Prostate Cancer Recurrent

Recurrent prostate cancer means the cancer has returned after treatment. Up to 40% of men treated for prostate cancer will experience a recurrence, but many effective treatment options are available to control the disease and extend life.

Table of contents

• Understanding Prostate Cancer Recurrence
• Biochemical Recurrence
• Risk Factors for Recurrence
• How Recurrence is Detected
• Where Cancer Can Return
• Treatment Options
• Coping with Recurrence

Understanding Prostate Cancer Recurrence

Recurrent prostate cancer is cancer that comes back after a period when no cancer cells could be detected in the body^[1]. The completion of prostate cancer treatment can bring both relief and worry. When caught early, initial treatment may mean you are considered free of disease. Most men diagnosed with prostate cancer will live cancer-free for years, and some even the rest of their lives^[1].

Unlike most cancers, prostate cancer can recur many years after the disease was thought to be cured by prostate radiation or surgery. In one large study of nearly 2,000 patients who had surgery, 25% of men with recurrence had their first sign of disease return occur five years or more after surgery^[6]. The time to a clinically meaningful recurrence can be even longer. In the same study, it took an additional median of eight more years for a metastatic recurrence after the initial PSA rise^[6].

Fortunately, the five-year survival rate for men with localized prostate cancer is nearly 100%. However, up to 40% of men will experience a recurrence^[1][5]. A fear of recurrence is normal and reasonable for all cancer survivors^[1].

Biochemical Recurrence

When PSA (prostate-specific antigen) levels rise to a certain threshold after treatment, this is called biochemical recurrence^[1]. Biochemical recurrence means that the only evidence of cancer recurring is a laboratory value—a rising PSA. No spots of cancer are seen on scans, either in the prostate area or elsewhere in the body^[4].

After prostate cancer treatment, PSA levels should drop significantly. After surgical removal of the prostate, PSA should drop to zero, and after radiation therapy, PSA levels usually drop to a stable and low level^[8]. If PSA levels begin to rise at any time after treatment, a local or distant recurrence may be occurring^[8].

The definition of biochemical recurrence differs based on the initial treatment. After surgery, it is defined as at least two PSA values that are 0.2 ng/mL or higher^[6]. After radiation therapy, the Phoenix criteria define it as an increase in PSA of at least 2 ng/mL above the postradiation PSA nadir (lowest point)^[6].

Patients with a rapidly rising PSA (doubling time of approximately 9 months or less) can be considered to have “high risk biochemical recurrence.” They are at greater risk for developing metastases and for death from prostate cancer^[4].

Risk Factors for Recurrence

Several factors can point to a higher likelihood that prostate cancer will recur after treatment:

• Lymph node involvement: Men who have cancer cells in the lymph nodes in the pelvic region may be more likely to have a recurrence^[8].
• Tumor size: In general, the larger the tumor, the greater the chance of recurrence^[8].
• Gleason score: The higher the grade, the greater the chance of recurrence^[8].
• Disease stage at initial diagnosis: The likelihood of recurrence is higher the more advanced the disease was when detected^[7].
• Time between diagnosis and treatment: More time between diagnosis and treatment increases recurrence risk^[7].

Recurrence may occur because the cancer was understaged (more extensive than originally estimated), graded too low (higher Gleason scores than the pretreatment biopsy showed), or both. These issues have been discovered in up to one-third of pathology studies of the entire prostate following surgery^[7].

The cancer may have been undertreated, or surgery may not have removed all of the cancer. Sometimes cancer cells may have already spread beyond the prostate before the initial treatment^[7].

How Recurrence is Detected

After prostate cancer treatment, regular medical check-ups are essential. At each follow-up appointment, your doctor will order a blood test to measure PSA levels. This test helps detect a cancer recurrence. You will also be examined, and new symptoms should be reported to the doctor^[8].

Regular PSA testing is one of the tools your treatment team will use to determine whether or not the treatment is working^[1]. Many men experience “PSA anxiety” around the time they’re due for testing, but learning to live with the inevitable uncertainty about treatment outcomes is part of the journey^[22].

Recurrent prostate cancer usually doesn’t cause symptoms unless it has spread to other parts of the body. When it does spread, you might experience trouble urinating, blood in your urine or semen, weight loss without trying, trouble getting an erection, or bone pain^[11].

When PSA test results suggest that the cancer has come back or continued to spread, imaging tests may be done. Advanced imaging tests now available include PSMA PET scans (prostate-specific membrane antigen positron emission tomography), which use a radioactive tracer to help detect and localize recurrent cancer. These newer scans are more sensitive than traditional imaging tests like bone scans, CT scans, and MRIs^[5][8].

Where Cancer Can Return

Prostate cancer can recur in different locations:

Local recurrence means the cancer has returned in or around the prostate. For men who had surgery, this would be in the tissue next to where the prostate was removed (the prostate bed). For men who had radiation, this would be in the prostate itself or in the seminal vesicles (two small sacs next to the prostate that store semen)^[8].

