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Gleason 6 Tumors Should Still Be Labeled as Cancer

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Active Surveillance for Localized Prostate Cancer

Part of the book series: Current Clinical Urology ((CCU))

Abstract

Gleason score 6 cancer currently has a better prognosis than in years past as patterns associated with more aggressive behavior have been shifted to Gleason score 7 with modifications to the Gleason system. A pure Gleason score 6 cancer at surgery has no potential for metastatic behavior. Consequently, some have questioned whether Gleason score 6 should even be called cancer. This chapter presents the issues and discusses why we are in favor of retaining the designation of Gleason score 6 adenocarcinoma. Clinically, a major issue is that in approximately 20% of needle biopsies with Gleason score 3 + 3 = 6, there is upgrading at radical prostatectomy which shows higher grade cancer unrecognized by biopsy. If a Gleason score 3 + 3 = 6 on needle biopsy was renamed as a more benign term, it would be in error in a significant minority of cases and could lead patients to drop out of active surveillance programs as they have not been diagnosed with “cancer.” Both morphological and molecular studies indicate that Gleason score 6 cancer shares many key hallmarks seen in all prostate cancer regardless of grade. While some molecular alterations are less common in Gleason score 6 tumors than in higher grades (e.g. PTEN loss, TP53 mutations), Gleason score 6 tumors are found among all of the major molecular subtypes of primary prostatic adenocarcinoma. For example, Gleason score 6 tumors commonly contain ETS-gene fusions as well as complex genomic rearrangements (e.g. chromoplexy). Finally, since studies have shown common clonal lineage relationships between prostatic tumors composed of both Gleason patterns 3 and 4, the possibility exists that Gleason score 6 tumors can progress to become higher grade over time.Rather than change Gleason score 6 to a non-cancerous term, there needs to be a change of what patients think when they are told that they have Gleason score 6 cancer, and, a new grading system with Grade Group 1 equivalent to Gleason score 3 + 3 = 6 has been introduced that provides help in this regard.

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Acknowledgments

Financial support and sponsorship:

This work was supported by the National Institutes of Health Prostate SPORE P50CA58236, the Prostate Cancer Foundation, the Department of Defense Prostate Cancer Biorepository Network (PCBN), and the Patrick C. Walsh Prostate Cancer Research Fund. A.M.D. is supported through the Patrick C. Walsh Prostate Cancer Research Fund as the Virginia and Warren Schwerin Scholar.

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  1. Departments of Pathology, Urology, and Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Brady Urological Research Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Angelo M. De Marzo & Jonathan I. Epstein

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    Laurence Klotz

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De Marzo, A.M., Epstein, J.I. (2018). Gleason 6 Tumors Should Still Be Labeled as Cancer. In: Klotz, L. (eds) Active Surveillance for Localized Prostate Cancer. Current Clinical Urology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-62710-6_5

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