A Patient's Guide to Managing Hormone-Refractory Prostate Cancer  

Chapter 19.  Monitoring Your Progress With Tests, Scans and Radiography
 

Learning to understand diagnostic data

One of the fastest ways to get involved in understanding and managing HRPCa is to learn the meaning of your blood tests, urinalyses, radiologic scans, and radiographic scans.  Your first tool is the book referenced in Chapter 6, Pocket Guide to Diagnostic Tests.  A second book, with more explanatory detail, is Mosby’s Manual of Diagnostic and Laboratory Tests.  Together with your medical dictionary, these references will enable you to understand the lab reports requested by your physicians. These are “must have” books if you wish to understand diagnostic testing. 

Get into the habit of always asking your doc for a copy of every report that goes into your file.  If you have a fax machine, you can ask the lab or your doc to send you copies of all tests and other reports as soon as they have been received.  Make it a practice to look at each of the test numbers; then use the references to understand their meaning.  The report usually indicates whether the result is high or low, as compared with the normal range.  Look at those numbers and attempt to determine the meaning of the abnormal level.  But, be careful, many of those abnormal numbers are not significant.  Don’t panic just because a number is slightly outside the normal range.  You will quickly come to understand which numbers are important to you.

Understanding diagnostic reports is an ongoing educational process.  This chapter will help you understand why each of the tests is done.  You will also find that a high or low value may have dozens of different potential causes.  You need to learn to look at these numbers in the context of your own disease.  For example, if you have a high alkaline phosphatase, it is more likely to be a reflection of growth of bone mets than a sign of Paget’s disease. Ask your doc, or ask the members of the on-line support list to help you understand the data that is outside the normal range. 

You will also learn to look at trends in test results.  Changes and rates of change can be as important as the numbers themselves.  In PSA and in bone scans, for example,  a single result has limited value.  Only when you get two or more results can you begin to assess what is happening.

You will also learn not to panic if a number is slightly high or low.  Most doctors “eyeball” the numbers, looking for indicators that are significantly out of line.  They also look for combinations of numbers that are out of line; you will learn these by reading and experience.  There are some variations that are potentially serious.  The Pocket Guide identifies “Panic” levels of some tests; those imply an immediate call to your doc, perhaps a trip to the emergency room.

Before long, you will be able to identify meaningful variations, while ignoring others.  You will be prepared with a set of good questions for your oncologist each time you visit.  Eventually, you may even be suggesting appropriate tests to your doc for inclusion on the test order. 

Remember, our overall strategy is to work as a member of a medical team—the more you know the more effective your team is.  Your purpose is to help the doc, not to replace him.  Warning:  interpretation of diagnostic tests is a complicated area; a little knowledge can truly make you dangerous.  We’re not doctors, and this chapter won’t make you a doctor, either.

This chapter presents the diagnostic tests that are used most commonly in the battle against HRPCa.  There are hundreds of tests available.  The tests are grouped according to the question that you wish to answer:  for example, what is the status of my cancer?  Do I have anemia?  Do I need to take Neupogen or Leukine?  Finally, the tests are presented in a schedule format that you can use as the basis for tailoring your own schedule of diagnostic tests.

What is the status of Your HRPCa?

1.  The PSA blood test (monthly) is the basic tool of managing HRPCa.  If you’ve had your prostate surgically removed, the ideal value is zero, as a reflection of the fact that there are no more prostate cells to generate PSA.  In fact there may have been some prostate tissue left behind in the surgery.  Systemic cancer cells are also producing PSA.

Trends are more important than the absolute PSA value, although you never want to let this indicator run free.  A value in the area of 100 and above indicates a high risk of metastatic growth.  The lower value is best, but keeping the value down in the range of 15-25 or below seems to be a workable strategy that can be maintained for years.  Keep a graph (semi-logarithmic) of these values as a visual indicator of the effectiveness of the various treatments.    The graph will also help you differentiate between trends that indicate cancerous growth and abnormal variations that indicate testing errors, infections or prostatitis.

