Tertiary Gleason Grade Research Articles

Prognostic significance of the presence of tertiary Gleason grade 5 in robot-assisted radical prostatectomy specimens in Japanese patients with clinically localized prostate cancer.

The aim of this study was to study the prognostic significance of tertiary Gleason grade (TGG) 5 in patients with clinically localized prostate cancer treated with robot-assisted radical prostatectomy (RARP). A total of 600 Japanese patients who underwent RARP for clinical stage T1-3N0M0 prostate cancer were evaluated. TGG5 was evaluated according to the International Society of Urological Pathology criterion. Cox hazard regression was used to evaluate the prognostic significance of prostate-specific antigen and pathological features in RARP specimens. Of the 600 RARP specimens, 92 (15%) had TGG5. TGG5 component was found in 30 (10%) of 287 cases with Gleason score (GS) 3 + 4, 55 (37%) of 149 cases with GS 4 + 3 and 7 (17%) of 40 cases with GS 4 + 4. There were no significant differences in pathological stage and surgical margin status between GS 3 + 4 with and without TGG5, as well as between GS 4 + 4 with and without TGG5. Of the 600 patients, 92 (15%) patients had biochemical recurrence (BCR) after surgery, with a median follow-up period of 42 (3-104) months. There were no differences in 5-year BCR-free survival rates between patients with GS 3 + 4 with and without TGG5 (92 vs. 100%, P = 0.16), as well as between patients with GS 4 + 3 with and without TGG5 (79 vs. 71%, P = 0.30). Similarly, there were no differences in 3-year BCRFS rates between patients with GS 4 + 4 with and without TGG5 (80 vs. 71%, P = 0.38). In our population, the presence of TGG5 in RARP specimens had no strong impact on pathological and prognostic outcomes.

PD30-05 THE IMPACT OF DOWNGRADING FROM BIOPSY GLEASON SCORE 7 TO RADICAL PROSTATECTOMY GLEASON SCORE 6 ON BIOCHEMICAL RECURRENCE

INTRODUCTION AND OBJECTIVES: Downgrading from biopsy Gleason score (Bx GS) 7 to radical prostatectomy (RP) GS 6 could occur if tangentially-sectioned small glands of Gleason 3 on Bx are overgraded as pattern 4, or alternatively if small foci of pattern 4 in the RP specimen are not recorded or unsampled deeper within the paraffin block. In the later scenario, downgraded men might have a worse prognosis than those with Bx and RP GS 6. We investigated whether there was a difference in biochemical recurrence-free survival (BCRFS) rates based on downgrading status. METHODS: Among 24,536 men with RP between 1984 and 2015, we reviewed 15,586 men (group I [Bx GS 6 to RP GS 6]1⁄4 10,538 [67.6%], group II [Bx GS 7 to RP GS 6]1⁄4 941 [6.0%], and group III [Bx GS 7 to RP GS 7]1⁄4 4,107 [26.4%]). For men with complete follow-up, the log-rank test was used to compare BCRFS between the groups. Cox regression analyses were used to determine the impact of downgrading on BCR. RESULTS: At a median follow-up of 5 years (IQR 2-12), 1,025 men experienced BCR. There were significant differences in age, preoperative prostate-specific antigen (PSA), year of surgery, clinicopathological stage, and positive surgical margin (PSM) between groups (all p<0.001). In group II, there was no difference in BCRFS between men with Bx GS 3+4 and men with 4+3, so they were combined into Bx GS 7. The BCRFS rate for group II was better than that of group III, but worse than that of group I (p<0.001, Fig 1). Downgrading from Bx GS 7 to RP GS 6 was an independent predictor for BCR after adjusting for clinico-pathological variables (HR 2.01, p<0.001 for group I versus group II, Table 1). CONCLUSIONS: Downgrading of a GS 7 tumor at Bx could be attributed in most cases to the presence of a small foci of tertiary Gleason grade 4 pattern in the RP specimen. Downgrading from Bx GS 7 to RP GS 6 was an independent predictor of BCR following RP. Source of Funding: none

Cribriform growth is highly predictive for postoperative metastasis and disease-specific death in Gleason score 7 prostate cancer

