Advanced Prostate Cancer: What Comes After Disease Progression

“Every patient with metastatic disease, if the patient has not had treatment to the prostate, should discuss treatment with a urologist and a radiation oncologist,” Dr. Alan Dal Pra, a radiation oncologist at the University of Miami, tells SurvivorNet.

“As the technology has allowed us to give treatments that are safer, we are developing more local therapies that are able to control locally and prevent high-risk bone metastasis, preventing complications in the future.”

The best treatment plan depends on many factors, including your cancer’s characteristics, your overall health, and your personal preferences. Working closely with your oncology team — and asking questions — will help ensure you receive care that is both effective and aligned with your goals.

Understanding Progressive Prostate Cancer: Diagnosis and Treatment Options

Progressive prostate cancer refers to a stage of the disease in which the cancer is no longer stable or dormant — it has begun to grow, spread, or become more resistant to current treatments. This progression may occur in men who were initially treated for localized prostate cancer or in those who have already been managing advanced disease.

Fortunately, advances in medical science have led to a wide array of treatment options that offer both hope and long-term disease control.

How Will I Be Monitored For Cancer Progression?

Prostate cancer progression is typically diagnosed using a combination of blood tests, imaging studies, and, occasionally, tissue biopsy. One of the most common early signs of progression is a rising prostate-specific antigen (PSA) level. PSA is a protein produced by both normal and cancerous prostate cells, and increasing levels can signal that the cancer is becoming active again.

In addition to PSA monitoring, imaging plays a crucial role. Your doctor may order a CT scan, bone scan, MRI, or more advanced techniques like PSMA PET scans to look for new sites of cancer spread. These tests can reveal whether the cancer has moved beyond the prostate to bones, lymph nodes, or other organs. The combination of rising PSA and abnormal findings on imaging often prompts a discussion about changing or intensifying treatment.

Androgen Receptor Pathway Inhibitors

Prostate cancer is fueled by androgens, a group of male hormones that includes testosterone. One of the first steps in treating advanced or progressive prostate cancer is to reduce or block the effects of these hormones. This is referred to as androgen deprivation therapy (ADT) and is often achieved using medications or, in some cases, surgery.

However, some cancers continue to grow even when testosterone levels are low. In these situations, androgen receptor pathway inhibitors (ARPIs) are used. These medications, such as enzalutamide, apalutamide, and darolutamide, block the androgen receptor on cancer cells, preventing any remaining hormones from stimulating growth. ARPIs are often added when a patient is diagnosed with castration-resistant prostate cancer, a form of the disease that no longer responds to traditional hormone therapy alone.

Patients typically tolerate ARPIs well, though side effects like fatigue, hot flashes, and increased risk of falls may occur. Your oncologist will monitor your response with regular PSA testing and imaging as needed.

Chemotherapy

Chemotherapy is another option for men with progressive prostate cancer, particularly when the cancer is aggressive or has spread extensively. The most commonly used chemotherapy drug in this setting is docetaxel, which works by interfering with the cancer cells’ ability to divide and grow.

Chemotherapy is usually reserved for patients who no longer respond to hormone therapy or those with widespread metastases. However, in some cases, it may be offered earlier, particularly in patients with high-volume metastatic hormone-sensitive prostate cancer, based on recent clinical trial data showing improved survival.

While chemotherapy can be effective, it also carries a risk of side effects, including fatigue, nausea, lowered blood counts, and hair loss. Supportive medications are often used to minimize these effects, and many patients find that the benefits outweigh the risks.

Immunotherapy

Immunotherapy, which helps your immune system recognize and attack cancer cells, has been a game changer in many cancers. However, its role in prostate cancer is more limited. The only FDA-approved immunotherapy specifically for prostate cancer is sipuleucel-T (Provenge), a personalized vaccine-like treatment for men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).

Sipuleucel-T is made by collecting a patient’s own immune cells, modifying them in a lab to target prostate cancer, and then infusing them back into the body. It’s a complex but generally well-tolerated treatment, and while it doesn’t shrink tumors significantly, it has been shown to extend survival modestly in some patients.

Research is ongoing to develop new forms of immunotherapy, including checkpoint inhibitors like pembrolizumab, but these are generally reserved for men with specific genetic mutations, such as microsatellite instability-high (MSI-H) tumors.

PARP Inhibitors

PARP inhibitors are a newer class of drugs that work by exploiting a weakness in the cancer’s ability to repair its DNA. Normally, cells have repair mechanisms to fix DNA damage, but in some prostate cancers — particularly those with mutations in the BRCA1, BRCA2, or other DNA repair genes — these mechanisms are faulty. PARP inhibitors block the backup repair system, leading to cancer cell death.

Medications like olaparib and rucaparib are now FDA-approved for men with mCRPC who have specific gene mutations. Genetic testing — either from a blood sample or tumor tissue — is required to determine if you’re a candidate.

PARP inhibitors are taken as pills and are usually well tolerated, though some patients may experience nausea, fatigue, anemia, or changes in blood counts. For eligible patients, these medications represent a major advancement in treatment.

Radiopharmaceuticals

Radiopharmaceuticals are a unique category of treatment that deliver radiation directly to cancer cells through the bloodstream. Unlike traditional external radiation therapy, which is aimed from outside the body, radiopharmaceuticals are injected into a vein and seek out cancer cells — particularly in the bone.

The most commonly used radiopharmaceutical for prostate cancer is Radium-223 (Xofigo), which mimics calcium and is taken up by bone metastases. It delivers targeted radiation that helps relieve pain and may extend survival in patients with bone-dominant disease.

Another exciting development is Lutetium-177 PSMA therapy (Pluvicto), which targets prostate-specific membrane antigen (PSMA) on cancer cells. This treatment is particularly effective in patients whose tumors show high PSMA expression on imaging. It’s usually reserved for later stages of disease but has shown significant promise in improving outcomes.

Radiation Therapy

Radiation therapy is a cornerstone of prostate cancer treatment and can still play a role in progressive disease. Even if you’ve had previous treatment, radiation may be used in several ways, including:

• Targeting new bone metastases to relieve pain or prevent fractures
• Treating the prostate itself, even in metastatic settings, based on studies suggesting that local control may improve survival
• Salvage radiation after surgery if there are signs of recurrence

Advanced techniques such as intensity-modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) allow for precise targeting of tumors while minimizing damage to surrounding tissue.

Questions To Ask Your Doctor

• What are my options for prostate cancer that is progressing?
• Can we weigh the risks vs. benefits of the possible treatment approaches?
• How will I be monitored after treatment?
• What can we do if the first treatment is unsuccessful?

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