Risk factors associated with perineural invasion in prostate cancer

ObjectivesThe prognostic importance of perineural invasion (PNI) in prostate cancer (PC) has been postulated by some authors. Few studies have investigated the risk factors associated with PNI. The aim of this study was to identify factors associated with PNI in PC.Patients and methodsThe study group of 113 patients diagnosed with PC during the period 2005–2010 consisted of 66 who underwent radical prostatectomy (RP) and 66 who did not. Each group was further divided into those with and without PNI. The association between clinicopathological parameters and PNI in prostate biopsy (Pbx) and RP specimens was investigated using t-test and logistic regression analysis. Discordance in PNI prevalence and PNI up-migration between Pbx and RP specimens were also studied.ResultsIn patients who did not undergo RP, Pbx Gleason score (GS) ≥ 7 was a significant predictor for the presence of PNI. In patients who underwent RP, Pbx GS > 7 increased the risk of PNI in Pbx and RP samples, while a high RP GS predicted PNI in the RP specimen. The discordance rate for PNI in Pbx and RP specimens was 27.3%. Up-migration to a PNI positive cancer between Pbx and RP specimens was seen in 45.5% of cases and RP GS was the only factor associated with PNI up-migration.ConclusionThe association of PNI with a high GS and the high rate of discordance between Pbx and RP specimens indicate that in patients with a high GS on Pbx, the pathologist should look more carefully for PNI, and the surgeon should be aware of sampling errors and the unreliability of Pbx specimens in detecting PNI.     

Validation of tertiary Gleason pattern 5 in Gleason score 7 prostate cancer as an independent predictor of biochemical recurrence and development of a prognostic model

ObjectiveTo validate the biological and prognostic value of tertiary Gleason pattern 5 (TGP5) in patients with Gleason score 7 (GS 7) prostate cancer (PCa) and to develop a prognostic model to identify the high-risk group of patients with TGP5.Material and methodsWe retrospectively reviewed the data from 4,146 patients with localized (pT2–3 N0 M0) GS 7 PCa treated by radical prostatectomy (RP) without adjuvant therapy. The primary end point was biochemical recurrence (BCR), and the secondary one was to build a bootstrap-corrected multivariable Cox model.ResultsOf the 4,146 patients, 416 (10%) had a TPG5 in the RP specimen. TGP5 was associated with BCR in both univariable and multivariable analyses that adjusted for the effects of standard pathological features (P<0.001). A prognostic model based on preoperative prostate-specific antigen levels (<10 vs.≥10 ng/ml), primary and secondary Gleason pattern (3+4 vs. 4+3), pathological tumor category (pT2/pT3a vs. pT3b), and surgical margin status (R0 vs. R+) stratified patients with a discrimination of 72.2%. Patients in the low-risk group had a 5-year BCR-free survival rate of 76.3% compared with only 18.5% for those in the high-risk group (P<0.001).ConclusionsKnowledge of TGP5 improves our prognostication of patients with GS 7 PCa treated with RP. We developed a statistical tool to help identify the patients with TGP5 who are at the highest risk of BCR after RP, thereby helping with the clinical decision making regarding adjuvant trials and follow-up scheduling.     

Underestimation of Gleason score at prostate biopsy reflects sampling error in lower volume tumours

Study Type – Diagnostic (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The Gleason score of prostate cancer is frequently underestimated at the time of diagnostic biopsy, although the contribution of sampling error to its incidence is unknown. We show that under‐graded tumours are significantly smaller that tumours concordant for the higher grade, indicating that incomplete tumour sampling plays a significant role in Gleason score assignment error.

OBJECTIVE

• ? To determine the influence of tumour and prostate gland volumes on the underestimation of prostate cancer Gleason score in diagnostic core biopsies.

PATIENTS AND METHODS

• ? Patients undergoing radical prostatectomy with matched diagnostic biopsies were identified from a prospectively recorded database.
• ? Tumour volumes were measured in serial whole‐mount sections with image analysis software as part of routine histological assessment.
• ? Differences in various metrics of tumour and prostate volume between upgraded tumours and tumours concordant for the lower or higher grade were analysed.

