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PSMA and Beyond 2025: When Should We Use FDG PET?

(UroToday.com) The 2025 PSMA and Beyond annual meeting featured a LuPSMA therapy session and a presentation by Dr. Andrei Iagaru discussing when we should use FDG PET. Dr. Iagaru started by emphasizing that there is a fine balance between doing no imaging and all possible imaging and that we should be striving for is appropriate imaging.

The following arguments could be made for no PSMA imaging being needed:

  • In VISION,1 85.1% of participants had a 68Ga-PSMA-11 PET/CT scan meeting the study eligibility definition
  • Complexity
  • Cost
  • It may limit access to care even more than it already does
  • Unproven as to whether there are better outcomes

Conversely, the following arguments could be made for PSMA imaging being needed:

  • One of the undisputed principles of treatment among patients with cancer is knowing the extent of disease to the best of one’s ability
  • By excluding patients unlikely to response, PSMA PET will save health-care costs in the long run
  • The additional resources and cost to obtain the useful information from PSMA PET are a small fraction of what a prostate cancer patient and the health care system will spend

Jadvar et al.2 previously assessed baseline 18F-FDG PET/CT parameters as imaging biomarkers of overall survival in mCRPC. Among the 87 patients, the median overall survival was 16.5 months (95% CI 12.1-23.4 months), and the overall survival probability at 24 months was 39% ± 6%. When the sum of SUVmax was grouped into quartile ranges, there was poorer survival probability for the patients in the fourth-quartile range than for those in the first-quartile range, with a univariate hazard ratio of 3.8 (95% CI, 1.8-7.9):

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What about access, cost, and reimbursement? The International Atomic Energy Agency can record the number of PET scanners and SPECT scanners (per 1 million), highlighting the geographical variation across the globe:

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Dr. Iagaru provided the following cost analysis, emphasizing that FDG PET/CT costs $2,545, PSMA PET/CT costs $6,445, and six cycles of 177Lu-PSMA-617 costs $300,000:

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To try and improve speed and accessibility for monitoring therapy, Dr. Iagaru’s team evaluated the feasibility of using the StarGuide, a new generation multi-detector cadmium-zinc-telluride (CZT)-based SPECT/CT, for whole-body imaging in the setting of post-therapy imaging of 177Lu-labeled radiopharmaceuticals.2 Among 31 patients, the StarGuide system acquired vertex to mid-thighs post-therapy SPECT/CT scans with 4 bed positions, 3 min/bed and a total scan time of 12 min. In comparison, the standard GE Discovery 670 Pro SPECT/CT system typically acquires images in 2 bed positions covering the chest, abdomen, and pelvis with a total scan time of 32 min. The post-therapy scans acquired with faster scanning time using StarGuide system had comparable detection/targeting rate compared to the Discovery 670 Pro SPECT/CT system, in addition to detecting larger lesions defined by RECIST criteria on the pre-therapy PET scans:

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In an effort to assess response rates and adjust treatment appropriately John et al.4 sought to evaluate change in 177Lu-PSMA SPECT quantitative parameters to monitor treatment response. Among 127 men with progressive mCRPC, at baseline and week 6, 76% had analyzable serial 177Lu-PSMA SPECT/CT imaging. SPECT total tumor volume was reduced between baseline and week 6 in 74% of patients. Any increase in SPECT total tumor volume between baseline and week 6 was associated with significantly shorter PSA progression free survival (HR 2.5, 95% CI, 1.5-4.2) but not overall survival. Thus, increasing PSMA SPECT total tumor volume on quantitative 177Lu-PSMA SPECT/CT predicted short progression-free survival and may play a future role as an imaging response biomarker, identifying when to cease or intensify 177Lu-PSMA therapy. Dr. Iagaru provided the following workflow for incorporating SPECT/CT and allowing switching to other therapies among those patients not responding to 177Lu-PSMA therapy:3

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In 2024, Dr. Iagaru’s group published results of their utilization of the StarGuide CZT SPECT/CT system in same-day post-infusion assessment and early treatment response to 177Lu-PSMA-617.5 Among 56 patients who underwent at least 2 post-therapy SPECT/CTs, the whole-body SPECT/CT scans (~ 12 min per scan) were well tolerated, with 221 same-day scans performed (89%). Quantitative analysis of SPECT/CT images showed that 37 patients (66%) had > 30% reduction in Lutetium-total tumor volume, associated with significantly improved overall survival (median not reached versus 6 months, p = 0.008) and PSA progression free survival (median 6 months versus 1 months, p < 0.001).

One scenario we should use 18F-FDG PET is to check eligibility before 177Lu-PSMA-617 therapy:

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A second scenario in which we should use 18F-FDG PET is for troubleshooting during 177Lu-PSMA-617 therapy, including stopping PSMA radioligand therapy due to FDG positive/PSMA negative progression:

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Dr. Iagaru concluded his presentation by discussing when we should use FDG PET with the following take home points:

  • 18F-FDG is reimbursed by CMS for “subsequent treatment strategy”
  • 18F-FDG should be used for proper patient selection prior to 177Lu-PSMA-617 treatment (although the label does not require it)
  • 18F-FDG can help troubleshoot during 177Lu-PSMA-617 treatment
  • The more we know about the biology of cancer, the better decisions we will make about our patient’s management

Presented by: Andrei Iagaru, MD, Stanford University, Palo Alto, CA

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 PSMA and Beyond Annual Meeting, Los Angeles, CA, Fri, Mar 28 – Sat, Mar 29, 2025. 

References:

  1. Sartor O, de Bono J, Chi KN et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep 16;385(12):1091-1103.
  2. Jadvar H, Desai B, Ji L, et al. Baseline 18F-FDG PET/CT parameters as imaging biomarkers of overall survival in castrate-resistant metastatic prostate cancer. J Nucl Med. 2013 Aug;54(8):1195-1201.
  3. Song H, Ferri V, Duan H, et al. SPECT at the speed of PET: A feasibility study of CZT-based whole-body SPECT/CT in the post 177Lu-DOTATE and 177Lu-PSMA-617 setting. Eur J Nucl Med Mol Imaging. 2023 Jul;50(8):2250-2257.
  4. John N, Pathmanandavel S, Crumbaker M, et al. 177Lu-PSMA SPECT quantification at 6 weeks (dose 2) predicts short progression-free survival for patients undergoing 177Lu-PSMA-I&T therapy. J Nucl Med. 2023 Mar;64(3):410-415.
  5. Song H, Leonio MI, Ferri V, et al. Same-day post-therapy imaging with a new generation whole-body digital SPECT/CT in assessing treatment response to 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging. 2024 Jul;51(9):2784-2793.