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. 2025 Aug 9:19:11795549251363324.
doi: 10.1177/11795549251363324. eCollection 2025.

Age-Specific Impact of Cribriform Pattern in Prostate Cancer Following Radical Prostatectomy

Ari S Hilibrand  1 , Yetkin Tuac  2 , Okan Argun  1 , Christina M Breneman  1 , Michelle Oh  1 , Shalini Moningi  1 , Jonathan E Leeman  1 , Mutlay Sayan  1
Affiliations

Age-Specific Impact of Cribriform Pattern in Prostate Cancer Following Radical Prostatectomy

Ari S Hilibrand et al. Clin Med Insights Oncol. .

Abstract

Background: Cribriform pattern 4 (CP4) is an aggressive variant in prostate cancer linked to worse clinical outcomes, including biochemical recurrence, metastases, and prostate cancer-specific mortality. However, its prognostic significance across age groups remains unclear. This study investigates whether the impact of CP4 on progression-free survival (PFS) differs by age in patients undergoing radical prostatectomy (RP).

Methods: This retrospective analysis used patient data from the TCGA database, evaluating patients who underwent RP stratified by CP4 status. The primary outcome was PFS, defined as the time from RP to biochemical recurrence, radiographic progression, or death from any cause. Multivariable Fine-Gray competing risk regression analyses assessed the association between CP4 and PFS, adjusting for preoperative prostate-specific antigen (PSA), Gleason score, tumor stage, and surgical margin status. An interaction term between age (dichotomized at 60 years to facilitate clinical interpretation and applicability, approximating the cohort median age of 61 years [interquartile range = 56-66]) and CP4 status was included in the analysis.

Results: Of 431 patients, CP4 was present in 134 (31%). In multivariable analysis, CP4 was associated with significantly worse PFS in patients older than 60 years (adjusted hazard ratio [AHR]: 1.99, 95% confidence interval [CI]: 1.01-3.92, P < .001), but not in younger patients (⩽60 years; AHR: 1.00, 95% CI: 0.49-2.04, P = .997). Adjusted 5-year PFS was significantly lower in older CP4-positive patients (50.8%, 95% CI: 33.0%-78.2%) compared with older CP4-negative patients (74.6%, 95% CI: 63.6%-87.6%; P < .001).

Conclusion: CP4 strongly predicts reduced PFS in patients above 60 years but not younger patients, suggesting that age may influence the clinical impact of CP4. These findings support age-specific risk stratification in CP4-positive prostate cancer. Prospective studies are needed to validate results and explore tailored treatment strategies based on age.

Keywords: Prostatic neoplasms; age factors; cribriform pattern; histopathology; radical prostatectomy.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Graph A shows survival curves for older patients and Graph B for 60 or younger patients with CP4 pattern, both over time.
Figure 1.
Covariate-adjusted estimates of progression-free survival (A) older than age 60 years and (B) 60 years or younger stratified by the presence of cribriform pattern 4.
See this image and copyright information in PMC

References

    1. Epstein JI, Amin MB, Reuter VE, Humphrey PA. Contemporary Gleason grading of prostatic carcinoma: an update with discussion on practical issues to implement the 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol. 2017;41:e1-e7. doi: 10.1097/PAS.0000000000000820 - DOI - PubMed
    1. Ericson KJ, Wu SS, Lundy SD, Thomas LJ, Klein EA, McKenney JK. Diagnostic accuracy of prostate biopsy for detecting cribriform Gleason pattern 4 carcinoma and intraductal carcinoma in paired radical prostatectomy specimens: implications for active surveillance. J Urol. 2020;203:311-319. doi: 10.1097/ju.0000000000000526 - DOI - PubMed
    1. Böttcher R, Kweldam CF, Livingstone J, et al. Cribriform and intraductal prostate cancer are associated with increased genomic instability and distinct genomic alterations. BMC Cancer. 2018;18:8. doi: 10.1186/s12885-017-3976-z - DOI - PMC - PubMed
    1. Iczkowski KA, Torkko KC, Kotnis GR, et al. Digital quantification of five high-grade prostate cancer patterns, including the cribriform pattern, and their association with adverse outcome. Am J Clin Pathol. 2011;136:98-107. doi: 10.1309/AJCPZ7WBU9YXSJPE - DOI - PMC - PubMed
    1. Kir G, Sarbay BC, Gümüş E, Topal CS. The association of the cribriform pattern with outcome for prostatic adenocarcinomas. Pathol Res Pract. 2014;210:640-644. doi: 10.1016/j.prp.2014.06.002 - DOI - PubMed

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