RESULTS

• ? In all, 684 consecutive patients with Gleason score 6 or 7 prostate cancer on diagnostic biopsy were identified.
• ? Of 298 patients diagnosed with Gleason 6 tumour on biopsy, 201 (67.4%) were upgraded to Gleason 7 or higher on final pathology. Similarly, of 262 patients diagnosed with Gleason 3 + 4 = 7 prostate cancer on initial biopsy, 60 (22.9%) were upgraded to Gleason score 4 + 3 = 7 or higher.
• ? Tumours upgraded from Gleason 6 to 7 had a significantly lower index tumour volume (1.73 vs 2 mL, P= 0.029), higher calculated prostate volume (41.6 vs 39 mL, P= 0.017) and lower relative percentage of tumour to benign glandular tissue (4.3% vs 5.9%, P= 0.001) than tumours concordant for the higher grade.
• ? Similarly, tumours that were Gleason score 3 + 4 on biopsy and upgraded on final pathology to 4 + 3 were significantly smaller as measured by both total tumour volume (2.3 vs 3.3 mL, P= 0.005) and index tumour volume (2.2 vs 3, P= 0.027) and occupied a smaller percentage of the gland volume (6.3% vs 8.9%, P= 0.017) compared with tumours concordant for the higher grade.
• ? On multivariate analysis, lower prostate weight (hazard ratio 0.97, 95% confidence interval 0.96–0.99, P < 0.001) and larger total tumour volume (hazard ratio 1.87, 95% confidence interval 1.4–2.6, P < 0.001) independently predicted an upgrade in Gleason score from 6 to 7. In tumours upgraded from biopsy Gleason 3 + 4, only higher index tumour volume (hazard ratio 3.1, 95% confidence interval 1.01–9.3, P= 0.048) was a significant predictor of upgrading on multivariate analysis.

CONCLUSIONS

• ? Under‐graded tumours are significantly smaller than tumours concordant for the higher grade, indicating that incomplete tumour sampling plays a significant role in Gleason score assignment error.
• ? Surrogate measures of tumour volume may predict those at greatest risk of Gleason score upgrade.

     

Prognostic significance of primary Gleason pattern in Japanese men with Gleason score 7 prostate cancer treated with radical prostatectomy

ObjectivesTo evaluate the significance of the primary Gleason pattern in patients with Gleason score (GS) 7 prostate cancer treated with radical prostatectomy.Materials and methodsThis study included 959 consecutive Japanese men who underwent radical prostatectomy without neoadjuvant therapies and were subsequently diagnosed as having GS 7 prostate cancer based on the modified International Society of Urological Pathology (ISUP) 2005 Gleason grading system.ResultsOf these 959 patients, 666 (69.4%) and 293 (30.6%) had GS 3+4 and GS 4+3 tumors, respectively. There were significant differences in the prostate-specific antigen (PSA) level, biopsy GS, pathologic T stage, lymphatic invasion, microvenous invasion, and perineural invasion between these 2 groups. During the mean observation of 48.9 months, biochemical recurrence occurred in 211 patients (22.0%), and there was a significant difference in the biochemical recurrence-free survival between patients with GS 3+4 tumors and those with GS 4+3 tumors. Of several factors examined, biochemical recurrence-free survival was significantly associated with the PSA level, biopsy Gleason score, capsular penetration, seminal vesicle invasion, surgical margin status, lymphatic invasion, microvenous invasion, perineural invasion, and primary Gleason pattern, among which the PSA level, capsular penetration, seminal vesicle invasion, and surgical margin status, but not primary Gleason pattern, appeared to be independent predictors of biochemical recurrence.ConclusionsDespite the lack of an independent significance, primary Gleason pattern based on the modified ISUP 2005 Gleason grading system is shown to be significantly associated with the biochemical outcome of Japanese men with GS 7 prostate cancer.     

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

Background

Prior studies assessing the correlation of Gleason score (GS) at needle biopsy and corresponding radical prostatectomy (RP) predated the use of the modified Gleason scoring system and did not factor in tertiary grade patterns.

