Immunotherapy for Advanced Prostate Cancer: 2025 Patient Guide

Introduction

What is Immunotherapy? Immunotherapy is a cancer treatment that empowers the body’s own immune system to recognize and attack cancer cells. Unlike chemotherapy or radiation which directly kill cancer cells, immunotherapy “trains” your immune defenses to do the work. It enhances the immune system’s ability to find and destroy cancer by improving how immune cells detect the tumor and by overcoming the cancer’s defenses. In prostate cancer, several tumor-specific targets (such as PSA or PSMA proteins) make it possible for immunotherapies to aim specifically at prostate cancer cells.

Role in Advanced Prostate Cancer: Immunotherapy has become an important area of research for advanced prostate cancer, especially for metastatic castration-resistant prostate cancer (mCRPC) – prostate cancer that no longer responds to hormone therapy. While early-stage prostate cancer is usually managed with surgery, radiation, or hormone therapy, advanced cases are harder to control. Immunotherapy offers a new approach for these advanced cases and has shown some initial success, particularly when combined with other treatments. As of 2025, doctors use immunotherapy mainly for advanced prostate cancer or in clinical trials, and ongoing research is working to expand its benefits.

Currently Approved Immunotherapies

Sipuleucel-T (Provenge): The first FDA-approved immunotherapy for prostate cancer was sipuleucel-T, a therapeutic vaccine approved in 2010 for certain men with mCRPC. It is a personalized immune cell therapy: doctors draw the patient’s blood to collect immune cells, modify those cells in a lab to target a prostate cancer protein (PAP), and then infuse them back into the patient. This process trains the immune system to attack prostate cancer cells. Sipuleucel-T is given as a series of three intravenous infusions (through a vein) usually spaced about 2 weeks apart. In a large trial, sipuleucel-T improved median overall survival by about 4 months (25.8 vs 21.7 months) compared to placebo. Notably, patients with lower disease burden (low PSA levels) seemed to benefit the most, suggesting that earlier use might be more effective. Side effects are generally mild; many patients experience flu-like symptoms (chills, fever, headache, muscle aches) for a day or two after infusion. Serious reactions are rare – less than 1% of patients were unable to complete infusions due to side effects. Overall, sipuleucel-T offers a safe treatment option that can modestly extend survival for men with advanced prostate cancer.

Pembrolizumab (Keytruda): Pembrolizumab is an immune checkpoint inhibitor – it blocks PD-1, a “brake” on immune T-cells, thereby freeing T-cells to attack cancer. While there is no checkpoint inhibitor specifically approved onlyfor prostate cancer, pembrolizumab received an FDA tumor-agnostic approval that includes prostate cancer patients whose tumors have certain genetic features. In particular, adults with metastatic solid tumors that are microsatellite instability-high (MSI-H) or DNA mismatch repair-deficient (dMMR) may be treated with pembrolizumab if no other good treatment options exist. A small percentage of advanced prostate cancers have these MSI-H or dMMR biomarkers. For those patients, pembrolizumab can be an option to stimulate an immune attack on the cancer. Pembrolizumab is given as an IV infusion, typically every 3 or 6 weeks, in an outpatient setting. Its side effects can include fatigue, rash, or inflammation in the body (because removing the immune “brakes” can sometimes cause the immune system to attack normal organs). Your doctor may test your tumor’s genetics to see if pembrolizumab or similar checkpoint inhibitors are likely to help. For most prostate cancer patients without those specific biomarkers, routine use of pembrolizumab is not yet proven effective, but it remains an important option in select cases and continues to be studied in clinical trials.

At this time, sipuleucel-T and pembrolizumab (for MSI-H/dMMR tumors) represent the key FDA-approved immunotherapies for advanced prostate cancer. Other immunotherapy approaches are only available through clinical trials or compassionate use.

