Reviewed by Katy Beckermann, MD, PhD, who leads Tennessee Oncology’s genitourinary clinical trials program as Medical Director of GU Research and chairs the GU Disease Group at OneOncology, and John Phillips, MD, Director of Radiation Oncology Services at Tennessee Oncology.
This article is for general information, doesn’t establish a doctor-patient relationship, and isn’t a substitute for advice from your own oncology team about your specific case.
Treatment Options and What to Expect
A diagnosis of metastatic prostate cancer means the cancer has spread beyond the prostate, most often to bone. It’s not the diagnosis it was even ten years ago. Most men now start on a combination of treatments, not a single drug, and later options have expanded considerably if the first approach stops working. Here’s how treatment actually unfolds. If you’re still working through PSA testing or a new, localized diagnosis, our guide to early prostate cancer warning signs may be more useful right now.
The first treatment: hormone therapy, intensified
The backbone of first treatment is androgen deprivation therapy, or ADT, which lowers testosterone since prostate cancer generally depends on it to grow. What’s changed is that ADT alone is rarely the whole plan anymore. Most men now add a second hormonal drug, called an ARPI, such as abiraterone, enzalutamide, apalutamide, or darolutamide, and some men with more extensive disease also add a short course of chemotherapy (docetaxel) up front, an approach called triplet therapy.
In the trial that established triplet therapy, adding docetaxel to ADT and darolutamide brought four-year survival to roughly 63%, compared with about 50% on ADT and docetaxel alone. That’s a meaningful difference, though not every man is a candidate for the added chemotherapy, and your oncologist will weigh how much cancer is present, your overall health, and your own preferences in that decision.
Additional treatment options based on individualized patient cancer characteristics such as genetics and protein function may be available and testing should happen at initial metastatic diagnosis.
Living with hormone therapy
ADT affects more than the cancer. Hot flashes, loss of libido, fatigue, and mood changes are common and should be discussed with your provider rather than pushing through quietly, there are things your care team can do for most of them. Longer term, ADT thins bone and raises cardiovascular and metabolic risk, so your oncologist should be tracking bone density and heart/metabolic health alongside the cancer itself, not treating those as separate from your cancer care.
Because prostate cancer so often involves bone, most men on ADT with bone metastases are also started on a bone-strengthening drug (denosumab or zoledronic acid) to lower the risk of fractures and other bone complications. Ask whether this applies to you if it hasn’t come up.
When hormone therapy stops working
Eventually, in most men, the cancer finds a way around hormone therapy. This stage is called castration-resistant, a technical term describing the cancer’s biology, not a description of you, and it doesn’t mean treatment is over. It means the next set of tools comes into play.
Genetic testing of the tumor and sometimes a blood test for inherited mutations, particularly in genes called BRCA1 and BRCA2, becomes important at this point, and ideally that testing happens as soon as metastatic disease is diagnosed rather than waiting. Men with these mutations may benefit from a class of drugs called PARP inhibitors, which are far more effective in that specific genetic setting.
Chemotherapy, either docetaxel or a related drug called cabazitaxel, remains a standard option. And for men whose scans show the cancer lighting up on a specific imaging test called a PSMA PET scan, a radioligand therapy called Lu-PSMA (brand name Pluvicto) delivers targeted radiation directly to cancer cells. In the trial that led to its approval, men receiving Lu-PSMA lived a median of just over 15 months compared with about 11 months without it, a meaningful gain in a population whose disease had already progressed through multiple prior treatments. In 2025, that same therapy was approved for use earlier, before chemotherapy is needed, and in 2026 it was approved earlier still, for use alongside hormone therapy at the time of initial metastatic diagnosis in men whose disease is PSMA-positive, though the research behind that newest use is still being finalized in print even though the approval itself is real. PSMA PET imaging and Lu-PSMA infusion aren’t offered everywhere, so ask directly whether they’re available at your center or whether a referral would get you there.
Clinical trials for patients with cancer offer additional ways to fight cancer and generally are building on previously approved standard of care treatment. Trials from Phase 1 to Phase 3 may be considered at any point in treatment.
Where radiation fits in
Radiation comes up in two different ways in metastatic prostate cancer, and it helps to know which one applies to you. The first is straightforward pain relief: a short course of radiation aimed at a bone metastasis that’s causing pain works fast and is usually well tolerated, and it’s used at any point in treatment when a specific spot is bothering you.