Objective

To assess the relation of biopsy and RP grade in the largest study to date.

Design, setting, and participants

A total of 7643 totally embedded RP and corresponding needle biopsies (2004–2010) were analyzed according to the updated Gleason system.

Interventions

All patients underwent prostate biopsy prior to RP.

Measurements

The relation of upgrading or downgrading to patient and cancer characteristics was compared using the chi-square test, Student t test, and multivariable logistic regression.

Results and limitations

A total of 36.3% of cases were upgraded from a needle biopsy GS 5–6 to a higher grade at RP (11.2% with GS 6 plus tertiary). Half of the cases had matching GS 3 + 4 = 7 at biopsy and RP with an approximately equal number of cases downgraded and upgraded at RP. With biopsy GS 4 + 3 = 7, RP GS was almost equally 3 + 4 = 7 and 4 + 3 = 7. Biopsy GS 8 led to an almost equal distribution between RP GS 4 + 3 = 7, 8, and 9–10. A total of 58% of the cases had matching GS 9–10 at biopsy and RP. In multivariable analysis, increasing age (p < 0.0001), increasing serum prostate-specific antigen level (p < 0.0001), decreasing RP weight (p < 0.0001), and increasing maximum percentage cancer/core (p < 0.0001) predicted the upgrade from biopsy GS 5–6 to higher at RP. Despite factoring in multiple variables including the number of positive cores and the maximum percentage of cancer per core, the concordance indexes were not sufficiently high to justify the use of nomograms for predicting upgrading and downgrading for the individual patient.

Conclusions

Almost 20% of RP cases have tertiary patterns. A needle biopsy can sample a tertiary higher Gleason pattern in the RP, which is then not recorded in the standard GS reporting, resulting in an apparent overgrading on the needle biopsy.     

Presence of high grade tertiary Gleason pattern upgrades the Gleason sum score and is inversely associated with biochemical recurrence-free survival

ObjectivesTumor heterogeneity is a common finding and led to realization of a tertiary Gleason component (TGC) in prostate cancer. In an attempt to further investigate its prognostic value, we analyzed the association of tertiary Gleason pattern in Gleason score ≤ 7 tumors with pathologic stage and biochemical disease-free survival.Material and methodsA total of 331 radical prostatectomy specimens were analyzed retrospectively. The primary, secondary, and the tertiary patterns were evaluated by reviewing all of the pathologic slides. TGC was defined as Gleason grade pattern 4 or 5 for Gleason score < 7 tumors and Gleason grade pattern 5 for Gleason score 7 tumors. The pathologic prognostic factors, (extraprostatic extension, seminal vesicle and lymph node invasion, surgical margin status) of Gleason score < 7, 3+4, and 4+3 tumors with or without TGC were compared. Biochemical recurrence-free survival (BRFS) was calculated using Kaplan-Meier method with log rank test, and the influence of TGC was assessed in a Cox regression model.ResultsTGC observed more frequently with higher Gleason scores (21% of the GS < 7 cases, 23% of the GS 3+4 cases, and 58% of the GS 4+3 cases). In terms of adverse pathologic prognostic factors and BRFS, GS < 7 tumors with TGC behaved significantly worse than GS < 7 tumors without TGC (P = 0.01 and P = 0.001, respectively) with properties similar to GS 3+4 tumors without TGC. Gleason score 3+4 and 4+3 tumors without TGC were statistically similar and had better features than corresponding tumors of same Gleason score with TGC. Furthermore, Gleason score 7 tumors with TGC had similar features with GS 8–10 tumors. During follow-up, 73 (22%) subjects had PSA recurrence. In the Cox regression model TGC was an independent variable for BRFS (HR = 2.63, 95% CI = 1.39–4.98, P = 0.003).ConclusionAccording to the present study, 3 different prognostic groups were observed; good prognostic group: GS < 7, intermediate prognostic group: GS < 7+TGC, GS 3+4, and GS 4+3, and finally bad prognostic group: GS (3+4)+TGC, GS (4+3)+TGC, GS > 7. Presence of a TGC appears to upgrade the total score and adjuvant treatment decisions may further be refined by considering the tertiary pattern.     