Emerging Immunotherapies in Clinical Trials

Researchers are actively testing new immunotherapies for advanced prostate cancer. These experimental treatments fall into several categories, including checkpoint inhibitors, therapeutic vaccines, and cellular therapies. Here we summarize some promising approaches in clinical trials:

  • Immune Checkpoint Inhibitors: These drugs release the brakes on immune cells, helping them attack cancer. Examples include PD-1/PD-L1 inhibitors (like nivolumab, atezolizumab) and CTLA-4 inhibitors (like ipilimumab). In prostate cancer, checkpoint inhibitors as single treatments have had limited success overall, but certain patients responded – especially those with high mutation burden or specific immune markers. For instance, in one trial combining nivolumab and ipilimumab (Checkpoint 650), some patients’ tumors shrank, showing that checkpoint immunotherapy can have activity in prostate cancer. To improve results, researchers are testing combinations – for example, pairing a checkpoint inhibitor with hormonal therapy or radiation to make the tumor more recognizable to the immune system. Ongoing trials are also looking at checkpoint inhibitors after other treatments (like after chemotherapy) to see if timing can improve effectiveness. While none of these combinations are standard yet, early findings are encouraging enough that over half of new prostate cancer immunotherapy trials involve a checkpoint blocker in some form.

  • Therapeutic Vaccines: Therapeutic cancer vaccines work by teaching the immune system to attack prostate cancer cells, usually by exposing the immune system to prostate cancer antigens (proteins unique to prostate tumors). Sipuleucel-T is already approved, but many next-generation vaccines are in trials. One example is PROSTVAC, a vaccine using two poxviruses engineered to produce PSA (a prostate cancer antigen) and immune-stimulating signals. In a Phase II study, PROSTVAC extended median survival by about 8.5 months, but a larger Phase III trial did not show a clear benefit, highlighting the need for further refinement. Researchers are now combining PROSTVAC with other therapies to see if it works better together. Other experimental vaccines include DNA vaccines (like pTVG-HP targeting prostatic acid phosphatase, and pTVG-AR targeting the androgen receptor) which aim to induce an immune response against prostate cancer genes. Early trials show these vaccines are safe and can activate the immune system, but more studies are needed to prove they help patients live longer. Overall, therapeutic vaccines are a promising strategy to prompt the body to fight prostate cancer, and ongoing trials will clarify how much they can contribute, especially in combination with other treatments.

  • Cellular Therapies (Adoptive Cell Transfer): These approaches use immune cells themselves as living drugs. A major area of excitement is CAR T-cell therapy. CAR T-cells are a patient’s own T lymphocytes genetically engineered to recognize a protein on cancer cells. In advanced prostate cancer, a key target is PSMA (prostate-specific membrane antigen), which is found on most prostate cancer cells. Scientists have created CAR T-cells that target PSMA and also overcome immune suppressive signals in the tumor (for example, by adding a receptor that resists TGF-beta, an immune suppressant). In a 2022 Phase 1 trial at the University of Pennsylvania, such PSMA-targeted CAR T-cells were tested in men with mCRPC. About 30% of treated patients saw a meaningful drop in their PSA levels – one patient’s PSA (a blood marker of prostate cancer) fell by over 98%, which is a dramatic response​pmc.ncbi.nlm.nih.gov. This suggests the CAR T-cells were killing cancer cells. Some patients had stable disease (no progression) for several months. Importantly, side effects like cytokine release syndrome (an intense immune reaction) were generally manageable, though one patient in that early trial did experience a serious adverse event. Researchers are learning how to improve CAR T safety and effectiveness, for example by adjusting the dose or adding “safety switches” to turn off the cells if needed. Aside from CAR T-cells, other cellular immunotherapies in trials include TCR-engineered T cells (which use a slightly different receptor approach) and bispecific T-cell engagers (BiTEs)– antibodies that bind both a T-cell and a cancer cell to bring them together. One BiTE drug targeting PSMA showed some tumor responses in early studies, but also some side effects, and combination with checkpoint inhibitors may enhance its effect. These cell-based therapies are still experimental but hold the potential for long-lasting control of cancer by literally re-arming the patient’s immune cells to hunt down prostate cancer throughout the body.

