treatment stopped working might be preventing these therapies from helping more patients; as many as 40% of these patients stop treatments when their disease progresses. This high attrition, he noted, is one of the reasons why using stronger therapy up front has worked in advanced prostate cancer.

So, he wanted to test using a PARP inhibitor during initial therapy, when more patients are feeling better and more enthusiastic about receiving it, he said.

Rather than using a PARP inhibitor alone as an initial treatment, he continued, they decided to combine it with a powerful hormone therapy (in this case enzalutamide), a decision based on data from laboratory studies showing that these drugs may be even more effective when combined.

The researchers enrolled two different cohorts of participants to test the combination therapy in a broader cohort of men and in those who are most likely to benefit from the new treatment. The first cohort included 805 men with metastatic castration-resistant prostate cancer, regardless of whether their tumors had any alterations in 12 specific DNA repair genes. The trial’s second cohort was limited to 399 men whose tumors had alterations in any of the 12 genes.

Participants in both cohorts received either enzalutamide plus talazoparib or enzalutamide plus a placebo, given by pill once daily. Then, the researchers measured the length of time until cancer growth could be seen on standard imaging scans, called radiographic progression-free survival.

In the cohort of men whose tumors had alterations in DNA repair genes—the part of the trial on which the new approval is based—the median amount of time until cancer growth could be seen on a scan was about 14 months for those who received enzalutamide alone. But among those who received the combination treatment, too few people had experienced a worsening of their cancer to even determine the median radiographic profession-free survival in this cohort.

Importantly, on standardized questionnaires given to these patients, those who received enzalutamide and talazoparib reported a better quality of life for longer than patients treated only with enzalutamide, Dr. Agarwal noted.

Although the drug combination was approved for people whose tumors have alterations in any of 12 DNA repair genes, when the researchers looked at the specific genes that were altered, they found that men with alterations to the BRCA1, BRCA2, or CDK12 genes improved most from the combination treatment, said study co-lead Karim Fizazi, M.D., Ph.D., of the Institut Gustave Roussy in France, during his presentation of the second cohort findings at the ASCO meeting.

About half of the participants in the second cohort had an alteration in at least one of the BRCA1, BRCA2, or CDK12 genes.

Weighing the risks of PARP inhibitor side effects

The enzalutamide–talazoparib combination is another option for people with metastatic castration-resistant prostate cancer that has these DNA damage repair alterations, “which is great,” said Dr. Karzai. But, she added, it’s critical for people to consider their quality of life and let their physicians know when they don’t feel well on the combination therapy.

“I think a lot of patients are afraid, especially when treated with drug combinations, that the doctor will take them off the drugs if they say anything about side effects,” Dr. Karzai said. “But I think it's really important that these patient outcomes are reported.”

PARP inhibitors can lead to a few serious side effects, explained Dr. Agarwal. These include a drop in blood cell counts, nausea and vomiting, and fatigue. Talazoparib, he noted, tends to cause substantial drops in red and white blood cell counts.

In the cohort of men whose tumors have a DNA repair gene alteration, about 10% of patients discontinued the combination treatment due to severe side effects of any kind, compared with 7% in the placebo group. The most common side effect was anemia, which occurred in nearly two-thirds of people receiving the drug combination—four times the number of people who developed anemia on enzalutamide alone.

The onset of anemia happens soon after starting treatment, Dr. Agarwal said. Typically, the oncologist will lower the dose, he explained, and at that point most patients are able to tolerate talazoparib well. In this cohort, he noted, only 4% of patients stopped receiving talazoparib due to anemia after initial dose reductions.

A broader approval remains uncertain

For now, FDA’s approval applies only to men whose metastatic castration-resistant prostate cancer has DNA repair gene alterations. But patients whose tumors lacked alterations in DNA repair genes also had improved radiographic progression-free survival when treated with the combination compared with those treated with enzalutamide alone—although not nearly to the same extent, Dr. Agarwal noted.

Findings from this larger cohort in the trial were published June 4 in The Lancet.

So, an important next step, he said, is to understand why these tumors responded to the treatment despite lacking this critical genetic change. If they can identify specific biological characteristics of patients’ tumors that make them more likely to respond to the drug, it may be possible to expand the number of people who can benefit from the combination.