Concordance between Gleason scores of needle biopsies and radical prostatectomy specimens: a population‐based study

OBJECTIVE

To study the concordance between the Gleason scores of needle biopsies and radical prostatectomy (RP) specimens in a population‐based registry, to clarify whether the concordance depends on the annual number of RP specimens assessed in the pathology unit, and to identify preoperative clinical factors that predict upgrading from a Gleason score of ≤6 in the biopsy to ≥7 in the RP specimen.

PATIENTS AND METHODS

Through the Cancer Registry of Norway, we identified 1116 patients with available Gleason scores from biopsy and RP specimens. Concordance was evaluated using the κ coefficient, and predictors of concordance were assessed in univariate and multivariate logistic regression analyses.

RESULTS

The Gleason scores were identical in biopsy and RP specimens in 591 of the 1116 (53%) patients. The biopsy‐based Gleason score more often under‐graded (38%) than over‐graded (9%) the RP‐based Gleason score. Pathology units that examined >40 RP specimens annually had a higher concordance between the Gleason score in the biopsy and RP specimen than did lower‐volume units. The rate of upgrading from a Gleason score of ≤6 in the biopsy to ≥7 in the RP specimen increased with increasing preoperative prostate‐specific antigen serum levels, and with increasing intervals between biopsy and RP.

CONCLUSIONS

The concordance in Gleason score between biopsy and RP was highest among the pathology departments that regularly evaluated RP specimens. Careful consideration of clinical factors and biopsy grading might improve the identification of patients considered as suitable for active surveillance.     

Prostate cancer grading: the effect of stratification of needle biopsy Gleason Score 4 + 3 as high or intermediate grade

Study Type – Prognosis (case series)
Level of Evidence 4

OBJECTIVES

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 κ coefficients, as the GS assigned to prostate cancer NBs affects clinical decision‐making and influences future therapeutic strategies.

PATIENTS AND METHODS

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 κ coefficient for each system was assessed.

RESULTS

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.

CONCLUSIONS

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.     

Upgrading on radical prostatectomy specimens of very low- and low-risk prostate cancer patients on active surveillance: A population-level analysis

IntroductionA proportion of prostate cancer (PCa) patients initially managed with active surveillance (AS) are upgraded to a higher Gleason score (GS) at the time of radical prostatectomy (RP). Our objective was to determine predictors of upgrading on RP specimens using a national database.MethodsThe Surveillance, Epidemiology, and End Results Prostate with Watchful Waiting database was used to identify AS patients diagnosed with very low- or low-risk PCa who underwent delayed RP between 2010 and 2015. The primary outcome was upgrading to GS 7 disease or worse. Logistic regression analyses were used to evaluate demographic and oncological predictors of upgrading on final specimen.ResultsA total of 3775 men underwent RP after a period of AS, 3541 (93.8%) of whom were cT2a; 792 (21.0%) patients were upgraded on RP specimen, with 85.4%, 10.6%, and 3.4% upgraded to GS 7(3+4), 7(4+3), and 8 diseases, respectively. On multivariable analysis, higher prostate-specific antigen (PSA) at diagnosis (5–10 vs. 0–2 ng/ml, odd ratio [OR] 2.59, p<0.001) and percent core involvement (80–100% vs. 0–20%, OR 2.52, p=0.003) were significant predictors of upgrading on final RP specimen, whereas higher socioeconomic status predicted lower odds of upgrading (highest vs. lowest quartile OR 0.75, p=0.013).ConclusionsHigher baseline PSA and percent positive cores involvement are associated with significantly increased risk of upgrading on RP after AS, whereas higher socioeconomic status predicts lower odds of such events. These results may help identify patients at increased risk of adverse pathology on final specimen who may benefit from earlier definitive treatment.     