     

In summary, numerous clinical trials are underway exploring immunotherapy for advanced prostate cancer. These include drugs that take the brakes off the immune system, vaccines that spark new immune attacks on tumor proteins, and living cell therapies that directly seek and destroy cancer cells. Many of these investigational treatments are in Phase I or II studies, evaluating safety and early signs of efficacy. While it’s too early to know which will become standard treatments, the fact that dozens of trials (one review counted 68 ongoing trials) are in progress shows the strong interest in immunotherapy for prostate cancer. Patients with advanced prostate cancer may consider enrolling in a clinical trial to access these emerging therapies (see Practical Tips and talk with your doctor). Each new trial brings us closer to understanding how to best harness the immune system against prostate cancer.

Comparison of Clinical Trial Types

When considering an immunotherapy clinical trial, it’s helpful to understand the different phases of clinical trials. Clinical trials progress in phases – Phase 1, 2, and 3 – each with a different purpose. The table below compares these trial phases, including what they involve and the pros and cons for patients:

Trial Phase Purpose & Typical Size Pros for Patients Cons for Patients
Phase 1 Tests a new treatment in a small group (usually 15–30 people). Aim: find a safe dose and identify side effects. Researchers also observe if it shows any effect on the cancer. – Access to a brand-new therapy when standard treatments have failed.
– Very close monitoring and care (safety is top priority).
– Even though the main goal is safety, some modern Phase 1 trials do show tumor shrinkage or disease control, especially with targeted drugs or immunotherapies.		 – Unknown risks: Side effects are not fully known; could be unexpected.
– Low chance of direct benefit. Historically, only ~4–5% of patients had major tumor shrinkage in Phase 1 oncology trials (though this is improving).
– Time and travel commitment for frequent visits, which can be hard for very sick patients.
Phase 2 Studies the treatment in more people (often 50–100+ patients with a specific cancer type) to see if it works (tumor response, slowed growth) and further evaluate safety. – Patients all usually receive the new treatment (no placebo in many Phase 2 trials), so everyone has a chance to benefit.
– Intermediate phase: some preliminary efficacy data exist, so there’s reason to hope it works based on Phase 1 results.
– Continued careful monitoring with a larger safety record established.		 – Still experimental: no guarantee it’s effective – the treatment could turn out not to help the cancer despite early promise.
– Side effects better known than Phase 1 but new issues can emerge as more patients try it.
– May require frequent hospital visits, scans, and possibly biopsies to measure response.
Phase 3 Compares the new treatment to the standard treatment in a large group (often 100s to 1000s of patients across many hospitals). Goal: confirm effectiveness and monitor side effects on a broader scale. This phase is usually needed for FDA approval. – Potential for better outcomes: The new treatment has shown promise in Phase 1/2, so it could be as good as or better than the standard therapy.
– You will at least get the standard of care (no one gets less than current best treatment; sometimes the new treatment is added to standard treatment rather than replacing it).
– Phase 3 data shape future care – by participating, you contribute to improving treatment for future patients.		 – Randomization: You may be randomly assigned to the standard treatment instead of the new one. If you were hoping for the new therapy, this can be disappointing (though standard care is still beneficial).
– More involved trial procedures: there may be extra clinic visits, paperwork, and longer follow-up since Phase 3 trials track outcomes over years.
– Possible side effects from the new treatment, and you might not know if it’s better until the trial ends.

How to use this table: If you are thinking about a trial, consider what phase it is. Phase 1 trials focus on safety and dose-finding – they are essential for progress but have more unknowns. Phase 2 trials give a clearer idea of efficacy and still offer all participants the new therapy. Phase 3 trials are closest to potential approval and compare against standard treatment – they may be a good choice if you want a proven therapy but are open to something potentially better. Discuss these trade-offs with your doctor. Remember, by the time a treatment gets to Phase 3, it has passed earlier testing, so there is a solid rationale that it might improve outcomes. In any phase, your rights and safety are protected, and you can leave the trial if you choose.