2.  The alkaline phosphatase (ALP) blood test (monthly) is an indicator of growing bone metastases.  A greatly elevated value indicates possible metastatic growth.  However, ALP enzyme can be produced either in the liver or the bone, so the general test is indicative, not definitive.  It is possible to differentiate between the sources of the ALP, but not necessary if you know that you don’t have liver problems.

3.  The bone scan (BS) is a radiologic test (semiannually) that indicates growth of bone metastases.  The purpose of the bone scan is to verify the blood tests and to double check whether bone mets are growing.  This test will reveal bone tumors of any origin.  (Mosby’s has an illustration of this scan.)

A radioisotope is injected into your vein; over a couple of hours, the radiochemical migrates to areas of pathological bone growth:  metastases, breaks, arthritis.  The radiologist can only tell which “hot spots” are cancerous by comparing two scans, separated by several months, that show increasing growth of highlighted areas.  This scan cannot see soft-tissue tumors. 

Results of the first scan will be interesting, but not definitive; on subsequent scans you will be able to discern metastatic growth if there is any.  If you change radiologists, be sure that the new one has the films from past scans.  Always ask for a copy of the written report.

Doctors seem, automatically, to ask you to bring your films to a consultation.  What they really want is the radiologist’s narrative report.  Reading scans and radiographs is difficult, and most doctors don’t do it.  If you are asked to bring along films, ask the doc if the narrative reports will be sufficient.  If you still need to bring the films, you can sign them out from the radiography department at the hospital.

You should also ask how long the hospital keeps the films on record.  If they will be destroyed, you should ask for them.

4.  The CT (computer-aided tomography) is a radiographic test (semiannually) that examines soft tissue, usually the body trunk (chest and abdomen) and head.  The purpose of the test is to determine if there are any soft-tissue metastases present.  This test will reveal soft-tissue tumors of any origin. 

The CT is a necessary companion test with the bone scan.  The computer analyzes multiple radiographs and enables the radiologist to visually “slice” your body into graphic sections and examine the soft tissue for the presence of tumors.  Soft tumors are more dangerous to survival because they invade the organs that are critical to life. 

Reading CT’s is difficult; so ask for a copy of the written report. 

The MRI (magnetic resonance imaging) does the same thing as a CT, only more precisely and without the use of x-rays; it is also more expensive.  The use of one or the other is your oncologist’s call.

Do I have osteoporosis?  Am I at risk?

1.  The DEXA(dual energy x-ray absorptiometry) scan measures bone mineral density (BMD) as an area(gm/cm²).  A QCT (quantitative computerized tomography test is an alternative method of evaluating BMD, especially for the lumbar spine region.

To read more about these tests see Bone Integrity in the main pages of this website.

The BMD T-Score taken from the DEXA or QCT report is the appropriate result to track your BMD. The T-Score is the number of standard deviations a given measurement falls above or below the mean BMD at that site in young normals(most often female as that is where the majority of the data exists).

A T-Score of -2.5 is currently used for both men and women and is the threshold for osteoporosis. T-scores between 0 and -2.5 are considered to be osteopenia. Get a copy of the written report and discuss your test results with the rheumatologist or endocrinologist who specializes in osteoporosis and its treatments.

As to when to get BMD tests, it is suggested that you have one before beginning hormone therapy and yearly thereafter. If you haven't had one yet and have been on hormone therapy for a while, get one as soon as possible and monitor at least on a yearly basis, but it is better to have one after 6 months if you obtained this test after already having been on hormone therapy.

This is a good time to go back to chapter chapter 11 - Protect your bones from deterioration and read about the role of testosterone, estrogens in osteoporosis as well as the use of bisphosphonates.

2.  Pyrilinks D is a urine test that measure the products of ongoing bone breakdown (resorption).  If the rate of bone loss is excessive, there is a risk of osteoporosis.  The test can also be used following treatment with bisphosphonates to determine if the treatment is effective.

Am I at risk for developing blood clots?  For hemorrhaging?

1.  The platelet count (done as needed) measures the number of blood-clotting platelets in your blood. This count is done as part of the CBC, below.  This test result is reported as thousands of platelets per microliter of blood. 

