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

Prospective Multi-centre Randomised Trial of the Additive Diagnostic Value of PSMA PET in Men With Negative/Equivocal MRI in the Diagnosis of Significant Prostate Cancer

This clinical trial will evaluate PSMA PET additive value for significant prostate cancer (sPCa) diagnosis in men with negative/equivocal MRI

This open label, phase III, multi-centre, randomised trial with a non-inferiority objective will evaluate the additive diagnostic value of PSMA PET for men with negative/equivocal MRI in the diagnosis of significant prostate cancer. Patients with a clinical suspicion of prostate cancer with PI-RADS 2 or 3 on MRI, meeting all the inclusion and none of the exclusion criteria will be randomised into experimental and control arms. Patients in the experimental arm would be subjected to Pelvic PSMA PET/CT, wherein the PSMA negative patients would not undergo biopsy as opposed to PSMA positive patients who will be subjected to Transperineal targeted prostate biopsy. Whereas patients in the control arm will only receive Standard of Care (SOC) with no additional imaging (PSMA PET) and will undergo Transperineal template prostate biopsy. The co-primary objectives are to assess (1) the percentage of men with sPCa in the experimental arm (transperineal targeted biopsy) compared to the control arm (transperineal template biopsy) defined as the presence of a single biopsy core indicating disease Gleason score (GS) 3+4(>10%)=7, grade group (GG) 2, and (2) the percentage of men who avoid transperineal prostate biopsy between both arms. The secondary objectives include determining the percentage of clinically insignificant PCa on targeted biopsy (experimental arm) versus transperineal template biopsy (control arm); estimating the difference in complications from transperineal prostate biopsy between both arms; the health economics impact between the experimental and control arms; estimating the mean difference between both arms in change from baseline in health-related quality of life (QoL); estimating the mean difference between both arms at each time point in generalised anxiety and cancer worry.

Inclusion Criteria:

• Patients must meet all the following criteria for study entry:

  1. Males aged ≥ 18 years at the time of consent

  2. No previously diagnosed prostate cancer

  3. No previous prostate biopsy

  4. Having undergone MRI within 9 months prior to randomisation and meet one of the following criteria:

     • PI-RADS 2 AND ≥1 red flag defined as:

       • PSA density >0.1
       • Abnormal DRE
       • Strong family history (1 first degree relative or ≥2 second degree)
       • BRCA mutation
       • PSA >10
       • PSA doubling time <36 months
       • PSA velocity >0.75/year

     • PI-RADS 3

  5. Intention for prostate biopsy

  6. Willing and able to comply with all study requirements

Exclusion Criteria:

• Patients who meet any of the following criteria will be excluded from study entry:

  1. Having a PSA >20ng/ml
  2. Having ≥ cT3 on DRE
  3. Significant morbidity that, in the judgement of the investigator, would limit compliance with study protocol