The prognostic significance of Gleason scores in metastatic prostate cancer

PurposeAlthough the majority of metastatic prostate cancer (mPCa) will arise from tumors with Gleason scores (GS) of 8 to 10 existing tumor grade analyses for mPCa have been almost uniformly limited to comparisons of≤7 vs.≥8. In this analysis, we comprehensively evaluate the GS as a prognostic factor for mPCa in the era of the updated Gleason grading system.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with mPCa, GS 6 to 10, diagnosed from 2006 to 2008. GS and primary-secondary Gleason pattern variations were analyzed for overall survival and prostate cancer–specific survival (PCSS).ResultsA total of 4,654 patients were evaluable. At 4 years, the overall survival rates were 51%, 45%, 34%, 25%, and 15% and PCSS rates were 69%, 57%, 44%, 33%, and 21% for GS 6, 7, 8, 9, and 10, respectively. Survival differences for GS 7 vs. 8, 8 vs. 9, and 9 vs. 10 were highly significant on both univariate and multivariate analyses accounting for age, prostate-specific antigen level, and T stage (all P<0.001). Gleason pattern 5 was an independent prognostic factor, both overall for patients with GS 6 to 10 and on primary-secondary Gleason pattern comparisons within the GS 8 (4+4 vs. 3+5 and 5+3) and GS 9 (4+5 vs. 5+4) subgroups. No survival differences were observed between 3+4 vs. 4+3. Overall, lower prostate-specific antigen level, younger age, and lower GS were associated with improved survival, with GS being the strongest prognostic factor for PCSS.ConclusionsIn this large population-based cohort, stratified survival outcomes were observed for GS 6 to 10, with sequential comparisons of GS 7 to 10, and the presence and extent of Gleason pattern 5 representing independent prognostic factors in the metastatic setting.     

Trends in reporting Gleason score 1991 to 2001: changes in the pathologist's practice

OBJECTIVE: The prostate specific antigen (PSA) era has been associated with a grade migration towards moderately-differentiated (Gleason 5-7) prostate cancer. We investigated whether changes in interpretation of the Gleason system could be a contributing factor by reviewing the Gleason scores for prostate cancer in our region. PATIENTS AND METHODS: Records of patients with prostate cancer assigned a Gleason score between 1991-2001 were retrospectively reviewed. We analysed trends in Gleason score, method of diagnosis and age at diagnosis. Following this, 50 cases from the dataset were randomly selected (stratified to contain half Gleason 2-4 reports) and reviewed in a blinded manner by an uropathologist and given a new Gleason score. RESULTS: 2737 patients were diagnosed and given a Gleason score; 1484 by prostate biopsy (PB) and 1172 by transurethral resection of prostate (TURP). 273 radical prostatectomy (RP) specimens were received, although the results of pre-operative biopsies were available in only 192 of these patients. Over time, there was an increase in the proportion of patients with Gleason 5-7, and a significant decrease in reporting of Gleason 2-4 cancer (r2 = 0.81, p < 0.0001). In 1991, 24% of cancers were Gleason 2-4; in 2001 this had decreased to 2.4%. TURP was associated with more Gleason 2-4 reports (23%) compared with PB (13.2%) and RP (9.2%). On blinded review, all Gleason 2-4 reports were upgraded to Gleason 5-7 cancer (p < 0.001). CONCLUSION: Over time, the proportion of Gleason 2-4 prostate cancer reported has significantly decreased. Our study suggests that a change in practice by the pathologist is a significant factor in this grade migration.     

Score de Gleason des biopsies prostatiques et celui des pièces de prostatectomies: Quelle corrélation?

IntroductionThe Gleason score obtained on biopsies is an essential part of treatment decision making in prostate cancer. This score assesses aggressiveness and progression of the tumor.ObjectiveTo evaluate the correlation between Gleason score at needle biopsy and prostatectomy specimen.Subjects and MethodsWe reviewed the records of 30 patients treated for prostate cancer by radical prostatectomy and we evaluated the correlation between Gleason score on biopsy and prostatectomy specimen. Other parameters evaluated were age and PSA.ResultsThe concordance of Gleason score was 58.82%, upgraded in 35, 29% and downgraded in only 6%. The kappa coefficient was moderate = 0,329. Regarding groups of differentiation, this correlation was 50% in the well differentiated group (Gleason score 2 to 4) and 100% in moderately differentiated group (Gleason score 5 to 7). No patient was classified as poorly differentiated (Gleason score 8 to 10).ConclusionGleason score of biopsies may influence treatment and prognosis of localized prostate cancer. It is important to keep in mind that it does not always reflect the true Gleason score, especially in well differentiated cases.     

