Twelve prostate biopsies detect significant cancer volumes (> 0.5 mL)

OBJECTIVES: To compare, in a retrospective study, pathological specimens of prostate cancer detected in additional areas of a 12-core biopsy with tumours detected using traditional sextant biopsy. PATIENTS AND METHODS: The study included 27 patients who had undergone radical prostatectomy (RP) for prostate cancer. Prostatectomy specimens of cancers detected using standard sextant biopsies were compared with those detected using six additional core biopsies. The RP specimens were analysed for cancer volume, Gleason score, tumour grade (Mostofi) and pathological stage. RESULTS: Of the 27 patients, six (29%) had cancer detected in the extra six biopsy cores which would have otherwise have been undetected using sextant biopsy. Only two insignificant cancers were detected. The mean Gleason score was 6.1 for cancer detected by the sextant or 12-core method (P = 0.907); the mean grade (Mostofi) was 2.1 and 2. 33, respectively (P = 0.29). The final tumour stage in the 21 patients undergoing sextant biopsy was pT2 in 13 and pT3 in eight, compared with six pT2 tumours in the six patients diagnosed using extra biopsies. The mean (median, range) tumour volume was 5.7 (3.5, 0.312-23.75) mL for cancers detected on sextant biopsy and 1.99 (1. 85, 0.4-3.6) mL in the six cancers detected using extra cores (P = 0. 0138). CONCLUSION: The detection of prostate cancer was increased using extra biopsy cores. There was a significant difference in tumour volume but not in Gleason score, Mostofi grade or final pathological tumour stage between tumours diagnosed using 12 cores and those detected on sextant biopsy.     

穿刺标本Gleason评分预测前列腺癌病理分级准确性的研究

目的 分析前列腺癌患者穿刺标本与根治术标本Gleason评分的相关性,探讨影响穿刺标本Gleason评分准确性的可能因素.方法 回顾性分析86例接受根治性前列腺切除术的前列腺癌患者资料,比较穿刺标本与根治术标本Gleason评分的符合情况,应用二分类Logistic回归分析筛选影响穿刺标本Gleason评分准确性的可能因素.结果 86例患者穿刺标本平均Gleason评分为6.1,根治术标本平均Gleason评分为6.5,穿刺标本与根治术标本Gleason评分相比,评分相符42例(48.8%),评分偏低32例(37.2%),评分偏高1 2例(14.0%),差异具有统计学意义(P＜0.05),偏差与患者年龄、血清PSA、前列腺体积、临床分期无显著相关性(P＞0.05),与穿刺针数(OR=2.905)及穿刺阳性率(OR=4.225)有显著相关(P＜0.05).结论 穿刺针数与穿刺阳性针数百分比是影响穿刺标本Gleason评分准确性的可能因素,增加前列腺穿刺活检针数将可能有助于提高穿刺标本预测前列腺癌病理分级的准确性.     

Differences in biopsy features between prostate cancers located in the transition and peripheral zone

OBJECTIVE: To identify the zonal location of prostate cancers before surgery, by analysing the mapping of ultrasonography-guided systematic sextant biopsies for differences between cancers located in the transition zone (TZ) and peripheral zone (PZ); and to compare the correlation between Gleason scores of needle biopsies and those of radical prostatectomy (RP) specimens. PATIENTS AND METHODS: In all, 186 patients with TZ (46) and PZ cancers (140) underwent ultrasonography-guided systematic sextant biopsy and RP at the same institution. The clinical and pathological characteristics, and the anatomical location of positive biopsies, were determined and compared using t-tests and chi-square tests. Differences between Gleason scores of needle biopsies and those of RP specimens were evaluated and compared by Cohen kappa testing. RESULTS: TZ cancers had a significantly lower rate of positive biopsies in the middle (63% vs 80%) and base (50% vs 80%) of the prostate than had PZ cancers. Positive biopsies were exclusively obtained from the apex in 19.6% of TZ and 5% of PZ cancers (P = 0.002). There was exact agreement between Gleason scores of needle biopsies and those of RP specimens in 15.2% of TZ (kappa = 0.02) and 55% of PZ cancers (kappa = 0.25), respectively. CONCLUSION: Compared with PZ cancers, TZ cancers had a different anatomical pattern of positive biopsies, with lower rates in the middle and base of the prostate. The finding of positive biopsies exclusively in the apex favoured prostate cancer located in the TZ. Furthermore, the correlation between needle biopsy Gleason scores and those of the RP specimens was clearly lower in TZ cancers.     

