Metastatic Prostate Cancer: Common Questions about Staging, Treatment, and Emerging Therapies

Prostate cancer starts in the prostate gland, part of the male reproductive system. It is the most common non-skin cancer in men in the U.S. and the second leading cause of cancer death, affecting about 1 in 8 men in their lifetime. Many prostate cancers are slow-growing and highly treatable when detected early. When the cancer spreads to other parts of the body, such as the bones or lymph nodes, it is considered metastatic disease, requiring more aggressive treatment and carrying a more serious prognosis.

At Private Health Management (PHM), we’ve helped clients with metastatic prostate cancer get access to cutting-edge care. According to our latest cancer whitepaper, PHM clients with advanced prostate cancer survived, on average, more than four years longer than patients in the National Cancer Institute registries.¹ Below, our experts answer common questions about metastatic prostate cancer, including disease staging, treatment options, and emerging therapies that may help patients to survive longer with better quality of life.

What are the screening recommendations for prostate cancer?
The American Cancer Society recommends that men make an informed decision about prostate cancer screening in consultation with their health care provider. This decision should be based on understanding the potential benefits, risks, and uncertainties of screening.² The US Preventive Services Task Force (USPSTF) recommends against PSA screening for men older than 70 years old because it tends to be unreliable in older men, especially those with enlarged prostates.³

RISK CATEGORY WHEN TO DISCUSS SCREENING

How is prostate cancer diagnosed and staged?
Prostate cancer is typically found with a prostate-specific antigen (PSA) blood test and a digital rectal exam (DRE). A biopsy of the suspected tumor tissue confirms the diagnosis and determines the aggressiveness of the cancer.²

• Gleason scores rate how aggressive the cancer looks under a microscope, with scores ranging from lowest-risk (Gleason 6 [3+3]), to highest-risk (Gleason 10 [5+5]).⁴ Recent guidelines have aligned Gleason scores into Grade Groups (1–5), with Gleason 6 corresponding to Grade Group 1 (least aggressive).
• Prostate cancer is staged (stage I-IV) using the TNM system, a standard staging method for all solid tumors which describes the size of the tumor, whether it has spread to lymph nodes, and if it has metastasized.
• Early-stage (stage I–II and some subcategories of stage III) prostate cancers are confined to the prostate, while advanced or metastatic cancers (stage IIIB and IV) have extended beyond the prostate into adjacent pelvic structures or distant sites such as bone.

What is the prognosis for patients with metastatic prostate cancer?
Early diagnosis of prostate cancer plays a major role in improving treatment outcomes. When detected at an early stage, the five-year survival rate is nearly 100%. In contrast, metastatic prostate cancer has a five-year survival rate of just 38%. Although it is not curable at this stage, it is still treatable.⁵ A number of therapies are approved for metastatic prostate cancer, and ongoing research continues to expand the range of available treatment options.

What are the standard treatments for metastatic prostate cancer?
Hormone therapy is the standard first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC), a type of cancer that is dependent on male hormones (androgens) to drive cancer growth. Hormone therapy works by lowering or blocking testosterone, which prostate cancer cells need to grow.

• Androgen Deprivation Therapy (ADT), which lowers testosterone production, includes leuprolide (Lupron®), degarelix (Firmagon®), and others.
• Androgen Receptor Pathway Inhibitors (ARPIs), which work differently than ADT to block the effects of testosterone rather than lowering testosterone, include enzalutamide (Xtandi®), darolutamide (Nubeqa®), and others.
• Depending on the volume of metastatic disease, ADT, ARPIs, and chemotherapy can used in combination.

Are precision medicine and targeted therapies useful for treatment-resistant prostate cancer?
When hormone therapy stops working, the cancer is called metastatic castration-resistant prostate cancer (mCRPC). There are several targeted treatment options for patients whose cancers express certain proteins or carry specific genetic mutations. To identify eligible patients, genetic testing of both normal and tumor cells is increasingly important, as it helps guide personalized treatment decisions.