But for now, he said, “we need more data on safety and long-term overall survival benefit for all patients before we can recommend this combination [to everyone].”

The importance of genetic testing

Even as researchers try to iron out some of the unknowns about how best to use PARP inhibitors in people with metastatic castration-resistant prostate cancer, one thing is clear, Dr. Karzai emphasized.

“Everybody who's getting diagnosed with metastatic prostate cancer should talk to their doctors about getting genetic testing,” from tumor biopsies and through specialized tests that identify inherited mutations that may be present in the cells of the body and have been present since birth, she urged.

Dr. Agarwal agreed, explaining that many people being treated in smaller hospitals and cancer centers in their own communities are not getting tested for DNA repair gene alterations.

“Maybe because of a lack of resources, a lack of awareness, I don't know why, but a significant number of patients are not getting tested in the community,” he said.

Testing tumors for specific genetic changes is important for two reasons, Dr. Agarwal said. First, as more targeted drugs enter the market, it is increasingly possible to target the specific alterations that drive someone’s tumor. And second, some of these genetic alterations, known as germline alterations, are associated with familial predisposition to the disease, which may prompt screening in other family members.

“For metastatic prostate cancer, everybody agrees now that they need genomic testing of the tumor and germline,” Dr. Agarwal emphasized.

October 13, 2022, by Nadia Jaber

If you were recently diagnosed with prostate cancer, there are a few different ways to gauge how aggressive the cancer is—in other words, to see if your cancer is likely to spread beyond the prostate. In a new study, a genomic test appeared to be better at finding aggressive prostate cancer than conventional tests.

The genomic test, called Decipher, looks at the activity of 22 genes and has been shown to predict the risk that a prostate tumor will spread (metastasize). Conventional tests, on the other hand, look at clinical markers like Gleason score and PSA level.

For some men in the study, the Decipher test showed that their cancer was high risk even though conventional tests pegged it as lower risk. This discrepancy appeared to happen more frequently for African-American men than other men, the study found.

Results of the study, partially funded by NCI, were published September 2 in JNCI: Journal of the National Cancer Institute.

It’s important to know how aggressive a patient’s cancer is so that their treatment can be tailored, explained the study’s lead scientist, Kosj Yamoah, M.D., Ph.D., chair of the department of Radiation Oncology at the Moffitt Cancer Center and Research Institute.

That typically means more treatment for high-risk tumors and less treatment or no active treatment for lower-risk tumors, he said.

“What this [study] points us to is, beyond just the clinical markers that we've been using, we now have to start thinking about genomics too,” said Fatima Karzai, M.D., of NCI’s Center for Cancer Research, who was not involved in the study.

“I would tell patients that if they're newly diagnosed [with prostate cancer] and they want to have a really in-depth conversation about how to get treated, they should ask their doctor if the Decipher [test] should be at least a part of their evaluation,” Dr. Karzai added.

The Decipher test has been in use for many years and is covered by Medicare, Dr. Karzai noted. But professional medical groups haven’t widely recommended the use of Decipher or other genomic tests by people with newly diagnosed, localized prostate cancer.

Adding genomic information

For many years, doctors have used clinical markers to estimate the risk that a prostate tumor will spread to other parts of the body.

But “as time went on, we realized that … we were missing certain more aggressive [tumors]. And that was happening more frequently in men of African origin,” Dr. Yamoah said.

“So, we started to consider whether our clinical classifications may be suboptimal. They are good, but not as good as they could be,” he explained.

He and his team wondered whether adding a layer of genomic information could reveal aggressive features of prostate tumors that the clinical methods were missing.

To test this idea in a prospective study, the researchers first enrolled a group of men who self-identified as African American. They then enrolled a group of men who self-identified as non–African American and who had matching clinical markers—such as age, PSA level, Gleason score, and the treatment they received.

“It's pretty significant that they were able to find so many African American men to go on the trial. Usually, if you look at other studies, the rate [of enrollment] is very low” for African Americans, Dr. Karzai noted.