Blood coagulation is a complex process involving a variety of factors.  An adequate number of platelets is required for the coagulation process to proceed within certain time limits.  The platelet test is done in conjunction with a measure of clotting time—called prothrombin time (below).  If you are taking a blood thinner (Coumadin), you will also get these tests to determine when you have reached the proper dose level.

2.  Prothrombin time simply measures the seconds taken for the blood to coagulate.  If the time is excessively long, then one or more of the clotting component factors is deficient.  Because of variability in the methods for this test, you need to use the normal limits of the testing lab to evaluate this number.  Because of the variability in this test, results are often reported as INR, as follows.

3.  The INR is a way of reporting prothrombin time.  Because there is so much discussion about this test, the following explanation from the Pocket Guide to Diagnostic Tests (2d ed., p. 154) is helpful:

“Efforts to standardize and report the prothrombin time as an INR (International Normalized Ratio) depend on assigning reagents an International Sensitivity Index (ISI) so that

                             INR = (PTpatient/PTnormal)ISI

However, assignment of incorrect ISI by reagent manufacturers has caused a greater lack of standardization.”

What this means is simply that you need to use the standards of your testing lab as the normal limits for evaluating your numbers.  And you need to be cautious about concluding why your numbers are different from someone else.

Is it safe to have a (another) chemo treatment?  Am I anemic?  Is my immune system ok? (the CBC – Complete Blood Count)

The Complete Blood Count (done prior to each chemo dose; also with routine blood tests) is an automated count of the numbers of different types of red and white cells in a sample of blood.  The results are usually reported as follows.

 1.  White blood cells (WBC) is a gross count of the white blood cells, the mainstay of your immune system.  If this number is low you are at risk of infection.  If this number is high, you probably have an infection, and you body is creating a profusion of white cells to fight off the invaders.  Prior to receiving chemo treatment, your white cells must be sufficiently high to withstand the “immunosuppression” of the chemotherapy. 

For Taxotere, for example, the PDR specifies that the neutrophil count must be at least 1,500 cells/cubic millimeter.  You can check this on your own by multiplying the neutrophil percentage times the white blood cells in thousands. If that number is below 1500, then the chemo is postponed until the WBC count can be restored with Neupogen or Leukine. 

White cells are called leukocytes and categorized as granulocytic or agranulocytic.  (Granulocytic cells have a grainy appearance under the microscope.)  White cells are also categorized according to the following types:  neutrophils, lymphocytes, monocytes, eosinophils, and basophils.

 2.  Red blood cells (RBC) is a gross count of the red cells in your blood.  Red blood cells (also called erythrocytes) do not have nuclei; thus, they also do not carry DNA.

 A number below the normal range is indicative of anemia (there are different types of anemia).  Anemia is a common result of cancer, and it is aggravated by chemotherapy and hormone therapy.  The result, once your RBC count drops down to the lower end of the normal range, is that you will begin to lose energy.  This can be countered to some extent with Procrit(Epoetin Alfa), which stimulates production of red cells.

 3. Hemoglobin is a protein and iron compound in the blood that carries oxygen.  Each red blood cell contains 200-300 molecules of hemoglobin.  This is reported as a weight per volume of the blood sample.  Hemoglobin will vary directly with the RBC count.  The tiredness associated with anemia is due to a lack of ability to deliver sufficient oxygen throughout the  body.

 4. Hematocrit is simply a measure of the red blood cells as a percentage of the total volume of the blood.  It will vary directly with the RBC. From this point on, the numbers are simply further—or different—breakdowns of the red and white cell counts.

 5.  MCV (mean corpuscular volume) is a measure of the volume of red corpuscles in the blood.  This indicator, and the next five, are supplemental data that are used in conjunction with the other blood results to diagnose problems.

 6.  MCH (mean corpuscular hemoglobin) is a measure of the hemoglobin content of the red corpuscles.

 7.  MCHC (mean corpuscular hemoglobin concentration) is a measure of the concentration of hemoglobin in the average red cell.

