(UroToday.com) The 37th Annual European Association of Urology Congress held in Amsterdam, the Netherlands between July 1st,and 4th 2022 was host to a prostate cancer “Game Changing Session”. Dr. Lih-Ming Wong discussed the results of PEDAL: A Phase III study comparing diagnostic accuracy of mpMRI prostate to 18F-DCPyL PSMA PET/CT.
Diagnosing prostate cancer in the setting of an elevated PSA remains imperfect. MRI has helped improve the detection of clinically significant disease; however, MRI retains a false negative rate of 10-20%. PSMA-PET/CT, although currently mainly used in the staging work up of high-risk disease patients and in salvage treatment planning following biochemical recurrence post-prostatectomy and/or radiation, may be of clinical utility in this setting.
Dr. Wong and colleagues hypothesized that PSMA-PET/CT could be superior to mpMRI prostate to detect prostate cancer and target lesions on prostate biopsy. The authors accordingly designed a phase III, prospective cross-sectional trial comparing the diagnostic accuracy of mpMRI and 18F-DCFPYL-PSMA-PET/CT across multiple centers in Australia (St Vincent’s, Melbourne Health, Epworth Health, Sydney Adventist) and New Zealand (Christchurch Pacific Radiology) between 2020 and 2022. The outcomes of interest were:
- Primary: Diagnostic accuracy to detect prostate cancer at biopsy (Receiver operating characteristic curve [ROC] Area under the curve [AUC])
- Secondary: Clinically significant prostate cancer, benefit of coregistration
To summarize, inclusion criteria were:
- Elevated PSA >3.0 or (elevated PSA >2.0 + positive family history)
- Low free/total ratio (<25%)
- Abnormal DRE
Exclusion criteria included:
- Known prostate cancer diagnosis
- Previous prostate biopsy within 3 years of recruitment (TURP permissible)
- Previous mpMRI within 3 years of recruitment
- History of active malignancy within the last 3 years (Except skin cancer or melanoma in situ)
- Contraindication to 3T mpMRI or previous total hip joint replacement
For the mpMRI arm:
- PIRADS v2.1 was utilized, lesion location by sector map was noted
- T2, DWI, ADC, DCE phases performed
- EPE, capsular abutment, SV invasion, LN status, and lesion size were assessed
- A positive lesion was defined as PIRADS 3, 4, or 5
- Lesion location by sector map was noted
- SUV max <4: Negative
- SUV max 4-7: Equivocal
- SUV max ≥7: Positive
- SV invasion, LN status, incidental lesions, and metastases were assessed
- Final designation of lesion positivity assigned by an expert reader using a combination of SUV max, focality, and ratio to background
The trial flow chart is demonstrated below. 253 patients were referred, of whom 235 completed both diagnostic imaging, and 180 patients had a prostate biopsy.
With regards to the primary outcome of diagnostic accuracy (ROC AUC) to detect any prostate cancer, mpMRI demonstrated superior accuracy: 0.77 for MRI (95% CI: 0.70 – 0.84) versus PET, irrespective if an SUVmax cutoff of 8.14 (0.62, 95% CI: 0.54 – 0.70) or SUVmax cutoff of 7 was assigned (0.64, 95% CI: 0.7 – 0.72).
mpMRI demonstrated superior sensitivity, specificity, and negative predictive values compared to PSMA-PET/CT as demonstrated in the table below.
How did findings from mpMRI correlate with those from PSMA-PET/CT and vice versa?
Of 116 patients with PET positive findings (SUVmax >7), 79 (68.1%) had PIRADS 4-5 lesions. However, highlighted in red below, is the number of patients with a negative mpMRI (PIRADS 0-2) and PET positive lesions SUVmax>7 (n=30). Also highlighted are those with a positive mpMRI (PIRADS 4-5) with negative PET SUVmax<4 lesions (n=8).
Of those 30 patients with a PET positive lesion and negative mpMRI, 24 underwent a prostate biopsy with 9 (37.5%) positive biopsies found. Of the 8 patients with a positive mpMRI (PIRSDS 4-5) and negative PET, all of whom underwent a biopsy, prostate cancer was found in 5 (62.5%) patients. Thus, these patients may potentially be those that may benefit from complimenting both imaging modalities together, albeit at an elevated financial toxicity burden.
No significant differences were seen between the two modalities with regards to diagnostic accuracy of clinically significant prostate cancer.
As with most trial designs, “contentious decisions” were made and there remain areas of concern:
- PSMA-PET/CT range of field
- Neck to pelvis in this study, also led to detection of metastatic prostate cancer in 13.9% of patients. This imaging modality thus served as both a diagnostic and staging scan.
- Reporting of PSMA-PET/CT: How to define “positive” lesions?
- Prostate biopsies were not mandated
- What was the optimal prostate biopsy technique? Should a PSMA-PET/CT-fusion biopsy technique now be developed?
Dr. Wong concluded as follows:
- mp-MRI has better diagnostic accuracy than 18F-DCFPYL PSMA-PET/CT (SUVmax) to detect any prostate cancer
- Diagnostic accuracy ROC AUC: 0.77 versus 0.62, p=0.01
- Performance of PSMA-PET/CT in this setting will certainly improve
- Learning curve: It will not be SUVmax alone, but also potentially patterns of tracer distribution, volumes, background to signal ratios, etc.
- mp-MRI of the prostate remains 1st line for now
- Does PSMA-PET/CT have a role currently? Potentially in patients with:
- A negative MRI incongruous with clinical features
- Equivocal MRI findings with the patient reluctant to have a biopsy
- Contraindications to MRI
- An elevated PSA (e.g. >20) with interest in an all-in-one diagnostic and staging scan
Presented by: Dr. Lih-Ming Wong, MBBS, Associate Professor, Department of Urology, University of Melbourne, Melbourne, Australia
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2022 European Association of Urology (EAU) Annual Hybrid Meeting, Amsterdam, NL, Fri, July 1 – Mon, July 4, 2022.