PSMA PET Additive Value for Prostate Cancer Diagnosis in Men With Negative/Equivocal MRI

sPCa defined as Gleason score 3+4(>10%)=7, Grade group 2 Patients without biopsy (negative PSMA PET) are considered not to have sPCa.

In the experimental arm, if PSMA PET is negative, the patient does not have biopsy

isPCa defined as GS 3+3=6, GG 1 or GS 3+4(≤10%)=7, GG 2

cost-effectiveness analysis to assess the cost per quality adjusted life year (QALY) gained associated with the use of PSMA PET in addition to MRI compared with MRI alone for the diagnosis of sPCa. Importantly, this analysis will take into consideration the impact on costs and QoL associated with the hypothesised reduction in unnecessary biopsies arising from the improved accuracy of PSMA+MRI and the comparative interventions).

Quality of life (QoL) will be assessed using QLQ-C30, which contains 30 items across five functional scales, three symptom scales, global health status, and six single items. Participant responses are collected using a four-point response scale ranging from 'Not at all' to "Very much". Higher scores indicate better QoL and function, while high scores for the symptom scale represent a high level of symptoms.

The generalized anxiety disorder Scale (GAD-7)14 is a 7-item, patient-rated questionnaire for screening and severity measuring of generalised anxiety disorder. The GAD-7 score is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of 'not at all', 'several days', 'more than half the days', and 'nearly every day', respectively, and adding together the scores for the seven questions. Scores of 5, 10, and 15 are taken as the cut-off points for mild, moderate and severe anxiety, respectively.

The modified Cancer Worry Scale adaptation of Cancer Worry Scale is a 3-item questionnaire used in context of cancer worry in abnormal PSA levels in men participating in community screening program. The score is calculated by assigning scores of 1, 2, 3, and 4, to the categories 'not at all or rarely', 'sometimes', 'often', and 'a lot', respectively, and adding together the scores for the 3 questions. A final question asks about feelings of distress related to cancer risk.

Experimental arm: For patients with a positive PSMA PET, the images, the report and a simplified template will be made available to the treating urologist. Up to four identified lesions on PSMA PET and/or MRI will be targeted with each lesion having a minimum 5 cores.

Control arm: Transperineal template prostate biopsies will be performed as per treating urologist's usual practice. No specific template for biopsy is prescribed for the purposes of the study. However, template sampling of the prostate is required, with a minimum of 12 cores,dependent on prostate volume.

Complications following biopsy will be assessed with a modified questionnaire validated in the PRECISION trial. Part 1 following randomisation is a 9 item questionnaire. Part 2 is a 23 item questionnaire administered at 3 and 6 months to assess complications from transperineal prostate biopsy. The following complications will be assessed via these forms: fever, blood in urine, blood in semen, blood in stool, acute urinary retention, erectile dysfunction, urinary incontinence, urinary tract infection and pain in the perineum.

The Sexual Health Inventory for Men (SHIM) is an adapted version of the 5 item International Index of Erectile Function (IIEF-5) score, developed to diagnose the presence and severity of erectile dysfunction. This validated questionnaire has a range of scores from 1 to 25, grading erectile dysfunction into 5 categories (none, mild, mild to moderate, moderate and severe).

Measured in the experimental arm in patients with positive PSMA PET and negative MRI (PIRADS 2). sPCa defined as Gleason score 3+4(>10%)=7, Grade group 2