Discrepancies in Gleason scoring of prostate biopsies and radical prostatectomy specimens and the effects of multiple needle biopsies on scoring accuracy. A regional experience in Tamworth, Australia

BACKGROUND: The aim of this study was to review the discrepancies in Gleason scores (GS) of prostate biopsies and radical prostatectomy specimens and the effects of multiple-needle biopsies on scoring accuracy. METHODS: One hundred patients who had undergone consecutive radical prostatectomies (RP) between January 2004 and May 2006 were reviewed retrospectively. Patient information including age, prebiopsy prostate-specific antigen levels, biopsy GS, RP GS and pathology details were recorded and compared. RESULTS: The concordance rate of biopsy GS and RP GS was found to be at 43%, with 46% of biopsy specimens being undergraded. Eleven per cent of the specimens were overgraded. The accuracy was fairly similar when specimens were reported by the same or different pathologists, at 42 and 44%, respectively. The accuracy of biopsy GS improved with increasing number of biopsies taken. CONCLUSION: There are significant discrepancies in Gleason scoring of biopsy and RP specimens, with a concordance rate of 43% and undergrading rate of 46%. Increasing the number of biopsies helps improve scoring accuracy. Clinicians and patients need to be mindful when deciding cancer treatment options, in view of these discrepancies.     

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.     

Usefulness of the 2005 International Society of Urologic Pathology Gleason grading system in prostate biopsy and radical prostatectomy specimens

OBJECTIVE

To determine whether the 2005 International Society of Urologic Pathology (ISUP) Gleason Grading Consensus is clinically more useful than the conventional Gleason score (CGS), we compared the CGS and ISUP GS (IGS) of prostate needle biopsy (NB) and radical prostatectomy (RP) specimens, and evaluated the prognostic value of the ISUP GS.

PATIENTS AND METHODS

Of 250 patients undergoing RP, 103 with clinical stage T1–2 N0M0 were enrolled. Pathological tumour grades of NB and RP specimens were classified according to CGS by experienced pathologists in the central pathology department of our hospital, and retrospectively according to IGS by one uropathologist at the central pathology department of another hospital. All patients had RP with no neoadjuvant or adjuvant therapy. We analysed associations of CGS and IGS with biochemical recurrence‐free survival (BRFS) after RP.

RESULTS

The concordance rates between NB and RP specimens by CGS and IGS were 64.1% and 69.9%. Under‐grading and over‐grading rates by CGS and IGS were 28.2% and 7.8% for NB, and 27.2% and 2.9% for RP, respectively. There was a significant difference in the over‐grading rate between CGS and IGS (P = 0.026). When CGS and IGS of NB and RP specimens were compared, the concordance rates were similar, at 67% and 69.9%. The IGS was higher, by 15.6% in NB and by 20.4% in RP specimens, than CGS. Patients were divided into three groups based on IGS of NB specimens (≤6, 7 and ≥8). These groups differed significantly in BRFS after RP (P = 0.022); CGS showed no such association.

CONCLUSIONS

The IGS of NB specimens were significantly associated with BRFS after RP. The ISUP system is thus clinically useful for determining the most appropriate treatments for patients with early‐stage prostate cancer.     

The outcome of patients with pathological Gleason score >or=8 prostate cancer after radical prostatectomy

OBJECTIVE

To analyse the outcome of patients undergoing radical prostatectomy (RP) for Gleason 8–10 clinically localized prostate cancer, and to evaluate the prognostic value of well‐known predictors of progression.

PATIENTS AND METHODS

In all, 1480 patients had RP between 1988 and 2006, of whom 180 had pathological Gleason score ≥8 and negative lymph nodes. Biochemical progression‐free survival was determined using the Kaplan‐Meier method. The effect of preoperative prostate‐specific antigen (PSA) level, pathological stage and margin status was assessed with univariate and multivariate analyses.

RESULTS

Of the 180 patients, the Gleason score in the RP specimen was 8, 9 or 10 in 70%, 27% and 3%, respectively; 24% had stage pT2 disease, 30% stage pT3a, 25% stage pT3b and 20% stage pT4a. The 5‐ and 7‐year biochemical progression‐free survival was 73 and 65% for stage pT2, 40% and 27% for stage pT3a, and 30% for stage pT3b (log rank test, P < 0.001). In the univariate model, preoperative PSA level, pathological stage and surgical margins were predictors of survival. In the multivariate analysis, preoperative PSA level and extracapsular extension predicted biochemical progression‐free survival.

CONCLUSION

Gleason 8–10 tumours have a poor prognosis. Patients with a PSA level of <10 ng/mL and stage pT2 disease have the greatest likelihood of having a longer progression‐free survival after RP.     

A contemporary update on pathology reporting for prostate cancer: biopsy and radical prostatectomy specimens

Context

The diagnosis of and reporting parameters for prostate cancer (PCa) have evolved over time, yet they remain key components in predicting clinical outcomes.

Objective

Update pathology reporting standards for PCa.