Hidden high-risk cancer

All 226 participants had prostate cancer that had not spread beyond the prostate (localized cancer).

The researchers compared the results of the Decipher test with those of the clinical methods. Because the men all had very similar clinical markers, the researchers expected to see similar Decipher results, Dr. Yamoah said.

Instead, they found a discrepancy: Some men had cancer that was classified as lower risk by clinical methods but as high risk by the Decipher test.

According to one clinical method, 11 African American men and 7 non–African American men had low-risk cancer. Yet the Decipher test found that 2 (18%) of those African American men were at high genomic risk of their cancer spreading within 5 years.

Clinical methods found 37 African American and 37 non–African American men with “favorable intermediate-risk” cancer (a term that describes cancers somewhere between low risk and intermediate risk).

But the Decipher test found that 14 (38%) of those African American men and 7 (19%) of the non–African American men had high genomic-risk cancer.

Imaging Technique Accurately Detects Prostate Cancer Spread

PSMA PET-CT finds metastases better than standard imaging approach.

Overall, African American men were more than twice as likely as non–African American men to have cancer that was recategorized as high risk based on the Decipher test, the researchers found.

“I think this [study] gives us a platform to move [the Decipher test] into even bigger trials,” Dr. Karzai said.

And in future studies, she said, it will be important to find out if prostate tumors at high genomic risk based on the Decipher test do in fact spread faster or grow back faster after treatment.

The next phase of the ongoing study will address that, Dr. Yamoah explained. Every year, participants with high genomic-risk cancer will get an imaging test, called a PSMA PET scan, to check if their tumors have spread beyond the prostate.

That, he said, will also help answer questions like, “What do we do with these so-called aggressive [tumors] when we catch them early? How can we actually do something about it?”

Considering the environment

African-American men are more likely to develop prostate cancer, to have it at an earlier age, and to die from the disease, but it’s not clear why.

It’s possible that conventional methods for assessing prostate cancer aggressiveness are missing more aggressive tumors in African American men, Dr. Karzai said, leading to worse outcomes.

Why African American men seem to have more aggressive tumors is another question, Dr. Yamoah said, but it’s likely related to environmental, social, and economic factors that can change tumor biology and genomics.

For example, “there are data suggesting that diet, metabolism, stress—all these other things impact disease,” he continued.

It’s possible that more African American men are exposed to conditions (such as high levels of air pollution or limited access to healthy foods) and other social determinants of health that lead to biological changes encouraging the development and growth of aggressive prostate cancer, Dr. Yamoah explained.

Ultimately, Dr. Karzai said, “one of the things we all need to do better is try to get people of all different backgrounds into clinical trials.” That way, researchers can make sure they are developing tools and treatments that work for everyone, she said.

June 23, 2022, by Carmen Phillips

Until about 10 years ago, most men diagnosed with prostate cancer that has a low risk of causing death had immediate treatment with surgery or radiation. Although both are considered to be cures for low-risk prostate cancer, they can also have serious and lifelong side effects, including urinary problems and erectile dysfunction.

But a recent study confirms findings from earlier studies that found men are increasingly opting against immediate treatment. Instead, they are working with their doctors to carefully monitor the cancer via a process known as active surveillance, holding off on treatment until there are signs of progression.

Overall, the study, which included data from 240 urology practices across the country, found that about 60% of US men diagnosed with low-risk prostate cancer are now being managed with active surveillance. In fact, the rates of active surveillance more than doubled between 2014 and 2021, the time period covered by the study.

The finding is encouraging and shows that the use of active surveillance is “headed in the right direction,” said the study’s lead investigator, Matt Cooperberg, M.D., of the University of California, San Francisco (UCSF), who reported the findings on May 15 at the American Urological Association’s (AUA) 2022 annual meeting. “But they are still not where they need to be.”

Of particular concern, Dr. Cooperberg noted, is the finding that in some urology practices only a small percentage of patients with low-risk prostate cancer are on active surveillance. There were urologists in some practices who did not have a single patient with low-risk disease on active surveillance.

Those findings fly in the face of recommendations from leading medical groups that say active surveillance is the preferred approach for men diagnosed with low-risk prostate cancer.

