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Managing Recurrent Disease

What to Expect Questions For The Doctor | Glossary

Although the percentage of men who are cured of their prostate cancer is very high, some will develop a recurrence. If you or your loved one has just been told by the doctor that prostate cancer has returned or that it is not responding to therapy, you probably have a million questions: Why isn’t the treatment working? What does this mean? What are the options for treating my current situation? You may be feeling anger, frustration, and even fear, but it is incredibly important that you work closely with the doctor to consider your options.

This section outlines the treatment options available to you or your loved one if prostate cancer has come back after receiving therapy or is not responding to hormone therapy. It also includes questions you may want to ask the doctor.

What to Expect

Although the percentage of men who are cured of their prostate cancer is very high, some will develop a recurrence. This will first be indicated by a rise in the PSA level usually without any other symptoms. Before treatment can be recommended, your doctor will order additional tests to determine if the prostate cancer has metastasized. Possible tests include a CT scan, MRI, bone scan, Prostascint scan and/or a PET scan.


The first indication that the cancer is still present in the body is the PSA will begin to rise. However, in some cases even a rise in the PSA does not mean that cancer has returned. If a man has undergone a radical prostatectomy, the PSA should drop to an undetectable level of less than 0.2 ng/ml. A small, slow increase could mean that some prostate tissue was accidentally left behind and it too can produce PSA. If a man has had radiation, a small increase in the PSA in the first two years could be a PSA bump, which is not caused by recurrent cancer. The PSA then gradually goes back down. A rise in the PSA after cryosurgery or HIFU could mean that normal prostate cells are still alive and they produce PSA. The bottom line is you should not assume that a rise in your PSA is definitely recurrent cancer.

Nevertheless, a rise in the PSA does need careful evaluation. The first thing most doctors will do is wait a few more weeks and repeat the PSA to confirm that it is real. Sometimes incorrect readings do occur. If the increase is confirmed, the next step is to conduct tests that may include a CAT scan of the abdomen and pelvis, a bone scan, a PET scan and in some cases a biopsy of the prostate bed if the prostate was removed or of the prostate gland if the previous treatment did not include a prostatectomy. The treatment options depend on the test results. One limitation of all of these scans is they have difficulty finding small amounts of cancer, which usually is the case when the PSA is less than 5 ng/ml. Therefore, if a test does not show any clear evidence of cancer then a conservative option is to have the patient return in a few more months for a repeat PSA and possibly a repeat of the tests. No definite guidelines exist for when the tests should be repeated. The reason to select this option is to avoid unnecessary treatment. For those men who want a more aggressive approach, the various treatment options following each local therapy are described below.


After a radical prostatectomy, the PSA should become undetectable by one month. A subsequent rise above 0.4 ng/ml could mean that the cancer has recurred either in the prostate bed or to other parts of the body or to both locations. Men should be aware that even if the PSA does increase above that level because of cancer, it is not always dangerous. The risk depends on how long after surgery the PSA began to raise, how fast it is rising and the findings from the surgical pathology report. Although your doctor will probably order one or more of the imaging tests when the PSA is above 0.4 ng/ml, they are highly likely to be negative even when the PSA is 5 ng/ml. Therefore the doctor will not know exactly where the cancer cells are located making the treatment decision difficult. The options for treating a rising PSA include radiation to the prostate bed, drugs that affect the male hormones or both. Although studies have shown that adjuvant radiation given very soon after prostatectomy helps about 1 out of 11 men live longer, similar evidence is not available for salvage radiation, defined as a delay from the time of surgery until there is a suggestion of recurrent disease. It does, however, appear to lower PSA in some of the men. There are two reasons why the radiation may not help. First, some cancer cells may have already spread to other parts of the body that are not affected by the radiation. Secondly, the radiation may not kill all the cancer cells in the prostate bed. The higher the dose of radiation administered the more likely any cancer cells will be killed, but it also raises the chance for side effects. It is important to discuss with the radiotherapist the dose that will be used and the odds of developing side effects. Studies have found that better results occur with salvage radiation if is given when the PSA is less than 1 ng/ml. Since scans are rarely abnormal at that low value, the radiation is often recommended based on the findings at the time of the prostatectomy. The best candidates are those men with cancer at the surgical margin and/or into the seminal vesicles. Since the frequency of side effects from radiation is low, men may choose this aggressive treatment approach even though the odds of benefitting are unclear. Another option is androgen deprivation therapy (see section on local therapy), either with an LHRH agonist or antagonist, or a first generation anti-androgen. If selected, the treatment can either be given continuously or intermittently. Although it will lower the PSA, no studies have proven that it will improve survival.


