Daria Pašalić
Department of Medical Chemistry, Biochemistry and Clinical Chemistry
Zagreb University School of Medicine
Šalata ul 2.
10 000 Zagreb, Croatia
Phone +385 (1) 4590 205; +385 (1) 4566 940
E-mail: dariapasalic [at] gmail [dot] com

Useful links



Tumor markers in laboratory practice – state of the art


Rafael Molina.Tumor markers in laboratory practice- state of the art. Biochemia Medica 2015;25(Suppl 1):S11-S12.

Oncobiology Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain


Tumor markers (TM) have been used for more than fifty years in clinical practice. However a excluding some special situations as for example testicular cancer, trophoblastic tumors, or colorectal cancer, their clinical utility is not well accepted in the majority of guidelines. The main difficulty is to interpret the tumor marker results, mainly to distinguish between benign or malignant origin. To minimize the problems previously indicated with tumor markers we use 3 criteria: (1) Serum levels of Tumor markers. TM false positive results are habitually slightly or moderate. Higher concentrations of TMs indicate higher probability of malignancy (risk). There are some TM serum levels that suggest cancer with high probability (99%). (2) Exclude or take in account benign diseases. TM false positive results are habitually related to the catabolism or with injuries in tissues rich in these TMs. Renal failure and liver diseases are the most frequent non-malignant disease associated to false positive results. However the majority of tumor markers had only slightly high serum levels in these diseases, that rarely arrive to 2-4 times higher than the habitual cut-off. However, some tumor markers had very high concentrations being difficult to distinguish benign from cancer as SCC, S-100 or HE4 in renal failure or CA 19-9 in jaundice. To avoid false interpretations with this TMs there are two options, first lo look for a second cut-off in these diseases, or do not use the TM in these situations. This is the case with SCC in patients with renal failure or in patients with systemic dermatological diseases with serum levels indistinguishable of those levels found in cancer. (3) Serial tumor marker evaluation. Serial determination is the most important criteria to distinguish between benign or malignant diseases, mainly in those patients with abnormal values but not clearly indicating cancer. In patients with doubts, TM may be repeated in 3 or 4 weeks, if there are increasing levels (>25%) in the abnormal range will suggest with high probability malignancy. By contrast patients with similar concentrations or lower had a low probability of cancer.

e-mail : RMOLINA [at] clinic [dot] at


Prostate specific antigen (PSA) – negative viewpoint
Overutilization of the PSA test


Ante Reljić. Prostate specific antigen (PSA) – negative viewpoint. Overutilization of the PSA test. Biochemia Medica 2015;25(Suppl 1):S12-S13.

Department of Urology, University Hospital Centre Sestre milosrdnice, Zagreb, Croatia


PSA is a test which is, in the past 20 years, performed by Croatian urologists in the clinical practice almost dogmatically – once a year on all men older than 50 years. We followed the principles of early diagnosis which is not synonymous to systematic screening, and even using the screening method is supported in only one study (ERSPC-European Randomised Study for Screening of Prostate Cancer) which indicated lower mortality rates by 21% during 11 years.

However, applying the PSA test as a method of early diagnosis has shown effects in two ways. The first one is significantly less patients with metastatic, incurable prostate cancer and the other one, drastically increased number of curative forms of treatments – radical prostatectomy or radical radiotherapy. Both effects leave a certain impression of improved diagnostic and therapeutic activity, but epidemiological data does not support that fact. In Croatia, like in the most of the countries which have used PSA test method extensively and uncritically, the incidence of prostate cancer is significantly increased while the mortality rate is not reduced. Precisely such epidemiological indicators are present in our country.

So, we could now point out three characteristics of our current practice: a) excessive, uncritical and irrational use of the PSA test (“overutilization” of PSA), b) excessive diagnosis of the low-risk cancer, whose treatment does not affect the specific mortality (“overdiagnosis”) and as consequently inevitable, c) too frequent radical treatment of those same patients (“overtreatment”). In other words – we undertake too much, and not enough is achieved. Prior to mass preforming of the PSA test, incidence and mortality rates were 2:1, whereas today they are 7.5:1 and the risk of death from prostate cancer is still 3% over a lifetime. This very well illustrates the extent of the terms “overdiagnosis” and “overtreatment”. I believe that the key to the solution is rational reduction of the frequency of PSA testing. Our search for patients with a high-risk prostate cancer should not be so massive, but more focused and rational. Recent AUA (American Urological Association), EAU (European Urological Association) guidelines and the conclusions of the USPSTF (US Preventive Services Task Force) confirm such viewpoints.