Evidence acquisition

A thorough literature review was performed for articles discussing PCa handling, grading, staging, and reporting published as of September 15, 2011. Electronic articles published ahead of print were also considered. Proceedings of recent international conferences addressing these areas were extensively reviewed.

Evidence synthesis

Two main areas of reporting were examined: (1) prostatic needle biopsy, including handling, contemporary Gleason grading, extent of involvement, and high-risk lesions/precursors and (2) radical prostatectomy (RP), including sectioning, multifocality, Gleason grading, staging of organ-confined and extraprostatic disease, lymph node involvement, tumor volume, and lymphovascular invasion. For each category, consensus views, controversial areas, and clinical import were reviewed.

Conclusions

Modern prostate needle biopsy and RP reports are extremely detailed so as to maximize clinical utility. Accurate diagnosis of cancer-specific features requires up-to-date knowledge of grading, quantitation, and staging criteria. While some areas remain controversial, efforts to codify existing knowledge have had a significant impact on pathology practice.     

Comparison of Gleason grade and score between preoperative biopsy and prostatectomy specimens in prostate cancer

AIM: Although the histopathological findings obtained from biopsy specimens are important for choosing the appropriate management of prostate cancer, there have been some discrepancies in Gleason grade and consequently, score between biopsy and surgical specimens. A comparison of findings between these two kinds of specimens was performed. METHODS: Radical prostatectomy was performed at Asahi General Hospital on 223 cases of T1b-T3 without previous cancer treatment, and the Gleason grade and score of the biopsy and surgical specimens were compared. RESULTS: A 37% coincidence in Gleason score was obtained between biopsy and surgical specimens; coincidence including one digit difference in score was approximately 70%. Upgrading was more than downgrading. Disagreement in secondary grade was greater than that in primary grade. Disagreement in Gleason score was roughly similar among different score items and was not influenced by level of prostate-specific antigen, however, the small volume of the cancer tissues more affected the discrepancy in score. CONCLUSION: The use of biopsy findings is required to be taken into account regarding the discrepancy.     

Predictors for clinically relevant Gleason score upgrade in patients undergoing radical prostatectomy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Clinically relevant GSU in the prostatectomy specimen is a common phenomenon. Clinically relevant GSU occurs in one of three patients with clinically ‘very’ low‐risk PCa, and a low number of biopsy cores is the key negative predictor.

OBJECTIVE

? To evaluate clinical predictors for Gleason score upgrade (GSU) in radical prostatectomy (RP) specimen, especially in patients with ‘very’ low risk PCA (T1c and biopsy Gleason score ≤6 and PSA <10 ng/ml and ≤2 positive biopsy cores and PSA density <0.15).

Patients and Methods

? 402 consecutive patients undergoing RP between 2004 and 2006, including a subgroup of 62 patients with ‘very’ low risk PCA, were examined. ? Patients were categorized for clinically relevant GSU (defined as upgrade into a higher PCA risk category). ? Parameters including number of biopsy cores obtained, positive biopsy cores, prostate weight, PSA, DRE and pathology department were evaluated for their role as predictors. ? Furthermore, GSU in RP specimen was analyzed for its impact on pT‐stage.

RESULTS

? Clinically relevant GSU occurred in 38.1% in the whole cohort and in 32.3% in the ‘very’ low risk PCA subgroup. Gleason score downgrade (GSD) occurred in 4.7%. ? Number of biopsy cores obtained and prostate weight were independent negative predictors of GSU in all 402 patients (P = 0.02 and P = 0.03, respectively). ? In the ‘very’ low risk group, only number of biopsy cores obtained revealed as an independent negative predictor of GSU (P = 0.02). ? PSA, DRE, number of positive cores or pathology department were not associated to GSU. ? In the ‘very’ low risk group, GSU was related with extracapsular tumor extension (P = 0.05).

Conclusions

? Clinically relevant GSU in RP specimen is still a challenging problem. ? Increasing the number of biopsy cores lower this risk significantly. GSD is rare and thus of minor importance for treatment decisions.     

Impact of prostate-specific antigen testing on the clinical and pathological outcomes after radical prostatectomy for Gleason 8-10 cancers

OBJECTIVE

To investigate whether the clinical and pathological outcomes after radical retropubic prostatectomy (RRP) have changed since the advent of prostate‐specific antigen (PSA) testing for patients with Gleason 8–10 cancers.

PATIENTS AND METHODS

We identified 584 men treated with RRP between 1988 and 2001 for pathological Gleason 8–10 tumours. Patients were divided for analysis by year of surgery, i.e. early (1988–93), mid (1994–97) and late PSA era (1998–2001). Survival rates after RRP were estimated using the Kaplan‐Meier method, and the effect of clinicopathological factors on outcome was analysed using Cox proportional hazard regression models.