Does site-specific labelling and individual processing of sextant biopsies improve the accuracy of prostate biopsy in predicting pathological stage in patients with T1c prostate cancer?

OBJECTIVE: To evaluate whether individual labelling and processing of the sextant of origin improves the accuracy of prostate biopsy in predicting the final pathological stage after radical prostatectomy in patients with T1c prostate cancer. PATIENTS AND METHODS: The charts of 386 patients treated for prostate cancer by radical prostatectomy between January 1996 and June 1999 were reviewed. In all, 124 patients fulfilled the following inclusion criteria: no abnormality on digital rectal examination (DRE) or transrectal ultrasonography, a prostate specific antigen (PSA) level before biopsy of < or = 20 ng/mL, and prostate cancer diagnosed after one set of random sextant biopsies, with the cores being submitted in six separate containers individually labelled for the sextant of origin. RESULTS: Within this series of patients with a low tumour burden, the preoperative PSA, biopsy Gleason score and unilateral vs bilateral involvement were not significant predictors of disease extension. The percentage of positive cores and the number and topography of positive sextants were both statistically significant predictors of organ-confined disease. Although these two variables appeared to be statistically equivalent on a first analysis in the overall series, a subgroup of patients was identified who benefited from the complete topographical information, i.e. those 52 (42%) patients with a Gleason score of < 7, 25-75% positive biopsies and < or =3 positive sextants. CONCLUSION: These results support the individual labelling of biopsy cores in selected patients with a normal DRE and a moderately elevated PSA, as it helps to better predict the final pathological stage. This substantial benefit outweighs the additional effort by the pathologist.     

Comparison of ultrasound-guided biopsies and prostatectomy specimens: predictive accuracy of Gleason score and tumor site

OBJECTIVE: To critically evaluate the accuracy of sextant biopsies in predicting Gleason score and the site of tumor location in patients with clinically localized prostate cancer treated by radical perineal prostatectomy. METHODS: The case records of 289 patients with clinically localized prostate cancer who underwent radical perineal prostatectomy were reviewed, comparing the Gleason score and tumor site location as determined by sextant ultrasound-guided core biopsies with the Gleason score and tumor distribution within the surgical specimens. The prostatectomy specimens were further characterized by extent of disease as organ-confined, specimen-confined or margin-positive. RESULTS: The Gleason score was identical in 126 (43.5%) patients. An upgrading in the surgical specimen occurred in 118 (40.8%) cases, a downgrading in 43 (14.8%). Overall, 193 (66.7%) patients had a unilateral positive biopsy, while 96 (33.2%) patients had bilateral positive biopsies. Sixty-four (33.1%) patients with a unilateral positive biopsy had cancer confined to one side of the gland, while 127 (65.8%) showed bilateral disease; 142 (73.5%) patients had organ-confined tumors versus 51 (26.4%) patients with capsular penetration. In the 96 patients with bilateral positive biopsies, 64 (66.6%) patients had intracapsular cancer versus 32 (33.3%) patients with either specimen-confined or margin-positive disease. The overall rate of positive margins was 14%. Fifty-one (61.4%) of the 83 patients with non-organ-confined disease had posterolateral capsular penetration in the region of the superior pedicle of the neurovascular bundle, while 28 (33.7%) patients had apical capsular penetration, in the region of the inferior neurovascular pedicle. CONCLUSIONS: The ability of sextant ultrasound-guided biopsies to estimate the pathological grading is satisfactory: when we consider a difference of +/- 1 in the final Gleason score, the overall correlation is 80%. In 66% of the cases, sextant biopsies predicted unilateral disease when bilateral disease existed. A unilateral positive biopsy does not predict unilateral disease.     