 8.  RDW-CV (red cell distribution of width-coefficient of variance) is a statistical view of the dimensions of the red cells.

 9.  RDW-SD (red cell distribution of width-standard deviation) is a statistical evaluation of the sizes of the red cells.  Excessively small or excessively large cells are abnormal.

 10.  MPV (mean platelet volume) is a measure of the volume of platelets in the blood.  A low value is related to hemorrhaging.  A high value is related to clotting.

 11.  Platelets are discussed above with blood clots.

 12.  Neutrophils are granular leukocytes (leukocytes = leucocytes = white blood cells). It is worth noting that white cells do have nuclei; thus, they also have DNA.  Granulocytopenia is a deficiency of those white cells that are granular.  Neutrophils are essential parts of the immune system; they consume and remove debris from immune destruction of bacteria and dead cells.

 13.  Lymphocytes are agranulocytic leukocytes, the centerpiece of the immune system.  They are either B or T cells.  These reproduce in profusion in response to infections.  The function of lymphocytes is rather complex.  But B cells produce plasma cells that secrete antibodies and memory cells (the basis of immunity).  And T cells produce “killer” cells that can destroy foreign matter.  T cells are also believed to be instrumental in resisting the onslaught of cancer.

 14.  Monocytes, when needed, grow into macrophages, cells that “eat” foreign agents and clean up damaged tissue, somewhat like neutrophils.

 15.  Eosinophils are granulocytic leukocytes.  They help fight off allergies and parasites.  The number of these is reduced by steroids.

 16.  Basophils are granulocytic leukocytes.  They help fight off inflammation.

 17.  Band is reported as a percentage of white blood cells.  Bands are immature white cells.  An increase in bands indicates bacterial infection or acute stress to the bone marrow.

 18.  Anisocytosis is an abnormal condition of the blood in which there are excessive red blood cells of variable and abnormal size.  This is reported as the number of statistical standard deviations in excess of the normal range.  The red cell sedimentation rate is usually decreased in anisocytosis.  This is a nonspecific indicator of disease.

 Is my calcium too high as a result of using calcitriol?

1.  A urinalysis of creatinine (not creatine) and calcium (monthly during high calcitriol usage) yields one measure of body calcium.  So long as the calcium is 35% or less of the creatinine level, the calcium is ok.  Above that level, there is an increased risk of kidney stones as a result of hypercalcemia.  If calcitriol usage is causing the increased calcium, it should be stopped.

2.  Serum calcium is used to monitor kidney function (see below).

 Is the Lupron treatment working?

1.  Serum testosterone needs to be below 20 ng/dl (some doctors place this limit as high as 50 ng/dl) in order to halt the growth of androgen-sensitive prostate cancer.  The usual criterion defining HRPCa is an increase in PSA while treatment with Lupron or Zoladex (or other LH-RH agonist) is in progress. 

It is important to check on the effectiveness of the Lupron (or Zoladex) treatment by measuring testosterone before concluding that the cancer is hormone refractory.  If the testosterone is above 20, have your LH level measured. If the LH-RH agonist is working, then LH will be < 1.  In rare cases, increasing the dose might be appropriate, but note that in Europe the standard dose of Lupron is 3.75mg and in the USA it is 7.5mg.  The other source of testosterone (or more precisely androgen pre-cursors such as androstenedione) is from the adrenal glands. These can be measured also and if high, an anti-androgen can block their uptake or adding ketoconazole or dexamethasone to suppress them can lead to lower testosterone levels. The use of dexamethasone is covered in this paper: Khandwala HM, Vassilopoulou-Sellin R, Logethetis CJ, et al: Corticosteroid-induced inhibition of adrenal androgen production in selected patients with prostate cancer. Endocr Pract 7:11-5, 2001.

Do I have kidney or liver damage?

A number of drugs (and herbs) used in treating cancer are toxic to the liver and kidneys.  Suffice it to say that you cannot live without adequately functioning kidneys and liver.  Therefore, it may be necessary with certain drugs to run some of the following tests periodically to determine whether those drugs are harming these vital organs.  Liver and kidney insufficiency are also dangerous associated diseases that can aggravate the problem of cancer.

