The highest rates of PSA are found in the seminal fluid; however a certain amount of PSA escapes the prostate ducts and joins the bloodstream, which allows for its dosage in the serum, which is at the heart of the development of the blood test.
This serous dosage of PSA is used to assess the response to treatment of men with prostate cancer.
The serous assay testing of PSA has never claimed to be a diagnostic test for prostate cancer, but it is still useful because it allows us to select the men in whom a prostate biopsy is indicated. PSA levels tend to rise in men with benign prostatic hypertrophy (BPH) (prostate adenoma), and PSA is also a good indicator of the prostate volume.
The serumal levels of PSA are often high and temporarily very high in cases of acute prostatitis, a bacterial infectious disease of the prostate.
The most useful information provided by the study of PSA in diagnosis of prostate cancer is derived from the observation of its variations over time. There is no PSA rate that can provide assurance that the prostate is normal and that there is no presence of cancer. There is no upper limit to the “normal” range of PSA levels beyond which prostate biopsies are always carried out and below which there is never a need to perform a biopsy.
The PSA blood test has been widely used to search for prostate cancer in large population groups and it has proven itself useful in this type of diagnosis. Scientific studies are being conducted to determine whether screening for prostate cancer by measuring serumal rates of PSA is of some interest in the evolution and survival of men with prostate cancer, but most urologists can testify that they see much less men suffer from advanced and incurable prostate cancer since the arrival of the PSA era.
This test has completely changed the way to assess the severity and treat prostate cancer. Before PSA was introduced into the diagnostic arsenal, nearly 70% of men diagnosed with prostate cancer already presented tumors that had grown beyond the limits of the gland capsule or had spread throughout the body through distant metastases. For a biopsy to be indicated, there had to be a tangible hardened nodule upon rectal examination.
Since the use of PSA less than 3% of men have metastatis when diagnosed and the cancer is not tangible on rectal examination in 75% of men in whom biopsies were positive. It is in this latter group of patients in particular that the diagnosis can be made through biopsies carried out due to a markedly elevated PSA rate or based on the observation of rapid kinetic growth rates of cancer markers.
Since this blood test was introduced into the diagnostic arsenal in 1986, early diagnosis and management of prostate cancer has been revolutionized. The PSA dosage is not only useful for early diagnosis of the disease, but also for assessing the effectiveness of the response to treatment put in place and also for its most controversial role: mass screening of prostate cancer.
The normal range levels of PSA is 0-4 ng / ml.
However, PSA rates tend to increase with age, the largest amounts come from the transition zone of the prostate and it is precisely this region of the prostate that increases the volume in benign prostate hyperplasia (adenoma).
Most urologists believe, however, that the 4 ng / ml rate is the threshold limit for detection of prostate cancer regardless of the age of the subject.However, among men younger than 50 years of age, 2.5 ng / ml is the recommended threshold limit.
The amount of PSA produced by prostate cancer cells vary inversely with the degree of differentiation of the tumor.This is why a patient with an aggressive form of prostate cancer can have low or undetectable serumal PSA rates.
Other factors can influence the measurement of PSA rates:
- 5-alpha reductase inhibitors reduce by half after 6 months of treatment;
- An ejaculation increases PSA rates for the following 48 hours;
- An acute or chronic prostatitis, or complete vesical retention increases rates;
- The rectal examination, cystoscopy, vesical catheterization through the urethra or the realization of a transrectal ultrasound (TRUS) of the prostate do not cause significant variations but a vigorous prostatic massage may cause a transitional elevation much like the realization of prostate biopsies (2 weeks to a month).
Other derivatives of PSA are useful especially for subjects with PSA levels in the 4-10 ng / ml.range, where 75% of men with such rates do not have prostate cancer.
In this range, the simple dosage of PSA (= PSA – T) lacks specificity with regards to a prostate cancer diagnosis and ¾ biopsies carried out are negative.
Among the most useful and verified information:
The adaptation of PSA rates in function of age.
Free PSA and free PSA index / total PSA = PSA L / T.
In the bloodstream, the majority of PSA measured is in complex form, the PSA molecule is linked to another molecule represented by a protease inhibitor, whereas in the ejaculate, it is mostly free PSA that we find.
The ratio of free / total is expected to be lower in men with prostate cancer than in those with simple adenomatosis hyperplasia and benign adenomatosis hyperplasia (BPH).
PSA Density = PSA – D.
This is the total PSA reported in prostate volume determined by a transrectal ultrasound. PSA density above the 15% threshold would most likely correspond to prostate cancer with the exception of the prostate volume estimation from an ultrasound that is highly variable and dependent on the operator.
PSA velocity = PSA-V.
There is rapid increase in PSA during the year. Ideally at least three assays performed during the previous 2 years.
A PSA-V greater than or equal to 0.75 ng / ml per year suggests the existence of prostate cancer with a sensitivity of 72% and a specificity of 95%.
The PSA doubling time = PSA – DT
It is a concept close to PSA – V and useful in practice.
PSA velocity or the doubling time of PSA prove to be much more reliable predictors than PSA rates alone, usually considered to present an indication of a prostate biopsy or refer a patient to an active treatment of prostate cancer rather than simple monitoring.
Because PSA is prostate-specific (PSA is in fact a prostate specific antigen and not a prostate cancer specific antigen), its use for cancer screening, however, is very interesting. Indeed, higher rates may be related to other prostate conditions, but will enable us to advisedly prescribe additional tests, such as biopsies.
As you can see from this diagram of delayed diagnosis in relation to the increase in cancer markers, PSA increases years before the discovery of the disease.
Given the doubling time usually observed, we can do a backwards projection. Thus, 10 years before the discovery of cancer in metastatic phase, statistically the patient had already presented elevated PSA, that is to say, their dosage may have allowed the discovery of the cancer at an early non-metastatic stage.
In prostate cancer, the way the marker declines after treatment may also be used in predictions as described above.
Thus, for the PSA after local treatment, we observe a fall in the PSA rate, immediately after surgery, slower after radiotherapy, depending on the mode of disappearance of PSA producing cancer cells.
Changes in PSA after local treatment of prostate cancer by prostatectomy: the green curve is the curve towards recovery, the violet curve shows that there are unrecognized metastases.Yellow and red curves show the presence of tumor tissue outside the prostatic boundaries. Notice the different time scales after curative treatment: in days for surgery.
Changes in PSA after local treatment of prostate cancer irradiation of the prostate. (same comments as for prostatectomy). Note the different time scale after curative treatment: in months for radiotherapy. The same curve is observed for prostate brachytherapy, whatever its mode of administration, since this consists of radiotherapy ‘from the inside’.
In the metastatic forms, it is important to see what slope will succeed the institution of hormonotherapy (surgical or chemical castration). When the fall of PSA is rapid and complete, we can hope for a prolonged remission of good quality. When it is incomplete, it indicates the existence of hormone-resistant clones (see works of Miller JI and al). In this diagram representing the evolution of PSA in metastatic prostate cancer, we can appreciate that:
- a complete and rapid collapse of PSA is a sign of complete remission.
- an incomplete and slow fall is a sign of early relapse.