Unique Advantages for African American Men

Research led by Oliver Sartor, MD, has suggested that African American men with advanced prostate cancer might derive particular benefit from immunotherapy. In the past, African American men have had higher prostate cancer death rates compared to Caucasian men, often due to disparities in access and biology. Intriguingly, with sipuleucel-T immunotherapy, this trend appeared to reverse. A large registry called PROCEED analyzed men with mCRPC who received sipuleucel-T (Provenge) in real-world settings. About 12% of the patients were African American. The analysis found that African American men lived significantly longer on average than Caucasian men after receiving sipuleucel-T:

  • In a matched comparison, African American patients had a median overall survival of 35.3 months, vs 25.8 months in Caucasian patients. In other words, Black patients lived nearly 9–10 months longer on median.
  • After adjusting for other prognostic factors, African American men still had about a 40% lower risk of death than Caucasian men in this study (hazard ratio ~0.60).

Dr. Sartor’s study (published in 2020) was exploratory but clearly showed a survival advantage for African American men treated with this immunotherapy. This is one of the largest race-based analyses in prostate cancer immunotherapy to date. The reasons are not yet fully understood. It’s possible that genetic or immune profile differences make the immunotherapy more effective in African American patients, or there may have been differences in disease characteristics. Notably, the benefit for African American men was most pronounced in those with lower PSA levels (earlier in the mCRPC disease course), which might indicate starting immunotherapy earlier yields better outcomes.

These findings are encouraging because they suggest immunotherapy could help reduce prostate cancer outcome disparities. If you are an African American man with advanced prostate cancer, you might want to discuss immunotherapy options with your doctor. While anyone can respond to immunotherapy, this research suggests you could have an especially favorable response. However, further research is ongoing to confirm these results and to understand why the benefit was observed. It will also be important to see if other immunotherapies (like checkpoint inhibitors) show similar trends.

Bottom line: Every patient is unique, but African American men should feel encouraged that immunotherapy is not less effective for them – it may be more effective in some cases. As always, treatment decisions should be individualized, but this data supports ensuring African American patients have equal access to trials and approved immunotherapies.

Practical Tips for Working with Clinical Trial Investigators

If you are considering or have decided to join an immunotherapy clinical trial, here are some practical tips to help you work effectively with the research team (doctors, nurses, and investigators). These tips can improve communication and make your experience as a participant smoother:

  • Ask Questions and Stay Informed: Don’t hesitate to ask the investigators any questions you have about the trial – from big-picture details to small concerns. The informed consent process (before you join the trial) is an ideal time to ask questions and make sure you understand the treatment, potential risks, and your responsibilities. Even after the trial starts, keep asking if anything is unclear. The research team is required to explain the study to you in plain language and answer all your questions so that you feel comfortable.

  • Build a Partnership with the Research Team: Think of the trial investigators as part of your care team. You should feel that you can trust them and openly discuss your concerns. Good communication is key. Make sure the doctors and nurses have answered your questions to your satisfaction and that you feel like a partner in the process. If something is worrying you – for example, a side effect or a scheduling problem – let them know. They are there to help and want you to succeed in the trial. Many trial participants find that being on a study actually gives them extra support, with a dedicated team following them closely.

  • Stay Organized and Committed: Clinical trials often have specific schedules for treatments, blood tests, scans, and check-ins. Keep a calendar or journal of all your appointments and any special instructions (for instance, fasting before a blood draw). Make sure you understand the time commitment and travel requirements for the trial upfront. If you have any conflicts or challenges (like needing transportation or help on treatment days), discuss them with the coordinators; they may be able to assist or adjust the schedule when possible. Being diligent about attending visits and following procedures will ensure the trial data is accurate and that you are getting the intended dose on time.