“Those [doctors] are doing their patients a disservice,” said Howard Parnes, M.D., chief of the Prostate and Urologic Cancer Research Group in NCI’s Division of Cancer Prevention, who was not involved in the study. “If a patient meets the criteria for low-risk disease, active surveillance needs to be a central part of the conversation.”

Reconsidering immediate treatment

Most prostate cancers diagnosed with PSA-based screening, which became widespread in the United States starting in the early 1990s, are low-risk. Generally speaking, that means they are small, confined to the prostate, and not considered to be aggressive according to a common grading system known as the Gleason score.

Nevertheless, throughout the 1990s and well into the 2010s, many men diagnosed with low-risk prostate cancer had immediate treatment with surgery or radiation.

What is low-risk prostate cancer?

According to the most recent guidelines from the AUA and National Comprehensive Cancer Network (NCCN), low-risk prostate cancers are those that meet these criteria:

• PSA level of less than 10
• Gleason grade group 1 (Gleason score 3 + 3)
• Clinical stage T1‒T2a

Learn more about PSA testing, Gleason grade groups, and clinical staging.

(NCCN also has a very-low-risk category, for which active surveillance is also recommended.)

But even in the early days of widespread PSA screening, questions were raised about whether these “screen-detected” cancers were actually dangerous. Studies followed that echoed those concerns, concluding that many of these cancers would likely never grow to the point where they would even cause symptoms, let alone become life-threatening.

Another alternative to immediate treatment is “watchful waiting,” simply waiting for symptoms before pursuing any further testing or treatment.

But because prostate cancer can be deadly once it spreads beyond the prostate, use of watchful waiting in men with low-risk prostate cancer has been limited.

Protocols for active surveillance were first proposed in the mid-1990s and have since been studied and implemented in various forms. It’s only fairly recently that leading medical organizations felt the data on the safety of active surveillance were strong enough to formally recommend it as the preferred approach for men with low-risk disease.

How is active surveillance done?

Although the protocol can vary, recommendations for active surveillance generally call for routine PSA tests and prostate biopsies to check for any indication that the cancer might be growing.

For example, patients at Montefiore Health System in New York City get a PSA test every 3‒6 months, at least initially, and an MRI-guided biopsy a year after diagnosis, said Kara Watts, M.D., a urologist at the hospital who specializes in treating prostate cancer but was not involved in the study.

After the initial PSA tests and biopsy, how often they are performed depends largely on the patient’s particular situation, Dr. Watts explained.

“We have a flexible protocol, particularly for people at both ends of the [age] spectrum,” she continued. For a man in his 70s and a life expectancy of 5‒10 years (based on other health conditions and other factors), she said, additional PSA tests or biopsies may only be conducted every few years or only if he has symptoms. An otherwise healthy man in his 50s, on the other hand, will usually continue to have PSA tests and MRI-guided biopsies on a schedule similar to the initial protocol.

At the NIH Clinical Center, where Dr. Parnes sees patients, in addition to routine PSA testing, MRI-guided biopsies are used to help inform decisions around whether to pursue active surveillance and as part of the surveillance protocol.

"MRI-guided biopsies have been shown to improve the detection of intermediate- and high-grade prostate cancer, but they aren’t required for active surveillance for low-risk prostate cancer," Dr. Parnes explained. “Many studies using standard ultrasound-guided biopsies have demonstrated the long-term safety of active surveillance in men with low-risk prostate cancer,” he said.

Genetic and molecular testing are also making their way into doctors’ decisions to recommend active surveillance and as part of the surveillance protocol. At NCI, for example, men with a family history of cancer or who are diagnosed with intermediate-risk prostate cancer are recommended to undergo testing for mutations in the BRCA2 gene or other genes involved repairing damaged DNA, Dr. Parnes said.

Finally, regardless of the doctor or hospital where a patient is being treated, if biopsy results suggest that the cancer grade is progressing, men will generally be advised to receive immediate treatment. The number of men on active surveillance who eventually get treated with surgery or radiation varies. In a recent, large observational study involving over 8,000 men, just under half of those on active surveillance received definitive treatment within 5 years.

