Limitations of biopsy Gleason grade: implications for counseling patients with biopsy Gleason score 6 prostate cancer

PURPOSE: We examined the implications of underestimating Gleason score by prostate biopsy in patients with biopsy Gleason 6 prostate cancer with respect to adverse pathological findings and biochemical recurrence after radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed clinical and pathological data on a cohort of 531 patients with Gleason score 6 on prostate biopsy who underwent radical retropubic prostatectomy between June 1992 and January 2002. Patients were excluded if they received neoadjuvant androgen deprivation. Concordance between biopsy and radical prostatectomy Gleason score was examined. A comparison was made with respect to final radical prostatectomy specimen pathology and the risk of biochemical recurrence between cases that remained Gleason 6 and those with a final grade of 7 or greater. RESULTS: A total of 451 patients were included in the analysis. Mean followup was 55.1 months (range 12 to 123.4). Of the patients 184 (41%) had a Gleason score of 7 or greater after a review of the entire prostate, while 37 (8%) had a score of less than 6 and 230 remained with Gleason 6. Patients who were under graded were more likely to have extraprostatic extension (22% vs 4%, p <0.01), seminal vesicle invasion (9% vs 2%, p <0.01) and biochemical recurrence (10% vs 3%, p <0.01) compared to those who remained with Gleason score 6. CONCLUSIONS: Gleason grade on needle biopsy is an inexact predictor of the final grade following radical prostatectomy. Patients with biopsy Gleason score 6 who are under graded are at significantly higher risk for adverse pathological features and biochemical recurrence than patients who remain with Gleason score 6 or less on final pathology findings.     

Extended prostate needle biopsy improves concordance of Gleason grading between prostate needle biopsy and radical prostatectomy

PURPOSE: We examined the concordance of Gleason scores in prostate needle biopsy specimens and the corresponding radical retropubic prostatectomy specimens in a cohort of patients grouped according to the number of cores obtained during diagnostic needle biopsy. MATERIALS AND METHODS: We reviewed clinical and pathological data on a cohort of 466 men diagnosed with localized prostate cancer by needle biopsies who underwent radical retropubic prostatectomy between January 1, 1990 and July 31, 2001. Two study groups were identified, including 126 patients diagnosed with prostate cancer by extended needle biopsies (10 or more cores) and 340 diagnosed with cancer by nonextended needle biopsies (9 or fewer cores). Mean age was 60 years and median prostate specific antigen was 5.8 ng./ml. The median number of cores in the extended and nonextended biopsy groups was 12 and 6, respectively. The concordance of Gleason score in the needle biopsy and prostatectomy specimens was compared and correlated with the number of cores on needle biopsy. RESULTS: In the whole cohort 311 patients (67%) had identical Gleason scores on the needle biopsy and prostatectomy specimens, while 53 (11%) were over graded and 102 (22%) were under graded on needle biopsy. In patients who underwent extended needle biopsies the accuracy rate for Gleason scoring was 76% with 10% over and 14% under graded. The highest accuracy rates were in patients with 13, 14 and 16 cores (89%, 87% and 100%, respectively). No patients in the extended needle biopsy group had a discrepancy of more than 2 Gleason units in grade in the biopsy and surgical specimens. In those who underwent nonextended needle biopsies the accuracy rate for Gleason scoring was 63% with 12% over and 25% under graded. There were significantly different rates of accuracy (p = 0.008) and under grading (p = 0.01) in the 2 needle biopsy groups. Patients with a needle biopsy Gleason score of less than 7 had significantly higher concordance with the prostatectomy Gleason score when extended biopsies were done compared with nonextended biopsies (p = 0.001). CONCLUSIONS: Prostate cancer grading by extended needle biopsy is a better predictor of the final Gleason score than nonextended needle biopsy, as determined by radical prostatectomy histological evaluation. Therefore, extended prostate needle biopsy provides better guidance to determine the appropriate treatment in patients with prostate cancer.     