The cancer may also affect surrounding lymph nodes in the pelvis or lymph nodes outside this area. It can also spread to tissues next to the prostate, such as the muscles that help control urination, the rectum, or the wall of the pelvis^[8].

Distant recurrence means the cancer has traveled through the bloodstream and recurred in distant locations. This spread is called metastasis. Prostate cancer most commonly spreads to bones or other organs^[8]. The bone marrow is thought to be an important site for dormant tumor cells, given the frequency of bone metastases^[6].

Treatment Options

The following are treatment options for recurrent prostate cancer. Your healthcare team will suggest treatments based on your needs. The type of treatment you receive will depend on the treatments you’ve already had, where the cancer comes back, whether the cancer has spread, your overall health, your age and life expectancy, and your personal preferences^[9].

After Surgery

Treatment options after surgery for cancer that recurs in or around the prostate include:

• Radiation therapy with or without hormone therapy: This may be offered for prostate cancer that recurs after surgery. External radiation therapy is the type most often used. If the cancer comes back in the same area of the prostate, radiation therapy may be used to treat it. This is called salvage radiation therapy^[9][4].
• Hormone therapy (also called androgen deprivation therapy): This decreases the levels of hormones or blocks certain hormones to slow the growth and spread of cancer cells^[9].
• Watchful waiting in some cases^[9].

After Radiation Therapy

Treatment options after radiation therapy for cancer that recurs in or around the prostate include:

• Watchful waiting^[9]
• Brachytherapy: A form of radiation therapy that uses a radioactive substance placed directly into the tumor. This may be offered to treat a recurrence if external radiation therapy was first used and if the cancer hasn’t spread to other parts of the body. If the cancer was treated with external radiation therapy, this treatment can’t be given to the same area again because the radiation would do too much damage to surrounding organs^[9].
• Salvage prostatectomy: Surgical removal of the prostate gland when cancer recurs after radiation treatment. This is a highly complex procedure but often the only remaining curative option for men with recurrent prostate cancer^[12].
• Cryotherapy: This treatment uses extreme cold to kill cancer cells^[9][11].
• Hormone therapy^[9]
• High-intensity focused ultrasound (HIFU)^[9]

For Distant Recurrence

Treatment options for prostate cancer that has spread to other parts of the body include:

• Hormone therapy: This is the main treatment for prostate cancer that recurs outside of the prostate area. It may be used to treat recurrent disease after surgery or radiation therapy. If one type of hormone therapy isn’t helpful, another type may be used. Different hormone therapies may be used on their own or combined^[9].
• Chemotherapy: This treatment uses strong medicines to kill cancer cells^[9][11].
• Targeted therapy (if the cancer has a specific genetic mutation)^[9]
• Treatments for bone metastases^[9]
• Lutetium-177 PSMA therapy (Pluvicto): An advanced treatment that targets prostate cancer cells with lower side effects than many alternative treatments^[12].

Emerging Treatments

New research has shown promising results for early treatment of high-risk biochemical recurrence. For men whose PSA doubled within nine months of initial treatment, treatment with enzalutamide, an androgen receptor pathway inhibitor, has been shown to help patients live longer without their disease progressing. This medicine can be given with or without hormone therapy^[4][18][19].

Coping with Recurrence

Learning that your cancer has returned can bring back some of the same emotions you felt after your initial diagnosis. You may feel numb, frightened, confused, or angry. You may swing between a sense of helpless despair and an impulse to take immediate action. These feelings are normal^[22].

It is important to remember that although you cannot control whether your cancer recurs, you can control how much you let the fear of recurrence affect your life^[1].

The most important step you can take is to seek help as soon as you realize you could use support. Don’t go through this experience alone. Let your family, trusted friends, and your doctors and their staff know about your struggles and any mood changes^[22].

Strategies that may help include:

• Become knowledgeable: Learning about prostate cancer and your treatment options can diminish distress and enable you to make informed decisions. You will also benefit emotionally from learning how to take charge of your treatment^[22].
• Seek support: A support group can help both you and your loved ones before, during, and after treatment. Studies have shown the value of support groups in aiding decision-making, enhancing quality of life, and possibly even in prolonging life. Talking with other men whose prostate cancer was successfully treated can be tremendously reassuring^[22].
• Professional counseling: Counseling can help manage spiraling thoughts and decision fatigue^[25].
• Daily practices: Simple daily practices like a ten-minute walk, breathing exercises, or mindfulness can help steady the nervous system^[25].
• Name your worries: Many people find it helpful to name specific worries—survival, side effects, work, intimacy, finances—and share them with their care team and trusted friends or partners^[25].

Despite a recurrence, many men with recurrent prostate cancer can continue to live full lives. There are many effective treatments available that can help control the growth of cancer, manage symptoms, and extend life expectancy, without necessarily diminishing quality of life^[25].