Patients with Gleason score 7 prostate cancer on radical prostatectomy demonstrate a wide range in clinical outcome. Gleason grade 4 prostate cancer encompasses a heterogeneous group of tumor growth patterns including fused, ill-defined, cribriform, and glomeruloid glandular structures. Our objective was to determine the prognostic value of different Gleason grade 4 growth patterns. We performed a nested case–control study among 535 patients with Gleason score 7 prostate cancer at radical prostatectomy, treated between March 1985 and July 2013 at a university hospital in the Netherlands. We analyzed 52 cases (with metastasis, disease-specific mortality or both) and 109 controls, matched for age, PSA level, and pT stage. Presence of the following Gleason grade 4 patterns was recorded: fused, ill-defined, cribriform, and glomeruloid. Intraductal carcinoma of the prostate and tertiary Gleason grade 5 were additionally assessed. Outcomes were metastasis-free survival and disease-specific survival. We used Cox proportional hazards regression to determine the predictive value of Gleason grade 4 patterns for survival time. The overall prevalence of Gleason grade 4 patterns was as follows: fused 75% (n=121), ill-defined 64% (n=102), cribriform 48% (n=83), and glomeruloid 25% (n=40). Cribriform pattern was the only pattern with an unequal distribution between cases and controls. Forty-two out of 52 cases (81%) had cribriform growth pattern versus 41/109 controls (38%). In multivariate analysis, presence of cribriform growth was an adverse independent predictor for distant metastasis-free survival (HR 8.0, 95% CI 3.0–21; P<0.001) and disease-specific survival (HR 5.4, 95% CI 2.0–15, P=0.001). In conclusion, cribriform growth in Gleason grade 4 is a strong prognostic marker for distant metastasis and disease-specific death in patients with Gleason score 7 prostate cancer at radical prostatectomy.

Downgrading of biopsy based Gleason score in prostatectomy specimens

AimsTo assess the frequency and possible causes of downgrading from a Gleason score (GS) 7 at biopsy to a GS ≤6 at radical prostatectomy (RP) in a Canadian referral centre.MethodsData...

Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Impact of a tertiary Gleason pattern 4 or 5 on clinical failure and mortality after radical prostatectomy for clinically localised prostate cancer

Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? It is known that a tertiary Gleason grade pattern 4 or 5 found in RP specimens has a negative impact on recurrence rate regarding biochemical relapse after radical prostatectomy. This is the first publication addressing clinical outcome in patients with a tertiary Gleason grade pattern 4 or 5 showing a negative influence on clinical failure rates. To investigate the impact of a tertiary Gleason grade (TGG) pattern 4 or 5 on clinical failure, as the presence of a TGG pattern 4 or 5 in radical prostatectomy (RP) specimens has been associated with biochemical failure. In all, 151 consecutive patients undergoing RP between 1985 and 2006 were reviewed, and 148 patients met study inclusion criteria. The RP specimens were pathologically re-examined and the presence of a TGG pattern 4 or 5 was recorded. The endpoint was clinical failure defined as local recurrence and/or development of metastasis at a mean follow-up of 108 months. Univariate analyses were performed using the Kaplan-Meier method. Multivariate analyses were performed using Cox proportional hazards regression. Clinical failure was more likely among men with presence of a TGG pattern 4 or 5 than in men without a TGG pattern 4 or 5 (P= 0.006). In the subgroup of patients with Gleason score 7 the presence of a TGG 5 was significantly associated with clinical failure rate (P= 0.002). In patients with Gleason score <7 or >7, a TGG pattern 4 or 5 was not associated with increased failure rates. Multivariate Cox regression analyses in patients with Gleason score 7 showed that a TGG pattern 5 was a statistically significant predictor of clinical failure when adjusting for pathological stage, surgical margin status, extraprostatic extension and seminal vesicle invasion (hazard ratio 4.03, 95% confidence interval 1.72-9.46; P= 0.001). Further subgroup analyses showed that a TGG pattern 5 was associated with statistically higher clinical progression rates in patients with Gleason score 3 + 4 (P= 0.03). In patients with Gleason score 4 + 3, a TGG pattern 5 was associated with a trend towards a higher clinical progression rate, although this was not statistically significant (P= 0.189). A TGG pattern 4 or 5 is associated with decreased clinical recurrence-free survival in Gleason score 7.

Does a tertiary Gleason pattern 4 or 5 influence the risk of biochemical relapse after radical prostatectomy for clinically localized prostate cancer?

