Prognostic Significance of the Cribriform Pattern in Prostate Cancer: Clinical Outcomes and Genomic Alterations

Simple Summary Prostate cancer is a condition with varying outcomes, and understanding its progression is vital for treatment. Our research focused on a specific pattern observed in tumor cells, known as cribriform pattern 4 (CP4), which can indicate how aggressive a cancer might be. By studying patients who had undergone surgery to remove the prostate gland, we found that those with CP4 tended to have a higher risk of cancer recurrence. Additionally, we discovered certain genes that behaved differently in patients with CP4, suggesting unique genetic changes associated with this pattern. Our findings suggest that patients with CP4 might need more intense treatment after surgery and could help doctors decide on the best course of action. Importantly, our research provides new insights that could lead to better management of prostate cancer, aiming to improve patient outcomes.Abstract Purpose: Given the diverse clinical progression of prostate cancer (PC) and the evolving significance of histopathological factors in its management, this study aimed to explore the impact of cribriform pattern 4 (CP4) on clinical outcomes in PC patients and examine its molecular characteristics. Methods: This retrospective study analyzed data from The Cancer Genome Atlas (TCGA) database and included PC patients who underwent radical prostatectomy (RP) and had pathology slides available for the assessment of CP4. A multivariable competing risk regression analysis was used to assess the association between CP4 and progression-free survival (PFS) while adjusting for established PC prognostic factors. The frequency of genomic alterations was compared between patients with and without CP4 using the Fisher's exact test. Results: Among the 394 patients analyzed, 129 (32.74%) had CP4. After a median follow-up of 40.50 months (IQR: 23.90, 65.60), the presence of CP4 was significantly associated with lower PFS (AHR, 1.84; 95% CI, 1.08 to 3.114; p = 0.023) after adjusting for covariates. Seven hub genes-KRT13, KRT5, KRT15, COL17A1, KRT14, KRT16, and TP63-had significantly lower mRNA expression levels in patients with CP4 compared to those without. Conclusions: PC patients with CP4 have distinct genomic alterations and are at a high risk of disease progression following RP. Therefore, these patients may benefit from additional post-RP treatments and should be the subject of a prospective randomized clinical trial.