Predicting the risk of patients with biopsy Gleason score 6 to harbor a higher grade cancer

PURPOSE: Prostate cancer Gleason score 3 + 3 = 6 is currently the most common score assigned on prostatic biopsies. We analyzed the clinical variables that predict the likelihood of a patient with biopsy Gleason score 6 to harbor a higher grade tumor. MATERIALS AND METHODS: The study population consisted of 448 patients with a mean age of 59.1 years who underwent radical prostatectomy between February 2003 to October 2006 for Gleason score 6 adenocarcinoma. The effect of preoperative variables on the probability of a Gleason score upgrade on final pathological evaluation was evaluated using logistic regression, and classification and regression tree analysis. RESULTS: Gleason score upgrade was found in 91 of 448 patients (20.3%). Logistic regression showed that only serum prostate specific antigen and the greatest percent of cancer in a core were significantly associated with a score upgrade (p = 0.0014 and 0.023, respectively). Classification and regression tree analysis showed that the risk of a Gleason score upgrade was 62% when serum prostate specific antigen was higher than 12 ng/ml and 18% when serum prostate specific antigen was 12 ng/ml or less. In patients with serum prostate specific antigen lower than 12 ng/ml the risk of a score upgrade could be dichotomized at a greatest percent of cancer in a core of 5%. The risk was 22.6% and 10.5% when the greatest percent of cancer in a core was higher than 5% and 5% or lower, respectively. CONCLUSIONS: The probability of patients with a prostate biopsy Gleason score of 6 to conceal a Gleason score of 7 or higher can be predicted using serum prostate specific antigen and the greatest percent of cancer in a core. With these parameters it is possible to predict upgrade rates as high as 62% and as low as 10.5%.     

Tertiary Gleason pattern 5 is a powerful predictor of biochemical relapse in patients with Gleason score 7 prostatic adenocarcinoma

PURPOSE: In radical prostatectomy specimens Gleason score 7 is among the most commonly assigned scores for prostate carcinoma accounting for 30% to 50% of cases. Gleason score 7 is different from other more differentiated prostate carcinomas (tumors of Gleason scores 5 and 6) with a significantly worse outcome and higher rate of recurrence. Nonetheless, Gleason score 7 tumors are heterogeneous. In this study we examined the differences in clinical outcome between primary Gleason grade 3 and 4 tumors in patients who underwent radical prostatectomy, and determined the influence of tertiary Gleason pattern 5 on patient outcome. MATERIALS AND METHODS: A total of 504 patients underwent radical prostatectomy for prostate cancer and 228 of the patients (45%) had a Gleason score of 7. Cases were analyzed for a variety of clinical and pathological parameters. The influence of primary Gleason pattern and tertiary Gleason pattern 5 on patient outcome was assessed in the Cox regression model. RESULTS: Among 228 patients with Gleason score 7 prostatic adenocarcinoma, 91 (40%) had a primary Gleason pattern 4 and 137 (60%) had primary Gleason pattern 3. Patients of the former group were more likely to have a higher pathological stage (p = 0.003), more likely to have PSA recurrence (p = 0.02) and more likely to have a tertiary Gleason pattern 5 (p <0.0001). A total of 37 (41%) patients with primary Gleason 4 had a tertiary Gleason pattern 5, whereas only 13 (9%) patients with primary Gleason 3 had a tertiary Gleason pattern 5. In the Cox regression model controlling for tumor stage and surgical margin status, the primary Gleason pattern was not an independent predictor of PSA recurrence (p = 0.80), whereas the presence of tertiary Gleason pattern 5 was a significant predictor of PSA recurrence (hazard ratio 2.10, 95% CI 1.24-3.55, p = 0.006). Five-year PSA recurrence-free survival was 70% for patients without a tertiary Gleason pattern 5 compared to 19% for those patients with a tertiary Gleason pattern 5. CONCLUSIONS: Among patients with Gleason score 7, primary Gleason grade 4 indicates a likelihood of higher tumor stage and higher probability of PSA recurrence than does primary pattern 3. However, it does not independently predict a worse outcome after controlling for other known prognostic parameters associated with disease progression. Regardless of whether the primary Gleason pattern is 3 or 4, a tertiary Gleason pattern 5 is the strongest predictor of a worse outcome in patients with Gleason grade 7 prostatic adenocarcinoma. Therefore, tertiary pattern 5 should be reported in radical prostatectomy specimens.     