More active surveillance, but not enough

To conduct their study, Dr. Cooperberg and his colleagues looked at data from all men newly diagnosed with prostate cancer in the AUA Quality Registry. This registry collects real-time data from more than 240 participating US urology practices and more than 2,100 urologists.

Overall, of the more than 84,000 patients covered by the study, 20.3% were diagnosed with low-risk disease. The number of men diagnosed with low-risk disease actually fell during the study period, from about 24.6% in 2014 to 14.0% in 2019. That finding is consistent with other recent studies showing a decline in low-risk diagnoses, which researchers have attributed to fewer men being screened via PSA testing.

But even as diagnoses of low-risk disease have dropped, more men with low-risk disease are opting for active surveillance, Dr. Cooperberg reported. In 2014, 26.5% of men with low-risk prostate cancer chose active surveillance. By the end of 2021, 59.6% did.

Rates of active surveillance also increased among men diagnosed with intermediate-risk prostate cancer, which is considered to have a modestly greater likelihood than low-risk prostate cancer of progressing to the point where it could be fatal.

The steady uptick is welcome news, Dr. Cooperberg said. But he also highlighted the “relatively extreme” variation in the use of active surveillance across the country. The researchers found that rates of active surveillance for men with low-risk prostate cancer “can range from 7% to nearly 80%” by urology practice, he said. “And, depending on which individual doctor’s door you knock on, even within a given practice, rates range from 0% to 100%.”

The variability in the use of active surveillance is alarming, Dr. Parnes said. It likely reflects, at least to some degree, entrenched patterns of care among some urologists. “For some, I suspect their feeling is, ‘I treat cancer, and this is cancer. I’m not having this conversation [about active surveillance],’” he said.

Dr. Watts agreed. It’s likely that some doctors “just aren’t discussing [active surveillance], or they’re portraying it in a way that biases [patients] toward definitive treatment,” she said.

Exceptions and barriers to active surveillance

In his UCSF program, Dr. Cooperberg said, about 95% of men diagnosed with low-risk prostate cancer are put on active surveillance. As an academic center that began implementing and studying active surveillance in the mid-1990s, that’s likely higher than what is typically seen in the United States, he acknowledged.

But a “reasonable target” for the time being is around 80%, he said. That’s consistent with where rates “top out” in countries like Sweden and in other large, integrated health care systems in Europe where active surveillance has long been standard practice.

The bottom line, Dr. Cooperberg said, is that even though the vast majority of men with low-risk prostate cancer should be put on active surveillance, “there will always be exceptions.”

Those exceptions, for example, can include men with a strong family history of prostate cancer or who have urological symptoms related to the disease that immediate treatment can help to alleviate.

There can also be considerations that go beyond clinical or biological factors. For patients in rural areas or those who lack reliable transportation, anything that requires regular visits to the hospital or doctor’s office over a long period could push some men toward choosing immediate treatment, Dr. Watts said.

In addition, she noted, it can be challenging to explain the medical basis for active surveillance. In some patient’s minds, opting for active surveillance means “missing a window of opportunity for cure,” she said.

“The ‘C word’ is scary for a lot of people,” Dr. Watts continued. And in this case, “a lot of the art of medicine is being able to explain … why active surveillance is appropriate.”

March 25, 2022, by Linda Wang

The drug darolutamide (Nubeqa) could become part of the standard treatment for some men diagnosed with advanced prostate cancer, based on results from a large clinical trial.

In the trial, men with hormone-sensitive prostate cancer that had spread to other parts of the body, or metastasized, were treated with either darolutamide plus two other therapies, docetaxel and androgen deprivation therapy (ADT), or only docetaxel and ADT.

Substantially more men who received all three treatments were still alive 4 years after starting treatment than those treated with only docetaxel and ADT. And adding darolutamide didn’t lead to more intense side effects.

Data from the ARASENS trial were published in the New England Journal of Medicine and presented at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium on February 17.

“Based on the results of ARASENS, we conclude that darolutamide in combination with ADT and docetaxel should become a new standard of care for the treatment of patients with metastatic hormone-sensitive prostate cancer,” said the study’s lead investigator, Matthew R. Smith, M.D., Ph.D., of Massachusetts General Hospital Cancer Center, during the meeting.

