Nomogram for predicting the Gleason Sum Upgrading in Clinically Diagnosed Localized Prostate Cancer

Luigi Benecchi1, Michele Potenzoni2, Fabrizio Russo1, Carlo Del boca1
  • 1 Istituti Ospitalieri (Cremona)
  • 2 Ospedale di Fidenza (Parma)


Although the Gleason score is commonly used in nomograms as the most powerful prognostic indicator and is thus useful in treatment decisions, its possible upgrade after radical prostatectomy (RP) is rarely taken into consideration.
In patients with low-grade prostate cancer on biopsy, inaccurate cancer grading can lead to a false sense of comfort for both physician and patient, and lead to under-treatment of intermediate and high-risk cases. In these patients with biopsy Gleason 6 prostate cancer, radical local therapy may be recommended because the clinician cannot guarantee that more aggressive cancer does not exist.
Patients undergoing radical prostatectomy have the advantage of comprehensive assessment of the Gleason score by examination of the whole radical prostatectomy specimen.
The objective of this study was to build a nomogram for prediction of Gleason Sum Upgrading in clinically diagnosed prostate cancer.

Methods and results

Patients undergoing radical prostatectomy with matched diagnostic biopsies were identified from a prospectively recorded database. The prostate-specific antigen level, percent freePSA, number of positive cores, biopsy Gleason score and clinical T stage were used in a multivariate logistic regression model for addressing the probability of Gleason Sum Upgrading. The developed nomogram was internally validated.
In all, 635 consecutive patients were identified. Of them, 197 (31%) were upgraded to higher Gleason sum on final pathology. By using 5 readily available variables (prostate-specific antigen level, percent freePSA, number of positive cores, biopsy Gleason score and clinical T stage), our nomogram showed a bootstrap corrected concordance index of 0.8 and good calibration. The nomogram also demonstrated satisfied statistical performance for predicting significant Gleason Sum Upgrading.


Gleason score is one of the strongest predictors of outcome following conservative management or active treatment of localized prostate cancer, and as such its accurate determination at the time of diagnosis is critical to the optimal management of patients with the disease.
Although pathologist error and borderline cases may contribute to Gleason score discordance in a small number of cases, most authors believe that sampling error is the most common cause of Gleason score under-grading. During a diagnostic biopsy, only a very small amount of the total prostate tissue is sampled for histological analysis, and given the heterogeneous and multifocal nature of prostate cancer it is easy to envisage how smaller volumes of higher grade elements may be missed leading to under-grading or, less commonly, how larger volumes of lower grade elements may be missed leading to over-grading (reverse sampling error).
Because the differences between different Gleason patterns are a continuum, there are borderline grades between small glands of pattern 3 and poorly formed glands of pattern 4. Similarly, there are borderline grades between poorly formed glands of pattern 4 and pattern 5 with barely appreciable glandular differentiation.
In summary, we have confirmed that sampling error at transrectal ultrasound biopsy (TRUSBx) is a significant cause of Gleason score under-grading at the time of initial diagnosis,
A new nomogram to predict Gleason Sum Upgrading in clinically diagnosed prostate cancer was developed and demonstrated good statistical performance in internal validation.


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