- New approaches to treatments such as PARP inhibitors, radioligand therapies, and immunotherapies are improving outcomes for patients with aggressive prostate cancer.
- Testing for genetic changes such as BRCA1 and BRCA2 mutations allows doctors to personalize treatment and match patients with the therapies most likely to work for them.
- Clinical trials are helping determine the best ways to combine therapies and use new medicines earlier in treatment, offering patients access to the latest advances.
New approaches to treatment are improving outcomes for patients with aggressive prostate cancer, which is prostate cancer that has spread or is at higher risk of spreading. In addition, new tests are helping guide treatment choices as more treatment options become available.
Therapies used to treat aggressive prostate cancer include chemotherapy, hormone therapy, and newer therapies such as:
- Combinations of PARP inhibitors, Radioligand therapies, and immunotherapies with other medicines
“When I talk to patients, I let them know that we’ve got a lot of different tools in our toolbox for treating prostate cancer,” says Dana-Farber medical oncologist Michael Serzan, MD. “Our focus now is on making those treatments even better by finding the best biological markers to guide treatment decisions and by combining different therapeutics to learn which treatments work well together.”
What is aggressive prostate cancer?
Prostate cancer is or is likely to be aggressive in several cases:
- When the cancer continues to grow and spread despite treatment with hormone therapies that block testosterone, a hormone that drives cancer growth. This condition is called castration-resistant prostate cancer.
- When the cancer has already spread to distant parts of the body at the time of diagnosis.
- When the cancer is found in younger men, under age 65, in patients of African descent, and in patients who have a strong family history of the disease.
- If the patient has an inherited gene mutation that affects DNA repair (called homologous recombination repair), such as in BRCA1 or BRCA2 gene mutations.
- If the patient has a high Gleason score, which is a score based on an evaluation of biopsied cells, or a high levels of the marker PSA in the blood.
Learn more about screening for prostate cancer.
How do oncologists decide which treatment is best for me?
Patients with aggressive or metastatic prostate cancer have more options for treatment than ever before. However, choosing the best next therapy for a patient has also become more complex.
Oncologists rely on treatment guidelines, which traditionally are updated every few years. But advances in treatments for patients with metastatic castration-resistant prostate cancer have moved quickly, and experts realized they need more frequent updates.
To respond to this need, the American Society of Clinical Oncology (ASCO) devised “living guidelines,” which are updated on an ongoing basis as new evidence emerges. The first ASCO living guideline in the genitourinary field was created for metastatic castration-resistant prostate cancer by a team led by Dana-Farber’s Mary-Ellen Taplin, MD.
Taplin collaborated with experts to use specially trained artificial intelligence to gather published evidence for review. Each month, a multidisciplinary team of experts in the field including oncologists and patient advocates reviews the evidence and adjusts the guidelines They published the latest guidelines in January 2026 in the Journal of Clinical Oncology (JCO).
The guidelines provide context for treatment decisions, such as a patient’s past treatments, inherited cancer risks, tumor genetics, and more, and will help ensure that treatment decisions are not out of date.
“There are many new treatment options for patients with prostate cancer that are helping people with advanced disease survive longer,” says Taplin. “We don’t want anyone to miss out on getting the best next treatment that could lead to positive outcomes such as delaying metastases or living longer.”
How are PARP inhibitors being used to treat advanced prostate cancer?
It is becoming standard for doctors to test patients with prostate cancer for BRCA1, BRCA2, and related DNA repair mutations. When one of these mutations is present, patients may be good candidates for treatment with a PARP inhibitor.
- PARP inhibitors are currently approved for use in patients with a mutation in a DNA repair related gene who have late-stage castration-resistant prostate cancer.
- A recent large phase 3 clinical trial of a PARP inhibitor plus hormone therapy showed notable benefits for patients with BRCA1, BRCA2, and related DNA repair mutations who have late-stage castration-sensitive cancer. If approved, this combination could become standard therapy for some patients.
- Dana-Farber investigators are studying PARP inhibitors in clinical trials to determine if they might be effective for patients with prostate cancer that has not spread.
- They also want to determine if there are more biomarkers that can be used to guide treatment choices.
“We’re trying to advance precision medicine for prostate cancer using genomics to match the right treatment to the right patient at the right time,” says Serzan.
Learn more about how prostate cancer is treated at Dana-Farber.
How are radioligand therapies being used to treat advanced prostate cancer?
Radioligand therapies attach a radioactive particle to a molecule that guides the radiation into the vicinity of cancer cells, where it can damage and kill them.
There are multiple forms of radioligand therapies approved for the treatment of metastatic prostate cancer and use of these therapies has been steadily broadening.
For example, a form of radioligand therapy called Pluvicto™ that was originally approved for late-stage treatment of metastatic disease was recently approved for use in earlier lines of treatment. It can now be used before a patient receives chemotherapy.
Dana-Farber investigators are testing a combination of Pluvicto and actinium-225, another radioligand therapy, to see if the combination improves outcomes.
“The expansion of use of radioligand therapy prior to giving a patient chemotherapy has the potential to improve outcomes for a large number of patients,” says Serzan. “Dana-Farber is one of the only centers in the region that is able to provide this therapy.”
Learn more about how Dana-Farber provides radioligand treatment for patients.
How are immunotherapies being used to treat advanced or aggressive prostate cancer?
Immunotherapies called bispecific antibodies are showing promise in the treatment of prostate cancer. These medicines recognize two markers – one on cancer cells and one on immune cells. The medicine brings the two types of cells closer together, helping the immune cells attack the cancer.
There are several bispecific antibodies – sometimes called bispecific T cell engagers, which are a subset of bispecific antibodies – that are in various phases of testing in clinical trials for prostate cancer and open at Dana-Farber.
How and when are clinical trials a good choice for advanced or aggressive prostate cancer?
There are many new and effective treatments approved for patients with advanced or aggressive prostate cancer. While these treatments are effective, they typically aren’t curative, and patients may find that their next best option is a clinical trial. Typically, clinical trials are considered for a patient either at the time of first diagnosis of prostate cancer or at the time a person’s cancer starts growing on a therapy and a new treatment is being considered.
At Dana-Farber, having an expansive clinical trial portfolio and selecting the best clinical trial for an individual patient is a priority.
“It’s a good thing for patients that we have so many treatment options, but it is important to see an oncologist who specializes in prostate cancer and can determine the best next treatment and if a clinical trial would potentially be a good fit,” says Serzan. “At Dana-Farber, we will incorporate results of PSMA PET scans, genetic testing, novel imaging diagnostics, and other factors in an effort to predict who will respond to which type of treatment.”
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