Castrate Resistant Prostate Cancer
Eventually, almost all metastatic prostate cancers become resistant to androgen ablation. In patients with castrate serum testosterone levels , castrate-resistant prostate cancer is defined as 2-3 consecutive rises in PSA levels obtained at intervals of greater than 2 weeks and/or documented disease progression based on findings from computed tomography scan and/or bone scan, bone pain, or obstructive voiding symptoms.
Rarely, a rise in PSA may reflect failure of LHRH treatment to control testosterone secretion, rather than the development of castrate-resistant disease. Therefore, the testosterone level should be measured when the PSA rises. If the serum testosterone level exceeds castrate levels, changing the antiandrogen therapy may drop the PSA and delay the need for other therapy.
Prior to the development of the most recent therapies, the median time to symptomatic progression after a rise in the PSA level of more than 4 ng/mL was approximately 6-8 months, with a median time to death of 12-18 months. Since then, however, the latter figure has increased.
Little information is available about the impact of maintaining hormone suppression when androgen-independent progression occurs, but the general consensus among specialists is that the treatment should continue. The reasoning is that tumor cells are still hormone sensitive and may grow faster if the testosterone is permitted to rise.
Docetaxel
What Factors Increase The Chance Of Cancer Recurrence
The likelihood of metastasis occurring increases with higher grade and stage of the cancer as the more aggressive and developed the cancer is, the higher the chance of it breaking out of the prostate. More specifically:
- High Gleason grades
- High clinical stages
- Positive surgical margins .
However, most prostate cancers are cured with surgery. As an example, using my results from operations performed on over 2,300 men with a variety of stages and grades, 96.3% of operations resulted in full cancer cure. Some combinations of minor prostate cancer had a 100% cancer cure rate, but the higher you go, the lower the full cancer cure rate.
The commonest sites of recurrence of prostate cancer following surgery are:
- the prostate bed 80% of recurrence cases
- lymph nodes 15% of cases
- bones 5% of cases.
Continuous Versus Intermittent Adt
Once the decision to use ADT has been made, a second controversial decision for BCR prostate cancer patients is whether to use intermittent or continuous administration of androgen deprivation. Intermittent androgen deprivation is a cyclic process in which induction treatment continues until maximal PSA response. ADT is then temporarily withdrawn until serum PSA levels rise to a predetermined level, agreed upon by patient and physician , at which point ADT is reinitiated. IAD can allow testosterone levels to recover during each off-treatment cycle, lessening sexual dysfunction and loss of bone mass often associated with continuous androgen deprivation.29 The lower cost and improved quality of life, combined with noninferiority of IAD in overall survival, have led many patients to choose IAD for treatment of BCR prostate cancer.
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An Emerging Treatment Option For Men With Recurring Prostate Cancer After Radiation Therapy
- By Charlie Schmidt, Editor, Harvard Medical School Annual Report on Prostate Diseases
Prostate cancer is often a multifocal disease, meaning that several tumors can be present in different parts of gland at the same time. Not all of these tumors are equally problematic, however. And its increasingly thought that the tumor with the most aggressive features called the index lesion dictates how a mans cancer is likely to behave overall. That concept has given rise to a new treatment option. Called partial gland ablation , and also focal therapy, it entails treating only the index lesion and its surrounding tissues, instead of removing the prostate surgically or treating the whole gland in other ways. Emerging evidence suggests that PGA controls prostate cancer effectively, but with fewer complications such as incontinence.
In February, researchers at Memorial Sloan Kettering Cancer Center in New York published findings that could pave the way for focal therapy in men with reoccurring prostate cancer. They focused specifically on men whose cancer had returned three to four years on average after initial treatment with radiation.
Their findings, while preliminary, suggest that MRI and biopsy results can allow doctors to select which patients with reoccurring prostate cancer might be eligible for PGA. The research was headed by Dr. Gregory Chesnut, an MSKCC urologist.
What Is Prostate Cancer Recurrence
Prostate cancer recurrence is the return of cancer after treatment and a period when no cancer activity could be detected. Local therapies with radical prostatectomy or radiation therapy are the two main ways to eliminate localized prostate cancer.
Both options are definitive treatments because they can cure prostate cancer altogether. However, local treatments are ineffective if cancer has spread outside the prostate gland. Here, other types of treatment are needed to target cancer cells located in other parts of the body.
Cancer cells remain after curative treatments because of positive surgical margins or metastasis if the disease is more advanced than initially thought. Prostate cancer cells can start to grow again from these sites.
Treatment relapse increases the possibility of developing advanced incurable disease that needs complex treatment decisions to manage. However, current clinical methods for treating recurred prostate cancer can result in both over-treatment and under-treatment due to a lack of adequate biomarkers to predict response.
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Cancer That Is Thought To Still Be In Or Around The Prostate
If the cancer is still thought to be just in the area of the prostate, a second attempt to cure it might be possible.
After surgery: If youve had a radical prostatectomy, radiation therapy might be an option, sometimes along with hormone therapy.