RESULTS

The median preoperative PSA level decreased from 15 ng/mL in the early to 10 ng/mL in the late PSA era (P < 0.001), while the rate of organ‐confined disease increased from 22.9% to 35.1% (P = 0.007). However, the 7‐year biochemical recurrence‐free (37% vs 45%, P = 0.087) and cancer‐specific survival (89% to 91%, P = 0.73) did not change significantly from the early to the late PSA era. Increased preoperative PSA level (P < 0.001), seminal vesicle invasion (P < 0.001) and positive lymph nodes (P = 0.02) were associated with biochemical recurrence. Seminal vesicle invasion (P = 0.005), positive nodes (P < 0.001) and positive surgical margins (P = 0.03) predicted death from cancer.

CONCLUSION

Although the pathological features of Gleason 8–10 cancers have become more favourable over the PSA era, survival has not changed. This lack of improvement in clinical outcome probably reflects the inherent biological aggressiveness of these cancers. While RRP provides long‐term cancer control in a subset of these patients, continued investigation of multi‐modal treatment options is warranted.     

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.

OBJECTIVE

• ? 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.

PATIENTS AND METHODS

• ? 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.

RESULTS

• ? 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).

CONCLUSION

• ? A TGG pattern 4 or 5 is associated with decreased clinical recurrence‐free survival in Gleason score 7.

     

Obtaining fresh prostate cancer tissue for research: a novel biopsy needle and sampling technique for radical prostatectomy specimens

BACKGROUND: Fresh or fresh-frozen tissue samples are preferred for molecular profiling as formalin fixation degrades intracellular nucleic acids. Radical prostatectomy (RP) specimens are a valuable source of prostate cancer tissue, but the reliance on whole-organ pathological processing for prognostication limits sampling opportunities. Few studies have addressed specific harvesting techniques using prostatectomy specimens. MATERIALS AND METHODS: Ex vivo biopsies were performed on 23 consecutive fresh RP specimens using a purpose-designed needle. A standard sextant approach was used with an additional lateral biopsy on each side. Cores from each lobe were snap-frozen together and sections assessed by a pathologist blinded to the RP and pre-operative biopsy pathology. Comparison with pre-operative biopsies was performed using the t-test and chi(2) statistical tests. Eleven randomly selected RP specimens were further evaluated for the effects of needle tracks and margin perforation. RESULTS: Cancer was detected in 19 of 23 specimens, giving a sensitivity of 83.6%. The average tumor involvement was 28.3% per section compared with 15.6% for pre-operative biopsies (P < 0.02). There was no statistically significant difference between the groups for either Gleason sum score concordance or tumor location concordance. In 3 of 11 cases, needle margin perforation was identified; in none of the cases did it compromise pathological assessment, although in one case a deeper block resection was required. CONCLUSIONS: Ex vivo biopsy is a useful technique for retrieving fresh tissue whilst preserving organ morphology in RP specimens. The purpose-designed needle and harvesting technique provide good yields of cancer tissue from a high proportion of sampled prostatectomy specimens.     

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.     

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).

Effect of prostate volume on tumor grade in patients undergoing radical prostatectomy in the era of extended prostatic biopsies

PURPOSE: We investigated the influence of prostate volume on biopsy and prostatectomy Gleason score, the incidence of upgrading and total tumor volume. MATERIALS AND METHODS: From 1997 to 2004, 247 patients were diagnosed with prostate cancer by multisite extended prostatic biopsy (10 or 11 cores) and underwent radical prostatectomy at our institution without neoadjuvant therapy. Medical records were reviewed to determine patient age at diagnosis, preoperative prostate specific antigen, prostate volume, clinical stage, biopsy Gleason score, pathological stage, prostatectomy Gleason score and total tumor volume. The Mann-Whitney and chi-square tests were used to compare variables among groups and multivariate regression analysis was used to determine predictors of Gleason score. RESULTS: Median patient age was 61 years and median preoperative prostate specific antigen was 5.5 ng/ml. Median prostate volume on transrectal ultrasound was 37 cc. Prostatectomy Gleason score was 6 in 31% of cases, 7 in 57% and 8-9 in 12%. Prostate volume greater than 50 cc was significantly associated with a higher incidence of well differentiated tumors (Gleason score 6) at prostatectomy, that is 17.9% in patients with a prostate volume of 25 cc or less, 28.9% in those with a prostate volume of 25 to 50 cc and 45.3% in those with a prostate volume of greater than 50 cc (p<0.01). In addition, the incidence of tumor upgrading was significantly lower in patients with a large prostate volume (greater than 50 cc) compared to that in those with a smaller prostate volume (20.8% vs 36.1%, p<0.05), particularly in the subset with biopsy Gleason score 6 (24% vs 54.1%, p<0.01). Patients with a large prostate volume (greater than 50 cc) had smaller total tumor volume with a trend toward statistical significance (median total tumor volume 0.86 vs 1.1 cc, p=0.0631). CONCLUSIONS: In the era of extended prostatic biopsies patients with a large prostate volume have a significantly higher incidence of well differentiated tumor at prostatectomy and a lower likelihood of tumor upgrading.