Lymphotropic Pattern of Prostate-specific Membrane Antigen-detected Metastases Among Biochemically Recurrent Radical Prostatectomy Patients with Cribriform Disease.

Background: Cribriform morphology portends worse oncologic outcomes, and has unique cellular intrinsic pathway alterations and tumor microenvironments that may impact metastatic spread patterns.

Objective: To determine whether the presence of cribriform morphology in prostatectomy specimens of patients with biochemical recurrence after radical prostatectomy (RP) is associated with the presence of metastasis on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) and a distinct pattern of spread.

Design, Setting, And Participants: A cross-sectional analysis was conducted of all prostate cancer patients with biochemical recurrence after RP undergoing F-DCFPyL-PET/CT between December 2018 and February 2021 at the Princess Margaret Cancer Centre.

Outcome Measurements And Statistical Analysis: Outcomes were presence of any metastasis in the overall cohort and lymphatic versus bone/visceral metastases among patients with metastatic disease. The associations between the presence of intraductal (IDC) and/or invasive cribriform (ICC) carcinoma on the RP specimen and study outcomes were evaluated using logistic regression analyses.

Results And Limitations: The cohort included 176 patients. IDC and ICC were observed in 77 (43.8%) and 80 (45.5%) RP specimens, respectively. The median time from RP to PSMA-PET/CT was 5.0 yr. The median serum prostate-specific antigen level at PSMA-PET/CT was 1.12 ng/ml. Overall, metastasis was observed in 77 patients, of whom 58 were had lymphatic-only metastasis. On a multivariable analysis, presence of IDC on RP was associated with increased odds of overall metastasis (odds ratio [OR]: 2.17; 95% confidence interval [CI]: 1.07-4.45; p = 0.033). Presence of ICC on RP was associated with significantly increased odds of lymphatic versus bone/visceral metastases (OR: 3.13; 95% CI: 1.09-21.7; p = 0.004).

Conclusions: Presence of cribriform morphology on RP specimens of patients with biochemical failure after RP is associated with increased odds of PSMA-PET/CT-detected metastases with a lymphatic predominant pattern of spread. These findings have implications for the design and evaluation of post-RP salvage therapies.

Patient Summary: We found that microscopic cribriform appearance correlates with disease spread on imaging in prostate cancer patients with recurrence and has a predilection for spread to lymph nodes, as opposed to bone or visceral organs.