Pseudoprogression on PSMA PET imaging of a mCRPC patient under anti-PD1 treatment

Excerpt

⁶⁸Ga-radiolabeled ligand with high affinity for prostate-specific membrane antigen PET/CT (PSMA-PET) is an emerging modality for therapy response assessment in prostate cancer (PCa), accurately detecting nodal, bone and visceral metastases better than conventional imaging [1]. Therapy monitoring after treatment remains troublesome, especially when evaluating response to chemotherapy and androgen-deprivation therapy (ADT). Immunotherapy has recently become available for metastatic PCa, notably in cases of multiple point mutations and high level of microsatellite instability (MSI-H) [2, 3]. We display here an 85-year-old Gleason 10 PCa patient initially treated with brachytherapy (13 years previous), followed by salvage prostatectomy (5 years previous) and ADT for the previous 3 years (bicalutamide, abiraterone and goserelin). The first set of PSMA-PET images (PSA: 16.0 ng/mL) diagnosed metastatic pelvic nodal disease (long arrows in (A) PET 3D volume rendering; (B) Axial CT; (C) Axial fused PET-CT). The patient underwent a biopsy of an MSI-H tumor—leading to the beginning of anti-PD1 therapy (Pembrolizumab 200 mg, 8 cycles). Two subsequent sets of PSMA-PET images (2 months, PSA: 0.03 ng/mL; and 4 weeks afterwards, PSA: 0.007 ng/mL) confirmed pseudoprogression after the appearance of new lesions (white arrow in D), along with a transient increase of disease burden, also reflected by increasing TL-PSMA and TV-PSMA notwithstanding substantial reduction of PSA levels (arrowheads in (D), (E), (F); short arrows in (G), (H), (I)). Two major hypotheses might be raised considering previous reports of ADT for PCa and immunotherapy for other cancers: (a) upregulation of PSMA molecular expression and (b) increased vascular permeability induced by the recruitment of activated T cells as a first response to treatment [4, 5]. Hence, the different patterns of response to checkpoint inhibitors—including pseudoprogression—require careful evaluation to avoid premature cessation of an effective immuno-oncology agent. …