Percentages of positive cores, cancer length and Gleason grade 4/5 cancer in systematic sextant biopsy are all predictive of adverse pathology and biochemical failure after radical prostatectomy

AIM: We investigated whether the quantitative parameters of systematic sextant biopsies were predictive of either adverse pathological findings or disease recurrence after radical prostatectomy (RP). METHODS: We retrospectively evaluated a total of 117 men with untreated prostate cancer whose needle biopsies were matched with RP specimens. The pretreatment parameters of the serum prostate-specific antigen (PSA), the PSA density, the percentage of positive biopsy cores, the percentage of cancer length and the percentage of Gleason grade 4/5 cancer in the biopsy were determined and compared with the pathological features of prostate cancer in RP specimens. These pretreatment parameters and pathological factors in the RP specimens, including the cancer volume, the percentage of Gleason grade 4/5 cancer, the positive surgical margin and the seminal vesicle invasion were evaluated for their ability to predict the disease recurrence. RESULTS: The percentages of positive biopsy cores, the Gleason grade 4/5 cancer in the biopsy and the cancer length in the biopsy had a weak correlation with the cancer volume in RP specimens (r = 0.373, 0.345, 0.408, respectively). All quantitative biopsy parameters were strongly predictive of the non-organ-confined status, the positive surgical margin and the seminal vesicle invasion in the logistic regression analysis. The percentage of positive biopsy cores and the percentage of Gleason grade 4/5 cancer in the biopsy predicted biochemical failure after RP. CONCLUSION: These results indicate that quantitative biopsy parameters are independent predictors of the adverse pathology of prostate cancers and disease recurrence after RP.     

Percentage of cancer in prostate biopsies as prognostic factor for staging and postoperative biochemical failure after radical prostatectomy

OBJECTIVE: To assess if the percentage of cancer in prostate needle biopsies provides independent prognostic information for predicting pathological stage and/or biochemical relapse after radical prostatectomy. METHODS: One hundred and forty prostate cancer patients who underwent radical prostatectomy were evaluated. Preoperative parameters analyzed were patient age, PSA, clinical stage, and the information obtained from sextant biopsies (Gleason score, maximum percentage of cancer in a core, percentage of tissue with cancer in all biopsies and the number of cores positive for cancer). Univariate and multivariate analyses (logistic regression) for the dependent variables (prostate cancer, organ-confined and biochemical relapse) were performed. RESULTS: The tumor was organ-confined in 73.6% of patients. In those patients studied for disease progression (n = 126), no biochemical recurrence was observed in 76.2%. In the multivariate analysis for organ-confined disease, the total percentage of biopsy tissue with cancer, the preoperative PSA level, the Gleason score and the clinical stage were the most accurate predictive factors of pathological stage. The multivariate analysis for the study of biochemical failure indicated that only the total percentage of biopsy tissue with cancer, the preoperative PSA level and the Gleason score were independent predictive factors. According to the logistic regression analysis for disease recurrence, 3 risk groups could be identified: low risk (less than 10% probability of disease progression), intermediate risk (30%) and high risk (more than 70%). CONCLUSIONS: The percentage of cancer in prostate biopsy provides independent prognostic information for predicting pathological stage and the risk of biochemical failure after radical prostatectomy.     

Extended 12-core prostate biopsy increases both the detection of prostate cancer and the accuracy of Gleason score

OBJECTIVE: To evaluate the effect of extended 12-core prostate biopsy in improving the detection rate of prostate cancer and increasing the accuracy of Gleason score. METHODS: This study included 113 patients who underwent TRUS-guided lateral sextant biopsy (group I) and 176 patients who underwent extended 12-core biopsy (group II). Inclusion criteria for prostate biopsy were elevated serum PSA levels (>3.0 ng/ml) and/or suspicious digital rectal examination (DRE). RESULTS: Clinical characteristics were similar in both groups. Cancer was detected in 28 (24.8%) and 64 (36.4%) patients in group I and II respectively, chi2=4.26, p=0.039. Among patients with cancer in group I, 14 were treated by radical prostatectomy (RP). The median Gleason sum was 6 (range 3-8) and 7 (range 5-9) for needle and prostatectomy specimens respectively. There was an agreement between the biopsy and prostatectomy Gleason sum in 7 (50%) patients while the biopsy Gleason sum was lower in 7 (50%) cases. Among patients with cancer in group II, 27 were treated by RP. The median and the range of Gleason sum was the same for needle and prostatectomy specimen (median 6, range 4-9). There was an agreement between the biopsy and prostatectomy specimen in 23 (85.2%) patients while the biopsy sum was lower than prostatectomy in 4 (14.8%) patients. The agreement between the biopsy and prostatectomy specimen was significantly higher in group II (82.5%) than group I (50%), Fisher's Exact Test, p=0.026. CONCLUSION: Extended 12-core prostate biopsy significantly increases both the detection rate of prostate cancer and the accuracy of biopsy Gleason score.     