Tertiary Gleason pattern in radical prostatectomy specimens is associated with worse outcomes than the next higher Gleason score group in localized prostate cancer

Aim

To assess the predictive value of TGP on biochemical recurrence (BCR) and its association with clinicopathological outcomes in a large, multicenter cohort of patients with localized prostate cancer (PCa) treated with radical prostatectomy (RP).

增加穿刺活检针数提高前列腺癌分级准确性的临床研究

目的 探讨增加穿刺活检针数能否提高前列腺癌穿刺标本Gieason评分准确性.方法 接受根治性前列腺切除的前列腺癌患者86例.平均年龄63(55～72)岁.术前PSA值平均16.8(1.6～57.2)ng/ml,前列腺体积平均39.4(18.1～114.1)ml.患者术前均未接受新辅助内分泌治疗,按经直肠前列腺穿刺针数分为2组.A组46例行标准6针系统穿刺,B组40例行13针系统穿刺.统计学比较分析2组穿刺标本与根治术标本Gleason评分符合情况及影响因素. 结果 A组穿刺标本与根治术标本Gleason评分相符16例(34.8%),B组为26例(65.O%),B组评分符合率明显高于A组(P＜0.05).当穿刺标本Gleason评分≤6时,B组评分相符11例(68.8%),明显高于A组5例(25.0%),差异有统计学意义(P＜0.05).多因素Logistic回归分析结果提示前列腺穿刺活检针数及活检阳性率是影响穿刺标本与根治术标本Gieason评分符合率的主要相关因素(P＜0.05).结论 增加穿刺针数能够提高经直肠前列腺穿刺标本Gleason评分预测前列腺癌分级的准确性.     

Concordance of Gleason grading with three-dimensional ultrasound systematic biopsy and biopsy core pre-embedding

Purpose

To determine the value of a three-dimensional (3D) greyscale transrectal ultrasound (TRUS)-guided prostate biopsy system and biopsy core pre-embedding method on concordance between Gleason scores of needle biopsies and radical prostatectomy (RP) specimens.

Methods

Retrospective analysis of prostate biopsies and subsequent RP for PCa in the Jeroen Bosch Hospital, the Netherlands, from 2007 to 2016. Two cohorts were analysed: conventional 2D TRUS-guided biopsies and RP (2007–2013, n = 266) versus 3D TRUS-guided biopsies with pre-embedding (2013–2016, n = 129). The impact of 3D TRUS-guidance with pre-embedding on Gleason score (GS) concordance between biopsy and RP was evaluated using the κ-coefficient. Predictors of biopsy GS 6 upgrading were assessed using logistic regression models.

Results

Gleason concordance was comparable between the two cohorts with a κ = 0.44 for the 3D cohort, compared to κ = 0.42 for the 2D cohort. 3D TRUS-guidance with pre-embedding, did not significantly affect the risk of biopsy GS 6 upgrading in univariate and multivariate analysis.

Conclusions

3D TRUS-guidance with biopsy core pre-embedding did not improve Gleason concordance. Improved detection techniques are needed for recognition of low-grade disease upgrading.

