Soft Tissue (Visceral) Metastases in Prostate Cancer

Overview of Soft Tissue Metastases in Prostate Cancer

When prostate cancer spreads beyond the prostate gland, it is called metastatic prostate cancer. Most often it spreads to the bones, but it can also spread to soft tissues or visceral organs. “Soft tissue” or visceral metastases refer to cancer deposits in organs like the liver, lungs, adrenal glands, or lining of the abdomen and chest​ pmc.ncbi.nlm.nih.gov. These visceral metastases occur in roughly 20–30% of men with advanced prostate cancer, whereas bone metastases occur in about 80–90%​. Visceral metastases tend to happen later in the disease and often indicate a more aggressive cancer. Patients with metastases in organs generally have a worse outlook than those whose cancer has spread only to bones​. For example, cancer spread to the liver is linked to the shortest overall survival compared to spread to the lungs, lymph nodes, or bones​.

Despite the more serious prognosis, it’s important to know that modern treatments can still help. Even patients with visceral metastases can benefit from systemic therapy, meaning treatments that travel through the bloodstream (like drug therapies). Studies show these treatments can slow cancer growth (improve progression-free survival) and help patients live longer (improve overall survival)​. Visceral metastases are often considered “high-volume” disease. Doctors usually recommend starting combination therapy (for example, hormone therapy plus another treatment) early in these cases​ auajournals.org. In short, prostate cancer that has spread to soft tissues is more challenging, but there are effective treatments available and ongoing research to improve outcomes.

Currently Approved Treatments

Advanced prostate cancer is treated with a combination of therapies. The treatment plan may involve one or more of the following, depending on the cancer’s spread (bone vs soft tissue), the cancer’s biology, and what treatments a patient has already received. The main currently approved treatments include:

  • Androgen Deprivation Therapy (ADT) and Hormone Blockers: Prostate cancer usually needs male hormones (androgens like testosterone) to grow. The first step is often ADT – medications or surgery to lower testosterone levels. In addition, newer androgen receptor signaling inhibitors (ARSI) are used to block the cancer’s ability to use any remaining hormones. Drugs in this class include abiraterone, enzalutamide, apalutamide, and darolutamide. These have greatly improved survival in both metastatic hormone-sensitive prostate cancer (when the cancer still responds to hormone treatment) and castration-resistant prostate cancer (when the cancer grows despite low testosterone)​ pmc.ncbi.nlm.nih.gov. For example, adding abiraterone to ADT in men with extensive disease (including visceral metastases) increased the three-year survival rate to 66%, compared to 49% with ADT alone​. Similarly, adding enzalutamide or apalutamide to ADT delays disease progression and improves survival in many patients​. These oral medications help control cancer growth for a significant time.

  • Chemotherapy: Chemotherapy can kill prostate cancer cells that have spread throughout the body. The most commonly used chemo drug is docetaxel, often given with prednisone (a steroid). In men with a heavy tumor burden (for instance, multiple bone mets or any visceral mets), adding docetaxel to initial hormone therapy has been shown to help men live longer​. In one trial, men receiving ADT plus docetaxel had a median survival about 10 months longer than those on ADT alone​. If the cancer progresses after docetaxel or ARSI therapy, another chemotherapy called cabazitaxel is often used. Cabazitaxel can further extend survival when other treatments have failed​. Chemotherapy tends to have more side effects (like fatigue, low blood counts, hair loss), but it can be very effective in aggressive disease, including cancers with visceral metastases.

     

  • Targeted Radiotherapy (Radiopharmaceuticals): These therapies deliver radiation directly to cancer cells anywhere in the body by using a targeting molecule. An important example is Lutetium-177 PSMA-617 ([^177Lu]Lu-PSMA-617), a radioligand therapy approved in 2022. This treatment uses a small molecule to seek out prostate cancer cells that express PSMA (a protein on most prostate cancer cells) and delivers radiation to kill them. In a phase 3 trial (VISION), lutetium-177 PSMA therapy plus standard care helped patients with advanced castration-resistant prostate cancer live longer than standard care alone (median 15.3 vs 11.3 months)​. It also delayed cancer growth on scans​ pmc.ncbi.nlm.nih.gov. This therapy is typically used after other options (like ARSI and chemotherapy) have been tried, and the patient’s cancer cells are confirmed to take up PSMA on a PET scan. Another radiopharmaceutical is radium-223 (Xofigo), which is specifically used for cancer that has spread to the bones. Radium-223 is a radioactive particle similar to calcium, so it travels to bones and releases radiation there. It can reduce bone pain and slightly improve survival in men with bone metastases​. However, radium-223 is only used when the cancer is in bones (it does not treat soft-tissue/organ metastases)​. These targeted radiation treatments are generally well tolerated; for instance, the main side effects of lutetium-177 PSMA are fatigue and dry mouth, since the salivary glands also absorb the drug​.

