PROSTAMIP

• ClinicalTrials.gov ID: 
• Status: Recruiting

Prostate cancer (PCa) is currently the most common cancer in men in Finland (www.cancerregistry.fi). Although prognosis is very good in majority of men, it is noteworthy that still up to 20% of PCa cases are metastatic at the time of initial diagnosis and yearly 900 men die because of prostate cancer. Robust primary staging is, therefore, one of the most important prognostic factors, and it is crucial for treatment decision. Despite their low sensitivity to detect metastasis, bone scintigraphy (BS) and contrast enhanced whole body computed tomography (ce-wbCT) are recommended by current guidelines for primary staging in men at risk of metastasis.

PSMA-PET Prostate specific membrane antigen (PSMA) is a transmembrane protein expressed in prostate cancer cells. Using this as an epitope, the PSMA positron emission tomography (PSMA-PET), is a promising newcomer in a field of prostate cancer imaging. It has rapidly gained popularity due to its high sensitivity, and recently published, large-scale randomized study demonstrated its superiority over BS and CT. Due to increasing scientific evidence, in near future, PSMA-PET most probably will replace BS and ce-wbCT in staging of men with high-risk prostate cancer.

Challenges in PSMA-PET imaging 1) Most importantly, it should be noted that PET-scanners are expensive to buy and are not that commonly found in small-scale health care units nationally or even internationally. 2) Also, the specificity of PSMA-PET imaging should be evaluated very carefully. In the PROSTAGE study, we have recently demonstrated that PSMA-PET yields bone lesions that are PSMA-avid but not seen by the conventional imaging i.e. BS or CT (PSMA-only lesions). It is not known if these lesions are prostate cancer at all, or some other benign PSMA-avid tissue. Especially, it is a true clinical dilemma whether a patient who presents only PSMA-only should be treated as having a metastatic or non-metastatic disease.

PSMA-SPECT Single photon emission computed tomography (SPECT) system differs from the PET system by utilizing a rotating gamma detector. The system is also advantageous because of its broader availability compared to PET system. Basically, every health care unit treating prostate cancer patients has a SPECT system. MIP-1404 is a small-molecule PSMA inhibitor that can be used in SPECT systems, and, in prospective and retrospective studies, it has shown high potential to detect prostate cancer lesions in primary staging.

Histopathology PSMA-only lesions are commonly seen in bone. To characterize these lesions in more detail, a histopathological analysis is mandatory. Today ultrasonography and especially CT or MRI targeted biopsies are clinically feasible and accurate to perform.

Circulating tumor DNA Liquid biopsy evaluates free DNA found in blood stream, the cell free DNA, of which part is derived from cancerous tissue, the circulating tumor DNA (ctDNA). The advantage of ctDNA method is its non-invasiveness and more importantly its ability to evaluate tumor and metastasis heterogeneity. Since the amount of ctDNA increases as the aggressiveness of the cancer increases, it might be possible to differentiate men with metastatic and non-metastatic prostate cancer according to ctDNA quantity or mutational load of ctDNA.

Our preliminary, unpublished data suggests that rectal microbiome is associated with malignant finding in men undergoing prostate biopsies due to clinical suspicion of prostate cancer. Also, microbiome seems to be associated with cancer aggressiveness in these men. No data exists, whether certain microbiome could differentiate men with non-metastatic and metastatic prostate cancer.