The presence of a tertiary Gleason grade (TGG) pattern 4 or 5 in radical prostatectomy (RP) specimens has been reported with adverse pathology and a higher biochemical relapse rate after RP. This study investigated the impact of a TGG pattern 4 or 5 on biochemical and pathological outcome in men operated with RP. The study reviewed 151 consecutive cases treated at the hospital between 1985 and 2006; 148 were included in the study. All prostatectomy specimens were re-examined by a genitourinary pathologist and among others parameters the presence of TGG pattern 4 or 5 was recorded. The hospital files were examined retrospectively for clinical follow-up data. Prostate-specific antigen (PSA) relapse was defined as two subsequent rising measurements above 0.20 ng/ml. The influence of a TGG pattern 4 or 5 on prognosis was assessed in a Cox proportional hazards regression model controlling for pathological stage, surgical margin (SM) status, seminal vesicle invasion (SVI) and extraprostatic extension (EPE). Fifty-six patients (38%) experienced PSA relapse during follow-up. Twenty-one patients (58%) with a TGG pattern 4 or 5 had a biochemical relapse compared with 35 patients (31%) without TGG pattern 4 or 5. In the Cox regression model, TGG pattern 4 or 5 was an independent predictor of biochemical failure (p = 0.020). In patients undergoing RP the presence of a TGG pattern 4 or 5 is an independent predictor for biochemical relapse. Consequently, the RP specimens should routinely be investigated for TGG pattern 4 or 5.

Prevalence of a Tertiary Gleason Grade and Its Impact on Adverse Histopathologic Parameters in a Contemporary Radical Prostatectomy Series

BackgroundThe presence of a tertiary Gleason grade (TGG) pattern in radical prostatectomy (RP) specimens has been described as associated with adverse pathology and a higher biochemical recurrence (BCR) rate after RP. ObjectiveTo assess the prevalence of a TGG in a contemporary, consecutive, single-centre RP series and its association with adverse pathology. Design, setting, and participantsFrom January to August 2007, 800 eligible patients (no prior neoadjuvant hormonal therapy) underwent RP for clinically localised prostate cancer (pCA) in our institution. The presence of the third most prevalent Gleason pattern was documented, regardless of whether it was better or worse than the two predominant Gleason grades. MeasurementsThe overall prevalence of a TGG was described. Uni- and multivariate logistic regression analyses tested the association between the presence of a TGG <5% versus ≥5% of the whole tumour volume and extracapsular extension (ECE), seminal vesicle invasion (SVI), positive surgical margins (PSM), and lymph node invasion (LNI). Subanalyses were performed to assess the impact of different TGGs at various Gleason scores. Results and limitationsA TGG was reported in 180 RP specimens (22.5%). In univariate analysis, the presence of a TGG ≥5% was significantly associated with ECE, SVI, PSM, and LNI (p<0.001). In multivariate analysis, a TGG ≥5% showed an independent association with ECE and PSM (p<0.05). Accordingly, in subanalyses, a significant association with adverse pathology was only documented if the amount of a TGG was at least 5% of the tumour volume. Our study is limited by the relatively low overall frequency of a TGG, thereby reducing the statistical expressiveness, especially for subanalyses. ConclusionsOur findings confirm the association of the presence of a TGG with adverse pathologic features. Further follow-up is needed to assess the prognostic impact of a TGG on the risk of BCR and overall survival following RP.

Editorial Comment on: Prevalence of a Tertiary Gleason Grade and Its Impact on Adverse Histopathologic Parameters in a Contemporary Radical Prostatectomy Series

Editorial Comment on: Prevalence of a Tertiary Gleason Grade and Its Impact on Adverse Histopathologic Parameters in a Contemporary Radical Prostatectomy Series

Editorial Comment on: Prevalence of a Tertiary Gleason Grade and Its Impact on Adverse Histopathologic Parameters in a Contemporary Radical Prostatectomy Series

Editorial Comment on: Prevalence of a Tertiary Gleason Grade and Its Impact on Adverse Histopathologic Parameters in a Contemporary Radical Prostatectomy Series

Editorial Comment on: Prevalence of a Tertiary Gleason Grade and Its Impact on Adverse Histopathologic Parameters in a Contemporary Radical Prostatectomy Series

Editorial Comment on: Prevalence of a Tertiary Gleason Grade and Its Impact on Adverse Histopathologic Parameters in a Contemporary Radical Prostatectomy Series

Tertiary Gleason Pattern 5 in Gleason 7 Prostate Cancer Predicts Pathological Stage and Biochemical Recurrence

