|Title||Computationally Derived Cribriform Area Index from Prostate Cancer Hematoxylin and Eosin Images Is Associated with Biochemical Recurrence Following Radical Prostatectomy and Is Most Prognostic in Gleason Grade Group 2.|
|Publication Type||Journal Article|
|Year of Publication||2021|
|Authors||Leo P, Chandramouli S, Farré X, Elliott R, Janowczyk A, Bera K, Fu P, Janaki N, El-Fahmawi A, Shahait M, Kim J, Lee D, Yamoah K, Rebbeck TR, Khani F, Robinson BD, Shih NNC, Feldman M, Gupta S, McKenney J, Lal P, Madabhushi A|
|Journal||Eur Urol Focus|
|Date Published||2021 Jul|
BACKGROUND: The presence of invasive cribriform adenocarcinoma (ICC), an expanse of cells containing punched-out lumina uninterrupted by stroma, in radical prostatectomy (RP) specimens has been associated with biochemical recurrence (BCR). However, ICC identification has only moderate inter-reviewer agreement.
OBJECTIVE: To investigate quantitative machine-based assessment of the extent and prognostic utility of ICC, especially within individual Gleason grade groups.
DESIGN, SETTING, AND PARTICIPANTS: A machine learning approach was developed for ICC segmentation using 70 RP patients and validated in a cohort of 749 patients from four sites whose median year of surgery was 2007 and with median follow-up of 28 mo. ICC was segmented on one representative hematoxylin and eosin RP slide per patient and the fraction of tumor area composed of ICC, the cribriform area index (CAI), was measured.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The association between CAI and BCR was measured in terms of the concordance index (c index) and hazard ratio (HR).
RESULTS AND LIMITATIONS: CAI was correlated with BCR (c index 0.62) in the validation set of 411 patients with ICC morphology, especially those with Gleason grade group 2 cancer (n = 192; c index 0.66), and was less prognostic when patients without ICC were included (c index 0.54). A doubling of CAI in the group with ICC morphology was prognostic after controlling for Gleason grade, surgical margin positivity, preoperative prostate-specific antigen level, pathological T stage, and age (HR 1.19, 95% confidence interval 1.03-1.38; p = 0.018).
CONCLUSIONS: Automated image analysis and machine learning could provide an objective, quantitative, reproducible, and high-throughput method of quantifying ICC area. The performance of CAI for grade group 2 cancer suggests that for patients with little Gleason 4 pattern, the ICC fraction has a strong prognostic role.
PATIENT SUMMARY: Machine-based measurement of a specific cell pattern (cribriform; sieve-like, with lots of spaces) in images of prostate specimens could improve risk stratification for patients with prostate cancer. In the future, this could help in expanding the criteria for active surveillance.
|Alternate Journal||Eur Urol Focus|
|PubMed Central ID||PMC8419103|
|Grant List||UL1 TR002548 / TR / NCATS NIH HHS / United States |
R01 CA216579 / CA / NCI NIH HHS / United States
C06 RR012463 / RR / NCRR NIH HHS / United States
U24 CA199374 / CA / NCI NIH HHS / United States
R43 EB028736 / EB / NIBIB NIH HHS / United States
U01 CA239055 / CA / NCI NIH HHS / United States
R01 CA249992 / CA / NCI NIH HHS / United States
R01 HL151277 / HL / NHLBI NIH HHS / United States
R01 CA220581 / CA / NCI NIH HHS / United States
R01 CA202752 / CA / NCI NIH HHS / United States
R01 CA208236 / CA / NCI NIH HHS / United States
U01 CA248226 / CA / NCI NIH HHS / United States
I01 BX004121 / BX / BLRD VA / United States
R01 CA257612 / CA / NCI NIH HHS / United States
U54 CA254566 / CA / NCI NIH HHS / United States
Brian Robinson, M.D. Francesca Khani, M.D.