What is the PSA?
The Prostatic Specific Antigen (PSA) is a serine protease produced by the prostate to liquefy the ejaculate and allow sperms to migrate once deposited within the vagina. Disruption of the prostatic gland architecture like in cancer, allows greater amounts of PSA to enter the bloodstream.
> the commonly used PSA, or total PSA is a very UNRELIABLE blood test with a very low sensitivity for prostate cancer, especially when used in screening for prostate cancer.
> the cut-off level of 4 ng/ml or less as being normal and anything above this level being abnormal is ARBITRARY and a PSA < 10 ng/ml is more reliable for BENIGN prostate disease than for prostate cancer.
> the bigger the prostate, the greater the PSA.
> the more inflammatory cells (chronic prostatitis), the greater the PSA.
> in reality, there is NO SAFE LEVEL of PSA for which you cannot have cancer.
> in addition, you should be aware of those drugs that can lower your PSA such as Statins, NSAIDS, Thiazides and 5 alpha reductase inhibitors (proscar, avodart). These drugs lower PSA levels artificially and this lowering MAY have no protective value from developing prostate cancer. Furthermore, there are situations which can raise your PSA in the absence of a cancer and give you a false-positive reading such as after sexual activity, a DRE, a prostate biopsy or a urinary tract infection.
> the PSA is unable to distinguish SIGNIFICANT aggressive prostate cancer from INSIGNIFICANT prostate cancer.
> the PSA under 10 ng/ml does not correlate well with prostate cancer in presence or amount.
> a man with a “normal” PSA under 4 ng/ml will have an approximately 15% chance of having prostate cancer, mostly insignificant.
> a man with a PSA between 4-10 ng/ml will have a 30% chance of having prostate cancer.
> a man with a PSA over 10 ng/ml has a 40-70% chance of having prostate cancer.
> 75% of the prostate cancers detected will be low-risk Gleason 3+3.
> a man of 65 years with a PSA < 1 ng/ml is unlikely to benefit from more PSA testing.
> a man of 75 years with a PSA < 3 ng/ml is unlikely to benefit from more PSA testing.
WHY YOU MAY NOT WANT TO CHECK YOUR PSA
> urologists are still unable to determine accurately which prostate cancers have the propensity for spreading by blood stream and which demand treatment from prostate cancers which do not.
Future BIOMARKERS may have reliable predictive value as to whom really needs treatment.
> many PSAs are elevated because of the associated benign prostate enlargement and NOT from the small area of insignificant, low-risk prostate cancer detected serendipitously.
(PSA and Prostate Cancer Screening? Maybe, Carefully and Selectively)
> needle biopsies of the prostate can be risky although not as risky as OVERTREATMENT.
> cancer will be identified in less than 5% of asymptomatic men screened for prostate cancer.
> many prostate cancers are low-risk Gleason 3+3 and OVERTREATED (especially with robotic prostatectomy) when they should have been monitored through active surveillance.
> treatments (especially with robotic prostatectomy) are risky, unlikely to be curative and often diminish quality of life because of urinary leakage, shortened penis, altered sexual experience, loss of ejaculation, infertility and impotence (or discharge of urine if fortunate enough to have some sexual function/orgasm) along with a general loss of manhood.
> the prostate cancer industry has a culture along with a well-oiled media machine, where there is pervasive use of self-serving definitions, gross subjectivity issues affecting imaging and pathology interpretations, inaccuracies in so-called “data bases”, philosophical approaches to treatment, pervasive use of scientifically unproven treatments, conjecture and creative reporting of “results” along with a lack of sincere end-result accountability that have clouded severely any appearance of patient advocacy.
> the credibility of urological surgeons is tainted even further by the manner in which the cancer “message” is delivered by many of these doctors.
WHY YOU MAY WANT TO CHECK YOUR PSA
Refining eligibility for PSA testing MAY be reasonable. First, you should consider reviewing an informed consent because of the many possible negative downstream effects stemming from evaluation and treatment for prostate cancer (The Imperfect PSA, the Fraudulent Robotic Prostatectomy and Medical Ethics).
PSA testing may be reasonable for:
> concerned healthy men with at least 20 years or so of anticipated active life and without significant co-morbidities such as a cardiac or diabetes history which may impact survival.
> those with an abnormal prostate examination. The digital rectal examination (DRE) is a very subjective test and firmness or a lump/nodule in your prostate MAY mean an area of cancer. Simple asymmetry of your prostate is not a valid reason for a prostate biopsy.
