The oncological characteristics of <scp>non‐prostate‐specific membrane antigen (PSMA)‐expressing</scp> primary prostate cancer on preoperative <scp>PSMA</scp> positron emission tomography/computed tomography

Abstract

Approximately 5% of patients with D'Amico intermediate- to high-risk, hormone-sensitive prostate cancer (PCa) have a tumour that lacks prostate-specific membrane antigen (PSMA) expression on preoperative positron emission tomography (PET)/CT (non-PSMAPET-expressing PCa) [1]. Our recent study showed that patients with non-PSMAPET-expressing PCa had similar clinical, pathological, and immunohistochemical characteristics to patients with PSMAPET-expressing tumours, suggesting that these patients may have similar prognostic features [1]. In the present study, oncological outcomes (i.e., biochemical recurrence [BCR] and detection of recurrent disease on restaging PSMA PET/CT in case of BCR) of patients with non-PSMAPET-expressing PCa were studied. This study was approved by the local Institutional Review Board (IRBdm19-348). A retrospective, cross-sectional cohort was created consisting of all patients who had hormone-sensitive, D'Amico intermediate- to high-risk PCa, who underwent a preoperative PSMA PET/CT, and who underwent robot-assisted radical prostatectomy (RARP) in a tertiary referral centre between 2016 and March 2020 [1]. The cohort was extended with five additional patients, collected during multidisciplinary oncological board meetings, with non-PSMAPET-expressing PCa who underwent RARP between March 2020 and September 2021. Patients underwent PSMA PET/CT with different radiotracers: 68Ga-PSMA-11, 18F-DCFPyL, 18F-PSMA-1007, or 18F-JK-PSMA-7. We did not perform subgroup analyses per radiotracer, because this would lower the power of the analyses and the tracers have similar staging accuracy [2]. All preoperative PSMA PET/CT scans were centrally reviewed by experienced nuclear medicine specialists. Non-PSMAPET-expressing PCa was defined as no focal tracer uptake in the prostate visually exceeding the background activity of normal prostate tissue, in accordance with Prostate Cancer Molecular Imaging Standardised Evaluation (PROMISE) criteria and the European Association of Nuclear Medicine standardised reporting guidelines for PSMA-PET (E-PSMA) [3, 4]. After RARP, patients received oncological follow-up at 4, 8, 12, 18, 24 months after surgery and yearly thereafter. At each visit, the PSA level was measured. We excluded five patients due to missing PSA data. In case of BCR (i.e., PSA level ≥0.2 ng/mL), a restaging PSMA PET/CT imaging was performed according to European Association of Urology (EAU) guidelines recommendations and interpreted according to local expertise. Pathological data, PSA values, tracer type and clinical reports of restaging PSMA PET/CT were collected. Differences between patients with non-PSMAPET-expressing and PSMAPET-expressing PCa were analysed. Categorical variables were analysed with the Fisher's exact test. Differences regarding BCR-free survival were analysed with multivariable Cox regression tests using known prognostic factors as covariates (pT3 stage, positive surgical margin, pathological Gleason score, and pathological nodal stage). Patients were censored at the time of last PSA test. Statistical significance was set at P ≤ 0.05. A total of 20 patients had non-PSMAPET-expressing PCa and 342 had PSMAPET-expressing PCa. No differences in pathological characteristics (pT3 stage, Gleason score, positive surgical margin rate or pathological nodal stage) were found between the two cohorts (Table S1). The median follow-up time for those who did not develop BCR was 25 (interquartile range [IQR] 16–32) months. BCR developed in six patients with non-PSMAPET-expressing PCa and in 117 patients with PSMAPET-expressing PCa. Restaging PSMA PET/CT was performed in 116/123 (94%) patients who developed BCR. The median PSA at the time of restaging PSMA PET/CT was 0.31 (IQR 0.22–0.61) ng/mL, with similar distribution between the cohorts (P = 0.34, Table S1). There were no differences in BCR-free survival (adjusted hazard ratio [HR] 1.3, 95% CI 0.6–2.9; P = 0.58) between the cohorts using the larger cohort (PSMA