Correlation of positive prostate sextant biopsy locations to sites of positive surgical margins in radical prostatectomy specimens.

OBJECTIVE: To investigate whether sextant location of positive prostate biopsy predicts the site of positive surgical margins (PSM) at the time of radical prostatectomy (RP) in patients with clinical stage T1c prostate cancer. METHODS: A retrospective query of the Center for Prostate Disease Research (CPDR) database at our institution identified 456 patients with clinical stage T1c prostate cancer who underwent standard sextant prostate biopsy prior to RP. Each biopsy was submitted separately for pathologic analysis according to sextant location. The sextant location of positive biopsies was compared to the sites of PSM after RP. RESULTS: PSM were found in 129 of 456 (28%) RP specimens. The incidence of PSM at the prostate apex in patients with a positive or negative apical sextant biopsy was similar (9 and 8% respectively, p>0.05). The incidence of PSM at the prostate base in patients with a positive or negative sextant biopsy of the prostate base was also the same (7% in both groups, p>0.05). As the number of positive biopsy cores on one side of the prostate increased (0, 1, 2, and 3) so did the chance of an ipsilateral PSM (5.4, 16.2, 35.7 and 45.0%, respectively; p<0.005). CONCLUSIONS: Positive sextant biopsy location (apex and base) does not correlate with site of PSM at RP. However, ipsilateral PSM are more likely as the number of positive sextant biopsies on that side increases. While pathologic processing of biopsy specimens according to longitudinal prostate location (base, mid and apex) is probably unnecessary, the number of positive biopsies on a given side may be useful preoperative information.     

The value of multiple core biopsies for predicting the Gleason score of prostate cancer

OBJECTIVE: To evaluate the accuracy of Gleason grading of prostate cancer in multiple core biopsies, compared with the final Gleason score of total prostatectomy specimens, and to investigate whether the prediction of the correct Gleason score is improved by increasing the number of biopsies. PATIENTS AND METHODS: Before total prostatectomy, 121 men had a mean (range) of 10.0 (8-14) transrectal ultrasonography (TRUS)-guided core biopsies taken from the apex, mid-medial, mid-lateral and basal regions, from the transition zone and from lesions detected on TRUS. The biopsies and prostatectomy specimens were reviewed and the Gleason scores assessed. RESULTS: The preoperative biopsies predicted the prostatectomy Gleason score exactly in 45.5% of the patients and within one Gleason score in 93.4%. The biopsies under-graded the prostate cancer in 38.8% and overgraded it in 15.7%. The weighted kappa value for exact agreement was 0.502. If one biopsy was positive for cancer, the prostatectomy Gleason score was predicted correctly in 43.8% and within one score in 93.8%, compared with 53.8% and 92.3%, respectively, if cancer was found in at least seven biopsies. If the mid-lateral and transition zone biopsies had been excluded from the biopsy protocol, 5% of the cancers would have been undetected. Among the remaining 115 cancers, grading accuracy only improved from 43.5% to 45.2% by adding biopsies to the sextant protocol. CONCLUSION: Despite a statistically significant agreement between biopsy and prostatectomy Gleason score, under-grading remains a major problem. The prediction of the prostatectomy Gleason score is only marginally improved by increasing the number of biopsies.     

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.     