• Pluvicto® (lutetium Lu 177 vipivotide tetraxetan) delivers targeted radiation to cancer cells that express a protein called prostate-specific membrane antigen (PSMA) and has been shown to improve overall survival in patients with mCRPC and may also improve quality of life by reducing tumor burden.⁶ PHM was an early adopter of this treatment strategy and helped a client get access to this treatment in Germany, while it was still being evaluated in clinical trials in the U.S.⁷
  • Pluvicto was previously used in patients who have already been treated with chemotherapy. As of March 28, 2025, the FDA expanded its approval to include use in castration-resistant prostate cancer prior to chemotherapy.⁸
• XOFIGO® (Radium-223), is a radioactive treatment that targets cancer that has spread to the bones.
• Two PARP inhibitor drugs (Lynparza® [olaparib] and Rubraca®[rucaparib]) are FDA-approved for patients with certain mutations in homologous recombination repair genes (e.g. BRCA1, BRCA2, ATM) that affect the body’s ability to repair DNA. These drugs work by blocking the PARP enzyme, which cancer cells rely on for DNA repair, leading to cancer cell death.

What emerging treatments are currently under investigation?
The treatment framework for prostate cancer has evolved significantly over the last 5–10 years. Treatment has shifted toward personalized medicine, using a patient’s specific cancer type and genetics to guide decisions. Newer therapies may help avoid or delay long-term hormone therapy, which can cause side effects like fatigue, weight gain, or bone loss. For mCRPC patients who have exhausted standard treatment options, investigational therapies show promise.

• STEAP1-targeting agents: Emerging therapies like AMG 509, help the immune system attack cancer cells with the STEAP1 protein.⁹
• Androgen receptor degraders: Next-generation therapies, such as ARV-766, break down the hormone receptor to stop cancer growth.¹⁰
• CAR-T cell therapies: Treatments that engineer a patient’s immune cells to recognize and destroy cancer cells that express tumor-specific antigens such as PSMA, PSCA, and STEAP2.^11,12
• SWOG S1802 clinical trial: This study is testing whether adding surgery or radiation to a few sites where the cancer has spread can improve survival.¹³

Staying informed about metastatic prostate cancer and the expanding treatment landscape can empower patients and families to make better decisions. While a diagnosis of metastatic disease can be overwhelming, new therapies and clinical trials offer real hope for extended survival and improved quality of life.

References

1. Improving Cancer Survival: PHM’s Impact on Cancer Care. Private Health Management https://solutions.privatehealth.com/phm-impact-on-cancer-survival.
2. American Cancer Society Recommendations for Prostate Cancer Early Detection. https://www.cancer.org/cancer/types/prostate-cancer/detection-diagnosis-staging/acs-recommendations.html.
3. Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement | Oncology | JAMA | JAMA Network. https://jamanetwork.com/journals/jama/fullarticle/2680553.
4. Litwin, M. S. & Tan, H.-J. The Diagnosis and Treatment of Prostate Cancer: A Review. JAMA 317, 2532–2542 (2017).
5. What Are the Survival Rates for Prostate Cancer? https://www.cancer.org/cancer/types/prostate-cancer/detection-diagnosis-staging/survival-rates.html.
6. Sartor, O. et al. Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. New England Journal of Medicine 385, 1091–1103 (2021).
7. Parker, D. et al. Case Report: Long-term complete response to PSMA-targeted radioligand therapy and abiraterone in a metastatic prostate cancer patient. Front Oncol 13, 1192792 (2023).
8. Research, C. for D. E. and. FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. FDA (2025).
9. Nolan-Stevaux, O. et al. AMG 509 (Xaluritamig), an Anti-STEAP1 XmAb 2+1 T-cell Redirecting Immune Therapy with Avidity-Dependent Activity against Prostate Cancer. Cancer Discovery 14, 90–103 (2024).
10. A phase 2 expansion study of ARV-766, a PROTAC androgen receptor (AR) degrader, in metastatic castration-resistant prostate cancer (mCRPC). | Journal of Clinical Oncology. https://ascopubs.org/doi/10.1200/JCO.2023.41.6_suppl.TPS290.
11. Dorff, T. B. et al. PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: a phase 1 trial. Nat Med 30, 1636–1644 (2024).
12. Schepisi, G. et al. CAR-T cell therapy: a potential new strategy against prostate cancer. J Immunother Cancer 7, 258 (2019).
13. SWOG S1802: Phase III Randomized Trial of Standard Systemic Therapy (SST) Versus Standard Systemic Therapy Plus Definitive Treatment (Surgery or Radiation) of the Primary Tumor in Metastatic Prostate Cancer | University of Iowa Clinical Research and Trials. https://clinicaltrials.uihealthcare.org/studies/swog-s1802-phase-iii-randomized-trial-standard-systemic-therapy-sst-versus-standard.