The second is more targeted. If scans show a small number of metastases, sometimes called oligometastatic disease, and everything is otherwise well controlled on hormone therapy, some men are offered focused radiation (SBRT) to those specific spots. In the trials that looked at this, adding SBRT lowered the chance of the cancer progressing compared with hormone therapy alone. It’s used alongside hormone therapy, not instead of it.
There’s also a bone-specific systemic option called radium-223 (Xofigo), a different kind of radiation therapy given as an infusion, for men with symptomatic bone metastases and no spread to organs like the liver or lungs. It’s a narrower option than it once was, since Lu-PSMA is now available for many of the same patients, but it’s still used in specific situations. Ask your oncologist whether any of this applies to you.
What treatment involves
Hormone therapy comes in pill or a shot given every one to three months. ARPIs are daily pills, each with its own side-effect pattern worth discussing directly, fatigue and fall risk with some, blood pressure and liver monitoring with others, rash with others. Docetaxel, if used, is an IV infusion every three weeks with expected effects like low blood counts, fatigue, and hair loss.
Lu-PSMA is given as an infusion roughly every six weeks for four to six cycles. Because it involves a small amount of radioactive material, your care team will go over specific safety precautions for the days right after each dose. Side effects are generally milder than chemotherapy, though dry mouth and fatigue are common.
Ask your care team early about genetic testing, both of the tumor and, if relevant, a blood test for inherited mutations. The results can open up specific treatment options, and testing later in the disease course is sometimes harder to arrange.
Getting through this
Bring someone with you to appointments when you can. Ask whether a second opinion or multidisciplinary review makes sense before starting treatment, most oncologists welcome this rather than treating it as a challenge to their judgment.
ARPIs, PARP inhibitors, and Lu-PSMA are all expensive. Ask your care team early about manufacturer copay assistance and independent foundations like the Patient Access Network Foundation, and ask Tennessee Oncology’s financial counselors what applies to you. ZERO Prostate Cancer and Us TOO both run patient education and peer-support programs specific to this disease.
Frequently asked questions
Will I need chemotherapy right away?
Not necessarily. Chemotherapy up front (triplet therapy) is added for some men with more extensive disease, but many men start on hormone therapy alone or hormone therapy plus a second hormonal drug, without chemotherapy.
What is Lu-PSMA (Pluvicto) and who is it for?
It’s a radioligand therapy that delivers targeted radiation to cancer cells that show up on a PSMA PET scan. It was originally approved for later-line use and has since been approved for earlier use, including alongside hormone therapy at initial metastatic diagnosis for men with PSMA-positive disease, though the trial data behind that newest use is still working its way into print. It isn’t available at every center, so ask directly whether it’s an option where you’re being treated.
What are the side effects of Lu-PSMA (Pluvicto)?
Generally milder than chemotherapy. Dry mouth and fatigue are the most common. Because it involves a small amount of radioactive material, your care team will walk you through specific safety precautions for the days right after each dose.
Will I need a bone-strengthening drug?
Likely, if the cancer has spread to bone. Denosumab or zoledronic acid is standard alongside ADT for most men with bone metastases, to lower the risk of fractures and other bone complications. Ask if this has come up for you.
Should I get genetic testing?
Yes, ask about it early. Testing for inherited mutations like BRCA1/2, along with testing of the tumor itself, can open up specific treatment options including PARP inhibitors, and it’s easier to arrange earlier in the disease course than later.
Does asking about a clinical trial mean I'm giving up on standard treatment?
No. Most trials add a new approach to standard treatment rather than replacing it, and you can decline or stop at any point. Asking early keeps options open rather than closing them off.
Is radiation part of metastatic prostate cancer treatment?
It can be, in a couple of ways. A short course of radiation to a painful bone metastasis is common and effective at any point in treatment. If only a small number of metastases show up on scans, some men are also offered focused radiation (SBRT) to those spots alongside hormone therapy. Ask your oncologist whether either applies to you.
How do I find out about clinical trials?
Tennessee Oncology’s GU cancer team has an active prostate cancer trials portfolio and on-site access to PSMA PET imaging and radioligand therapy. Ask at diagnosis, not only after standard options are exhausted. Find a location Here
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- U.S. Food and Drug Administration. FDA approves lutetium Lu 177 vipivotide tetraxetan with an androgen receptor pathway inhibitor for metastatic hormone-sensitive prostate cancer. 2026. Based on the PSMAddition trial (presented ESMO/SUO 2025; full peer-reviewed publication pending).