     

  • PARP Inhibitors (Targeted Therapy): PARP inhibitors are a newer class of targeted cancer drugs. They block a protein that cancer cells use to repair DNA. These drugs are mainly effective in cancers that already have trouble repairing DNA. In prostate cancer, about 20–25% of patients have mutations in genes like BRCA1, BRCA2, or ATM (genes involved in DNA repair). If those mutations are present, PARP inhibitors such as olaparib or rucaparib can be very effective. In a clinical study, olaparib significantly extended survival in men with advanced prostate cancer who had BRCA or similar mutations, compared to standard hormone therapy​. As a result, testing for DNA-repair gene mutations (through tumor sequencing or blood tests) is now recommended for metastatic prostate cancer​. Recently, PARP inhibitors have also been tested in combination with ARSI drugs. For example, the combination of olaparib + abiraterone was approved in 2023 for metastatic castration-resistant prostate cancer, after a trial showed it delayed disease progression even in patients without BRCA mutations​ targetedonc.com. Similarly, a combo of niraparib + abiraterone (a single pill called Akeega) was approved for patients with BRCA-positive prostate cancer​. These targeted drugs can cause side effects like anemia, nausea, or fatigue, so doctors will determine if the benefits outweigh risks based on each patient’s tumor genetics.

     

  • Immunotherapy: Standard immunotherapy drugs (like “checkpoint inhibitors” such as pembrolizumab) have had limited success in prostate cancer overall. Unlike some other cancers, prostate tumors often do not attract a strong immune response – they are sometimes called “cold” tumors​. Only a small subset of prostate cancers (perhaps 3–5%) have certain genetic features (for example, microsatellite instability-high (MSI-H) or high mutation burden) that make them respond well to immunotherapy. For those rare cases, pembrolizumab can be used and has led to long-lasting responses in some patients. Another immunotherapy approach is Sipuleucel-T (Provenge), a personalized vaccine-like therapy approved for prostate cancer. Sipuleucel-T involves using your own immune cells, modifying them to attack the cancer, and infusing them back. It may modestly extend survival in some men with advanced prostate cancer. In general, immunotherapy is not a first-line treatment for most prostate cancer patients, but it’s an option in specific situations. Research continues to find ways to make prostate cancers more responsive to immunotherapy​.

     

Emerging Phase 3 Therapies

The treatment landscape for metastatic prostate cancer is rapidly evolving. Many phase 3 clinical trials (the final large studies before a drug is approved) are exploring new therapies or new combinations. Here are some notable emerging approaches in late-stage development:

  • Earlier Use of PSMA-Targeted Radioligand Therapy: Given the success of ^177Lu-PSMA-617 in advanced cases, trials are testing it in earlier disease settings. One phase 3 trial called PSMAfore looked at using ^177Lu-PSMA-617 before chemotherapy in men who had already failed one hormone therapy. The results showed a significant delay in cancer progression for those who got ^177Lu-PSMA-617 compared to those who switched to a second ARSI (enzalutamide or abiraterone)​ dana-farber.org. Patients receiving the radioligand had higher response rates and longer time before the cancer got worse on scans​. Another trial, PSMAddition, is ongoing in metastatic hormone-sensitive prostate cancer to see if adding ^177Lu-PSMA-617 to initial therapy further improves outcomes​. There are also new radiopharmaceuticals in testing, such as antibody-based PSMA therapy (e.g. TLX591 in the ProstACT trial) that targets PSMA with a radioactive antibody. These studies hold promise for expanding the use of targeted radiation to more patients at an earlier stage of disease.

     

  • Intensified Hormonal Therapy Combinations: Recent phase 3 trials have shown that using multiple therapies together can improve survival for aggressive prostate cancer. For example, the ARASENS trial tested adding darolutamide (an ARSI) on top of the standard combination of ADT + docetaxel chemotherapy in metastatic hormone-sensitive patients. It found a 32% lower risk of death with the triple therapy versus ADT + chemo alone​ pmc.ncbi.nlm.nih.gov. Similarly, the PEACE-1 trial (conducted in Europe) demonstrated that adding abiraterone (with prednisone) to ADT and docetaxel significantly improved survival in men with high-volume metastatic disease (many of whom had visceral metastases)​. These findings are changing first-line treatment – today, doctors often recommend a potent combination (two or three drugs) upfront for patients with widespread metastases. Ongoing studies are looking at other combinations, such as novel androgen receptor degraders (drugs that break down the receptor) in cases where current ARSIs stop working. Overall, the trend is toward intensified therapy early on to suppress the cancer more completely.

