Prostate Cancer Malignancy Grading Using Prostate Specific Membrane Antigen (PSMA) PET and Machine Learning

Prostate cancer is the number one cancer diagnosed in Norwegian men, with a total number of 5118 new cases in 2016. One in seven men will have a Prostate cancer diagnosis by the age of 75. Complications significantly affecting quality of life, such as impotence and incontinence, are common after treatment of prostate cancer even with modern surgical methods and radiation therapy. Focal therapies trying to limit the damage on healthy surrounding tissue is currently being investigated as treatment alternatives even for patients with high-risk prostate cancer. Many malignant lesions in the prostate will however not have clinical significance as they are slow growing.

Grade of malignancy is assessed on histopathological examination by using Gleason grading: A pathologist grades the pattern in the most dominant and second most dominant parts of the prostate cancer. The resulting Gleason Score is the sum of the two grades. Gleason Score, PSA and disease stage evaluated from clinical examination and MRI is used for risk assessment of the malignancy. When deciding between treatment alternatives one must take into consideration the grade of malignancy, and the burden associated with complications after treatment, as well as life expectancy and comorbidity. Although MRI has good sensitivity in finding clinically significant prostate cancer for targeting biopsy, it remains unclear if biopsy can be avoided when MRI is negative. MRI of the prostate is standardized through the PI-RADS V2 recommendations, but image reader experience affects the detection rate of prostate cancer. For patients with low-risk prostate cancer, who are eligible for active surveillance instead of immediate treatment, regular follow-up and repeated biopsies with risk of infection, sepsis and bleeding is necessary, as current imaging does not provide the necessary specificity.

The new PET tracers targeting prostate specific membrane antigen (PSMA) can improve localization of primary tumours as well as suspicious lesions and improve diagnosis of recurrent prostate cancer. PSMA-PET can provide improved assessment of prostate cancer when used in diagnostic imaging, compared to MRI alone. PSMA expressions is increased in prostate cancer cells and correlate with disease aggressiveness. With PET-imaging it is possible to quantify the uptake of radioactive PSMA tracers, even at multiple time points (dynamic PET-imaging). In conventional PSMA PET, a static scan is performed around one hour after tracer injection. By performing a dynamic scan, tracer uptake can be recorded from the time immediately after tracer injection and on succeeding time points.

The PSMA radiotracer that will be used in the study, is one of the most common radiotracers used for detection of prostate cancer. Despite this, recent studies of the biodistribution of this tracer provides limited evidence of its metabolic pathways. Therefore, we intend to perform a more extensive metabolite analysis in this project.

PET scanners are combined with CT or MRI in order to provide anatomical correlation of PET tracer uptake. CT has the benefit of being well suited for use in attenuation correction of the PET images. In contrast MRI is a bit harder to use in attenuation correction, but it has excellent soft tissue contrast, enabling good visualization of the prostate and surrounding soft tissue structures.