Prognostic factors for survival of patients with pathological Gleason score 7 prostate cancer: differences in outcome between primary Gleason grades 3 and 4

PURPOSE: We evaluated differences in clinical and pathological outcomes between Gleason 3 + 4 and 4 + 3 prostate cancer. MATERIALS AND METHODS: The radical prostatectomy whole mounted specimens from 263 men with pathological Gleason 7 tumors were identified. Gleason 3 + 4 and 4 + 3 tumors were compared in regard to pathological variables and outcome. Significance of clinical and pathological data on progression-free survival was analyzed. RESULTS: Of the tumors 34% had a primary Gleason grade of 4, and were more likely than those with primary grade 3 to have seminal vesicle involvement (34% versus 18%, p = 0.006), a higher pathological stage (pT3 55% versus 42%, N+ 13% versus 3%, 0.001), extraprostatic extension (58% versus 38%, 0.001) and higher median preoperative prostate specific antigen (PSA) (13.5 versus 9.0 ng./ml., respectively <0.001). Mean followup plus or minus standard deviation was 6.8 +/- 1.9 years. The overall 10-year crude, cancer specific and progression-free survival rates were 83%, 99% and 58%, respectively. Primary Gleason grade was significantly associated with progression-free (risk ratio 1.6, 95% confidence interval 1.08 to 2.5, p = 0.02) but not crude and cancer-specific survival. Univariately, primary Gleason grade 4 was associated with progression-free survival, as were percent Gleason 4, seminal vesicle invasion, lymph node involvement, pT stage, margin status, DNA ploidy, preoperative PSA, cancer volume and extent of extraprostatic extension. Multivariately, only preoperative PSA (p <0.001), seminal vesicle invasion (<0.001) and DNA ploidy (0.002) were associated with progression-free survival. Primary Gleason grade and percent Gleason 4 were not identified as independently associated with progression-free survival. CONCLUSIONS: In patients with Gleason 7 score prostate cancer primary Gleason grade 3 and 4 cancers are different in pathological parameters and prognosis. However, primary Gleason grade does not provide any additional information than other known prognostic factors, such as preoperative PSA, seminal vesicle invasion and DNA ploidy.     

Discrepancy between Gleason scores of biopsy and radical prostatectomy specimens

OBJECTIVE: The grade of the prostate cancer is an important factor in defining prognosis and deciding on treatment. In this study, we compared the Gleason score determined by 18-gauge core needle biopsies with both the Gleason score and pathological staging of the radical prostatectomy specimens. PATIENTS AND METHODS: Between July 1992 and September 1998, we performed 144 radical retropubic prostatectomies for clinically localized prostatic carcinoma, after a negative frozen section in bilateral pelvic lymphadenectomy in all cases. Ten patients with pathologic stage T1a and T1b were excluded. The final study group consisted of 134 patients, all of whom had been diagnosed with adenocarcinoma by transrectal needle biopsies with an 18-gauge automated spring-loaded biopsy gun. No patients received neoadjuvant therapy, including androgen deprivation and radiation therapy. All patients had a designated Gleason score on the needle biopsy and prostatectomy specimens. RESULTS: We found that grading error was greatest with well-differentiated (Gleason score 2-4) tumors, The accuracy was 15% for Gleason score 2-4 on needle biopsy. Of the 113 evaluable patients with Gleason score 5-7 on needle biopsy, 110 (97%) were graded correctly. All of the Gleason score 8-10 on needle biopsy was graded correctly. But only 1 patient in our series had Gleason score 8 on needle biopsy. Twenty-seven (25%) of 110 patients with a biopsy grade of Gleason score <7 had the cancer upgraded to 7. Of patients with both Gleason score <7 in the needle biopsy and Gleason score 7 in the prostatectomy specimen, only 3 (11%) had tumor confined to the prostate. CONCLUSION: The potential for grading error is greatest with well-differentiated tumors and of patients with both Gleason scores <7 in the needle biopsy and Gleason score 7 in the prostatectomy specimen, only 11% had tumor confined to the prostate. This effects treatment policy, especially for watchful waiting criteria.     