After radiation therapy: If your first treatment was radiation, treatment options might include cryotherapy or radical prostatectomy, but when these treatments are done after radiation, they carry a higher risk for side effects such as incontinence. Having radiation therapy again is usually not an option because of the increased potential for serious side effects, although in some cases brachytherapy may be an option as a second treatment after external radiation.
Sometimes it might not be clear exactly where the remaining cancer is in the body. If the only sign of cancer recurrence is a rising PSA level , another option for some men might be active surveillance instead of active treatment. Prostate cancer often grows slowly, so even if it does come back, it might not cause problems for many years, at which time further treatment could then be considered.
Factors such as how quickly the PSA is going up and the original Gleason score of the cancer can help predict how soon the cancer might show up in distant parts of the body and cause problems. If the PSA is going up very quickly, some doctors might recommend that you start treatment even before the cancer can be seen on tests or causes symptoms.
Thinking About Taking Part In A Clinical Trial
Clinical trials are carefully controlled research studies that are done to get a closer look at promising new treatments or procedures. Clinical trials are one way to get state-of-the art cancer treatment. In some cases they may be the only way to get access to newer treatments. They are also the best way for doctors to learn better methods to treat cancer. Still, theyre not right for everyone.
If you would like to learn more about clinical trials that might be right for you, start by asking your doctor if your clinic or hospital conducts clinical trials.
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Just One Weapon Against Cancer
Before treatment with PLUVICTOTM is recommended, patients undergo a PSMA-PET/CT scan to determine if their tumor contains the PSMA target. If it does not, PLUVICTOTM would not be appropriate, explained Dr. Wong. At Duke we treat you as an individual. Each case is discussed among a multidisciplinary team of surgeons, radiation oncologists, medical oncologists, radiologists, and nuclear medicine specialists. He emphasized that PLUVICTOTM is not for everyone and is just one weapon in the arsenal for fighting cancer. Our team will determine how and if this new option fits in with all the others we offer.
Duke can provide PLUVICTOTM and other novel treatments because it is a Comprehensive Cancer Center with the latest advances in diagnosing and treating prostate cancer. Duke is also recognized as a Comprehensive Radiopharmaceutical Therapy Center of Excellence, which requires strict adherence to safety and treatment criteria that ensures the best care for patients.
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Assessing Metastases And Local Recurrence
Once BCR has been detected, it is important to try to establish whether this represents local recurrence or disseminated disease, or both, in order to guide subsequent treatment decisions. Importantly, metastatic disease must be acceptably ruled out before subjecting patients to local salvage treatment, owing to the significant morbidity associated with such treatments. Regardless of whether BCR is detected post-RP or post-RT, the same principles of imaging apply.
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Traditional Treatment Options For Prostate Cancer Recurrence
For patients who initially had radiation, doctors used to recommend removing both the prostate and the bladder after a recurrence, Dr. Greenberg tells us. The problem was that the prostate after radiation was kind of scarred, and it was hard to remove it without damage to the bladder, says Dr. Greenberg. It was a very morbid operation and patients would basically have to use a catheter for the rest of their life.
And for those who had prostate surgery? Normally, if a patient had surgery, we would add radiation after, but it wasnt the kind of radiation that we use now, says Dr. Greenberg. We used bigger fields that included the whole prostate bed and it took almost eight weeks of treatment.
The Natural History Of Bcr
Although a rising PSA level universally precedes metastasis and PCa-specific mortality , BCR is not a surrogate for PCa-specific mortality or OS, and may pre-date local recurrence or metastasis by several years. On average, BCR precedes the appearance of clinical metastasis by 8 years after RP and by 7 years after primary definitive RT .
The natural history of BCR and the risk of subsequent metastasis may be predicted by pre- and post-treatment clinical features . These prognostic indicators are used as a means to assess the patients level of risk, and therefore, help physicians to determine whether to initiate early treatment or to adopt a strategy of active surveillance. Treatment decisions following BCR must balance the risk of metastatic disease or death with the impact of treatment, and necessitate involvement of a multi-disciplinary team, as well as informing the patient of the potential for a prolonged natural history of PSA-only recurrence .
Table 1.
Pre- and post-treatment prognostic factors in PSA-recurrent prostate cancer
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How Does My Doctor Choose A Treatment
Once you know that your cancer has returned, you and your doctor will choose a treatment. A few factors go into making the decision, including:
- Which type of treatment you had before
- How aggressive your cancer is
- Whether, and where, it has spread
- How much time has passed since your first treatment
- How quickly your PSA level is rising
- Your overall health
If Your Prostate Cancer Has Spread
If cancer has spread to other parts of your body it cant be cured. This is advanced prostate cancer. Treatment can help to control the cancer and your symptoms. This might be:
- hormone treatment to lower your testosterone levels
- bisphosphonates to help with bone pain
- radiotherapy to particular parts of the skeleton
- radioactive liquid treatment radiotherapy , such as radium-223
If hormone therapy is no longer working for you, you might have:
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Advanced And Recurrent Cancer
If prostate cancer spreads beyond the prostate, it usually spreads to the bones. This is called secondary cancer or metastasis. Cancer in the bones can be painful and might lead to bone fractures or other complications.
