Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Oct 27;13(21):5378.
doi: 10.3390/cancers13215378.

Significant Inter- and Intralaboratory Variation in Gleason Grading of Prostate Cancer: A Nationwide Study of 35,258 Patients in The Netherlands

Rachel N Flach  1 , Peter-Paul M Willemse  1 , Britt B M Suelmann  2 , Ivette A G Deckers  3 , Trudy N Jonges  4 , Carmen van Dooijeweert  4 , Paul J van Diest  4 , Richard P Meijer  1
Affiliations

Significant Inter- and Intralaboratory Variation in Gleason Grading of Prostate Cancer: A Nationwide Study of 35,258 Patients in The Netherlands

Rachel N Flach et al. Cancers (Basel). .

Abstract

Purpose: Our aim was to analyze grading variation between pathology laboratories and between pathologists within individual laboratories using nationwide real-life data.

Methods: We retrieved synoptic (n = 13,397) and narrative (n = 29,377) needle biopsy reports from the Dutch Pathology Registry and prostate-specific antigen values from The Netherlands Cancer Registration for prostate cancer patients diagnosed between January 2017 and December 2019. We determined laboratory-specific proportions per histologic grade and unadjusted odds ratios (ORs) for International Society of Urological Pathologists Grades 1 vs. 2-5 for 40 laboratories due to treatment implications for higher grades. Pathologist-specific proportions were determined for 21 laboratories that consented to this part of analysis. The synoptic reports of 21 laboratories were used for analysis of case-mix correction for PSA, age, year of diagnosis, number of biopsies and positive cores.

Results: A total of 38,321 reports of 35,258 patients were included. Grade 1 ranged between 19.7% and 44.3% per laboratory (national mean = 34.1%). Out of 40 laboratories, 22 (55%) reported a significantly deviant OR, ranging from 0.48 (95% confidence interval (CI) 0.39-0.59) to 1.54 (CI 1.22-1.93). Case-mix correction was performed for 10,294 reports, altering the status of 3/21 (14%) laboratories, but increasing the observed variation (20.8% vs. 17.7%). Within 15/21 (71%) of laboratories, significant inter-pathologist variation existed.

Conclusion: Substantial variation in prostate cancer grading was observed between and within Dutch pathology laboratories. Case-mix correction did not explain the variation. Better standardization of prostate cancer grading is warranted to optimize and harmonize treatment.

Keywords: Gleason grading; interlaboratory variation; pathology; prostate cancer.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Funnel plot showing the observed proportion for ISUP Grade 1 prostate cancer grade per laboratory (dots) relative to the mean national proportion and its 95% confidence intervals.
Figure 2
Figure 2
Forest plot showing the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of ISUP Grades 1 versus 2–5 prostate cancer grade in comparison to the reference laboratory (#11). Dot size indicates the total number of reported prostate cancers per laboratory. Orange dots indicate laboratories with a significantly deviant OR compared to the reference laboratory.
Figure 3
Figure 3
Box plots showing the observed proportion of ISUP Grades 1 versus 2–5 per pathologist (dots) within 21 laboratories relative to the mean national proportion for ISUP grade.
See this image and copyright information in PMC

References

    1. Ferlay J., Colombet M., Soerjomataram I., Dyba T., Randi G., Bettio M., Gavin A., Visser O., Bray F. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur. J. Cancer. 2018;103:356–387. doi: 10.1016/j.ejca.2018.07.005. - DOI - PubMed
    1. Cijfers Over Kanker Netherlands Cancer Registry supplied by IKNL. [(accessed on 25 May 2020)]. Published 2020. Available online: www.cijfersoverkanker.nl.
    1. Pierorazio P.M., Walsh P.C., Partin A.W., Epstein J.I. Prognostic Gleason grade grouping: Data based on the modified Gleason- scoring system. BJU Int. 2013;111:753–760. doi: 10.1111/j.1464-410X.2012.11611.x. - DOI - PMC - PubMed
    1. Joniau S., Briganti A., Gontero P., Gandaglia G., Tosco L., Fieuws S., Tombal B., Marchioro G., Walz J., Kneitz B., et al. Stratification of High-risk Prostate Cancer into Prognostic Categories: A European Multi-institutional Study. Eur. Urol. 2015;67:157–164. doi: 10.1016/j.eururo.2014.01.020. - DOI - PubMed
    1. Mottet N., Bellmunt J., Bolla M., Briers E., Cumberbatch M.G., De Santis M., Fossati N., Gross T., Henry A.M., Joniau S., et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur. Urol. 2017;71:618–629. doi: 10.1016/j.eururo.2016.08.003. - DOI - PubMed