Changing nature of high risk patients undergoing radical prostatectomy

PURPOSE: We examined the outcomes of radical prostatectomy alone in high risk patients with prostate cancer and evaluated changes in high risk prostate cancer outcomes with time. MATERIALS AND METHODS: From 1988 to 2003, 251 men with high risk prostate cancer (prostate specific antigen more than 20 ng/ml and/or biopsy Gleason greater than 7) were identified in a cohort of 1,796 (14%) enrolled in the Shared Equal Access Regional Cancer Hospital Database. Temporal changes in clinicopathological characteristics and prostate specific antigen recurrence rates were examined stratified by 4, 4-year periods. RESULTS: With time significantly more men were considered at high risk due to a high biopsy Gleason score relative to prior years, when the most common reason for being considered at high risk was increased PSA (p <0.001). Only 3% of high risk men from 2000 to 2003 had increased prostate specific antigen and high biopsy Gleason score compared to 23% from 1988 to 1991. With time there were no differences in biochemical recurrence rates (p = 0.147). Men with a high biopsy Gleason score and increased prostate specific antigen had worse outcomes than men with only a high Gleason score or men with only high prostate specific antigen (p = 0.046 and 0.081, respectively). On multivariate analysis that only included preoperative clinical characteristics only prostate specific antigen was an independent predictor of prostate specific antigen failure following radical prostatectomy (p = 0.014). There was a trend, which did not attain statistical significance, for higher biopsy Gleason scores and higher clinical stage to be associated with higher failure rates (p = 0.060 and 0.081, respectively). CONCLUSIONS: Patients are designated as high risk by Gleason grade more commonly now than early in the prostate specific antigen era. Outcomes in high risk patients undergoing radical prostatectomy alone have not significantly improved with time. New treatment strategies, such as multimodality therapy, are needed to improve outcomes in high risk patients with prostate cancer.     

Perineural invasion and MIB-1 positivity in addition to Gleason score are significant preoperative predictors of progression after radical retropubic prostatectomy for prostate cancer

We assessed the use of clinical stage, serum prostate specific antigen, DNA ploidy, proliferation, and traditional histologic findings from the biopsy to predict prostate cancer progression after radical retropubic prostatectomy. Between 1995 and 1998, 454 consecutive patients with cancer on biopsy were treated by radical retropubic prostatectomy. Preoperative serum prostate specific antigen, clinical stage, Gleason score, percentage of cores and surface area positive for cancer, perineural invasion, and DNA ploidy and MIB-1 immunostain quantitation by image analysis were evaluated in a multivariate Cox proportional hazards regression model to predict cancer progression. Cancer progression was defined as a postoperative serum prostate specific antigen level of > or = 0.4 ng/mL, local recurrence, or systemic progression. Mean follow-up was 3.4 years (range 17 days to 5.8 years). Cancer progression was observed in 73 patients with a mean time to progression of 2.1 years (range 33 days to 5.1 years). Gleason score (p <0.001), MIB-1 cancer proliferation (p = 0.008), and perineural invasion (p = 0.008) were significantly associated with progression. Patients with cancer Gleason scores of 7 and >7 had a 2.5-fold and nearly 4-fold increased risk, respectively, of cancer progression compared with patients with cancer Gleason scores of < or = 6. Patients with perineural invasion at biopsy were twice as likely to progress compared with patients without perineural invasion. Each 1-unit increase in MIB-1 on the natural logarithmic scale increased the risk of cancer progression by 64%. Cancer progression models that include serum prostate specific antigen and clinical stage may require revision to incorporate perineural invasion and MIB-1 proliferative activity in addition to Gleason score.     

Poorly differentiated prostate cancer treated with radical prostatectomy: long-term outcome and incidence of pathological downgrading

PURPOSE: Patients with high grade (Gleason score 8 to 10) prostate cancer on biopsy are at high risk for cancer recurrence after local treatment, such as radiation therapy and radical prostatectomy. We examined long-term outcomes in patients with high grade prostate cancer on biopsy who were treated with radical prostatectomy alone. We also investigated the impact on outcomes of changes in the radical prostatectomy Gleason score. MATERIALS AND METHODS: Of 5,662 patients who underwent radical prostatectomy during 20 years 238 had a biopsy Gleason score of 8 to 10. We analyzed the rate of biochemical recurrence in this subgroup according to the Gleason grade of cancer in the radical prostatectomy specimen. RESULTS: Ten-year biochemical recurrence-free probability in the cohort was 39%. However, 45% of patients (95% CI 38 to 51%) with Gleason score 8 to 10 cancer on biopsy had a Gleason score of 7 or less in the radical prostatectomy specimen. These patients had a 10-year biochemical recurrence-free probability of 56% compared to 27% in those with a final Gleason score that remained 8 to 10 (p = 0.0004). On multivariate analysis neither prostate specific antigen nor biopsy features, including total number of cores, number of cores with cancer and percent of cancer in the cores, was a significant predictor of downgrading. However, clinical stage and biopsy Gleason score were significant with 58% of cT1c and 51% of biopsy Gleason score 8 cancers downgraded. Almost 65% of cT1c Gleason score 8 cancers were downgraded compared to 11% of cT3 Gleason score 9 cancers. CONCLUSIONS: Patients diagnosed with poorly differentiated prostate cancer (Gleason score 8 to 10) on biopsy do not uniformly have a poor prognosis. Of the patients 39% remain free of cancer recurrence 10 years after radical prostatectomy. Of these cancers 45% have a lower Gleason score in the radical prostatectomy specimen and a correspondingly more favorable long-term outcome. Predictors of downgrading are lower clinical stage (cT1c) and Gleason score 8 in the biopsy specimen.     