Gleason sum 7 prostate cancers are a heterogeneous group with diverse tumor behaviors and disease outcomes. Tertiary Gleason patterns are reported with increasing frequency, particularly in prostatectomy pathology reports. We studied the pathological and biochemical outcome following radical prostatectomy in men with Gleason sum 7 and tertiary Gleason pattern 5. We reviewed 1,110 cases of clinically localized prostate cancer treated with primary radical prostatectomy between January 1998 and August 2006 through a prospectively collected prostate cancer database. Patients who underwent neoadjuvant or adjuvant hormonal deprivation, radiation or systemic chemotherapy were excluded. Of the 1,110 patients 509 had Gleason sum 7 cancer. Tertiary Gleason pattern was present in 66 of 509 cases (13%) and it was absent in 443 (87%). On multivariate analysis tertiary Gleason pattern 5 was associated with higher pT stage (OR 2.55, 95% CI 1.40-4.65) and biochemical recurrence (HR 1.78, 95% CI 1.00-3.17). On subgroup analysis when patients with Gleason sum 3 + 4 + 5 and 4 + 3 + 5 were compared to their respective referent groups without the tertiary Gleason pattern, the 2 groups showed a trend toward higher pathological stage and prostate specific antigen progression. Patients with Gleason sum 3 + 4 with no tertiary pattern had higher PSA recurrence-free probability than those with Gleason sum 3 + 4 + 5 or 4 + 3 and patients with Gleason sum 4 + 3 + 5 had the lowest PSA recurrence-free probability. In patients with Gleason sum 7 prostate cancer tertiary Gleason grade 5 is significantly associated with higher pT stage and biochemical recurrence. Larger studies are needed to assess the predictive value of tertiary grade compared to other established parameters in predicting the long-term oncological outcome after radical prostatectomy.

Interobserver agreement of gleason score and modified gleason score in needle biopsy and in surgical specimen of prostate cancer

Gleason score, which has a high interobserver variability, is used to classify prostate cancer. The most recent consensus valued the tertiary Gleason pattern and recommended its use in the final score of needle biopsies (modified Gleason score). This pattern is considered to be of high prognostic value in surgical specimens. This study emphasized the evaluation of the modified score agreement in needle biopsies and in surgical specimen, as well as the interobserver variability of this score. Three pathologists evaluated the slides of needle biopsies and surgical specimens of 110 patients, reporting primary, secondary and tertiary Gleason patterns and after that, traditional and modified Gleason scores were calculated. Kappa test (K) assessed the interobserver agreement and the agreement between the traditional and modified scores of the biopsy and of the surgical specimen. Interobserver agreement in the biopsy was K = 0.36 and K = 0.35, and in the surgical specimen it was K = 0.46 and K = 0.36, for the traditional and modified scores, respectively. The tertiary Gleason grade was found in 8%, 0% and 2% of the biopsies and in 8%, 0% and 13% of the surgical specimens, according to observers 1, 2 and 3, respectively. When evaluating the agreement of the traditional and modified Gleason scores in needle biopsy with both scores of the surgical specimen, a similar agreement was found through Kappa. Contrary to what was expected, the modified Gleason score was not superior in the agreement between the biopsy score and the specimen, or in interobserver reproducibility, in this study.

Tertiary Gleason Grade 5 on Prostate Needle Biopsy and Recurrence Following Definitive Therapy in Men With Gleason Score 7 Prostate Cancer

Tertiary Gleason Grade 5 on Prostate Needle Biopsy and Recurrence Following Definitive Therapy in Men With Gleason Score 7 Prostate Cancer

Should the Gleason grading system for prostate cancer be modified to account for high-grade tertiary components? A systematic review and meta-analysis

The Gleason system for grading prostate cancer assigns a score on the basis of the most prevalent and second most prevalent grade. Several studies have investigated the clinical significance of a tertiary grade in radical prostatectomy samples. A systematic search of the published work identified seven studies that reported the prognostic value of a tertiary Gleason grade. Three studies correlated the presence of a tertiary grade with pathological stage, and six with prostate-specific antigen recurrence or clinical progression. In the small number of studies available, the frequency of a tertiary grade was consistently higher in samples characterised with pathological variables of poor outcome, such as extra-prostatic extension and positive surgical margins, but not lymph-node metastases. In five studies the presence of a tertiary grade increased the risk of prostate-specific antigen recurrence after radical prostatectomy by a factor of 2.5. However, modification of the Gleason score to include a tertiary grade in Gleason 4+3 tumours might overestimate the risk of seminal-vesicle or lymph-node invasion. This systematic review has established the association of a tertiary grade with poorer outcome than that associated with no tertiary grade. A tertiary grade should, therefore, be included in the pathological reporting of prostate cancer and be considered in the interpretation and design of clinical trials. However, all studies assessed for this review were retrospective, potentially affected by selection bias, and based on radical prostatectomy samples or transurethral resections rather than biopsy samples. Therefore, more evidence is needed to warrant the adaptation of the Gleason system to account for the presence of a tertiary grade, especially when scoring prostatic biopsies and applying predictive algorithms.