Prostate cancer grading: The effect of stratification of needle biopsy Gleason Score 4 + 3 as high or intermediate grade
UCD School of Medicine and Medical Science, Conway Institute of Biomolecular and Biomedical Research, Dublin, Ireland. BJU International
(Impact Factor: 3.53).
10/2009; 105(5):631-5. DOI: 10.1111/j.1464-410X.2009.08810.x
To assess the discrepancy between needle biopsy (NB) and radical prostatectomy (RP) Gleason score (GS) in Irish men, specifically the influence of the stratification of GS 4 + 3 on overall levels of agreement, levels of discrepancy and kappa coefficients, as the GS assigned to prostate cancer NBs affects clinical decision-making and influences future therapeutic strategies.
We reviewed retrospectively a database of the discrepancies between NB and RP Gleason grades (GG) from 2003 to 2008. All patients had clinically localized prostate cancer, and none had had neoadjuvant therapy. Grading of 206 NB specimens was compared with their corresponding RP specimens. The discrepancy rate between NB and RP GS was assessed for each combination of GG. Intermediate- (GS 7, defined as GS 3 + 4 alone vs GS 7) and high-grade (GS 4 + 3 and GS 8-10 vs GS 8-10) classifications were compared. The level of agreement and the kappa coefficient for each system was assessed.
In NB, GS 6 was most frequently diagnosed (53%); after RP, GS 3 + 4 was most frequent (36%). In 42% of cases the exact GG remained unchanged after RP, increasing to 48% for GS 6 and GS 3 + 4. Overall 42% of cases showed an increase in their GG. In GS 6 NBs, the rate of increase in the primary GG or increase in the GS was 52%. Biopsy GS 6 and 3 + 4 showed the highest levels of agreement between NB and RP. Low-grade prostate cancer on NB was upgraded in 52% of cases; high-grade prostatic adenocarcinoma was downgraded in 27-77% of cases depending on the grading system used.
Classification of high-grade prostate cancer as GS 4 + 3 and GS 8-10 results in higher levels of agreement between NB and RP GS. Reliable identification of well differentiated prostatic adenocarcinoma in NB specimens represents an ongoing diagnostic challenge, necessitating careful preoperative consideration of the definitive grade of a patient's disease.
Available from: Carlos Mandarim-de-Lacerda
- "The reliable identification of well-differentiated prostatic adenocarcinoma in biopsy specimens remains challenging . To measure this reliability, agreement among pathologists was tested, and the GSc assigned by 15 expert uropathologists for fifteen PCa biopsy samples were compared GSc assigned by 337 members of the European Network of Uropathology. "
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Efforts to improve the diagnosis, prognosis and surveillance of prostate cancer (PCa) are relevant. Gleason score (GSc) overestimation may subject individuals to unnecessary aggressive treatment. We aimed to use stereology in PCa evaluations and investigate whether mean nuclear volume (MNV) correlates with the Gleason primary pattern (Gpp) and to improve the subjective GSc to obtain an objective and reliable method without inter-observer dissension.
We identified 74 radical prostatectomy specimens that were divided into six groups based on Gpp, from 3 to 5. Controls (C) were designed in paired non-tumor regions of the same specimens. MNV was estimated using the “point-sampled intercepts” method. Differences in MNV among the C groups and the Gpp groups were tested with the Kruskall-Wallis test and Dunn post-hoc test. Differences between each Gpp group and its control counterpart were tested with the Wilcoxon test. Correlations were evaluated with the Spearman rank correlation (R[Spearman]).
The correlations between prostate-specific antigen (PSA) and GSc (R[Spearman] of 0.76) and between PSA and MNV (R[Spearman] of 0.78) were moderately strong and highly significant, and the correlation between MNV and Gpp (R[Spearman] of 0.53) was moderate and highly significant. MNV was significantly greater in cancerous regions than in paired-control regions. Limitations included sample size.
Proper planning of a study, as well as the availability of equipment and software for morphological quantification, can provide incentive to quickly and accurately estimate MNV as an adjunct parameter in the assessment of PCa. Current data are in favor of the use of MNV associated with GSc and PSA in the assessment of PCa.