Improved risk stratification for biochemical recurrence after radical prostatectomy using a novel risk group system based on prostate specific antigen density and biopsy Gleason score

PURPOSE: Previous studies have suggested that prostate specific antigen (PSA) density is a significant independent predictor of biochemical failure after primary therapy. We determined whether pathological PSA density using surgical weight of the radical prostatectomy specimen was an independent predictor of adverse pathological features or biochemical recurrence after radical prostatectomy. We also examined whether combining pathological PSA density with biopsy Gleason score improved risk stratification compared with serum PSA and biopsy Gleason score for predicting PSA recurrence after prostatectomy. MATERIALS AND METHODS: Multivariate analysis was used to determine whether pathological PSA density was an independent predictor of adverse pathology or PSA recurrence after radical prostatectomy in 325 patients treated at a Veterans Affairs medical center. Cutoff points of pathological PSA density were generated to identify patients at various risks for biochemical recurrence. These cutoffs were combined with biopsy Gleason cutoff points 2 to 6, 7 and 8 to 10 to generate a risk stratification system that was compared with a previous risk stratification system using PSA and biopsy Gleason score cutoff points. The validity of the risk stratification system using pathological PSA density and biopsy Gleason score was evaluated in another cohort of 490 patients treated with radical prostatectomy at a tertiary care medical center. RESULTS: Pathological PSA density was an independent predictor of positive surgical margins (p <0.001), nonorgan confined disease (p <0.001), seminal vesicle invasion (p = 0.003) and biochemical recurrence after radical prostatectomy (p <0.001). The cutoff points for pathological PSA density of less than 0.3, 0.3 to 0.7 and greater than 0.7 ng./ml./gm. separated patients into 3 distinct groups at increasing risk for biochemical failure after radical prostatectomy (p <0.001). Pathological PSA density cutoffs combined with biopsy Gleason score cutoffs 2 to 6, 7 and 8 to 10 provided better risk stratification for biochemical failure than cutoffs based on a combination of PSA and biopsy Gleason score in patients treated at the Veterans Affairs (hazards ratio 3.04, confidence interval 2.25 to 4.11, p <0.001) and tertiary care (hazards ratio 2.38, confidence interval 1.78 to 3.18, p <0.001) medical centers. CONCLUSIONS: Pathological PSA density was a strong predictor of advanced pathology and biochemical failure after radical prostatectomy. Pathological PSA density combined with biopsy Gleason score defined a novel risk group system that improved risk stratification compared with a combination of PSA and biopsy Gleason score. These results were validated in another cohort of patients treated with radical prostatectomy at a tertiary care medical center. Further studies are required using PSA density values calculated from preoperative transrectal ultrasound measurements to determine whether a combination of PSA density and biopsy Gleason score provides significant pretreatment risk stratification.     

How accurately does prostate biopsy Gleason score predict pathologic findings and disease free survival?