  • Communicate Changes in Your Health Promptly: While on the trial, report any new symptoms or side effects to the investigators right away, even if you’re not sure they are related to the treatment. For example, if you develop a fever, rash, or any unusual pain, inform your study nurse or doctor. They will advise you on what to do. Trials have specific protocols for managing side effects, and the team needs to know about issues in real time to help you and to document the treatment’s safety. You will typically be given a 24-hour contact number – don’t hesitate to use it if needed.

  • Keep Personal Records: It may help to keep your own notes about how you feel each day during the trial. Note your energy level, any side effects, and questions that come to mind. This can help you remember details during clinic visits. It also empowers you – you become an active participant in monitoring your health. If you prefer using technology, some trials provide diary apps or you can use your own. Bringing a family member or friend to appointments as an extra set of ears and support can also be valuable.

  • Stay Positive but Realistic: Participating in a trial can be emotionally challenging. There may be uncertainty about whether the treatment is helping. Maintain hope – many patients have had good outcomes from trial therapies – but also understand the trial’s goal is to gather data, and not every individual will benefit. It’s okay to ask the researchers about any preliminary findings or what they’ve observed so far (sometimes they can share general updates). They should be honest with you. Regardless of outcome, know that by participating you are contributing to research that could help future patients. The investigators truly appreciate your involvement and will treat you with respect and gratitude.

Remember, you have rights as a clinical trial participant. You can withdraw from the study at any time if you choose. However, if you encounter any issues or are considering stopping, talk to the research doctor first – they may be able to address the problems or clarify misunderstandings. Good communication with the investigative team can turn your trial experience into a partnership where everyone is working towards the same goal: finding the best possible treatment for you and others.

Questions to Ask Your Doctor

When discussing immunotherapy for advanced prostate cancer with your doctor, it’s important to get all the information you need to make an informed decision. Here is a list of questions you might consider asking your oncologist or healthcare team about immunotherapy. These can help you understand if immunotherapy is right for you and what to expect from treatment:

  • Is immunotherapy a treatment option for me, given my specific cancer stage and health?​(Not all prostate cancer patients are candidates for immunotherapy. This question helps you learn if you have features (like certain biomarkers or disease status) that make immunotherapy worthwhile to consider.)

  • What type of immunotherapy would you recommend in my case, and how does it work?​
    (For example, is it a vaccine like sipuleucel-T, a checkpoint inhibitor, or a trial therapy? Understanding the mechanism in simple terms can help you follow your treatment.)

  • What are the potential benefits and the risks or side effects of this immunotherapy?​
    (Every treatment has pros and cons. Ask how likely the immunotherapy is to improve your cancer control or symptoms, and what side effects are common. For side effects, also ask which ones need urgent medical attention.)

  • How is the immunotherapy given and what will the schedule be?​
    (Is it an IV infusion, an injection, or a pill? How often do I receive treatment – weekly, every few weeks? Do I need to stay at the clinic or hospital, and for how long each time?)

  • Where will I receive the treatment? Can it be done locally or do I need to travel to a specialized center?​
    (Some immunotherapies might only be available at certain centers or as part of trials. Know if you’ll need to arrange transportation or lodging.)

     

  • Will I need any special preparation before starting immunotherapy (such as stopping other medications or getting certain vaccines)?​
    (For instance, some treatments might recommend getting flu or COVID vaccines beforehand, or avoiding steroid medications that could dampen the immune response.)

  • How will we know if the immunotherapy is working?​
    (Ask what tests or scans will be done to monitor your cancer. Will your PSA levels be tracked, and how often? When will the first evaluation occur? It’s important to know the plan for assessing response.)

  • What are the possible side effects of immunotherapy, and how can we manage them if they occur?​
    (Different immunotherapies have different side effects. For example, checkpoint inhibitors can cause immune reactions in organs. Know the warning signs to watch for. Also ask if side effects typically resolve quickly or require medications like steroids to treat.)