Thanks to the analysis by Lilja and Vickers it is possible to rationalize the use of the PSA test according to the risk stratification based on the determination of the so-called basal PSA in the age of 45-49. The frequency of the further testing can be determined depending on that basal value. Only about 10% of the group that age represent a high-risk candidate for metastasis or death due to the prostate cancer. It is a population that needs to be very closely monitored by regular PSA testing. With the remaining majority, PSA test can definitely be indicated in much rarer intervals. According to the abovementioned sources, for at least half of the men it only takes three PSA tests in a lifetime - in the late 40’s, early 50’s and when turned 60 years of age. At the age over 70 PSA test loses its significance.

If first 20 years of systematic testing on a “PSA-once-a-year” principle resulted in increased incidence without a significant decline in mortality, it is necessary to adapt the model of PSA testing on a more rational grounds. Without that we cannot expect to reduce redundant detection (overdiagnosis) or complications according to unnecessarily frequent treatment (overtreatment). The ultimate goal of systematic and rational early diagnosis is to reduce mortality from prostate cancer for at least 30% and at the same time to reduce the “overdiagnosis” and “overtreatment” to a minimum.

e-mail: reljic [dot] ante [at] gmail [dot] com 


Prostate specific antigen – affirmative viewpoint

Igor Tomašković. Prostate specific antigen – affirmative viewpoint. Biochemia Medica 2015;25(Suppl 1):S14-S15.

Department of Urology, University Hospital Centre Sestre milosrdnice, Zagreb, Croatia

Department of Urology, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia


Testing by serum prostate specific antigen (PSA) has revolutionized our ability to diagnose, treat, and monitor treatment outcomes in patients with prostate cancer. While it is clear that PSA is not a perfect marker and even not specific to prostate cancer since it changes with inflammation, benign prostatic hyperplasia, ejaculation, mechanical manipulation and instrumentation of the lower urinary tract and some drugs, this marker is still used just as a tumor marker. Use of the PSA since the mid-90s of the last century, resulted in a detection of a large number of prostate cancer patients and a significant increase in the incidence of this disease. Favourable results of the widespread use of PSA for the early detection of prostate cancer include a larger number of patients with localized disease and increased number of well-differentiated tumors. The above effects facilitate better treatment of patients, especially with radical surgery that is primarily indicated in the localized disease. This has given the opportunity to greater number of patients for curative rather than palliative treatment. Furthermore, the use of the PSA is still the basis for monitoring the effect of treatment regardless of whether the patient underwent surgical treatment, radiation or hormonal therapy, and it is another, undeniable benefit of this marker.

Trends in the mortality from prostate cancer reported in the United States (National Cancer Institute) showed a steady decline of 3.4% annually in the period from 2001. to 2011. Reduction in mortality of 40% in the period from 1992 till today in the US is a possible consequence of early detection and / or a better treatment of this disease.

Two randomized, prospective studies dealt with the issue of the benefit of mass use of PSA for the early detection of prostate cancer, which in places is reaching screening proportions (mass screening): European randomized study for prostate cancer (ERSPC) and the Prostate, Lung, Colorectal and Ovary trial (PLCO). While the ERSPC has shown a reduction in mortality of 27% (0.73, 0.61-0.88, P<0.0007), PLCO study failed to show benefit from screening. Objections to PLCO study were high rate of contamination of PSA testing in the control group (52%), and compliance with the study protocol in only 86% of respondents and less than 50% of men with indication who underwent biopsy in the screening group.

Despite possible reduction of mortality with PSA screening, the price of this procedure is not small: last results after 13 years of follow up in the ERSPC showed that it is necessary to invite 781 men in the screening program and treat 27 to avoid one death from prostate cancer. It is believed that the excessive rate of unnecessary diagnosis (“overdiagnosis”) is around 50% and it is the major adverse effect of screening. Therefore, leading urological organizations including the European Urology Association recommend programs for early detection of prostate cancer, but not mass PSA screening. Because of the risk of over-diagnosis of indolent disease and consequent excessive treatment and its effect on the quality of life, it is necessary to review previous recommendations of use of PSA, but not discard the benefits that it brings.

By introducing the concept of basal PSA, determining the frequency of testing according to the degree of risk and avoidance of active treatment of indolent disease (active surveillance) we can significantly reduce the negative while preserving the positive effects of PSA testing.

e-mail: igor [dot] tomaskovic [at] kbcsm [dot] hr