OBJECTIVE: Due to the significant impact on prognosis by subgrouping of prostatectomy Gleason scores < 7, 7, and > 7, we undertook this study to answer whether the biopsy Gleason score was as predictive of disease free survival and assess the correlation with the prostatectomy Gleason score in a modern prostatectomy series. METHODS: An analysis of 1,031 patients who underwent radical prostatectomy for clinically localized prostate cancer was performed. All data was prospectively collected. The Gleason score was categorized into 3 different groups (< 7, 7, and > 7) for biopsy and prostatectomy specimens. Disease free survival was then analyzed for each group. Discrepancies between scores and outcomes were evaluated. RESULTS: Accurate correlation was noted in 54.8, 66.8, and 47.4% of Gleason scores < 7, 7, and > 7, respectively. Overall accuracy was 58.3%. Both, biopsy and prostatectomy Gleason score correlated significantly with disease free survival (P = 0.001), furthermore the classification (Gleason scores < 7, 7 and > 7) was highly significant (P = 0.001). Patients with prostatectomy Gleason < 7 tumors had significant survival advantage over those with biopsy Gleason < 7, (P = 0.001). However, disease free survival was superior for patients with biopsy Gleason > 7 than those with prostatectomy Gleason > 7, (P = 0.02). The overall disease free survival was similar among the patients with Gleason score of 7 (P = 0.12). CONCLUSIONS: It appears that biopsy Gleason score, although oftentimes not correlating strongly with the prostatectomy Gleason score, is an important prognostic factor in prostate cancer. There are significant differences in disease free survival between biopsy and prostatectomy Gleason score categories.     

Needle biopsy DNA ploidy status predicts grade shifting in prostate cancer

DNA ploidy analysis of prostate needle biopsy specimens was performed to determine whether ploidy status could predict tumor grade shifting at radical prostatectomy. The paired needle biopsy and radical prostatectomy specimens from 111 randomly selected men with prostate cancer were obtained from the surgical pathology files of the Albany Medical Center Hospital. The original tumor grades were assigned by a staff of 12 surgical pathologists according to the Gleason system. Tumors with original Gleason scores < or = 6 were classified as low grade, and tumors with scores of > or = 7 were considered high grade. DNA ploidy analysis was performed on the needle biopsy specimens using the CAS 200 image analyzer (Becton Dickinson Immunocytometry Systems, Mountain View, CA, USA) on Feulgen stained 5-microm tissue sections. There were 88 diploid and 23 nondiploid cases. Thirty-eight of 111 (34%) of cases had grade shifting from needle biopsy to radical prostatectomy specimens. Of 89 low-grade needle biopsy cases, 28 (31%) were upgraded at radical prostatectomy. Of 22 high-grade needle biopsy cases, 10 (45%) were downgraded to low grade at radical prostatectomy. Of the 28 low-grade needle biopsy specimens that were upgraded at radical prostatectomy, 19 (68%) featured an aneuploid histogram and 9 (32%) were diploid. Nineteen of 28 (68%) of aneuploid low-grade tumors on needle biopsy became high-grade at radical prostatectomy. Nine of 10 (90%) diploid high-grade tumors at needle biopsy became low-grade at radical prostatectomy. Of the 38 cases in which ploidy and grade were incongruous, 28 (74%) had grade shifting. In a multivariate regression analysis, a high-grade Gleason score on radical prostatectomy specimens correlated significantly with needle biopsy ploidy (p = 0.0001) but not with needle biopsy grade (p = 0.15). The sensitivity of the needle biopsy grade in the detection of high-grade tumors on radical prostatectomy was 30%, and the specificity was 86%. The sensitivity of ploidy status in the prediction of high grade at radical prostatectomy was 78%, and the specificity was 96%. With a prostate-specific antigen (PSA) level of >0.4 ng/ml as the indicator of post-radical prostatectomy disease recurrence on a subset of 106 patients, on univariate analysis, disease recurrence was predicted by needle biopsy ploidy (p = 0.001) and radical prostatectomy grade (p = 0.04) but not by needle biopsy grade (p = 0.39). On multivariate analysis, needle biopsy DNA ploidy status independently predicted disease recurrence (p = 0.002), whereas needle biopsy and prostatectomy grade did not. These results indicate that DNA ploidy analysis of needle biopsy specimens of prostate cancer predicts grade shifting, that it is a more sensitive and specific indicator of final tumor grade at radical prostatectomy than is the original needle biopsy grade, and that ploidy status independently predicts postoperative disease recurrence.     

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.     

Radical prostatectomy for pathological Gleason 8 or greater prostate cancer: influence of concomitant pathological variables.

