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Managing Recurrent Disease

What to Expect Questions For The Doctor | Glossary

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.


An ongoing challenge for men on active surveillance is deciding when to stop it and proceed with one of the other options for local therapy. Some doctors may suggest treatment when the PSA reaches a certain level, while others will suggest a new biopsy to see if the Gleason score has changed or more cancer is present. Some men will decide they want therapy for any rise in the PSA because they no longer can cope emotionally with the anxiety. At present, there is no uniform or best approach, which means the decision should be individualized.


After a radical prostatectomy, the PSA should become undetectable, defined as less than 0.2 ng/ml. A 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 to that level, it is not always dangerous. The risk partly depends on how long after surgery the PSA begins to raise, how fast it is rising and the findings on the pathology report. Although your doctor will probably order one or more of the imaging tests when the PSA is above 0.4 ng/ml, tests may not be sensitive enough to find small amounts of cancer to identify where the cancer is located. 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 soon after prostatectomy helps about 1 out of 11 men live longer, similar evidence is not available for salvage radiation. 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 and second, the radiation may not kill all the cancer cells in the prostate bed. Radiation for a rising PSA after prostatectomy is most effective when the PSA is less than 1 ng/ml. Unfortunately, the scans usually cannot find cancer at that low PSA level. If the scans are negative, radiation still may help. The best candidates for salvage radiation are determined by reviewing the pathology report from the radical prostatectomy. They are men with tumor at the edge of the prostate gland, extracapsular disease (cancer outside the prostate capsule) or those with cancer in 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. Other options include some form of hormone therapy, although it remains unclear whether 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.


Men may go on hormone therapy in several situations including when the cancer is localized and other therapies are not appropriate, when the cancer recurs after surgery or radiation, or when the cancer has spread to other parts of the body. Most doctors believe that if a man has been treated with hormone therapy for cancer that has spread outside the prostate, it should not be discontinued when the PSA begins to increase because it still provides a benefit. In that case, additional hormone therapies should be added and the number of options is increasing. The choices include a first generation anti-androgen ((bicalutamide (CASODEX), flutamide (EULEXIN), and nilutamide (NILANDRON or ANANDRON)) or one of the newer agents ((enzalutamide (XTANDI), Abiraterone acetate (Zytiga) combined with prednisone, or apalutamide (ERLEADA). Recently, the FDA approved another drug called darolutamide (NUBEQA) for men with a rising PSA on hormone therapy without evidence of metastases. Studies showed that it prolonged the time until metastastic disease but so far it is unclear if it also improves survival. Currently, studies have not determined which, if any, of these options is best or the best sequence of the various options. Another option for a rising PSA when the cancer has spread is chemotherapy using docetaxel (Taxotere) plus prednisone, which is usually delayed until after one or more of the hormonal agents have been used. Treatment options for cancer that is in the bones include focal radiation to painful areas or bones at risk for fracture or drugs that reduce the risk for a bone-related event such as a fracture or pain. These include bisphosphonates (zoledronic acid (ZOMETA) or denosumab (XGEVA). Another option for painful bone metastases is Radium-223 (XOFIGO), an injectable form of radiation that has been shown to increase survival. Other systemic radiation therapies such as samarian-153 (Quadramet®) and strontium-89 (Metastron®) can reduce bone pain caused by metastases.


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.