Background Intraductal carcinoma (IDC) and cribriform pattern (Crib) of prostate cancer are increasingly recognized as independent prognosticators of poor outcome, both in prostate biopsies and radical prostatectomy (RP) specimens. Objective The aim of our project is to assess the impact of false negative biopsies for these two characteristics on oncological outcomes. Material and methods Patients who underwent RP between January 2015 and December 2022 were included in the study. Predictors of Biochemical Failure were examined using a multivariate Cox proportional hazards model. Results and limitation Among the 836 patients who underwent RP, 233 (27.9%) had Crib, and 125 (15.0%) had IDC on prostate biopsy, with 71 (8.5%) patients having both IDC and Crib. Concerning IDC/Crib status at biopsy, 217 (26%) patients had a false-negative biopsy, 332 (39.7%) had a true-negative biopsy, 256 (30.6%) showed a true-positive biopsy, and 24 (3.7%) exhibited a false-positive biopsy, with respect to either pattern. When comparing false-negative, false-positive, true-negative and true-positive biopsies for IDC/Crib, we found that patients with a false-negative biopsy for IDC/Crib versus those with a true-negative biopsy for IDC/Crib disclosed a rate of advanced pathological stage (≥pT3) which was twice that of patients with a true-negative biopsy for IDC/Crib: 56.8% versus 28.1%, respectively (p < 0.001). On multivariate Cox analysis, log PSA before RP (hazard ratio [HR] 2.07, 95% CI 1.53–2.82; p < 0.001), a higher percentage of positive cores at biopsy ( ≥ 33%) (HR 1.68, 95% CI 1.07–2.63; p = 0.024), and false negative biopsy for IDC/Crib (HR 2.14, 95% CI 1.41–3.25; p < 0.001), were each significantly associated with an increased risk of BCR. Conclusions A false-negative biopsy for IDC/Crib is independently associated with higher risk of BCR and advanced pathological stage compared to a true negative biopsy.

Intraductal prostate cancer (IDC) is linked to unfavorable oncologic outcomes, marked by distinctive cellular intrinsic pathway changes and intricate immunosuppressive microenvironments that could impact the way cancer spreads. The aim of this study was to determine whether the presence of IDC in prostate biopsy specimens obtained from patients before primary prostate cancer (PCa) treatment is associated with a lymph node metastatic propensity in prostate-specific membrane antigen (PSMA)‒positron emission tomography (PET)/CT. This was a cross-sectional analysis of all PCa patients undergoing a pretreatment ¹⁸F-DCFPyL-PSMA-PET/CT between January 1, 2016, and August 2021 at The Princess Margaret Cancer Centre. Outcomes were presence of any metastasis in the overall cohort, presence of lymphatic vs no metastases, and presence of lymphatic vs bone metastasis among patients who underwent PSMA-PET/CT as PCa primary staging. The associations between IDC presence on the prostate biopsy and the study outcomes were evaluated using univariable and multivariable logistic regression analyses. The cohort consisted of 120 patients. IDC and cribriform pattern were observed in 55 (46%) and 48 (40%) prostate biopsies, respectively. Overall, 52 patients (43%) had evidence of metastasis. Presence of IDC on biopsy was associated with increased odds of overall metastasis (odds ratio: 2.47, 95% CI: 1.09-5.61, P = .03). Of the 52 patients with evidence of metastasis, 41 (79%) had evidence of lymphatic metastasis. Presence of IDC on biopsy was associated with significantly increased odds of lymphatic metastasis vs nonmetastases (odds ratio: 3.03, 95% CI: 1.24-7.40, P = .01). The identification of IDC morphology in prostate biopsy specimens has been observed to be significantly linked with lymph node metastasis on 18F-DCFPyL-PET/CT imaging in a PCa pretreatment staging setting. We found that presence of IDC in prostate biopsy appears to be a marker for lymph node metastasis on 18F-DCFPyL-PET/CT.

PURPOSE: Active surveillance (AS) is a standard management strategy for low-risk prostate cancer (PCa), but a significant proportion of patients ultimately experience disease progression. Metformin, a commonly prescribed antidiabetic agent, has demonstrated antitumor activity in preclinical studies and observational data, prompting investigation into its potential to delay PCa progression. PATIENTS AND METHODS: The Metformin Active Surveillance Trial (MAST) was a multicenter, randomized, double-blind, placebo-controlled phase III trial evaluating the efficacy of metformin in men with low-risk, localized PCa managed with AS. Eligible participants were randomly assigned 1:1 to receive either metformin (850 mg twice daily) or placebo and were followed for up to 36 months. The primary end point was time to progression, defined as therapeutic and/or pathologic progression. Progression-free survival (PFS) was assessed using Kaplan-Meier analysis and Cox proportional hazards models. RESULTS: A total of 408 patients were randomly assigned (205 metformin, 203 placebo). After a median follow-up of 36 months, 144 participants experienced progression (70 metformin, 74 placebo), with no significant difference in PFS (hazard ratio [HR], 1.09 [95% CI, 0.79 to 1.52]; P = .59). Negative biopsy rates at 36 months were 41.0% (metformin) versus 31.1% (placebo; P = .181). In prespecified subgroup analysis, metformin was associated with increased pathologic progression among obese patients (BMI ≥ 30; HR, 2.36 [95% CI, 1.21 to 4.59]; P = .0092). CONCLUSION: Metformin did not reduce progression in men with low-risk PCa on AS. The observed adverse effect in obese patients merits further investigation.

Prognostic tests and treatment approaches for optimized clinical care of prostatic neoplasms are an unmet need. Prostate cancer (PCa) and derived extracellular vesicles (EVs) proteome changes occur during initiation and progression of the disease. PCa tissue proteome has been previously characterized, but screening of tissue samples constitutes an invasive procedure. Consequently, we focused this study on liquid biopsies, such as urine samples. More specifically, urinary small extracellular vesicle and particles proteome profiles of 100 subjects were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC–MS/MS). We identified 171 proteins that were differentially expressed between intraductal prostate cancer/cribriform (IDC/Crib) and non-IDC/non-Crib after correction for multiple testing. However, the strong correlation between IDC/Crib and Gleason Grade complicates the disentanglement of the underlying factors driving this association. Nevertheless, even after accounting for multiple testing and adjusting for ISUP (International Society of Urological Pathology) grading, two proteins continued to exhibit significant differential expression between IDC/Crib and non-IDC/non-Crib. Functional enrichment analysis based on cancer hallmark proteins disclosed a clear pattern of androgen response down-regulation in urinary EVs from IDC/Crib compared to non-IDC/non-Crib. Interestingly, proteome differences between IDC and cribriform were more subtle, suggesting high proteome heterogeneity. Overall, the urinary EV proteome reflected partly the prostate pathology.