Short summary

Our study aim is to improve the overall sensitity and detection of clinical significant prostate cancer when performing prostate biopsies. In the present study we will use mutiparametric magnetic resonans scan (mpMRI) and a new set of biomarkers in combination, prior to performing standard biopsies in order to develop a prediction model for the biopsy outcome. If proven successful the model would offer excellent risk stratification and possibly mitigating the need for biopsies.

Rationale

Background:

Prostate cancer (PC) remains a significant cause of morbidity and death among men in Denmark and the rest of the western world. Over 4000 PC cases are diagnosed every year being the second most common malignancy among men in Denmark. With increasing life expectancy, the incidence of PC is projected to increase. Pivotal to the successful treatment of prostate cancer is establishing an early diagnosis. Localised PC is potentially curable and current curative treatment options have shown efficacy in reducing cancer related mortality. 

TRUS biopsies:

Transrectal ultrasound guided prostate biopsies (TRUS biopsies) are conducted routinely for histopathological confirmation in cases of suspected PC. Indication for prostate biopsies includes elevated Prostate Specific Antigen (PSA) levels or palpable tumor on digital rectal examination. TRUS biopsies is associated with morbidity in the form of infection, hematuria, rectal bleeding and discomfort. Some of these complications may require hospital admission and can be life threatening. Current standard biopsy regimes include 10 to 14 systemic biopsy cores taken from the peripheral zone of the prostate. The majority of PC involve the posterior peripheral zone of the prostate readily available for biopsies. The remaining PC are isolated to the transition-, central- and anterior zone of the prostate which are not routinely biopsied on systemic biopsies. Thus, anteriorly located cancers may not be sampled with routine investigations and TRUS biopsies may yield false negative results. As the biopsies are taken randomly throughout the gland, significant cancers located in the peripheral zone will in some cases be missed. 

Biomarkers and liquid biopsies:

PSA testing has been widely adopted and more cancers are being detected in Denmark due to unsystematic screening with PSA. PSA is a glycoprotein of the human kallikrein family, and elevated serum concentrations are associated to PC. It is organ specific but not cancer specific, therefore other causes may elevate values, including benign prostatic hyperplasia, prostatitis, urinary tract infections and bladder outlet obstruction. To distinguish prostate cancer from other causes of PSA elevation and to confirm the diagnosis, TRUS biopsies are currently the standard diagnostic test. 

A range of novel biomarkers has been purposed to overcome the limitations of PSA's low specificity. Few of these biomarkers have been implemented in clinical practice. In a recently published study, Albitar et al, using a panel of urine and plasma biomarkers, where able to predict biopsy outcomes with a positive predictive value (PPV) of 90% and negative predictive value (NPV) of 89% tolerating some low grade cancers (Gleason score < 7). This idea has been disseminated as liquid biopsies. 

mpMRI of the prostate:

Multiparametric magnetic resonance imaging (mpMRI) of the prostate has emerged as a new technology with the ability to detect PC. Especially in the setting of previously negative TRUS biopsies, mpMRI can provide important additional information enabling targeting of biopsies towards suspected PC lesions. Nevertheless, a PC negative mpMRI may fail to detect cancers in 43% of cases and miss 16% of PCs classified as clinical significant. Thus a negative mpMRI will currently still mandate systemic biopsies. Therefore, novel approaches are needed to better direct biopsies and select patient for biopsies.

Aim:

The purpose of the current thesis is to study the following issues:

1. Assessing the value of prebiopsy mpMRI combined with liquid biopsies in biopsy naïve men in predicting biopsy results and possible deriving a diagnostic predictive model.

2. Assessment of the performance of TRUS mpMRI fusion guided biopsies vs. systemic biopsies combined with liquid biopsies.

3. Confirming the value of liquid biopsies and investigating its relation to tumour grade and volume.

Description of the cohort

Adult competent men referred for prostate biopsies between18-75 years of age, with a PSA below 20 and no previous history of prostate biopsies. 

Data and biological material

Multiparametric magnetic resonans scan images, demographic baseline characteristics and biopsy results. Blood and urine samples will be collected and processed.

Collaborating researchers and departments

Department of Urology, Odense University Hospital

• Professor DMSc, Lars Lund, Consultant
• MD, PhD, Mads Hvid Poulsen, Consultant

Department of Radiology, Odense University Hospital

• Associate Professor, MD, PhD, Ole Graumann,  Chief Consultant.
• MD, Jon Asmussen, Consultant

Publications associated with the project

Prostatectomy-based validation of combined urine and plasma test for predicting high grade prostate cancer. Albitar, M., Ma, W., Lund, L., Shahbaba, B., Uchio, E., Feddersen, S., ... Shore, N. (2018). The Prostate, 78(4), 294-299. https://doi.org/10.1002/pros.23473