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      Impact of tertiary Gleason pattern 5 on prostate cancer aggressiveness: Lessons from a contemporary single institution radical prostatectomy series

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          Abstract

          Objective

          To better evaluate tertiary Gleason pattern reporting and to evaluate the impact of tertiary Gleason pattern 5 (TP5) on prostate cancer pathological features and biochemical recurrence at our large single institution.

          Methods

          We retrospectively reviewed 1962 patients who underwent radical prostatectomy (RP) for prostate cancer; TP5 was reported in 159 cases (8.1%). Men with Gleason score (GS) 7 and GS 8 disease were divided into subgroups with and without TP5, and histopathological features were compared. Multivariate analyses were conducted to assess the impact on TP5 on biochemical-free survival (BFS).

          Results

          Tumors possessing GS 3 + 4 with TP5 were more likely to exhibit extraprostatic extension (EPE) and had a larger tumor diameter (TD) than GS 3 + 4 alone. GS 3 + 4 with TP5 was also associated with positive surgical margins (SM), seminal vesicle involvement (SVI), and higher pre-operative prostate-specific antigen (PSA) values, but without statistical significance. GS 4 + 3 with TP5 more commonly presented with EPE, positive SM, SVI, and greater TD and pre-operative PSA level than GS 4 + 3 alone. In multivariate analysis, Gleason score, EPE, and TP5 were overall independent risk factors for PSA recurrence in this cohort. Additionally, GS 4 + 3 with TP5 was associated with shorter time to recurrence versus GS 4 + 3 alone.

          Conclusion

          Our results emphasize the importance of TP5 and suggest that criteria for tertiary pattern reporting in prostate cancer should be standardized. Further studies are needed to evaluate the role of tertiary patterns in prognostic models.

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          Most cited references 24

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          The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma.

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            An update of the Gleason grading system.

            An update is provided of the Gleason grading system, which has evolved significantly since its initial description. A search was performed using the MEDLINE(R) database and referenced lists of relevant studies to obtain articles concerning changes to the Gleason grading system. Since the introduction of the Gleason grading system more than 40 years ago many aspects of prostate cancer have changed, including prostate specific antigen testing, transrectal ultrasound guided prostate needle biopsy with greater sampling, immunohistochemistry for basal cells that changed the classification of prostate cancer and new prostate cancer variants. The system was updated at a 2005 consensus conference of international experts in urological pathology, under the auspices of the International Society of Urological Pathology. Gleason score 2-4 should rarely if ever be diagnosed on needle biopsy, certain patterns (ie poorly formed glands) originally considered Gleason pattern 3 are now considered Gleason pattern 4 and all cribriform cancer should be graded pattern 4. The grading of variants and subtypes of acinar adenocarcinoma of the prostate, including cancer with vacuoles, foamy gland carcinoma, ductal adenocarcinoma, pseudohyperplastic carcinoma and small cell carcinoma have also been modified. Other recent issues include reporting secondary patterns of lower and higher grades when present to a limited extent, and commenting on tertiary grade patterns which differ depending on whether the specimen is from needle biopsy or radical prostatectomy. Whereas there is little debate on the definition of tertiary pattern on needle biopsy, this issue is controversial in radical prostatectomy specimens. Although tertiary Gleason patterns are typically added to pathology reports, they are routinely omitted in practice since there is no simple way to incorporate them in predictive nomograms/tables, research studies and patient counseling. Thus, a modified radical prostatectomy Gleason scoring system was recently proposed to incorporate tertiary Gleason patterns in an intuitive fashion. For needle biopsy with different cores showing different grades, the current recommendation is to report the grades of each core separately, whereby the highest grade tumor is selected as the grade of the entire case to determine treatment, regardless of the percent involvement. After the 2005 consensus conference several studies confirmed the superiority of the modified Gleason system as well as its impact on urological practice. It is remarkable that nearly 40 years after its inception the Gleason grading system remains one of the most powerful prognostic factors for prostate cancer. This system has remained timely because of gradual adaptations by urological pathologists to accommodate the changing practice of medicine. Copyright 2010 American Urological Association. Published by Elsevier Inc. All rights reserved.
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              Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update.

              To combine the clinical data from 3 academic institutions that serve as centers of excellence for the surgical treatment of clinically localized prostate cancer and develop a multi-institutional model combining serum prostate-specific antigen (PSA) level, clinical stage, and Gleason score to predict pathological stage for men with clinically localized prostate cancer. In this update, we have combined clinical and pathological data for a group of 4133 men treated by several surgeons from 3 major academic urologic centers within the United States. Multinomial log-linear regression was performed for the simultaneous prediction of organ-confined disease, isolated capsular penetration, seminal vesicle involvement, or pelvic lymph node involvement. Bootstrap estimates of the predicted probabilities were used to develop nomograms to predict pathological stage. Additional bootstrap analyses were then obtained to validate the performance of the nomograms. A total of 4133 men who had undergone radical retropubic prostatectomy for clinically localized prostate cancer at The Johns Hopkins Hospital (n=3116), Baylor College of Medicine (n=782), and the University of Michigan School of Medicine (n=235) were enrolled into this study. None of the patients had received preoperative hormonal or radiation therapy. Simultaneous prediction of organ-confined disease, isolated capsular penetration, seminal vesicle involvement, or pelvic lymph node involvement using updated nomograms. Prostate-specific antigen level, TNM clinical stage, and Gleason score contributed significantly to the prediction of pathological stage (P<.001). Bootstrap estimates of the median and 95% confidence interval of the predicted probabilities are presented in the nomograms. For most cells in the nomograms, there is a greater than 25% probability of qualifying for more than one of the pathological stages. In the validation analyses, 72.4% of the time the nomograms correctly predicted the probability of a pathological stage to within 10% (organ-confined disease, 67.3%; isolated capsular penetration, 59.6%; seminal vesicle involvement, 79.6%; pelvic lymph node involvement, 82.9%). The data represent a multi-institutional modeling and validation of the clinical utility of combining PSA level measurement, clinical stage, and Gleason score to predict pathological stage for a group of men with localized prostate cancer. Clinicians can use these nomograms when counseling individual patients regarding the probability of their tumor being a specific pathological stage; this will enable patients and physicians to make more informed treatment decisions based on the probability of a pathological stage, as well as risk tolerance and the values they place on various potential outcomes.
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                Author and article information

                Contributors
                Journal
                Asian J Urol
                Asian J Urol
                Asian Journal of Urology
                Second Military Medical University
                2214-3882
                2214-3890
                16 April 2015
                January 2015
                16 April 2015
                : 2
                : 1
                : 53-58
                Affiliations
                [a ]Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA
                [b ]Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA
                [c ]Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA
                Author notes
                []Corresponding author. mrohit@ 123456med.umich.edu
                Article
                S2214-3882(15)00030-2
                10.1016/j.ajur.2015.04.007
                5730694
                © 2015 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier (Singapore) Pte Ltd.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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