Increasing the number of biopsy cores improves the concordance of biopsy Gleason score to prostatectomy Gleason score

OBJECTIVE: To evaluate taking more biopsy cores for predicting the radical prostatectomy (RP) Gleason score compared with the biopsy Gleason score, as although random sextant biopsies are the standard for a tissue diagnosis of prostate cancer, and taking more biopsies increases the detection rate, it is uncertain whether taking more cores improves the prediction of the RP Gleason score. PATIENTS AND METHODS: We analysed retrospectively 404 patients from three centres (Seattle 162, Washington 107 and Chicago 135) who had RP for prostate cancer. Six, eight or 10 biopsies were taken based on the physician's preference and the patient's characteristics. RESULTS: Before RP, 158 (39%) patients had six, 65 (16%) had eight and 181 (45%) had 10 biopsy cores taken. The accuracy of the Gleason sum of the three groups was 65/158 (41%), 26/65 (40%) and 104/181 (57.5%), respectively (P < 0.004, 10-core vs six-core). However, when comparing the Gleason score separately (i.e. 4 + 3 is not equal to 3 + 4), the accuracy of the three groups was 48/158 (30%), 20/65 (31%), and 95/181 (52.5%), respectively (P < 0.001, 10-core vs six core). CONCLUSIONS: Taking more biopsy cores improves the accuracy of the biopsy Gleason score in predicting the final Gleason score at RP; the predictive accuracy of the final Gleason score may be increased from 41% to 58% by increasing the number of biopsies from six to 10.     

Is seminal vesicle ablation mandatory for all patients undergoing radical prostatectomy? A multivariate analysis on 1283 patients

OBJECTIVE: With a shift in prostate cancer stage and a majority of patients operated nowadays with PSA levels <10 ng/ml, rates of seminal vesicle (SV) invasion found on radical prostatectomy specimens have decreased as compared to historical data. Since SV-sparing surgery may possibly have an influence on post-operative erectile dysfunction and urinary recovery, we tried to determine which patients could be safely spared SV excision during radical prostatectomy. MATERIAL AND METHODS: We used preoperative data from 1283 patients operated by radical retropubic prostatectomy--777 with serum PSA <10.0 ng/ml--to predict SV invasion on final pathological examination. Variables analyzed included age, digital rectal examination, serum PSA, biopsy Gleason score and percentage of biopsy cores invaded by prostate cancer. Statistical analysis included univariate, multivariate logistic regression analysis and receiver operating characteristic (ROC) curves. RESULTS: Out of 1283 patients, 137 (10.6%) had SV involvement, 41/777 (5.2%) with PSA <10.0 ng/ml, 16.1% in the 10-20 ng/ml range and 26.2% when PSA was >20 ng/ml. Percentage of biopsies affected by prostate cancer and biopsy Gleason score were significant predictors of SV invasion in multivariate analysis, both in the entire population and in the subset of patients with PSA <10.0 ng/ml (p < 0.0001). Probability graphs created for patients with PSA <10 ng/ml indicate a risk of seminal invasion <5% when Gleason score on biopsy is <7 or when the percentage of biopsies affected by cancer is <50%. CONCLUSIONS: Resection of SV might not be "oncologically" necessary in all patients undergoing RP when PSA levels are below 10 ng/ml except when biopsy Gleason score is > or =7 or when more than 50% of prostate biopsy cores show cancer involvement. SV-sparing surgery could be prospectively compared to standard retropubic prostatectomy in selected individuals analyzing potential benefits on erectile function and urinary continence.     

Early detection of prostate cancer with low PSA cut-off values leads to significant stage migration in radical prostatectomy specimens

BACKGROUND: The introduction of prostate-specific antigen (PSA) contributed to a shift in tumor stage at diagnosis in patients with prostate cancer. The aim of the present study was to evaluate the effects of PSA screening with low PSA cut-off values on mean total and percent-free PSA levels in patients with prostate cancers at the time of diagnosis as well as on pathologic stage and mean Gleason scores in positive biopsies and radical prostatectomy specimens. METHODS: Data of 875 patients who were diagnosed with prostate cancers between 1996 and 2001 were analyzed. Patients were stratified into six groups according to the year of biopsy. Annual changes in total and percent-free PSA values, in Gleason scores of biopsies and radical prostatectomy specimens, and in pathologic stages of radical prostatectomy specimens were assessed. RESULTS: Mean PSA of patients diagnosed with prostate cancer decreased from 13.11 ng/ml (percent-free PSA: 11.89%) in 1996 to 7.33 ng/ml (percent-free PSA: 12.58%) in 2001 (P < 0.05). The percentage of organ-confined prostatectomy specimens increased from 64.3% in 1996 to 81.5% in 2001 (P < 0.05). However, mean Gleason scores increased from 5.23 to 6.33 over the 6 years (P < 0.05). The percentage of patients with biopsy-proven prostate cancers and PSA values below 4 ng/ml increased from 14.0% in 1996 to 39.2% in 2001. In the group with PSA values below 4 ng/ml organ-confined cancers were found in 80.0-95.2% of patients. CONCLUSIONS: PSAg screening with low cut-off levels has led to a significant reduction of mean baseline PSA levels in prostate cancer patients and to a significant increase in the percentage of organ-confined radical prostatectomy specimens, whereas mean Gleason scores have remained relatively constant.     

