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Prostate Specific Membrane Antigen Focal Ablation Imaging (PSMA-FAB) - Beyond the Abstract

Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) has revolutionized prostate cancer imaging in the last decade. Not only does the modality improve the detection of intra-prostatic lesions, especially when considering clinically significant prostate cancer, but what is most relevant in primary assessment, it discloses the presence of extra-prostatic involvement with enhanced cancer staging.1-4

This is potentially extensible to localized treatment, including focal therapy, which is particularly appropriate for patients with tumors confined to specific areas, typically identified by means of advanced imaging and biopsy techniques.5-10 At present, the European Association of Urology (EAU) guidelines consider focal therapy with high-intensity focused ultrasound (HIFU) or cryotherapy in low-intermediate risk prostate cancer patients, as an alternative to active surveillance or radical therapy, in the context of clinical trials or prospective registries.11-16 Advances in imaging technologies, particularly multiparametric magnetic resonance imaging (mpMRI), have enhanced the precision of tumor localization, making focal therapy a viable option for selected patients.

In 2023, Giganti et al. proposed a standardized system for scoring the appearance of the prostate on mpMRI after focal therapy in localized prostate cancer.17 The authors introduce the Prostate Imaging after Focal Ablation (PI-FAB) classification, divided into a 3-point scale for mpMRI. PI-FAB employs key MRI sequences in a specific order: dynamic contrast-enhanced (DCE) imaging first, followed by diffusion-weighted imaging (DWI)—including both high b-value images and apparent diffusion coefficient (ADC) maps—and lastly, T2-weighted imaging. Initial research has shown that PI-FAB is highly sensitive in detecting in-field recurrence of clinically significant prostate cancer after focal therapy, although specificity and positive predictive value require further validation.18,19
In our Institution, thanks to a decade of fruitful collaboration between Urology, Nuclear Medicine and Radiology departments, thousands of prostate cancer patients have been imaged and assessed at various clinical settings, including the enrollment in our dedicated prospective trials on primary cancer diagnosis (protocols ICH/382/216 and PROSPET-BX ID 3131) and focal therapy (HIFU) assessment (ICH-018: Focal Therapy for organ-confined prostate cancer).5-9,20,21 Based on our experience, and given the lack of proper recommendations, herein we propose specific PSMA-PET criteria for focal therapy monitoring (designed for HIFU, but extensible to other focal ablation treatments) to be considered as complementary to mpMRI and to be embedded in a dedicated combined scoring system. 22

These criteria (Table 1), denominated Prostate Specific Membrane Antigen Focal Ablation Imaging (PSMA-FAB) score, have been developed, finding inspiration in the above-mentioned PI-FAB scoring system.17 The PSMA-FAB classification is divided into three categories of response: a) PSMA-FAB1, corresponding to a PSMA-PET positive pre-HIFU and negative 1 year later (continue monitoring); b) PSMA-FAB2, corresponding to a PSMA-PET negative before and after HIFU (assess PSA kinetics and MRI, with biopsy to be considered in case of suspicion); and c) PSMA-FAB 3, corresponding to either positive or negative pre-HIFU PSMA-PET, with positive post-HIFU PSMA-PET (recommend biopsy).

Table 1: Response criteria adapted from Giganti et al.17 to be used to assess recurrence of prostate cancer on PSMA PET/CT imaging after focal ablation using the PSMA-FAB score.


Patients’ management according to PSMA-FAB would follow a similar pathway to the one proposed by PI-FAB. For the definition of PSMA-PET positivity, we recommend the previously published criteria, including PRIMARY score,5,23,24, and SUVmax or SUVratio cutoffs.20-23 In particular, Primary scores 4 and 5 are always to be considered positive, whereas for score 3, the positivity can be based on SUVratio ≥2.2 or SUVmax ≥ 5.4 (as previously published in our casuistic), which have resulted able to identify clinically significant prostate cancer with an accuracy of 81% and 90%, respectively.6-9, 25 To better understand the different scenarios, some explicatory cases have been illustrated (Figure 1). The principal aim of our proposed scoring system is to limit the number of unnecessary biopsies at follow-up, while maintaining the optimal diagnostic performance of our advanced imaging modalities.


Figure 1: Illustrative examples of various PSMA-FAB scores.

Failure rates after focal therapy vary depending on patient risk factors and the specific treatment used, generally ranging from 10% to 30%. These failure rates highlight the importance of careful patient selection, close monitoring through PSA testing and imaging, and readiness to provide salvage therapies when needed.26,27 The proven cost-effectiveness of PSMA-PET in other settings,28, 29 and the boosted performance in case of combination with mpMRI,5,23 have suggested to us a similar combined score for focal therapy. More specifically, we developed a dedicated Focal-therapy Imaging Response Evaluation Score (FIRE-SCORE) to be used in prostate cancer patients treated with focal therapy.

More specifically, FIRE-SCORE 1 would correspond to a complete response to focal therapy. FIRE-SCORE 3, on the counterpart, would comply with treatment failure to be confirmed by a new reclassification biopsy. Vice versa, FIRE-SCORE 2 would leave more discretionarily to the urologist, allowing a complementary role for PSA kinetics, clinical assessment, and imaging comparison. Being aware that PI-FAB has a high specificity (86-93%), and sensitivity (78-84%) in depicting clinically significant prostate cancer at surveillance imaging 14-16 months post-HIFU,30 whereas PSMA-PET complements the 25% of clinically significant cancers missed by mpMRI, particularly in cases with negative or equivocal findings.7 Both PSMA-FAB and FIRE-SCORE are under investigation in our prospective cohort, and we have the intention to extend the collaboration to other Centers of excellence, thus embracing the proposal made by Giganti et al.17 in the optics of an International validation.

DECLARATIONS
This article is reproduced from Lopci et al.22 licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License, http://creativecommons.org/licenses/by-nc-nd/4.0/.

Written by: Egesta Lopci, Nuclear Medicine, IRCCS, Humanitas Research Hospital, Rozzano, Italy

References:

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  19. Gelikman DG, Kenigsberg AP, Mee Law Y, Yilmaz EC, Harmon SA, Parikh SH, et al. Evaluating Diagnostic Accuracy and Inter-reader Agreement of the Prostate Imaging After Focal Ablation Scoring System. Eur Urol Open Sci. 2024 Mar 4;62:74-80.
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