(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. Jochen Walz led a discussion session following Dr. Lih-Ming Wong’s presentation: “Phase III study comparing diagnostic accuracy of mpMRI prostate to 18F-DCPyL PSMA PET/CT.”
Dr. Walz began by noting that mpMRI has been the diagnostic standard of care for prostate cancer diagnosis since 2019. Compared to systematic biopsy alone, targeted biopsy improves detection of clinically significant prostate cancer (csPCa) as has been demonstrated in several trials such as PROMIS.1 Standard biopsy has low diagnostic yields of ~40% detection rate at time of first biopsy and has a false negative rate of 25-35% for csPCa, when compared to template biopsies.
But given the imperfect sensitivity of mpMRI, do we still need to do even better?
Referencing Dr. Wong’s prior presentation of the PEDAL trial, a head-to-head superiority trial of DCFPYL-PET/CT versus mpMRI, Dr. Walz argued that a non-inferiority trial design may have been better in this setting given the high benchmarks that mpMRI has set to date. From a practical standpoint, this would’ve required a larger sample size, but from a clinical standpoint, such a non-inferiority design would’ve likely been more relevant.
Dr. Walz next compared the sensitivites of mpMRI alone, PSMA alone, and combination of mpMRI + PSMA using the PEDAL trial, PRIMARY trial,2 and a systematic review. It appears that the combination of mpMRI and PSMA improves the overall sensitivity of imaging techniques (i.e. lowers the false negative rate). So what are the remaining unmet needs?
One is improved specificity to avoid unnecessary prostate biopsies in patients without csPCa. The specificity of these imaging modalities, even in combination, remains quite low, thus necessitating continued biopsies in patients at elevated risk.
Another is improved negative predictive value performance to rule out the need for prostate biopsies.
According to Dr. Walz, the combination of mpMRI with PSMA-PET/CT does not improve the NPV sufficiently.
One potential solution proposed by Dr. Walz is to use strict cut-offs for mpMRI and PSMA to predict csPCa (i.e. ISUP 2 disease or worse). In 459 patients with both mpMRI and PSMA-PET/CT, all patients with SUVmax ≥16 had ISUP 2 disease or worse on biopsy.
The cost issue of combining these two tests remains prohibitive. Currently, in France, an MRI costs approximately 300 Euros, whereas a PSMA costs 1500 Euros. Until PSMA usage shows unquestioned benefit in this setting, it is unlikely to be approved in the pre-biopsy work up of at-risk patients.
As such, it appears that PSMA is currently best served in the salvage setting as demonstrated by the EMPIRE-1 trial, a single center, open-label, phase 2/3 trial that evaluated 18F-fluciclovine-PET/CT versus conventional imagine to guide postprostatectomy salvage radiotherapy for prostate cancer patients.3
Dr. Walz ended his presentation with the following questions:
- How do we perform fusion biopsies in the PSMA setting? Can we just use MRI fusion software?
- How do we deal with “incidental” metastatic patients?
Presented by: Dr. Jochen Walz, MD, Associate Professor, Head, Department of Urology, Institut Paoli-Calmettes Cancer Centre, Marseille, France
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.
References:
- Ahmed HU, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017;389(10071):815-22.
- Emmett L, et al. The Additive Diagnostic Value of Prostate-specific Membrane Antigen Positron Emission Tomography Computed Tomography to Multiparametric Magnetic Resonance Imaging Triage in the Diagnosis of Prostate Cancer (PRIMARY): A Prospective Multicentre Study. Eur Urol. 2021;80(6):682-9.
- Jani AB, et al.18 F-fluciclovine-PET/CT imaging versus conventional imaging alone to guide postprostatectomy salvage radiotherapy for prostate cancer (EMPIRE-1): a single centre, open-label, phase 2/3 randomised controlled trial. Lancet. 2021;397(10288):1895-904.