Micro-focal prostate cancer: a comparison of biopsy and radical prostatectomy specimen features

OBJECTIVES: To study the pathologic features of radical prostatectomy (RP) specimens of patients operated on the basis of a potentially "Insignificant" prostate cancer (Ca P) characterized by one single focus (less than 3mm) of moderately differentiated adenocarcinoma - Gleason score < or =6, out of 6-10 biopsies and to determine which characteristics, if any, are predictive of the presence of a "non significant" prostate cancer in the specimen characterized by a low volume (<0.5 ml) moderately differentiated organ confined, cancer (Gleason score less than 6). PATIENTS AND METHODS: PSA, biopsy features, and surgical specimens of a series of 56 patients submitted to RP for "insignificant Ca P" on TRUS prostate biopsies between 1988 and 2004 were compared regarding the number of tumor foci, Gleason grade and score, tumor volume determined by the cylinder method, as well as extraprostatic extension (EPE) and positive surgical margins (P.SM.). RESULTS: 70% of the patients had multifocal microfocal cancer apart from the index tumor. The presence of grade 4 was ignored by the biopsy in 50% of the cases, however the primary grade was correctly evaluated in more than 70% of the biopsy sets. 42% of the patients had a cancer volume less than 0.5 ml and 29% met the definition of insignificant/unimportant cancer characterized by a moderately differentiated (Gleason score < or =6) of low volume (less than 0.5 ml) however no feature accurately predictive of insignificant cancer could be individualized. In this whole series, only 8% of the patients had EPE. When the pre-operative PSA was <10 ng/ml, 98% of the patients had an organ confined tumor. CONCLUSION: Patients diagnosed with prostate cancer on the basis of one single focus less than 3 mm of moderately differentiated (Gleason < or =6) prostate cancer have 30% of chances of harboring an insignificant tumor in their prostate and are therefore, at risk of being overtreated, however there is at this time no specific feature able to identify these patients pre operatively.     

Increased detection of clinically significant prostate cancer by additional sampling from the anterior lateral horns of the peripheral zone in combination with the standard sextant biopsy

BACKGROUND: The objective of the present study was to investigate whether obtaining an increased number of biopsy cores by sampling additional areas, along with the standard sextant biopsy, results in a higher rate of detection of potentially insignificant prostate cancer. METHODS: We included 130 patients who underwent radical retropubic prostatectomy at our institution between January 1999 and June 2003 after being diagnosed as having prostate cancer based on systematic prostate biopsies that included the areas examined by standard sextant biopsies and the bilateral anterior lateral horns (ALHs) of the peripheral zone (PZ). Several clinicopathological factors were analyzed, focusing on the significance of additional sampling from ALHs in relation to the incidence of potentially insignificant cancer, which was defined as organ confined disease with tumor volume less than 0.5 cc and Gleason scores <7. RESULTS: According to the location of positive biopsy results, these 130 patients were divided into three groups as follows: 61 patients (46.9%) with cancer detected from the cores taken by standard sextant biopsy only (group A), 15 (11.6%) from ALHs of the PZ only (group B), and 54 (41.5%) from both sites (group C). There were no significant differences in age, incidence of abnormal digital rectal examination, prostate volume, or biopsy Gleason score among these three groups; however, pretreatment serum PSA value in group C was significantly higher than that in groups A or B. Pathological examinations of radical prostatectomy specimens demonstrated that there were no significant differences in the incidence of lymphatic invasion, vascular invasion and perineural invasion, or Gleason score among the three groups; however, group C had a significantly larger tumor volume than groups A or B. Furthermore, insignificant tumor was detected in eight patients in group A (13.1%), two in group B (13.3%), and four in group C (7.4%). CONCLUSION: These findings suggest that the additional sampling of biopsy cores from ALHs does not appear to increase the detection of potentially insignificant cancer, and that biological tumor characteristics seem to be similar irrespective of cancer location on the needle biopsy.     

