Nomogram for Gleason Sum Upgrading risk after radical prostatectomy in patients with biopsy Gleason score 6 or 7

Luigi Benecchi1, Michele Potenzoni2, Serena Corti1, Fabrizio Russo1, Fernando Echeverria1, Carlo Del Boca1
  • 1 Ospedale Civile (Cremona)
  • 2 Ospedale di Fidenza (Parma)


In the era of prostate specific antigen (PSA) screening, more and more patients are primarily diagnosed with insignificant prostate cancer. Since most of these cancers will not become clinically symptomatic, deferred treatment modalities have been introduced to offer similar therapeutic effects while preserving sexual function and continence.3 The criteria to define those patients who are suitable to enter conservative treatment protocols are mainly based on PSA, clinical stage, and tumour grade.
The Gleason grade is the only factor that is not influenced by other pathological entities and consequently represents the most powerful and reliable predictor.
In patients with low and intermediate 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.
The objective of this study was to build a nomogram for prediction of Gleason Sum Upgrading in biopsy Gleason score 6 or 7.

Materials and Methods

Patients undergoing radical prostatectomy with matched diagnostic biopsies were identified from a prospectively recorded database. Prostate specimens were processed according to the Stanford protocol, and biopsies and specimens were graded according to the Gleason system as initially reported by Gleason. Pretreatment prostate specific antigen was measured before digital rectal examination (DRE) and transrectal ultrasound (TRUS).The prostate specific antigen level, percent free PSA, prostate volume, number of positive cores, biopsy Gleason score, clinical T stage and age were used in a multivariate logistic regression model for addressing the probability of Gleason Sum Upgrading.
The developed nomogram was internally validated.
Statistical tests were carried out using R Software.


In total, 266 patients met our inclusion criteria and entered our analysis.
The median patient age was 69 years (range 47-78 yerars), median PSA was 6.56 ng/mL (range 2.1 – 91), median Prostate Volume was 38 (range 9 – 130cc).
Of them, 83 (31.2%) were upgraded to higher Gleason sum on final pathology. By using 6 readily available variables (prostate-specific antigen level, percent freePSA, prostate Volume, number of positive cores, biopsy Gleason score and clinical T stage), our nomogram showed a bootstrap corrected concordance index of 0.78 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.


Gleason Sum Upgrading can affects patients undergoing radical prostatectomy. To address the paucity of information regarding Gleason Sum Upgrading rates in patients with low and intermediate Gleason score, we examined the rate of Gleason Sum Upgrading in our patients and found that 31% of such men will harbor cancer upgrading at final pathology when undergoing radical prostatectomy.
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.


Epstein JI, Feng Z, Trock BJ, Pierorazio PM.: Upgrading and downgrading of prostate cancer from biopsy to radical prostatectomy: incidence and predictive factors using the modified Gleason grading system and factoring in tertiary grades. Eur Urol. 2012 May;61(5):1019-24
Corcoran NM, Casey RG, Hong MK, Connolly S: The ability of prostate-specific antigen (PSA) density to predict an upgrade in Gleason score between initial prostate biopsy and prostatectomy diminishes with increasing tumour grade due to reduced PSA secretion per unit tumour volume. BJU Int. 2012 Jul;110(1):36-42.
Freedland SJ, Kane CJ, Amling CL, Aronson WJ, Terris MK, Presti JC Jr. Upgrading and downgrading of prostate needle biopsy specimens: risk factors and clinical implications. Urology. 2007;69:495-499.
Gofrit ON, Zorn KC et al. Predicting the risk of patients with biopsy Gleason score 6 to harbor a higher grade cancer. J Urol. 2007;178:1925-1928.
Chun FK, Briganti A, Shariat SF, et al. Significant upgrading affects a third of men diagnosed with prostate cancer: predictive nomogram and internal validation. BJU Int. 2006;98:329-334.
Kulkarni GS, Lockwood G, Evans A, et al. Clinical predictors of Gleason score upgrading: implications for patients considering watchful waiting, active surveillance, or brachytherapy. Cancer. 2007;109:2432-2438.
Moussa AS, Kattan MW, Berglund R, Yu C, Fareed K, Jones JS. A nomogram for predicting upgrading in patients with low- and intermediate-grade prostate cancer in the era of extended prostate sampling. BJU Int. 2010;105:352-358.
Capitanio U, Karakiewicz PI et al. Biopsy core number represents 1 of foremost predictors of clinically significant Gleason sum upgrading in patients with low-risk prostate cancer. Urology. 2009;73:1087-1091.

Lars Budaus: The novel nomogram of Gleason sum upgrade: Possible application for the eligible criteria of low dose rate brachytherapy. International Journal of Urology (2010) 17, 862–868

Viacheslav Iremashvili. Clinically Significant Gleason Sum Upgrade External Validation and Head-to-Head Comparison of the Existing Nomograms. Cancer 118, 2011