Available from: Thomas Brendan Murphy
- "This represents a 30% staging error, as the entire study cohort were assumed to have OC disease and hence underwent RP. 47.1% of patient’s biopsy Gleason score was an incorrect estimate of their true Gleason score at RP, indicating that only 52.9% of patients did not experience an upgrading or downgrading of their Gleason score. Our group had previously shown a 42% Gleason score error between biopsy and RP in a smaller sample (N = 206) of the same patient cohort . This level of upgrading or downgrading (42%) has been illustrated in other studies . "
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ABSTRACT: There are dilemmas associated with the diagnosis and prognosis of prostate cancer which has lead to over diagnosis and over treatment. Prediction tools have been developed to assist the treatment of the disease.
A retrospective review was performed of the Irish Prostate Cancer Research Consortium database and 603 patients were used in the study. Statistical models based on routinely used clinical variables were built using logistic regression, random forests and k nearest neighbours to predict prostate cancer stage. The predictive ability of the models was examined using discrimination metrics calibration curves and clinical relevance, explored using decision curve analysis. The N = 603 patients were then applied to the 2007 Partin table to compare the predictions from the current gold standard in staging prediction to the models developed in this study.
30 % of the study cohort had non organ-confined disease. The model built using logistic regression illustrated the highest discrimination metrics (AUC = 0.622, Sens = 0.647, Spec = 0.601), best calibration and the most clinical relevance based on decision curve analysis. This model also achieved higher discrimination than the 2007 Partin table (ECE AUC = 0.572 & 0.509 for T1c and T2a respectively). However, even the best statistical model does not accurately predict prostate cancer stage.
This study has illustrated the inability of the current clinical variables and the 2007 Partin table to accurately predict prostate cancer stage. New biomarker features are urgently required to address the problem clinician's face in identifying the most appropriate treatment for their patients. This paper also demonstrated a concise methodological approach to evaluate novel features or prediction models.
Available from: Radka Saldova
- "Altered glycosylation in Gleason stages is consistent with clinical data The outcome of prostate cancer patients is significantly correlated with the Gleason score. Patients with Gleason score 7 (high-grade disease) is more commonly found to have advanced disease, and thus, the likelihood of relapse is higher than patient with low-grade prostate cancer (Fanning et al. 2010). We found a decrease in triantennary trigalactosylated glycans and in tetraantennary tetrasialylated outer armfucosylated glycans and increase in tetraantennary tetrasialylated glycans in Gleason 7 compared with Gleason 5 prostate cancer patients. "
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ABSTRACT: One of the most urgent requirements in prostate cancer diagnosis is the development of a blood-based test which would be able to distinguish prostate cancer from benign prostate hyperplasia (BPH). Previously published results found a significant difference between specific glycan levels in patients with advanced prostate cancer and healthy controls. N-Glycans from the whole serum glycoproteins were measured using our fully quantitative high-throughput N-glycan analysis in combination with exoglycosidase digestions in sera from 13 BPH and 34 prostate cancer samples (17 Gleason score 5 and 17 Gleason score 7). The levels of core-fucosylated biantennary glycans and α2-3-linked sialic acids were significantly increased in prostate cancer patients compared with patients with BPH. Triantennary trigalactosylated glycans and tetraantennary tetrasialylated glycans with outer arm fucose were significantly decreased, and tetraantennary tetrasialylated glycans increased in Gleason 7 compared with Gleason 5. All these glycans can distinguish prostate cancer patients from BPH or Gleason 7 from Gleason 5 prostate cancer patients better than the current clinical test, prostate-specific antigen; therefore, their measurement may provide a new noninvasive approach to diagnose prostate cancer. However, additional validation studies would need to be carried out to further support this finding. Decreases in triantennary trigalactosylated glycans and/or bisected core-fucosylated biantennary monosialylated glycans and increases in tetraantennary tetrasialylated glycans correlate with perineural invasion, which could further help to diagnose tumor spread and predict patients' survival.
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