Predictors of first repeat biopsy cancer detection with suspected local stage prostate cancer

PURPOSE: We determine demographic and tumor related predictors of repeat biopsy cancer detection in men with suspected stage T1c-2 prostate cancer. MATERIALS AND METHODS: The study population included 298 consecutive men with suspected stage T1c-2 prostate cancer who had a benign prostate biopsy at 1 institution between January 1, 1992 and April 1, 1999 and underwent 1 repeat biopsy. Mean age plus or minus standard deviation was 66.8+/-6.7 years for 133 black (55%) and 165 white (45%) patients. Clinical measures included determination of high grade prostatic intraepithelial neoplasia in benign biopsy specimens, Gleason score of malignant biopsy specimens, prostate specific antigen (PSA), PSA density, annualized interbiopsy PSA change, percent free PSA (201 cases) and PSA velocity (171). RESULTS: Cancer was detected on repeat biopsy in 80 cases (27%). Significant differences between patients with benign and malignant repeat biopsies included age (p = 0.001), PSA density (p = 0.0001), percent free PSA (p = 0.0001) and PSA velocity (p = 0.009). High grade prostatic intraepithelial neoplasia in an initial benign biopsy was not predictive of cancer in repeat biopsy (p = 0.12). Multiple logistic regression analysis of all cases showed that age (p = 0.002) and PSA density (p = 0.0002) were independent predictors of cancer. Subset multiple logistic regression analysis modeled with age, PSA density and percent free PSA demonstrated that age (p = 0.002) and percent free PSA (p = 0.0001) were significant independent predictors of malignancy. Subset multiple logistic regression analysis modeled with age, PSA density, percent free PSA and PSA velocity revealed that age (p = 0.02) and percent free PSA (p = 0.0003) were significant independent predictors of cancer. There were no significant differences between the Gleason scores of cancers detected on repeat biopsy compared to 587 stage T1c-2 cancers detected on initial biopsy during the study period (p = 0.09). PSA, PSA density, percent free PSA and PSA velocity were not significantly different among men without a cancer diagnosis who had high grade neoplasia in 1 or 2 benign biopsies. CONCLUSIONS: Greater than 25% of this population of select patients with suspected stage T1c-2 prostate cancer had malignancy detected on repeat biopsy. Percent free PSA was the most powerful predictor of cancer. High grade prostatic intraepithelial neoplasia was not a predictor of repeat biopsy cancer detection and PSA functions were similar among men without cancer who did and did not have high grade neoplasia in 1 or more benign biopsies. This finding suggests that high grade prostatic intraepithelial neoplasia may not be a reliable indicator of clinically significant existing prostate cancer.     

High-intensity focused ultrasound and localized prostate cancer: efficacy results from the European multicentric study

PURPOSE: To describe the safety and efficacy of high-intensity focused ultrasound (HIFU) for the treatment of prostate cancer as assessed in a Phase II/III prospective multicentric clinical trial. PATIENTS AND METHODS: Patients (N = 402) presenting with localized (stage T(1-2)N(0-x)M(0)) prostate cancer between 1995 and 1999 at six European sites who were not candidates for radical prostatectomy were treated with HIFU under general or spinal anesthesia. Their mean age was 69.3 +/- 7.1 (SD) years, the mean prostate volume 28.0 +/- 13.8 cc, and the mean serum prostate specific antigen (PSA) concentration 10.9 +/- 8.7 ng/mL. Nearly all (92.2%) of the patients had one to four positive biopsy samples at baseline. The Gleason scores were 2 to 4 for 13.2% of the patients, 5 to 7 for 77.5%, and 8 to 10 for 9.3%. During the follow-up, random sextant biopsies and serum PSA measurements were performed. Any positive sample in biopsies performed after the last treatment session resulted in a "HIFU failure" classification. RESULTS: The patients received a mean of 1.4 HIFU sessions. The mean follow-up duration was 407 days (quartile 1 135 days, median 321 days, quartile 3 598 days). The negative biopsy rate observed in the T1-2 primary-care population was 87.2%. These results were also stratified according to the usual disease-related risk classification, and as much as a 92.1% negative biopsy rate was observed in low-risk patients. Nadir PSA results correlated with prostate size and the clinical procedure. CONCLUSION: These short-term results obtained on a large cohort confirm that HIFU is an option to be considered for the primary treatment of localized prostate cancer.     