A rising PSA after either seed implantation (brachytherapy) or external radiation also presents a challenge. A spike in PSA called a PSA Bounce can occur within 1-2 years, which is not caused by a cancer recurrence. The PSA eventually goes back down. The definition of a recurrence after radiation therapy is somewhat controversial. Currently, the most widely accepted definition is a rise of 2 ng/ml above the nadir, or the lowest level achieved after radiation was completed. Similar to a radical prostatectomy, a rising PSA after radiation therapy is not always dangerous. It also depends on the interval from the radiation to the recurrence and the rate of rise of the PSA. Treatment options include hormone therapy, salvage prostatectomy, cryotherapy and brachytherapy. Some physicians are also using HIFU (high intensity focal ultrasound but its use is currently limited in the U.S. The benefits for each of these is not well defined and each comes with significant risks for side effects. Before considering a treatment, a prostate biopsy should be performed. None of the local therapies makes sense unless a biopsy shows cancer is present in the radiated prostate tissue. Even then, survival may not be improved because there also may be undetectable prostate cancer cells in other parts of the body. Because surgery after radiation is very challenging, men who are considering this treatment should seek out a surgeon who has significant experience with salvage prostatectomy. Similar to a rising PSA after surgery, men can be offered one of the hormone therapies options; although here too, the impact on survival is unclear. However, In almost all cases the PSA will go down.


Similar to radiation therapy, a rise in the PSA after cryotherapy requires a prostate biopsy to determine if cancer is still present in the gland or has spread elsewhere in the body. If cancer is present in the prostate and the other scans are negative, then local therapy can be offered including a salvage prostatectomy, or radiation therapy. These treatments have more side effects compared to men who have not had cryotherapy and patients are advised to seek out urologists that have experience with this condition. Alternatively, any of the hormonal therapy agents can be considered.


A prostate biopsy is again necessary to determine whether cancer remains. If it is and the scans are negative then the options include radical prostatectomy, radiation or cryotherapy but HIFU can also be repeated. The long-term impact of these options is unclear. Also, side effects from each of the options are more common compared to men not having had this procedure first. No studies have proven if one is better. Hormone therapy is again an option.


Men may have received an LHRH agonist or antagonist for different reasons. It could have been as a primary treatment for localized disease, for a rising PSA after any of the local therapies or if the cancer had spread to other parts of the body. Regardless, a CAT, MRI, PET and/or bone scan should be done to determine if the cancer has appeared in other parts of the body. If it has not spread outside the prostate then the next option would be a first generation anti-androgen [(bicalutamide (CASODEX), flutamide (EULEXIN), or nilutamide (NILANDRON or ANANDRON)) or one of the newer anti-androgens (enzalutamide [XTANDI], Abiraterone acetate [Zytiga] combined with prednisone, apalutamide [ERLEADA] or darolutamide [NUBEQA]. Presently, doctors are not sure which one of these should be selected first. In all cases, the LHRH agonist or antagonist should be continued because it still provides a benefit.

If the studies show that the cancer has metastasized, then chemotherapy with docetaxel (Taxotere) plus prednisone is the next option along with a bone-protective agent [zoledronic acid {Zometa} or denosumab (XGEVA}] if the cancer has spread to the bones.


Another option for any man with a rising PSA is to participate in a clinical trial. Clinical trials offer an opportunity to receive a new treatment years before it is made available as an FDA-approved treatment for prostate cancer. Although it is not known whether a particular treatment will be successful, a participant will be cared for and closely monitored by a team of experts during the trial. The doctor can explain more about specific clinical trials that are going on now and the risks and benefits of participating in a clinical trial. Since not all doctors participate in these trials, patients may need to do their own investigation to find a suitable study. The best place to find information is the National Cancer Institute website.

Questions For The Doctors

The following is a list of questions to ask the doctor if you or your loved one has been diagnosed with hormone-resistant prostate cancer or has experienced a relapse. It may be worthwhile to audio record your conversation with your doctor so that you can review the answers to each question and be able to make informed decisions about treatment options.

  • Has the cancer spread and if so, how far?
  • What are the treatment options?
  • What are the benefits and risks of the type of therapy you are recommending?
  • What side effects are associated with the type of therapy that you are recommending?
  • Are there other treatment options available?
  • Can you refer us to a colleague or another expert for a second opinion?
  • What can I do to improve the success of my or my loved one’s therapy?
  • What kind of follow-up can we expect after treatment?
  • What are the short-term and long-term side effects of treatment?
  • Where can I find out more about hormone-resistant prostate cancer and the treatment options?
  • What can you tell me about new experimental treatment options?
  • Should I or my loved one consider participating in a clinical trial?

Read a list of questions for urologists, radiation oncologists and medical oncologists , as compiled by an experienced prostate cancer patient.

You can also post questions for physicians and join discussions on specific topics about prostate cancer on the Inspire online prostate cancer community.