Prostate-Specific Membrane Antigen Expression on PET/CT in Patients with Metastatic Castration-Resistant Prostate Cancer: A Retrospective Observational Study

Abstract

Rationale: Monitoring therapy response in patients with metastatic castration-resistant prostate cancer ([m]CRPC) treated with novel hormonal therapies, taxanes and newly approved therapies is crucial for optimizing treatment. [ 68 Ga]Ga-prostate-specific membrane antigen (PSMA)-11 positron emission tomography/computed tomography (PSMA PET/CT) is a promising target for managing treatment in patients with prostate cancer. PSMA is overexpressed in patients with mCRPC; understanding how expression might change in patients undergoing treatment could determine its potential for guiding clinical decisions. We examined PSMA expression in patients with CRPC and compared PET/CT response with prostate-specific antigen (PSA) variation as prognostic factor for progression-free and overall survival (PFS and OS). Methods: Single-centre, retrospective observational cohort study in patients with CRPC enrolled in the PSMA-PROSTATA registry study (EudraCT: 2015-004589-27). First and second (if applicable) PSMA PET/CT were performed to determine PSMA expression (absence/presence). PET/CT response was assessed as responders (patients with stable disease, partial or complete response) versus non-responders (patients with progressive disease) comparing the first with the second PET/CT PET/CT. PSA variation (increase/decrease from baseline) was assessed across the same time period. PFS was defined as time between second PET/CT and PSA recurrence or evidence of radiological progression. Results: Overall, 160 patients with CRPC were included in the analysis. At first PET/CT, nearly all (n=152; 95.0%) patients had PSMA expression (classified as mCRPC), irrespective of prior systemic therapy. Maximized standardized uptake value (SUVmax) was positively associated with baseline PSA levels and velocity (both P<0.001). According to PET/CT response, median SUVmax on first PET/CT was numerically lower in non-responders versus responders (17.5 vs 20.4; P=0.127). Similarly, patients with a PSA increase had significantly lower median SUVmax on first PET/CT (15.8) compared with those with a PSA decrease (30.4; P=0.018). PSA change was, on average, 146% in non-responders and -57% in responders between first and second PET/CT (P<0.001). Agreement between PET/CT and PSA response was 79% (k=0.553, P<0.001).Among the 63 patients included in PFS/OS analyses, 76.2% had a relapse and 36.5% died before 24month follow-up; median PFS and OS were 6.1 months and 24 months, respectively. PET/CT response, independent of PSA variation, was a significant prognostic factor for PFS. OS was not significantly different between PET/CT responders and non-responders. Conclusion: PSMA PET/CT may be a useful imaging method predictive of treatment response in patients with mCRPC, regardless of ongoing systemic therapy. Data also suggest that response assessed by PET/CT is a potentially more significant prognostic factor than PSA for PFS. Further studies are needed to understand the potential involvement of PSMA expression on survival.

A prospective study on the early evaluation of response to androgen receptor-targeted agents with 11C-Choline, 68Ga-PSMA, and 18F-FACBC PET in metastatic castration-resistant prostate cancer: a single-center experience

“… 18 In detail, while the analysis conducted by Esen et al. showed considerable concordance between 68 Ga-PSMA PET data and PSA response, 26 Calderoni and colleagues suggested that 68 Ga-PSMA PET could possibly represent a better prognostic factor than PSA in terms of PFS, 20 suggesting that this novel imaging technique may play a crucial role in treatment response evaluation in mCRPC.…”

“…Nonetheless, our analysis adds to previous preliminary data in the literature supporting the use of 68 Ga-PSMA PET for the precocious assessment of therapy with ARTA. 18 , 20 , 26 , 27 However, even if carried out on a larger sample size, three of these above-mentioned studies were characterized by a retrospective design, 20 , 26 , 27 of which one enrolled both mHSPC and mCRPC patients, 26 and the other one was a systematic review of the literature. 18 In detail, while the analysis conducted by Esen et al.…”

“… 19 Another retrospective, observational trial showed that 68 Ga-PSMA PET seems to be a more reliable prognostic factor for progression-free survival (PFS) than PSA levels in mCRPC. 20 …”

Novel [68Ga/177Lu]Ga/Lu-AZ-093 as PSMA-Targeting Agent for Diagnosis and Radiotherapy

“…In the past few years, the U.S. Food and Drug Administration (FDA) has approved three diagnostic imaging agents for positron emission tomography (PET) imaging: [ 68 Ga]­Ga-PSMA-11 (Ga68 gozetotide), − [ 18 F]­DCFPyL (PYLARIFY, piflufolastat F18), − and [ 18 F]­rhPSMA-7.3 (POSLUMA, flotufolostat F 18) − (Figure ). PET imaging studies in conjunction with the PSMA-targeting agents are now routinely applied in nuclear medicine clinics to assist the diagnosis and monitoring therapy for patients with prostate cancer − (Figure ). Additionally, radioligand therapy (RLT) based on PSMA targeting, using α- or β-emitting radionuclides (actinium-225 or lutetium-177), is a new area of drug development for the treatment of various tumors, including prostate cancer.…”

Diffusion-Weighted MRI for Treatment Response Assessment in Osteoblastic Metastases—A Repeatability Study

“…PSMA-PET uses radiotracers specifically targeting the prostate-specific membrane antigen (PSMA), a surface protein highly overexpressed by most prostate cancer cells, allowing for highly sensitive and specific detection of prostate cancer manifestations. Recent studies indicate that PSMA-PET is not only highly sensitive in the detection of prostate cancer lesions but that change in PSMA uptake under therapy can serve as a marker for treatment response [23][24][25][26].…”