Fatima Karzai, M.D., of NCI’s Genitourinary Malignancies Branch, agreed, calling the results “practice changing.”

ARASENS was funded by Bayer and Orion Pharma, the co-manufacturers of darolutamide. Bayer has submitted an application to the Food and Drug Administration to expand the drug’s approval to include people with metastatic hormone-sensitive prostate cancer. The drug is currently only approved for people with nonmetastatic prostate cancer that does not respond to hormone therapy (hormone-resistant).

An evolving standard of care

Hormone-sensitive (also called castration-sensitive) prostate cancer means a patient’s tumors are still largely being fueled by male sex hormones called androgens. For many years, metastatic hormone-sensitive prostate cancer was treated with ADT alone, which blocks the production of androgens by the testicles.

In 2014, a large clinical trial showed that adding the chemotherapy drug docetaxel to ADT improved survival in men with metastatic hormone-sensitive prostate cancer. Since then, this combination has become the standard of care for this group of patients.

More recently, studies have shown that adding other drugs that block the production or binding of androgens—including abiraterone (Zytiga), enzalutamide (Xtandi), and apalutamide (Erleada)—to ADT also helps people with metastatic hormone-sensitive prostate cancer live longer. In a trial combining apalutamide with ADT, for example, approximately 82% of men were still alive after 2 years compared with 74% of men treated with ADT alone.

Several clinical trials were then launched to see if combining any of these drugs with ADT and docetaxel could build on those survival gains. Results of those studies, however, have been mixed, with one showing an improvement in survival without the disease progressing and another finding no increase in overall survival.

Like other androgen receptor inhibitors, darolutamide works by blocking androgens from binding to receptors on cancer cells. Unlike other androgen receptor inhibitors, however, darolutamide does not cross from the bloodstream into the brain, which may be why studies have found fewer central nervous system–related side effects (e.g., seizures) with darolutamide than with other such drugs.

The trio of darolutamide, ADT, and docetaxel has already been shown to improve survival in men with hormone-resistant prostate cancer that has not spread. So ARASENS was launched to see if it could do the same in men with prostate cancer that has spread.

Improved survival at 4 years

In the ARASENS trial, nearly 1,300 participants were randomly assigned to receive darolutamide or a placebo (both taken as a pill, twice a day). All participants received ADT within 12 weeks before randomization and six cycles of docetaxel starting within 6 weeks after randomization.

After 4 years, about 63% of patients who received darolutamide were still alive compared with about 50% of patients who received placebo. The group that received darolutamide lived longer even though most participants in the placebo group (75%) received other commonly used treatments, including abiraterone and enzalutamide, during follow-up.

Darolutamide resulted in other improvements as well. For example, among those treated with darolutamide, the time for their cancers to become resistant to hormone-suppressing therapies was longer, as was the time until the pain caused by their cancer got worse.

The frequency of serious side effects—which included fatigue, falls, fractures, and cardiac issues—was similar in the two groups. Roughly two-thirds of the patients in both groups experienced serious side effects, most of which occurred when darolutamide (or placebo) were given at the same time as docetaxel.

More options lead to more questions

Elisabeth Heath, M.D., director of prostate cancer research at Karmanos Cancer Institute in Detroit, agreed that the ARASENS results should have an immediate impact on how this form of the disease is treated.

Speaking at the ASCO symposium, Dr. Heath, who was not involved in the study, highlighted an important difference between ARASENS and other trials that tested androgen receptor–blocking drugs in men with this form of prostate cancer. In those other trials, she explained, some participants received docetaxel prior to treatment with the androgen receptor–blocking drugs rather than at the same time.

Based on the ARASENS results, Dr. Heath said, giving all three treatments simultaneously looks to be the preferred option for some patients.

Dr. Karzai noted that despite there being multiple options to treat metastatic hormone-sensitive prostate cancer, many questions remain. “We don't have guidelines on who should start with what drug and whether one drug is better than another for a [specific] patient,” she said.

She also pointed out that more research is needed on how the order in which the drugs are given impact their effectiveness and the frequency of side effects.

