Prostate cancer (PCa) is a leading cause of cancer-related death of men globally. Since its introduction, there has been intense debate as to the effectiveness of the prostate specific antigen (PSA) test as a screening tool for PCa. It is now evident that the PSA test produces unacceptably high rates of false positive results and is not prognostic. Here we review the current status of molecular biomarkers that promise to be prognostic and that might inform individual patient management. It highlights current efforts to identify biomarkers obtained by minimally invasive methods and discusses current knowledge with regard to gene fusions, mRNA and microRNAs, immunology, and cancer-associated microparticles.

e565 Background: Metastatic or recurrent cancer continues to be a challenge in patients with urogenital and pancreatic cancers despite the development of newer anti-androgen therapies. MIL-38 is an IgG1 murine monoclonal antibody directed against Glypican-1 (GPC-1). The proteoglycan GPC-1 is upregulated in prostate, pancreatic and bladder cancer cell lines. Targeting of tumor xenografts and lack of adverse events in pre-clinical models suggest chimeric MIL-38 (chMIL-38) is a good candidate for both radioimmunotherapy and antibody-drug conjugate development. Methods: Patients with known metastatic prostate and pancreatic cancer were injected with a single dose of MILGa drug (1mg, 250MBq dose) and imaged with whole body gamma camera scans and SPECT/CT at 30 minutes, 6 h, 24 h, 48 h, 72 h (if required) and 144h post infusion. Blood and urine samples for pharmacokinetic, biomarker studies, cancer markers and hematology and biochemistry analysis were collected at each time point. Dosimetry analysis of tumour images was performed to determine the relative accumulation of MILGa in different organs. Results: To date one pancreatic cancer patient and one prostate cancer patient with metastatic disease have been infused with the MILGa drug. The drug was safe and well tolerated in both patients with no infusion reactions or drug-related adverse events. Tracer uptake was observed in the liver, with mild tracer uptake in the spleen, skeletal system and kidneys. Significant MILGa targeting was seen in Patient 2 24 hours post infusion onwards with uptake in the right foot (right calcaneum and cuneiform bones). SPECT/CT at 24 hours confirmed uptake was in the bone, not in the joint space or soft tissue. Conclusions: MILGa has shown a promising safety profile to date with indication of tumour targeting in metastatic prostate cancer. Additional data from this study may permit the selection and evaluation of potentially sensitive tumor types to be studied for further therapeutic and diagnostic studies. Clinical trial information: ACTRN12616000787482.

e588 Background: Biomarkers that can assist clinicians and patients to proceed when PSA and /or DRE are equivocal. Such biomarkers should establish both sensitivity and specificity for prostate cancer detection in order to improve go-forward decisions to perform prostate biopsy. Following the successful use of a three-protein marker panel to increase the specificity of prostate cancer detection1 we have now used the same technology to examine whether an MIA assay can assist in differentiating aggressive from non-aggressive cancer in prostate cancer patients. Methods: Samples from patients with either aggressive prostate cancer or non- aggressive prostate cancer were obtained from two sources. The cohort criteria comprised of serum samples where blood was drawn from patients with adenocarcinoma and a PSA greater than or equal to 2ng/mL. All men were Caucasian with the exception of 3 who were African American. Non-aggressive prostate cancer was defined as having a Gleason score of 6 (n = 35) and aggressive prostate cancer was characterized as Gleason score 7 and above (n = 69). Biomarker levels were determined using a plate based ELISA for GPC-12 and a bead-based MIA assay for the other markers. Results: By using biostatistical analysis (Simplicity Bio, Switzerland) two models were identified that were able to differentiate between aggressive and non-aggressive prostate cancer. One consisted of a combination of 5 analytes and the other used 6 analytes. Model 1 containing PSA and GPC-1 plus 4 analytes produced a combined sensitivity of 81% and specificity of 78% (AUC 0.81). The second model comprising of GPC-1 with an additional 4 analytes achieved a sensitivity of 72% with a specificity of 76% (AUC 0.76). Both models had a p value of less than 0.05. By itself PSA was a poor predictor of prostate cancer with a sensitivity of 58% and specificity of 43% (AUC 0.55). Conclusions: The analytes identified by the two statistical models demonstrate potential utility for using the combined markers as a new means of differentiating aggressive prostate cancer from non-aggressive cancer. An additional study to further validate these models is currently being constructed.