PURPOSE: We evaluated the long-term outcome of radical prostatectomy for pathological Gleason score 8 or greater prostate cancer and characterized the prognostic significance of other pathological variables. MATERIALS AND METHODS: A total of 6,419 patients underwent radical prostatectomy between 1987 and 1996. There were 407 patients classified as having pathological Gleason 8 or greater, including 8 in 48%, 9 in 49% and 10 in 3%. Adjuvant treatment was used in 45% of patients and adjuvant hormonal therapy was administered to 155 (38%). Progression-free, including local or systemic, and/or prostate specific antigen (PSA) 0.4 ng./ml. or greater, and cancer specific survival were determined by the Kaplan-Meier method. The effect of pathological grade and stage, preoperative PSA, DNA ploidy, margin status, tumor dimension, seminal vesicle invasion, and adjuvant treatment was assessed with the univariate and multivariate analyses. RESULTS: Pathological stage distribution was pT2 in 26% of patients, pT3 48% and pTxN+ 27%. Overall and progression-free survival at 10 years was 67% and 36%, respectively, compared to cancer specific survival 85%. Adjuvant treatment, pathological stage, preoperative PSA and pathological grade were significant (less than 0.05) univariate predictors of progression-free survival. Pathological stage, margin status and ploidy were univariately associated with cancer specific survival. Progression-free survival at 10 years of those patients who did and did not receive adjuvant treatment was 52% and 23%, respectively. In the multivariate analysis pathological grade (p=0.02), preoperative PSA (p <0.0001), adjuvant therapy (p <0.0001) and pathological stage (p=0.036) were significant independent predictors of progression-free survival. CONCLUSIONS: High grade prostate cancer can be controlled with radical prostatectomy in some patients with disease confined pathologically, and 10-year cause specific survival is 96%. Predictors of outcome in patients with Gleason 8 disease or greater are similar to established predictors derived by using all grades. Although adjuvant hormonal therapy appears to improve disease progression rates after radical prostatectomy on the basis of this nonrandomized study, it may not affect prostate cancer death rates within 10 years in patients with high grade cancer.     

Histopathological prostate cancer characteristics at radical prostatectomy after population based screening

PURPOSE: Although early detection of prostate cancer by prostate specific antigen based screening results in a shift towards more clinically organ confined tumors, changes in prostate cancer characteristics after radical prostatectomy are less clear. MATERIALS AND METHODS: We studied 121 totally embedded radical prostatectomy specimens that were obtained from consecutive participants of the European Randomized Study of Screening for Prostate Cancer who were systematically screened and treated surgically. In each specimen pathological stage, Gleason score and proportion of high grade cancer (Gleason pattern 4 or 5) were determined. Lymph node status at operation, stage and grade were compared to a historical series of 72 surgical procedures performed for clinically localized prostate cancer at our hospital before the introduction of serum prostate specific antigen as a diagnostic tool. RESULTS: Although none of the screen detected cases had positive lymph nodes at surgery, operation was discontinued in 13 (18%) of the 72 historical cases because of positive lymph nodes. Compared with the remaining 59 historical prostatectomy specimens, the screen detected specimens showed a definite increase in the frequency of pathologically organ confined tumors and a relative decrease in Gleason score 8 to 10 tumors. However, 60% of screen detected tumors contained areas with high grade cancer (Gleason pattern 4 or 5) and 50% had a Gleason score of 7. The relative amount of high grade cancer in each tumor was related to volume (Kruskal-Wallis test p <0. 001). CONCLUSIONS: Screening for prostate cancer leads to an increase in surgical treatment for relatively small tumors that have a higher probability of being organ confined. Although the frequency of positive lymph nodes at operation decreases dramatically and the proportion of organ confined tumors after surgery increases, there is a shift from Gleason 8 to 10 tumors towards lower grade tumors at radical prostatectomy. Still, judged by the high frequency of focal dedifferentiation in screen detected tumors, most of them and surgically treated tumors are likely to be clinically important. The relatively large accumulation of these tumors in the Gleason 7 category is a concern because it could lead to a decrease in the clinical usefulness of the Gleason score system.     