Additionally, she said, the survival improvement in the ARASENS trial was seen in patients whose cancer had spread in multiple areas beyond the prostate (known as high-volume disease).

“We don’t know if people with lower-volume [disease would] benefit from [the addition of darolutamide] as much as the patients with higher-volume disease do,” she said.

“You have to really think about [the group with lower-volume disease]. Do you want to give them this therapy that causes side effects when you don't know if they are going to get the survival benefit and the other secondary benefits like the high-volume group does?” she said.

Dr. Smith said that future studies could look at whether darolutamide and ADT alone could improve survival as well as darolutamide, ADT, and docetaxel. Removing docetaxel from the combination could reduce some of the side effects, he said.

November 18, 2021, by Sharon Reynolds

Many people with prostate cancer can safely receive a shorter, more intensive course of radiation therapy after surgery than has conventionally been used, a new study has found.

In a large clinical trial, people who received the shorter course of treatment, which lasted for 5 weeks, reported more bowel problems immediately following treatment than those who underwent the standard 7 weeks of less-intensive radiation. However, by 6 months after treatment, both groups reported similar levels of bowel problems and an overall equivalent quality of life.

The study relied on patients reporting the side effects related to treatment and their overall well-being, known as patient-reported outcomes.

“Physician-reported toxicities can sometimes lead us astray,” said Mark Buyyounouski, M.D., a radiation oncologist at Stanford University who led the trial. “Not everything that can be counted [by us] counts to patients. So we wanted to know: When do [people] tell us that they’re feeling good again?”

The results of the study, which was run by the NCI-funded clinical cooperative group NRG Oncology, were presented on October 25 at the 2021 American Society for Radiation Oncology Annual Meeting.

Even though the use of higher radiation doses over a shorter period, called hypofractionated postoperative prostate bed radiotherapy, or HYPORT, did have more side effects in the near term, many people are likely to consider that a worthwhile tradeoff for 2 fewer weeks of treatment, said Deborah Citrin, M.D., of NCI’s Center for Cancer Research, who was not involved in the study.

“For a lot of patients, coming in every [weekday] for 7 weeks has a major impact on their lives,” she said. “There’s a lot of interest in hypofractionation because getting treatment done more quickly is so much easier, financially and otherwise.”

A Large Role for Radiation Therapy

People diagnosed with localized prostate cancer—that is, disease that hasn’t spread outside the prostate region—have many potential treatment options, depending on the stage and grade (potential aggressiveness of the tumor). Some may have surgery alone. Others may only have radiation therapy.

And some may have a combination of the two. This often happens when there’s concern that surgery hadn’t removed all the tumor tissue. Or, if someone’s prostate-specific antigen (PSA) levels start to rise months or years after surgery, radiation therapy may be recommended even if imaging hasn’t been able to identify tumor growth.

Hypofractionated radiation therapy is already an accepted treatment option for some people undergoing radiation therapy alone to treat prostate cancer. But whether this type of radiation therapy is appropriate for use after surgery has been unclear.

When radiation is used after surgery, it's delivered to a larger area of the body, including sensitive areas in the bladder and rectum, Dr. Buyyounouski explained. This raises the possibility that the higher doses used in hypofractionation may cause long-term side effects that could outweigh the benefit of two fewer weeks of treatment for these patients.

“And a lot of people do have some urinary complications after surgery,” said Dr. Citrin. “So even a small increase in urinary or bowel symptoms that persist after treatment with one [treatment] regimen versus the other could be quite impactful in terms of quality of life.”

To test whether hypofractionation affected these patients’ quality of life differently than conventional fractionation, the NRG Oncology researchers enrolled almost 300 participants from more than 90 treatment centers across the country into the trial.

An Inclusive Clinical Trial

The team designed the phase 3 trial to be as inclusive as possible to capture a population that looks like people commonly treated in the community, Dr. Buyyounouski explained. The participants included both people getting radiation immediately after surgery and those who waited until they had rising PSA levels.

Participants who had some invasion of their cancer into nearby tissue were eligible, although those whose cancer had spread to their lymph nodes were excluded. They could also receive up to 6 months of androgen deprivation therapy, a type of hormone therapy, if recommended by their doctor.