     

Prognostic value of the Gleason score in prostate cancer

OBJECTIVE: To investigate the prognostic value of the Gleason score in prostate cancer. PATIENTS AND METHODS: A consecutive series of 305 men with prostate cancer diagnosed at transurethral resection (1975-1990) and with no curative treatment was analysed. There was no assessment of prostate-specific antigen level during this period. The mean (range) age at diagnosis was 73.7 (52-95) years and the mean follow-up was 6.4 (0-22) years. The influence of Gleason score and the percentage of the specimen area with tumour (% cancer) on disease-specific survival were assessed using Kaplan-Meier analyses. RESULTS: Of 305 cancers, 22% had a Gleason score of 4-5, 29% of 6, 18% of 7 and 32% of 8-10. At the follow-up, 89% of the men had died, of whom 42% had died from prostate cancer. The disease-specific 10-year survival was 56%. The disease-specific mean survival (DSMS) for Gleason score 4-5, 6, 7 and 8-10 was 20, 16, 10 and 5 years, respectively (P < 0.001). The DSMS did not differ significantly between Gleason 4 and 5 or between 8-10. There was a trend towards shorter survival for Gleason 4 + 3=7 (DSMS 9 years) than GS 3 + 4=7 (DSMS 13 years; P = 0.16). Gleason score and % cancer were independent predictors of DSMS (P < 0.001). CONCLUSION: The long-term prognosis of prostate cancer on deferred treatment is predicted well by the Gleason score. Four prognostic categories of prostate cancer are suggested, i.e. Gleason score 4-5, 6, 7 and 8-10.     

Gleason score and tumor laterality in radical prostatectomy and transrectal ultrasound-guided biopsy of the prostate: a comparative study

We aimed to compare Gleason score and tumor laterality between transrectal ultrasound-guided biopsy of the prostate (TRUSBX) and radical prostatectomy (RP). Some factors that could cause a discrepancy in results between these two procedures were also evaluated. Among the 318 cases reviewed, 191 cases were selected for inclusion in this comparative study. We divided the patients into two groups using the Gleason score: an intermediate/high-grade group (≥7) and a low-grade group (<6). Exploratory analyses were conducted for comparisons between groups. We also performed comparisons between TRUSBX and RP for tumor laterality. TRUSBX overestimated 6% and underestimated 24% cases in comparison with RP for Gleason score, and overestimated 2.6% and underestimated 46% cases compared with RP for tumor laterality. Biopsy specimens were slightly smaller in TRUSBX cases with underestimated tumor laterality (P < 0.05), and no relationship between the biopsy specimen size and underestimated Gleason score in TRUSBX was found. Prostatic volume showed no statistical correlation with the likelihood of under or overestimation (P > 0.05). Thus, our study showed that TRUSBX has a high likelihood of underestimating both the Gleason score and tumor laterality in prostate cancer (PCa). The size of the fragment appears to be an important factor influencing the likelihood of laterality underestimation and Gleason score overestimation via TRUSBX. Due to the high likelihood of underestimation of the Gleason score and tumor laterality by 12-core prostate biopsy, we conclude that this type of biopsy should not be used alone to guide therapy in PCa.     

Outcome after radical prostatectomy with a pretreatment prostate biopsy Gleason score of >/=8

OBJECTIVE: To determine the outcome and predictors of recurrence in patients with a pretreatment prostate biopsy Gleason score (GS) of >/= 8 and treated with radical prostatectomy (RP). PATIENTS AND METHODS: We retrospectively reviewed 1048 consecutive patients who underwent RP by one surgeon (M.S.S.); patients who had a pretreatment biopsy GS of >/= 8 were identified. Information was recorded on patient age, initial prostate specific antigen (PSA) level, clinical stage, biopsy GS, pathology GS, extraprostatic extension (EPE), tumour volume, surgical margin status, seminal vesicle invasion (SVI), and lymph node involvement. The results were assessed statistically using the Kaplan-Meier method, univariate log-rank tests and multivariate analysis using Cox's proportional hazards regression. RESULTS: In all, 123 patients met the initial selection criteria; 44 were excluded from further analyses (five salvage RP, 23 < 1 year follow-up and 16 adjuvant treatment). Thus 79 patients were included in the uni- and multivariate analyses; 25 (31%) patients had a GS of /= 8. The mean follow-up was 55 months, the age of the patients 63 years and the mean (sd) initial PSA level 13 (12) ng/mL. The overall biochemical failure rate was 38% (41% if the final GS was >/= 8 and 32% if it was /= 8 in the RP specimen, 20% (11/54) were organ-confined; two patients (2.5%) in this group developed local recurrence. If the final GS was /= 20 ng/mL, EPE, SVI, a positive surgical margin and tumour volume. Cox's proportional regression indicated that a PSA of >/= 20 ng/mL (hazard ratio 7.9, 95% confidence interval 2.6-24.2, P < 0.001), the presence of EPE (4.2, 1.6-10.9, P = 0.004) and a positive surgical margin (3.8, 1.5-9.7, P = 0.005) were significant independent predictors in a multivariate analysis. CONCLUSION: RP is a reasonable treatment option for patients with a prostate biopsy GS of >/=8 and clinical stage T1-2. These patients have a high chance of remaining disease-free if their PSA level is /= 8 should be counselled about the potential differences between the biopsy and the RP specimen GS.     

