Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Approximately 400,000 European men develop prostate cancer (PCa) every year1. The diagnosis of prostate is based on serum prostate specific antigen (PSA) testing, digital rectal examination and multi-core biopsy.

However, multiple factors not related to prostate malignancy may affect the level of blood PSA (inflammation, infection, presence of benign prostate hyperplasia /BPH etc.). According to the current guidelines, a suspicious result of a PSA test should be clarified by biopsy. PSA lacks specificity in the intermediate range, so called PSA “grey zone”(4.0–10.0 ng/mL) and only 25% of the patients in the “grey zone”, are confirmed with PCa after biopsy.

Figure 1. The diagnosis of prostate cancer is based on the invasive biopsies

In additional, introduction of PSA testing and multi-core biopsy resulted in increased detection of slow growing PCa unlikely to progress in the absence of treatment (low risk disease). Uncertainty to properly assess PCa resulted in patients’ overtreatment. This imposes a significant social and economic burden on patients and health-care holders, as a result of the side effects and the high associated treatment costs.

Figure 2. Slow growing PCa is unlikely to progress in the absence of treatment (low risk disease). Selection of patients for active surveillance helps to avoid over-treatment.

Active surveillance is currently the only valid alternative to immediate therapy and overtreatment of patients with low risk disease. Active surveillance implies intervention only in patients with local tumour progression. Around 45% of patients initially diagnosed with PCa experience slow growing form, thus are eligible for active surveillance. Selection of patients for active surveillance currently relies on repeated invasive biopsies, series of PSA measurements and DRE. Although various criteria are used for patient selection and follow-up, incorrect patient exclusion or misclassification becomes a concern.

Urinary Proteomics Analysis: The CE-MS based DiaPat® PCa-PROteom Test

Mosaiques applies urinary profiling using capillary electrophoresis online coupled to mass spectrometry (CE-MS) to the non-invasive diagnosis of prostate cancer, to reduce the unnecessary biopsies and patients’ over-treatment and the associated costs. The urinary proteomic profiling of patients with prostate cancer and benign conditions (benign prostate hyperplasia- BPH) enables the identification of specific proteomic biomarkers that are combined in a diagnostic test (DiaPat® PCa-PROteom Test) to enable efficient prostate cancer detection.

The DiaPat® PCa-PROteom Test simultaneously determines 12 peptide biomarkers indicative for PC. The diagnostic accuracy of the PCa proteomic test is supported by two blinded prospective studies in a total of over 500 patients.

In the first study by Theodorescu et al., prostate cancer was detected with 89% sensitivity at 51% specificity^. Combination of the DiaPat® PCa-PROteom Test with age and percent-free PSA resulted in 91% sensitivity at 69% specificity

In a consecutive study, DiaPat® PCa-PROteom Test showed a sensitivity of 86% and specificity of 59%. Importantly, the diagnostic accuracy of DiaPat® PCa-PROteom Test (AUC of 72%) was significantly better in comparison to total PSA (AUC of 60%) as well as percent-free PSA (AUC of 69%)

.

Recommendation for patients

The DiaPat® PCa-PROteom Test is recommended for patients with suspicious PSA and/or digital rectal examination results prior to intended biopsy. The test allows distinguishing patients with a positive PSA test who have PC from those who do not have it. A positive test result gives a clearer indication for a biopsy than PSA testing alone; whereas due to the high negative predictive value of >90%, in patients with negative test result biopsy is not indicated.

Figure 3. PCa-PROteom Test is recommended to correct false positive PSA results.

Benefits of using the DiaPat® PCa-PROteom Test

DiaPat® PCa-PROteom Test is a helpful addition to the state-of-the art management of patients with suspicious PSA and/or DRE prior to intended biopsy. The high diagnostic accuracy allows to correct the false positive results of PSA testing and continuously can help to reduce the number of painful and unnecessary biopsies as well as related side effects (e.g. bleeding, pain, problems with urination). In addition, severe anxiety in men and their families associated with the false-positive results of the PSA test is an uncomfortable medical condition and can be minimized with the application of the test. Moreover, DiaPat® PCa-PROteom Test is non-invasive and there is no risk associated with sample collection. The benefits associated with the use of this test are further supported by the cost–effectiveness analysis

. With the use of the PCa-PROteom test before the first biopsy, number of biopsy sessions was projected to decrease by 49% along with the reduction of expected diagnostic costs by 19%.

New study results for improving over-treatment

So far, the treatment of prostate cancer is not always successful. Non-aggressive prostate cancer grows slowly, is asymptomatic and frequently do not cause complications that can cause mortality. Therefore, it is crucial to operate only on patients with aggressive prostate cancer, while patients with non-aggressive prostate cancer remain under constant observation.

In another study, proteomic analysis of seminal plasma enables accurate discrimination of patients with non-aggressive cancer from patients with aggressive cancer. A good performance of proteomic patterns was reported with a sensitivity of 80% and a specificity of 82%

Figure 4. The proteomic analysis reveals specific signatures that can indicate presence of prostate cancer and also discriminate between the high risk from low risk disease.

Bibliography

1.    Ferlay, J. et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49, 1374-403 (2013).

2.    Godtman, R.A., Holmberg, E., Khatami, A., Stranne, J. & Hugosson, J. Outcome following active surveillance of men with screen-detected prostate cancer.
       Results from the Goteborg randomised population-based prostate cancer screening trial. Eur Urol 63, 101-7 (2013).

3.    Klotz, L. Active surveillance and focal therapy for low-intermediate risk prostate cancer. Transl Androl Urol 4, 342-54 (2015).

4.    Theodorescu, D. et al. Discovery and validation of urinary biomarkers for prostate cancer. Proteomics Clin Appl 2, 556-570 (2008).

5.    Schiffer, E., Bick, C., Grizelj, B., Pietzker, S. & Schofer, W. Urinary proteome analysis for prostate cancer diagnosis: cost-effective
       application in routine clinical practice in Germany. Int J Urol 19, 118-25 (2012).

6.    Neuhaus, J. et al. Seminal plasma as a source of prostate cancer peptide biomarker candidates for detection of indolent and advanced disease. PLoS One 8, e67514 (2013).