1.  LDH (lactate dehydrogenase) is a blood test.  This is an enzyme found in the kidneys, liver, heart, muscle, brain, lungs and red blood cells.  An increased level is indicative of disease in one of those areas.  When matched with elevated liver or kidney enzymes, an elevated LDH confirms disease in one of those organs.

2.  SGOT/AST (serum glutamic-oxaloacetic transaminase/aspartate aminotransferase) is a blood test.  It is elevated in the case of liver disease

3.  SGPT/ALT (serum glutamic-pyruvic transaminase/alanine aminotransferase) is a blood test.  The level is increased in cases of liver trauma or damage.

4.  Bilirubin is a blood test.  Bilirubin (bile) results from the breakdown and removal of hemoglobin.  Bilirubin is elevated in the case of liver disease or with the use of drugs that are toxic to the liver (hepatotoxic).  The total bilirubin may be reported as a sum of “direct” and “indirect.”  Water-insoluble bilirubin (indirect) travels in the blood to the liver, where it binds to albumin in a water-soluble form (direct) that is mixed into the bile for excretion.  The direct and indirect designations are not reliable indicators.

 5.  BUN (blood urea nitrogen) is a blood test.  It is a waste product of metabolism and reflects the metabolic function of the liver and the excretory function of the kidneys.  Individuals with liver disease will have a decreased level of BUN.  The BUN level may be increased in the case of kidney disease. 

 6.  Creatinine is a blood test.  The creatinine is produced as a waste product that is excreted through the kidneys.  It is elevated in the case of kidney failure.

7.  Albumin is a blood test. The albumin is a component of total protein.  A decreased value may indicate liver or kidney disease.

8.  Total protein is a blood test.  Protein consists of albumin and globulin.  Albumin is formed in the liver; it transports blood constituents.  Globulin is a building block of antibodies, proteins, and  clotting factors     A decreased value of total protein may indicate liver or kidney disease.

How is my general health, as reflected by electrolyte balance?

The general tone of body health is reflected in the electrolytes, or ions.  These chemicals, by conducting electricity, enable the reactions that take place throughout the body.  The electrolytes are found in the body humors (liquids), including the blood plasma, the intercellular fluid, and the intracellular cytoplasm.  Both quantities and proportions of the various electrolytes are important for various body functions.

Deficiencies in some of these electrolytes can result in catastrophic shock.  It is important to notice that the normal range for some of these ions, as identified in the Pocket Guide to Diagnostic Tests also includes some “panic” levels.  If these are reached, immediate medical attention is needed.  Chronic diarrhea can deplete the body of electrolytes to the point at which IV liquids must be administered on an emergency basis.  Heat exhaustion is another situation in which liquids and electrolytes have been depleted to a dangerous level.

The results of each of these electrolyte tests must be placed in a context of multiple tests to reach a meaningful diagnosis.  The Pocket Guide will provide an indication as to the wide range of medical conditions that can be affected by decreased or elevated levels of these electrolytes.  The variety of conditions that can be indicated is so wide that it is not possible to summarize them here.

1.  Calcium (Ca) ion is critical to muscle relaxation and heart contraction.

2.  Potassium (K) ion is needed for contraction of muscles and for heart muscle relaxation.

3.  Sodium (Na) ion helps to maintain the proper level of fluids throughout the body.

4.  Magnesium (Mg) ion supports the function of enzymes.  It is also involved in neuromuscular activity.

5.  Chloride (Cl) ion helps to maintain the body pH, i.e., acidity or alkalinity. 

6.  CO2 (carbon dioxide) is part of the body’s buffering system with bicarbonate (HCO3) that helps to maintain the proper level of acidity and alkalinity (pH) in the body. 

7.  Phosphate (HPO4) ion is involved in the body’s energy production.

A suggested schedule of diagnostic tests

The following table can be used as an aid to setting up your own schedule of diagnostic tests to monitor the progress of treatments.  Most oncologists will have their own list of tests, but this will provide you with material for asking questions to increase your understanding.

 

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Updated 2/11/04