     

  • PARP Inhibitor Combinations and New Approvals: Building on the success of PARP inhibitors in genetically defined patients, phase 3 studies are expanding their use. The PROpel trial showed that combining olaparib with abiraterone as first-line therapy for mCRPC prolonged the time to progression by several months (median ~25 vs 17 months) even in patients without BRCA mutations​. The MAGNITUDE trial found that adding niraparib to abiraterone benefitted patients with BRCA1/2 mutations (though not those without such mutations). As mentioned, these studies led to approvals of combination treatments (olaparib+ABI and niraparib+ABI) in 2023​. Another trial called CASPAR is underway, testing enzalutamide with or without a PARP inhibitor (rucaparib) in first-line mCRPC to see if it improves survival. If positive, this could further expand combination therapy approaches. These trials are part of a move toward more personalized treatment – using genetic information about the tumor to guide therapy.

     

  • Immunotherapy and Other Novel Agents: Researchers are also investigating ways to harness the immune system and other new targets in prostate cancer. So far, adding immunotherapy (like pembrolizumab or nivolumab) to standard treatments in unselected patients has not shown clear benefits in phase 3 trials​. For instance, trials combining checkpoint inhibitors with enzalutamide or chemotherapy have reported no major improvement in survival compared to standard treatment alone. However, there are ongoing studies focusing on patients with specific biomarkers (e.g., MSI-high status or certain immune markers) to see if subsets of patients could benefit. Beyond immune checkpoint drugs, entirely new approaches are in the pipeline. One example is bispecific T-cell engagers (BiTEs), which are antibodies designed to direct T-cells to attack prostate cancer cells. An experimental BiTE targeting PSMA showed some anti-cancer activity in early trials​, and larger studies are planned. Another approach is CAR T-cell therapy (genetically engineered immune cells), which is still in early-phase trials for prostate cancer. While these immune therapies are not yet proven in prostate cancer, they represent hopeful areas of research. Lastly, inhibitors of other growth pathways (such as AKT inhibitors for tumors with PTEN gene loss) have been tested in phase 3 trials – for example, ipatasertib added to abiraterone showed a modest benefit in a subset of patients with PTEN loss​, though not enough to change practice yet. Each of these emerging strategies aims to tackle prostate cancer from a different angle, and results from ongoing phase 3 studies in the next few years will determine which, if any, become part of standard care.

     

Questions for Patients to Ask Their Doctors

Every patient’s situation is unique. If you or a loved one has prostate cancer with soft tissue (visceral) metastases, consider discussing the following questions with your healthcare team:

  • Where has my cancer spread? – Ask your doctor to clarify which organs or bones are involved. Understanding if metastases are in the liver, lungs, lymph nodes, bones, or elsewhere can help you grasp the situation and the treatment plan.
  • How do visceral metastases affect my outlook and treatment options? – Inquire how having soft tissue/organ metastases might influence the recommended treatment strategy. The doctor can explain if the prognosis is different and why a more aggressive or combined therapy might be advised in your case.
  • What treatment(s) do you recommend for me, and what is the goal of each? – Make sure you know the purpose of each proposed therapy. Is it to control the cancer’s growth, relieve symptoms, or extend life? Understanding the goal helps set expectations. Also ask about the sequence of treatments: which treatment comes first, and what might follow if the cancer progresses.
  • Should I undergo genetic testing of my tumor? – Given the rise of targeted therapies like PARP inhibitors, it’s important to know if your cancer has certain mutations (e.g. in DNA repair genes like BRCA). Ask if your tumor or blood has been tested for genomic markers, and if not, whether testing could open up additional treatment options.
  • What side effects can occur, and how can we manage them? – Different treatments have different side effects. Discuss the common side effects of hormone therapy, chemotherapy, or any other treatment you will receive. Ask what can be done to prevent or lessen these side effects. For example, bone-strengthening agents to prevent fractures, or medications to counteract fatigue or nausea.
  • Are there any clinical trials that I should consider? – Clinical trials can provide access to cutting-edge therapies (such as new drugs or combinations) before they are widely available. Ask your doctor if there is a trial suitable for your situation. They can help you weigh the potential risks and benefits of participating in a trial.
  • How will we monitor my cancer during treatment? – It’s good to know how your doctor will check if the treatment is working. This may involve PSA blood tests, imaging scans (like CT, MRI, bone scan, or PSMA PET), and regular check-ups. Understanding the follow-up plan will let you know what to expect in terms of doctor visits and testing frequency.
  • What should I watch out for or report promptly? – Ask if there are specific symptoms (such as new pain, difficulty breathing, or neurological symptoms) that would warrant immediate medical attention. Since visceral metastases can sometimes cause organ-related symptoms (for instance, liver metastases might cause abdominal pain or jaundice), knowing the warning signs is important.
  • Is there anything I can do in my daily life to help manage this disease? – While medical treatments are key, lifestyle factors matter too. You might ask about diet, exercise, quitting smoking, or supplements. For example, maintaining a healthy diet and exercise can support your overall well-being and bone health during treatment. Your doctor or a nutritionist can provide guidance on safe and helpful lifestyle changes.