Treatment to prevent prostate cancer from spreading to the bones, or to relieve symptoms associated with secondary cancer in the bones may include:
- bisphosphonates, which can help strengthen bones, and is also used in men who have had hormone therapy
- external beam radiotherapy, which can help relieve bone pain
- monoclonal antibodies such as denosumab injected under the skin to help protect bones
- corticosteroids, which can relieve pain and lower PSA levels
- radiopharmaceuticals , which are injected into the body and settle in areas of damaged bone, where they can destroy cancer cells
- pain medications.
Prostate cancer may recur after treatment. The cancer can recur in the prostate or somewhere else in the body, and is classified as local or distant .
If prostate cancer has come back, the type of treatment you have may depend on how your primary cancer was treated. You might have the same treatment again, or a different treatment.
Good Prostate Cancer Care
Your MDT will be able to recommend what they feel are the best treatment options, but ultimately the decision is yours.
You should be able to talk with a named specialist nurse about treatment options and possible side effects to help you make a decision.
You should also be told about any clinical trials you may be eligible for.
If you have side effects from treatment, you should be referred to specialist services to help stop or ease these side effects.
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How Is A Recurrence Detected
After prostate cancer treatment, you will go for medical check-ups every few months as determined by your doctor. At each follow-up appointment, your doctor will order a blood test to measure PSA levels. This test helps your doctor detect a cancer recurrence. You will also be examined. New symptoms should be reported to the doctor, as these may prompt other testing.
When PSA test results suggest that the cancer has come back or continued to spread, X-rays or other imaging tests may be done, depending on your situation and symptoms. Your doctor may use a radioactive tracer called Axumin with a PET scan to help detect and localize any recurrent cancer so that it could be biopsied or treated.
Your doctor may also use a new drug called Ga 68 PSMA-11 in the scan which binds to PSMA-positive prostate cancer lesions in the tissues of the body so they can be targeted for treatment.
How To Handle A Relapse After Treatment For Prostate Cancer
Am I going to die? This is the first question a patient usually asks me when a follow-up blood test reveals that his prostate-specific antigen level has risen after he has already undergone treatment for prostate cancer . The fear is understandable: When PSA levels rise to a certain threshold after prostate cancer treatment, the patient has suffered what is known technically as a biochemical recurrence, sometimes also referred to as a biochemical relapse or stage D1.5 disease. Whatever term is used, it means that prostate cancer remains within the prostate after radiation therapy, that it survived outside the excised area after radical prostatectomy, or that it has reappeared in metastatic form in other tissues and organs. In most cases the cancer remains at a microscopic level, and many years will pass before any physical evidence of it is detectable on a clinical exam or any abnormalities are seen on a bone scan or CT scan.
Thats usually of small comfort to the patient whose PSA has risen. Its emotionally traumatic to go through treatment for prostate cancer, thinking it is cured, and then learn that it might have come back. For many men, its as if theyre dealing with another diagnosis of cancer, except this time its much worse because there is less likelihood of getting cured. A mans confidence and sense of safety may be shattered, especially because the popular misconception is that when prostate cancer recurs, it is deadly.
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Why Your Decisions Matter
In the past, doctors sometimes made decisions without talking with patients. Today, the situation is different. Your health care team wants to know your concerns and answer your questions. They also believe that you have the right to make your own decisions. Working with your health care team to make a treatment plan can help you feel more in control.
Radiation Therapy Plus Androgen Ablation Therapy
Androgen ablation has been shown to improve survival in men with localized disease who are treated with external radiation. DAmico et al reported higher overall survival with the combination of radiation therapy and 6 months of ADT in men with intermediate-risk prostate cancer. Median follow-up was 7.6 years.
A study by Jones et al found that for patients with stage T1b, T1c, T2a, or T2b prostate cancer and a PSA level of 20 ng/mL or less, short-term ADT increased overall survival in intermediate-riskbut not low-riskmen. The 10-year rate of overall survival was 62% with combination therapy, versus 57% with radiation therapy alone 10-year disease-specific mortality was 4% and 8%, respectively. In this study, ADT was given for 4 months, starting 2 months before radiation therapy.
In a study by Pisansky et al of 1489 intermediate-risk prostate cancer patients, disease-specific survival was not significantly different whether total androgen suppression was given for 8 weeks or for 28 weeks prior to radiation therapy. Patients in the study were randomized to 8 or 28 weeks of TAS with LHRH agonist, along with a daily nonsteroidal antiandrogen, prior to radiation treatment. This was followed in both groups by an additional 8 weeks of androgen suppression, administered concurrently with radiotherapy.
Taken together, radiation therapy is generally given for 4-36 months, depending on the risk group of the patient.
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