> an abnormal DRE in the presence of a so-called normal PSA under 4 ng/ml has about a 30% chance of an associated prostate cancer.
> older men; prostate cancer increases with age faster than any other cancer and 75% of prostate cancers are diagnosed in men after age 65 years but mostly low-risk Gleason 3+3 (about 70% of 90-year-olds can have asymptomatic prostate cancer).
> men with low serum testosterone and in particular those with low percent-free testosterone.
> men of African heritage (particularly Jamaican).
> obese men.
> men with a family history of prostate cancer; some 5% of prostate cancers may be inherited.
> men with low-risk prostate cancer undertaking active surveillance (AS) and monitoring PSA doubling time.
> monitoring after prostate cancer treatment.
WHICH PSAs and WHAT PSA ENDPOINT may SUGGEST the NEED for a PROSTATE BIOPSY?
It is difficult to determine at what PSA endpoint there is enough of a concern for you to consider a prostate needle biopsy in order to determine the possible presence of a significant cancer.
Each patient and his physician will need to come to a consensus as to what level of PSA causes concern for a possible prostate cancer.
> PSA Derivatives (total, free PSA and percent free PSA)
PSA (ng/ml) percent free PSA Estimated Probability of Cancer
0-2.5 ? ?
2.6-4.0 0-27 24%
4.1-10 0-10 56%
>or =26 8%
> 10 N/A > 50%
It is evident from this table that as the percent free PSA rises, the probability of prostate cancer diminishes. This is the converse of what a high total PSA can mean.
Rather than using just the common total PSA, using PSA derivatives such as the free PSA to determine the percent free PSA can approximate the “estimated probability of having a cancer”. From the Table, the lower the percentage free PSA, the greater the probability of prostate cancer. i.e. with a percent free between 0-10 you have a 56% estimated “probability” of having a prostate cancer.
However, these estimates are NOT foolproof and may vary with age, ethnicity, family history and DRE findings. Furthermore, although the diagnostic usefulness of the percent free PSA has not been established in men with a total PSA below 2.6 ng/ml, I do begin to pay attention to this number when the PSA reaches a level somewhere between 1.8-2 ng/ml.
Values obtained from different testing methods and laboratories cannot be used interchangeably.
> PSA Kinetics (velocity, PSAV and doubling time, PSADT)
A PSA increase (velocity) of 0.75 ng/ml/y in a PSA range of 4-10 ng/ml over at least 18 months is considered to be significant.
Determining the PSADT, which is the length of time in months for a PSA to double based upon exponential growth with a shorter (but faster) doubling time having a poorer outlook, may be meaningful. For example, a PSADT of under 2 years should raise suspicion for either the presence of a prostate cancer or a cancer on active surveillance which may be progressing. A long PSA doubling time has a low likelihood of significant impact.
> PSA density
The dPSA is measured by dividing the weight of your prostate into your current PSA.
A dPSA > 0.15 may be significant.
> age-specific PSA ranges
Using tables showing the normal increasing PSA ranges for advancing age.
> evaluating the PSA after a 3-month course of finasteride (proscar)
To see if the PSA drops by about 50% after a 3-month course of finasteride; if so, it is thought that the chances of having a prostate cancer are diminished.
> performing the PCa3 test
This involves a vigorous prostatic massage and an mRNA analysis of the seminal fluid washed out in the initial urine sample after the massage. This test may be useful when the information is combined with the PSA derivatives. On its own, the PCa3 is associated with too many false positive and false negative results to be reliable.
> ultrasensitive PSAs
May be more useful for detecting prostate cancer recurrences after a treatment.
> newer biomarkers
Blood biomarkers like the pro-PSA and others as well as new urinary and tissue biomarkers like the PTEN are still undergoing evaluation. These new biomarkers may predict reliably prostate cancer progression and which cancers truly demand treatment.
> unlike its inaccuracy as a prostate cancer screening marker, the PSA is a reliable indicator of presence or absence of cancer after prostate cancer treatment.
> high-risk or aggressive prostate cancers such as small cell cancers may produce little if any PSA rise, even with prostate cancer progression.
> the upgrading of a residual prostate cancer to a more aggressive prostate cancer may occur after ANY TREATMENT option without a significant rise in PSA. Therefore, PSA monitoring needs to be interpreted very judiciously.