Post-Treatment Monitoring

Monitoring of patients after treatment involves following patients for adverse effects of treatment and checking patients for cancer recurrence. Some background information on how outcomes in cancer surgery are described may be helpful and can be found here. The risk of disease recurrence is best described as a probability at a specific time point after treatment. Management of complications can be found here.

 

In general, the simplest way to check for cancer recurrence is by checking a PSA.

 

Important Definitions

Biochemical recurrence = PSA recurrence after treatment for prostate cancer

Clinical recurrence = patient has symptoms of recurrent disease. e.g. bony pain, blood in the urine or urinary symptoms

 

Biochemical recurrence is almost always the earliest sign that prostate cancer has returned. A rise in the PSA will usually be detected many years before a patient will have any signs or symptoms or recurrent cancer. Clinical recurrence is when a patient actually has symptoms such as bony pain, urinary symptoms, weight loss or imaging findings of recurrence (e.g. bone scan). Because it is so unusual for patients to develop clinical recurrences in the absence of a large rise in PSA after treatment, patients should be reassurred that in the presence of a low PSA that any symptoms (such as difficulty urinating or back pain) are very unlikely to be the result of recurrent cancer. If you have questions, please see your urologist.

 

Biochemical recurrence - rising PSA after treatment - does not always lead to clinical recurrence.

 

In fact, in men who have biochemical recurrences many years after treatment and have slowly rising PSA's it is unlikley that biochemical recurrence will progress to clinical recurrence. Many men who have biochemical recurrence will not die from prostate cancer and it is usually many years before any symptoms of recurrent disease are felt in those men who ultimately progress to clinical recurrences.

 

Disease recurrence is about more than an increase in PSA after treatment - the characteristics of the increase in PSA and the context are critically important.

 

The interpretation of PSA levels after treatment is depends on multiple factors:

  1. The initial type of treatment - surgery or radiation and if hormone treatment was used. 
  2. Characteristics of the PSA rise
    1. Timing: earlier increases (or the abensce of a drop in PSA to an undetectable level) and any rise in PSA within the first 2 years after surgery are more serious
    2. Rate of rise ('PSA kinetics'): more rapid rises (faster doubling times) are more serious. 
  3. Initial disease characterisitics: the initial PSA, stage and grade are important as are additional features gleaned during treatment such as the status of the surgical margins and lymph nodes.

 

The main reason why different definitions are required is that radical prostatectomy removes the entire prostate whereas radiation (external beam and brachytherapy) leave the prostate in place. The remaining prostate tissue will release small amounts of PSA even if cancer is not present. The use of hormonal therapy can also affect interpretation of the PSA levels post-treatment - and can mask residual cancer. As a result, it is virtually impossible to compare treatment outcomes using biochemical recurrence as the yardstick. It has been estimated that if the same definition which is used for biochemical recurrence following radiation therapy were applied to men having undergone prostate surgery, the time to biochemical recurrence would be delayed for 5 years when compared to the more stringent criteria used for biochemical recurrence following radical prostatectomy. That is, biochemical recurrence results for radical prostatectomy at 5 years should probably be compared to 10 year radiation results. The development of clinical recurrence and/or death related to prostate cancer are much better yardsticks for comparing treatments. Ideally, we would have well designed randomized controlled trials to sort out the best treatments for different kinds of patients.

 

PSA levels tend to rise logarithmically with disease recurrence and consequently changes are often described as 'doubling times' (e.g. the time it takes to change from 1 to 2 to 4 to 8 to 16 and so on). The time that the PSA takes to double in value tends to be relatively consistent - that is, the time for a PSA to go from 1 to 2 is similar to what it takes to go from 8 to 16 or 32 to 64. It can, however, take 2-3 years of measurements to assess the doubling time and assessment of doubling times at very low levels of PSA (especially less than about 2 mcg/L) can be challenging because of background noise. Rapid doubling times are defined as anything faster than 6-12 months. This is associated with more rapid progression of disease.

 

In many cases, the initial disease characteristics are the most important factor in disease recurrence. Patients who had higher grade disease, higher volumes of disease, higher PSA's and higher stages are more likely to develop recurrence. In addition, for men whom have had surgery, the presence of positive surgical margins (especially those that are unlikely to be an artifact of specimen preparation and surgical handling) are more likely to have disease recurrence. In this context, even low levels of detectable PSA can be a sign that a clinically significant recurrence is likely to occur - whereas the same level of PSA in a man who had low risk disease may not be as significant. It is important to note that it is the disease that determines the risk of PSA recurrence and treatment failure and not the other way around. Stated another way, high risk disease and recurrence and progression usually go hand in hand; most men with low risk disease do not develop recurrence and if they do have a rising PSA it is less likely to progress to anything serious.

