Cribriform morphology, characterized by sheets of cells with intercellular lamina giving it a “cribrum” (ie, sieve) appearance [1], has been described in patients with both invasive cribriform carcinoma (ICC) and intraductal carcinoma (IDC), an ICC variant featuring malignant epithelial cell proliferation within the prostatic ducts [2]. ICC and IDC frequently co-occur, with 47% of cribriform prostate cancer (PCa) containing areas of IDC and 68% of IDC containing cribriform patterns [3]. Presence of cribriform morphology has consistently been demonstrated to be associated with adverse oncologic outcomes, including increased risks of biochemical recurrence (BCR) [3], [4], [5], [6], metastasis [7], and cancer-specific mortality [2], [4], [8], [9]. Accordingly, the International Society of Urological Pathology 2014 revisions recommended that all cribriform patterns be classified as Gleason pattern 4, irrespective of size/morphology [10].

With the increased utilization of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) scans following BCR [11], [12], novel patterns of metastatic spread have been described [29], adding complexity to the stage shift and migration phenomena introduced by the higher sensitivity of this imaging modality [11], [12]. Given the adverse oncologic potential of cribriform disease [2], [3], [4], [5], [6], [7], [8], [9], we hypothesize that the presence of ICC or IDC in radical prostatectomy (RP) specimens would be associated with an increased incidence of metastatic disease in patients with BCR undergoing PSMA-PET/CT. Furthermore, given the recent findings of unique cribriform cellular intrinsic pathway alterations and complex immunosuppressive tumor microenvironments [13], we postulate that the presence of cribriform pattern in the prostatectomy specimen may be associated with a unique metastatic pattern of spread. Our study objectives were thus to determine whether the presence of cribriform pattern disease in prostatectomy specimens of patients with BCR after RP is associated with an increased incidence of overall metastasis on PSMA-PET/CT, and specifically among those with metastatic disease, whether there was a predilection for bone/visceral versus lymphatic involvement.