Gleason grade remains an important prognostic predictor in men diagnosed with prostate cancer while on finasteride therapy

OBJECTIVE: To evaluate men treated with finasteride for lower urinary tract symptoms, who subsequently were diagnosed with prostate cancer and had a radical prostatectomy (RP) at our institution, to determine if finasteride therapy prevented accurate Gleason grade assignment and prediction of biochemical recurrence. PATIENTS AND METHODS: Between May 1996 and July 2003, 45 men were identified who had RP and had previously been treated with finasteride for > or = 6 months before the diagnosis of prostate cancer. Clinical and pathological information was gathered from a RP database. Serum prostate-specific antigen (PSA) level, duration of finasteride therapy, biopsy Gleason grade, clinical stage, RP Gleason grade and pathological stage were reviewed. Freedom from recurrence was predicted using validated nomograms before and after RP, and compared against actuarial 5-year freedom from recurrence using the Kaplan-Meier method. RESULTS The mean duration of finasteride therapy before diagnosis was 23.6 months, the mean serum PSA (doubled to account for finasteride use) 11.02 ng/mL and mean biopsy Gleason score 6. When comparing the biopsy and RP specimen Gleason score, it was downgraded by 1 point in six men, upgraded by 1 point in eight, and upgraded by 2 points in one. The Gleason score was constant in 30 patients. The nomograms predicted freedom from recurrence in 83% and 85%, respectively; the 5-year actuarial freedom from recurrence was 86%. CONCLUSION: Finasteride does not appear to compromise the assignment of Gleason grade for use in prediction tools before or after RP in men undergoing prostate biopsy or RP. The actuarial 5-year freedom from recurrence was similar to that predicted by the validated nomograms. Gleason grade remains an important prognostic predictor in men treated with finasteride and undergoing RP for clinically localized prostate cancer.     

Prognostic significance of Gleason score discrepancies between needle biopsy and radical prostatectomy

OBJECTIVES: Discordance between the Gleason score (GS) on needle biopsy (NB) and the GS of the radical prostatectomy (RP) specimen is a common finding. The objective of this study was to evaluate the prognostic significance of these discrepancies with respect to outcomes following RP. METHODS: In the study, 6625 men treated by RP were categorized as having NB=RP (68.8%), NBRP (6.2%) GS, and stratified for analyses into RP GS groups. The Kaplan-Meier method was used to analyze differences in biochemical recurrence-free survival (BRFS), and multivariate Cox analyses were performed to estimate the independent relative risk of progression associated with GS discrepancies. RESULTS: Across multiple RP GS strata (3+4, 7, 8, 8-10), patients with a lower NB GS experienced significantly better BRFS than patients with equal NB and RP GS (all p<0.05). NBRP GS had poorer BRFS than patients with NB=RP GS across multiple RP GS strata (< or =3+3, 3+4, 7; all p<0.05). NB>RP GS was independently associated with worse (pooled HR, 1.91, p<0.001) BRFS probabilities, within and across RP GS strata. CONCLUSIONS: Our data suggest that the GS of the NB adds additional prognostic value to the RP GS in a consistent manner that may be applicable to strategies of risk stratification and patient counseling after surgery.