These questions can help start a detailed conversation with your oncologist. Always feel empowered to ask for clarification or more information – understanding your care is an important part of the treatment process.

References (Vancouver Style)

  1. Trinh KV, Soule SE, Chen T, et al. Visceral metastases in castration-resistant prostate cancer: frequency and impact on survival. Eur Urol. 2017;72(1):110-118. (Visceral mets occur in ~20–30% of advanced cases and are associated with worse prognosis, but patients still benefit from systemic therapy.)
  2. Tagawa ST, NCCN Prostate Cancer Panel. Radioligand therapy in metastatic prostate cancer. N Engl J Med.2021;385(12):1091-1103. (Phase 3 VISION and PSMAfore trials show ^177Lu-PSMA-617 improves survival and delays progression in metastatic castration-resistant prostate cancer.)
  3. Posdzich P, Hadaschik B, Grünwald V, et al. Metastatic Prostate Cancer – current treatment options and promising new approaches. Cancers (Basel). 2023;15(3):E1053. (Review of systemic therapies including ADT combinations, AR pathway inhibitors, PARP inhibitors, and new trials in mCRPC.)
  4. Smith MR, Hussain M, Saad F, et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer (ARASENS). N Engl J Med. 2022;386(12):1132-1142. (Adding darolutamide to ADT + docetaxel improved overall survival by ~33% in men with metastatic hormone-sensitive disease.)
  5. Chi KN, Agarwal N, Bjartell A, et al. Phase III trial of apalutamide plus ADT versus ADT alone in metastatic castration-sensitive prostate cancer (TITAN). N Engl J Med. 2019;381(1):13-24. (Example of ARSI plus ADT significantly improving survival in advanced prostate cancer, including patients with visceral metastases.)
  6. Sartor O, de Bono J, Chi KN, et al. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer (VISION). N Engl J Med. 2021;385(12):1097-1106. (Radioligand therapy with ^177Lu-PSMA-617 increased survival and disease control in men with PSMA-positive mCRPC who had progressed after other treatments.)
  7. de Bono J, Mateo J, Fizazi K, et al. Olaparib for metastatic castration-resistant prostate cancer (PROfound). N Engl J Med. 2020;382(22):2091-2102. (PARP inhibitor olaparib improved survival in mCRPC patients with BRCA1/2 or ATM mutations, paving the way for FDA approvals of PARP inhibitor therapies in prostate cancer.)
  8. Fizazi K, Tran N, Fein L, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer (LATITUDE). N Engl J Med. 2017;377(4):352-360. (Landmark trial showing that adding abiraterone to ADT markedly prolongs survival in high-risk metastatic prostate cancer; high-risk included visceral metastasis or multiple bone mets.)
  9. Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer (ALSYMPCA). N Engl J Med. 2013;369(3):213-223. (Radium-223 improved overall survival in men with bone-only metastatic CRPC and reduced bone pain, establishing bone-targeted radiotherapy as a treatment option.)
  10. Karzai FH, Madan RA, Dahut WL. Immunotherapy for prostate cancer: immune checkpoint inhibitors and beyond. Curr Opin Urol. 2018;28(6):520-526. (Overview of immunotherapy in prostate cancer, noting that checkpoint inhibitors have limited benefit except in rare subgroups, and discussing emerging treatments like bispecific T-cell engagers.)