Abstract
AbstractCribriform growth pattern is well-established as an adverse pathologic feature in prostate cancer. The literature suggests “large” cribriform glands associate with aggressive behavior; however, published studies use varying definitions for “large”. We aimed to identify an outcome-based quantitative cut-off for “large” vs “small” cribriform glands. We conducted an initial training phase using the tissue microarray based Canary retrospective radical prostatectomy cohort. Of 1287 patients analyzed, cribriform growth was observed in 307 (24%). Using Kaplan–Meier estimates of recurrence-free survival curves (RFS) that were stratified by cribriform gland size, we identified 0.25 mm as the optimal cutoff to identify more aggressive disease. In univariable and multivariable Cox proportional hazard analyses, size >0.25 mm was a significant predictor of worse RFS compared to patients with cribriform glands ≤0.25 mm, independent of pre-operative PSA, grade, stage and margin status (p < 0.001). In addition, two different subset analyses of low-intermediate risk cases (cases with Gleason score ≤ 3 + 4 = 7; and cases with Gleason score = 3 + 4 = 7/4 + 3 = 7) likewise demonstrated patients with largest cribriform diameter >0.25 mm had a significantly lower RFS relative to patients with cribriform glands ≤0.25 mm (each subset p = 0.004). Furthermore, there was no significant difference in outcomes between patients with cribriform glands ≤ 0.25 mm and patients without cribriform glands. The >0.25 mm cut-off was validated as statistically significant in a separate 419 patient, completely embedded whole-section radical prostatectomy cohort by biochemical recurrence, metastasis-free survival, and disease specific death, even when cases with admixed Gleason pattern 5 carcinoma were excluded. In summary, our findings support reporting cribriform gland size and identify 0.25 mm as an optimal outcome-based quantitative measure for defining “large” cribriform glands. Moreover, cribriform glands >0.25 mm are associated with potential for metastatic disease independent of Gleason pattern 5 adenocarcinoma.
Highlights
Recent consensus statements by the two major urologic pathology societies (International Society of Urologic Pathology, International Society of Urological Pathologists (ISUP); and Genitourinary Pathology Society, GUPS) both recommend including the presence or absence of cribriform glands in the pathology report based on strong evidence that cribriform architecture is associated with adverse clinical outcomes[1,2]
Training cohort We used a multi-institutional prostate cancer tissue microarray, the Canary Prostate Cancer Tissue Microarray (CPCTM), which was constructed from radical prostatectomy (RP) samples from 1995 to 2004 to evaluate the prognostic value of tissue biomarkers in men diagnosed with prostate cancer[9]
Likewise, when we evaluated the subset of patients with Gleason score (GS) 7 carcinomas [Subset: GS = 3 + 4 = 7/4 + 3 = 7, N = 496 patients], we found that cribriform glands >0.25 mm was associated with lower recurrence-free survival curves (RFS), whereas cribriform glands alone was not a significant prognostic indicator
Summary
Recent consensus statements by the two major urologic pathology societies (International Society of Urologic Pathology, ISUP; and Genitourinary Pathology Society, GUPS) both recommend including the presence or absence of cribriform glands in the pathology report based on strong evidence that cribriform architecture is associated with adverse clinical outcomes[1,2]. A number of additional size descriptors including “small” or “simple,” and “large” or “expansile,” have been used in the literature to subclassify cribriform glands. Early studies failed to find any correlation between cribriform gland size with other adverse prognostic features or outcomes[3,4], recent studies show that “large” cribriform glands are a significant adverse prognostic factor[5,6,7,8]. These differences are likely due, at least in part, to the use of different qualitative definitions. Received: 29 September 2021 Revised: 5 January 2022 Accepted: 5 January 2022
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