(UroToday.com) The second session of the Advanced Prostate Cancer Consensus Conference 2021 which was hosted in the context of the COVID-19 pandemic focused on the role of prostate-specific membrane antigen (PSMA) imaging in prostate cancer diagnostics and therapy. Dr. Michael Hofman discussed the role of concomitant FDG-based PET with PSMA-PET for patient selection.
Dr. Hofman began by highlighting that, at the 2019 APCCC meeting, the majority (60%) of respondents suggested that both PSMA-PET/CT and FDG-PET/CT were required in addition to standard imaging to select patients for lutetium-PSMA (Lu-PSMA) therapy. However, since that time, he emphasized that a lot has changed: most notably, the VISION trial, which did not mandate or utilize FDG-PET/CT for inclusion demonstrated improved outcomes for patients treated with Lu-PSMA. Thus, the use of FDG-PET/CT may not be necessary. However, quoting Thomas McCrae, Dr. Hofman suggested that “more is missed by not looking than not knowing” and that we may still derive useful information from performing FDG-PET/CT in this setting.
Supporting this rationale, he provided a comparison of the two randomized controlled trials of 177-Lu-PSMA-617, TheraP, and VISION and patient anecdotes. First, he noted that exclusion rates were higher in the TheraP trial (28%) compared to VISION (12%; difference = 16%) and that there was a higher PSA50 response rate observed in TheraP (66%) than in VISION (46%; difference = 20%). He suggested that the patients who were excluded from TheraP, who may have been included in VISION likely did not benefit from therapy with Lu-PSMA. Thus, the additional exclusion criteria applied in TheraP may enrich the population for those likely to benefit from treatment.
Dr. Hofman then highlighted a number of examples where FDG-PET/CT may provide additional clinical information that is actionable. He first cited the case of a patient who, based on the PSMA-PET/CT, would be eligible for Lu-PSMA based on both criteria used in TheraP and VISION. However, imaging with FDG-PET/CT demonstrated a higher burden of FDG-avid disease than PSMA-avid disease. Thurs, a large burden of this patient’s disease would not be targeted with Lu-PSMA. Thus, the use of FDG-PET/CT allows the treating physician to select for other treatments (eg. cabazitaxel) which may be more effective.
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Dr. Hofman then cited another example highlighting the difference in how PSMA positivity is defined between TheraP (SUVmax ≥20%) and VISION (intensity > liver in lymph nodes greater than 2.5cm or viscera >10 cm). In the example highlighted a patient with a moderately intense lymph node (SUVmax 7) would be eligible for Lu-PSMA based on VISION criteria but not TheraP. As a result, this patient was excluded from TheraP. However, they underwent off-protocol FDG-PET/CT which demonstrated PSMA-negative and FDG-positive disease which may be better treated by a non-theranostic approach.
Further to this point, Dr. Hofman emphasized the important relationship between dosimetry and response. In particularly, he highlighted that for patients with lesions where the delivered dose is <10 Gy, patients have poor response rates.
Additionally, he highlighted that PSMA-PET SUVmax corresponds to dose delivery. Thus, routine use of PSMA-PET/CT may act as a biomarker of response and may be prognostic.
A recent 270 patient study of Australian, American, and German patients demonstrated that both the volume of FDG-avid disease and PSMA-intensity are prognostic for overall survival among patients who receive Lu-PSMA, with worse survival for patients with higher volumes FDG-avid disease and better overall survival for patients with higher SUVMean.
Additionally, Dr. Hofman emphasized that disease-related heterogeneity is a problem in current cancer treatment. The use of FDG-PET/CT provides information about highest risk, and most metabolically active, disease. Thus, use of FDG-PET/CT may allow biopsy to target the sites of disease with the most aggressive radiographic approach or to target multiple sites with different phenotypes.
Further, Dr. Hofman noted that the TheraP trial mandated post-therapy SPECT-CT. Doing so allowed identification of a subset of patients with profound responses in the early cycles of Lu-PSMA therapy. Thus, treatment can be paused and saved for progressive disease in the future.
In conclusion, he emphasized that theranostic treatment with 177Lu-PSMA allows you to see what you’re treating. Further, FDG-PET/CT positive disease is clinically relevant with a high-proliferative rate and represents the subset of disease that is most likely to cause symptoms.
Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2021 Advanced Prostate Cancer Consensus Conference, Saturday, October 9, 2021.