 

Monitoring for Recurrence after Treatment of Localized Prostate Cancer

 

Patients can check their PSA levels online. If you do, please note that the 'reference ranges' do not apply to men who have had treatment. An undetectable PSA is any level which is preceeded by the 'less than' or '<' symbol. This is good - your PSA is below the threshold of detection. Note that this is different than having a PSA of zero since it is not currently possible to measure PSA to that level.

 

The definitions of biochemical recurrence continue to change as we learn more about the patterns of prostate cancer recurrence. Because not all rises in PSA are associated with clinical recurrence, definitions attempt to strike a balance between detecting cancer early enough so that effective salvage therapy can be given and 'overcalling' recurrences which would never cause the patient any problem in the future. The generally accepted definitions for biochemical recurrence are listed below.

 

The definitions of biochemical recurrence are not intended to be used as a trigger for specific additional treatment. They are levels at which further discussion regarding a change in management should occur.

 

After Radical Prostatectomy After Radiation

PSA > 0.2-0.4 mcg/L

 

While biochemical recurrence can occur any time after surgery, the most important ones occur earlier, especially in the first couple of years. It is important that you continue to see your Urologist after surgery. PSA is usually measured

  1. 3 months after surgery
  2. 6 months after surgery
  3. 12 months after surgery
  4. 18 months after surgery
  5. 24 months after surgery
  6. Every year afterwards

Nadir PSA +2 mcg/L

'Increase in PSA of 2 mcg/L above the lowest PSA recorded"

 

PSA is usually measured every 6 months or so after completion of treatment with transition to yearly checks after a few years. The frequency of checks depends on the characteristics of the initial tumor.

 

What if you have had a radical prostatectomy and the PSA is less than 0.2 mcg/L, but it is not undetectable? This is a relatively common scenario and requires an explanation of the improvements in the sensitivity of the PSA test for very low levels of PSA. When PSA was initially introduced in the late 1980's, the lowest PSA that was detectable was 0.2 mcg/L. With improvements in technology, in 2011 PSA's as low as 0.002 mcg/L can be detected - 100 x lower than was previously detectable. Improvements in measurement have outstripped our ability to interpret such low levels. These low levels may result from a number of different causes, including residual benign prostate tissue, PSA secreting glands in the urethral stump or bladder neck and persistent or recurrent prostate cancer. In some cases, low levels above the threshold of detection but below the definition of biochemical recurrence wil lbe noted. Management is contextual and should be discussed with your urologist.

 

Men with intermediate and high risk cancer who undergo radiation are also given medications to lower testosterone - such as LHRH agonists and antiandrogens (e.g. Zoladex, Leupron, Eligard, Suprefact, Casodex) . These medications can cause the PSA to remain low even in the presence of viable cancer. Therefore, the PSA should be interpreted with caution under these circumstances.

 

Monitoring for Recurrence after Treatment of Advanced or Metastatic Prostate Cancer

 

There are several treatments for postate cancer which are capable of putting prostate cancer into remission - often for a very long time. Unfortunately, there are none that are capable of curing prostate cancer. In general, the following PSA characteristics are desireable and associated with better outcomes

 

  1. Low absolute levels of PSA. Clinical symptoms of prostate cancer are rare when the PSA is less than 5-10 mcg/L and uncommon unless the PSA is above 30 mcg/L.
  2. PSA remains low.
  3. If PSA is rising, it rises slowly.
  4. PSA decreases in response to treatment.

On the Web

General Prostate Cancer Web-Resources

Memorial Sloan-Kettering Cancer Center in New York is an excellent resource for information on prostate cancer. Balanced, unbiased discussions of the disease, including discussion regarding some of the controversies in prostate cancer.

General Information on Cancer

UNDERSTANDING CANCER - Metrovan Urology info on the principles of diagnosis, staging, prognosis and more.

American Cancer Society

BC Cancer Agency: Good general website from the British Columbia Cancer Agency. Has contact information on locations.

National Cancer Institute: Excellent source of understandable and mainly unbiased information. Several very good brochures on every stage of prostate cancer.

National Comprehensive Cancer Network: peer-reviewed expert content/prostate cancer guidance on evidence-based cancer diagnosis and management. Best for Prostate and Kidney Cancer. The most in-depth information is located in the physician section and requires registration.