Participants were randomly assigned to treatment with HYPORT, consisting of a higher dose (or fraction) of radiation every weekday for 5 weeks or the commonly used, lower dose every weekday for 7 weeks. They were asked about urinary and bowel symptoms before radiation and 6, 12, and 24 months after treatment, using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire.

After prostate cancer treatments, common urinary symptoms can include urine leakage or pain or burning when urinating. Common bowel symptoms can include bowel leakage or urgency. The trial did not measure sexual side effects, such as erectile dysfunction, since these can also be affected by hormone therapy.

About three-quarters of the participants completed all questionnaires. At the end of treatment, people who received HYPORT reported more bowel side effects, although urinary side effects were equivalent between groups.

By 6 months after treatment, this difference in bowel symptoms had disappeared, and people in both groups reported equivalent quality of life for both bowel and urinary symptoms. The groups continued to report similar and relatively low levels of symptoms for up to 2 years after finishing treatment.

No differences in cancer recurrence were seen between the two groups. The NRG Oncology team will continue to track recurrences over time but do not expect to see any difference emerge, Dr. Buyyounouski said. The two groups received the same overall radiation dose, and other trials of hypofractionation compared with conventionally fractionated radiation therapy in people with similar forms of prostate cancer who did not have surgery have not shown differences in recurrence or survival.

“That’s why, in a situation where the disease control outcomes are likely to be similar, what really matters to a patient is: How am I going to feel?” Dr. Citrin said.

Helping People Imagine Their Future

“The hardest thing we can do as physicians is help patients envision their future selves,” Dr. Buyyounouski said. “So patient-reported outcomes are very helpful, because you can tell [other] patients exactly what side effects people had, and the frequency and bother of those side effects at [different] points in time.”

For many, he added, the trade-off in more side effects right after treatment will be worth it for a shorter treatment duration.

“Unless you’ve been a patient, it’s hard for folks to imagine all the things that need to happen for somebody to go and get treatment every [weekday]” for weeks, Dr. Buyyounouski said.

“There’s transportation costs, gas, parking, co-pays. And there are costs associated with the things you’re not doing, like time away from work or responsibilities at home. It’s more than just the medical bills.”

“I think people are itching to shorten the treatment [duration] because there are a lot of patients for whom it’s a barrier to getting treatment. And radiation therapy is a potentially curative treatment,” added Dr. Citrin. “So, making it easier for patients without increasing the long-term side effects … is a huge win.”

However, a less-intensive standard course of radiation will still likely appeal to some people, she added, especially if they are experiencing ongoing side effects from surgery.

The results of the current study also aren’t immediately applicable to everyone having radiation therapy after prostate cancer surgery. For example, the study didn’t include people who needed radiation to their lymph nodes. The results can’t explicitly provide guidance on the impact of hypofractionation on quality of life for these patients, Dr. Citrin explained.

But for people who have tumors similar to those treated in the current trial, the machines and expertise used for this type of radiation can be commonly found across the country, Dr. Buyyounouski explained.

“So we want people to know that this is available near you,” he said. The only caveat for someone looking to receive HYPORT is that the trial used image guidance for all patients. This procedure uses technologies like CT or ultrasound to help clinicians guide where the radiation therapy is delivered. “That’s something to make sure [your local provider] is using,” he added.

Several ongoing clinical trials are looking at whether prostate radiation therapy can be compressed any further for select patients, Dr. Citrin added. For example, her group is currently running a clinical trial testing hypofractionated radiation delivered over the course of 2 to 4 weeks.

Recent advances in prostate imaging may also allow for more personalized radiation therapy, which could potentially help reduce side effects, said Dr. Citrin. For example, the Food and Drug Administration recently approved PSMA-based PET-CT imaging to look for tiny cancer deposits in the prostate or elsewhere in the body. This may allow oncologists to target smaller areas of tissue more effectively, or to avoid radiation treatment in patients who are unlikely to benefit from it.

“Ongoing research in radiation oncology is often aimed at making radiation therapy more convenient, less toxic, and less expensive for patients, while maintaining excellent cure rates,” Dr. Citrin said.