  • Will immunotherapy affect my daily life?​
    (Can I continue to work or exercise during treatment? Should I avoid any activities, certain foods, or supplements while on therapy? Knowing this helps you plan your routine and any needed support at home.)

  • How long will I receive the immunotherapy?
    (Is there a set number of treatments (e.g., sipuleucel-T is 3 doses) or do I continue until disease progression? Also, ask about the overall time frame – for example, some trials have a fixed duration of therapy.)

  • Are there other treatments (like hormone therapy, radiation, or chemotherapy) that will be given along with the immunotherapy or afterward?​
    (Immunotherapy might be one part of your treatment plan. Clarify if you will continue on ADT (hormone shots) or other medications simultaneously. If the immunotherapy works, is there a maintenance plan? If it doesn’t, what is plan B?)

  • Have you treated other prostate cancer patients with immunotherapy? What were their outcomes?
    (While every patient is different, your doctor’s experience can provide insight. If they have treated similar cases, they can share anecdotal expectations and tips.)

  • Should I consider joining a clinical trial for immunotherapy?
    (If the recommended immunotherapy is only available via trial, or if there are new options in trials, ask about this. Trials can offer access to cutting-edge treatments. Ensure you understand the requirements of any trial – see the Practical Tips section above for guidance on this topic.)

  • What costs should I expect with this treatment, and will my insurance cover immunotherapy?
    (While this guide doesn’t delve into cost, it is a practical question for many. Your healthcare team’s financial counselor can help with insurance approvals for FDA-approved immunotherapies or trial coordinators can explain cost coverage in a study.)

Feel free to take this list to your appointment. Add any other questions you think of. There are no bad questions – being informed will help you feel more confident and in control of your treatment plan. Your doctor should welcome the opportunity to address each of these points. Open communication with your healthcare team is essential, and a good doctor will take the time to discuss all of your concerns about immunotherapy for advanced prostate cancer.

References

  1. Liang H, Liu Z, Guo X, et al. Progression in immunotherapy for advanced prostate cancer. Front Oncol. 2023; 13:1121234. PMID: 36925917

  2. Rehman L, Nisar MH, Fatima W, et al. Immunotherapy for prostate cancer: a current systematic review and patient-centric perspectives. J Clin Med. 2023; 12(4):1267. PMID: 36835981

  3. Sartor AO, Armstrong AJ, Ahaghotu C, et al. Survival of African-American and Caucasian men after sipuleucel-T immunotherapy: outcomes from the PROCEED registry. Prostate Cancer Prostatic Dis. 2020; 23(3):517-526. PMID: 32111923

  4. Narayan V, Barber-Rotenberg JS, Franco AM, et al. PSMA-targeting TGFβ-insensitive armored CAR T cells in metastatic castration-resistant prostate cancer: a phase 1 trial. Nature Medicine. 2022; 28(4):724-734. PMID: 35361988​ pmc.ncbi.nlm.nih.gov

  5. Jaber N. FDA approves pembrolizumab for tumors with specific genetic features (MSI-H or dMMR). NCI Cancer Currents (News). June 20, 2017 [updated Mar 28, 2023]. Available from: National Cancer Institute

  6. Reynolds S. Changing the perception of early-phase cancer clinical trials: a conversation with Dr. Naoko Takebe. NCI Cancer Currents (Blog). Nov 10, 2022. Available from: National Cancer Institute

  7. National Cancer Institute. How Do Clinical Trials Work? (Patient Education Page). Bethesda, MD: NCI; Updated 2021. [Accessed 2025].

  8. Pfizer, Inc. Joining a Clinical Trial: What to Know Before You Enroll. Pfizer News Article. 2018. [Accessed 2025].

  9. Canadian Cancer Society. Questions to Ask about Immunotherapy. Canadian Cancer Society (cancer.ca) 2025. [Accessed 2025].​