Preoperative p53, bcl-2, CD44 and E-cadherin immunohistochemistry as predictors of biochemical relapse after radical prostatectomy

PURPOSE: Since radical prostatectomy is performed to cure prostate cancer, identification of markers enabling preoperative prediction of relapse after radical prostatectomy is essential to counsel and select patients for adjuvant therapy. Aberrant p53, bcl-2, CD44 and E-cadherin immunohistochemistry has been associated with aggressiveness in prostate cancer. We assessed these biomarkers in biopsy and radical prostatectomy specimens as predictors of biochemical relapse. MATERIALS AND METHODS: A total of 76 patients with untreated clinically localized prostatic adenocarcinoma underwent radical prostatectomy. Preoperative (prostate specific antigen, biopsy Gleason score) and postoperative (pathological stage and margin status) variables, biopsy and radical prostatectomy biomarker immunohistochemistry were correlated with relapse. Univariate and multivariate statistical analyses identified significant predictors. RESULTS: Of the 76 patients 23 (30%) had relapse (mean followup 38 months). Aberrant p53, bcl-2, CD44 and E-cadherin expression was observed in 64, 12, 85 and 12% of biopsies and 57, 20, 64 and 49% of radical prostatectomy specimens, respectively. Biopsy Gleason 7 to 10 and biopsy p53, respectively, gave the highest positive and negative predictive values for relapse. Relapse occurred in 13% of patients with normal biopsy p53 and in half with aberrant p53. Multivariate analysis revealed Gleason score and p53 to be independent preoperative predictors (p = 0.01 and 0.02, respectively). Estimated risk of relapse was 3.5 times higher in patients with Gleason scores 7 to 10 and 24% higher in those with aberrant p53. Significant postoperative predictors were bcl-2, p53, Gleason score and margin status (p = 0.01, 0.01, 0.04 and 0.01, respectively). CONCLUSIONS: Aberrant biopsy p53 is associated with a significantly worse outcome after radical prostatectomy than normal p53, highlighting a potential clinical role for p53. Postoperative p53 and bcl-2 were significant predictors of outcome after radical prostatectomy.     

Preoperative prostate needle biopsy p27 correlates with subsequent radical prostatectomy p27, Gleason grade and pathological stage

PURPOSE: Loss of p27 protein expression in radical prostatectomy specimens has been shown to be an adverse prognostic factor in patients with clinically localized prostate cancer. To our knowledge no studies have examined p27 expression in prostate needle biopsies. To test the potential predictive power of p27 in prostate biopsies we compared p27 expression in preoperative biopsies and matched prostatectomy specimens of patients with clinically localized prostate cancer. MATERIALS AND METHODS: Matched biopsies and radical prostatectomy specimens from 44 patients were examined. Mean followup was 22.7 months (range 1 to 46). Tumors expressing less than 30% positive nuclei were classified as low expressors and tumors expressing greater than 30% positive nuclei were classified as high expressors of p27 protein. RESULTS: Expression of p27 in prostate biopsies correlated significantly with subsequent p27 expression in radical prostatectomy specimens (p = 0.002). Sensitivity and specificity of biopsy p27 for predicting subsequent prostatectomy p27 were 87.5% and 88.9%, respectively (p <0.001). Univariate analysis showed that low expression of p27 in the biopsy correlated significantly with biopsy and prostatectomy Gleason score (p = 0.000 and 0.001, respectively), and final pathological stage (p = 0.028). Despite the small sample size and short followup, 36.4% of patients with low p27 expression had a biochemical recurrence compared to only 12.1% with high expression (hazards ratio 3.56). In addition, Kaplan-Meier analysis suggested that low p27 expression in prostate biopsies may be associated with a shorter time to recurrence, although this did not reach statistical significance (p = 0.081). CONCLUSIONS: Expression of p27 in prostate biopsies can be used to predict the degree of expression in radical prostatectomy specimens. As loss of p27 protein expression in prostatectomy specimens has been shown to correlate with biochemical recurrence and shortened prostate specific survival, these results suggest that biopsy p27 may help identify high risk patients preoperatively.     

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.     

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.     

Lower prostate specific antigen outcome than expected following radical prostatectomy in patients with high grade prostate and a prostatic specific antigen level of 4 ng/ml. Or less

PURPOSE: We report the estimates of 10-year prostate specific antigen (PSA) outcome following radical prostatectomy in patients with or without grade 4 or 5 disease in the needle biopsy or prostatectomy specimen stratified by the presenting PSA level. MATERIALS AND METHODS: From 1989 to 2001, 2,254 patients treated with radical prostatectomy for clinically localized prostate cancer comprised the study cohort. PSA outcome was estimated using the actuarial method of Kaplan and Meier, and was stratified by the presenting PSA level and needle biopsy and prostatectomy Gleason score. RESULTS: The 10-year estimates of PSA outcome declined significantly (p 相似文献