Histopathologic effects of three-dimensional conformal external beam radiation therapy on benign and malignant prostate tissues.

We reviewed 137 prostate sextant needle biopsies from 137 patients obtained at a median of 35.7 months after three-dimensional conformal external beam radiation therapy (3DCRT). Thirty-one patients (23%) received 3 months of androgen deprivation therapy (ADT) before 3DCRT. We also retrospectively reviewed and assigned a combined Gleason score to the pre-3DCRT needle biopsies (97 patients) or transurethral resection of the prostate gland (1 patient). High-molecular-weight cytokeratin (34betaE12) and prostate-specific antigen (PSA) immunohistochemistry was performed in select cases. After 3DCRT, histopathologic changes in benign prostate gland consisted of glandular atrophy, cytologic atypia, and basal cell prominence. The benign glands showed intensely positive reactions with antibodies to high-molecular-weight cytokeratin (34betaE12) and negative to weakly positive reactions to PSA. Paneth cell-like change was seen in 44 (32%) of the biopsies, mucinous metaplasia in 29 (21%), luminal blue-tinged mucinous secretions in 14 (10%), and squamous metaplasia in 8 (6%). The changes in benign prostate tissues were similar between patients treated with ADT and 3DCRT and those treated with 3DCRT alone. After 3DCRT, we recognized two histologic patterns of prostate cancer: (1) prostate cancer showing radiation therapy (RT)-related changes characterized by PSA-positive/34betaE12-negative poorly formed glands or individual cells with abundant clear to finely granular cytoplasm, and (2) prostate cancer showing no apparent RT effect. High-grade prostatic intraepithelial neoplasia (PIN) was seen in 12 post-3DCRT biopsies (8.8%). The use of neoadjuvant ADT had a significant impact on the results of post-RT biopsy. Of the 31 patients treated with neoadjuvant ADT and 3DCRT, 3 (10%) had post-3DCRT biopsies showing prostate cancer without RT effect compared to 44 of 106 men (41%) treated with 3DCRT alone (p = 0.004). Compared to the Gleason score pre-RT, the Gleason score of cancers showing no RT effect was the same in 25 patients (71%), +/-1 point in 8 patients (23%), and +2 points in 2 patients (6%). The mean combined Gleason score post-RT was slightly, although significantly, higher than that pre-RT (7.29 +/- 0.71 versus 7.00 +/- 0.59, p = 0.01). Serum PSA at the time of post-3DCRT biopsy correlated with biopsy results. Prostate cancer without therapy effect was seen in only one of 43 patients (2%) with a serum PSA level < or = 1 ng/ml compared to 46 of 94 patients (49%) with a PSA level > 1 ng/ml (p = 0.0001). After 3DCRT, benign prostate glands show profound histopathologic changes and may be confused with prostate cancer. The effects of 3DCRT on prostate cancer are variable, with some cases showing profound therapy-related changes and others showing no apparent therapy effect.     

Clinical significance of nonpalpable prostate cancer with favorable biopsy features in Japanese men

OBJECTIVE: To assess the clinical significance of nonpalpable localized prostate cancers with relatively favorable six sextant biopsy features in Japanese men. PATIENTS AND METHODS: 136 nonpalpable prostate cancers of which biopsy features confined to (1) a Gleason score of 6 or less, (2) one or two positive cores per six sextant cores, and (3) 50% or less involvement of any positive core were collected. The Gleason score, tumor extension, and cancer volume were compared with preoperative serum PSA and PSA density for the patients who underwent radical prostatectomy. PSA doubling time was measured for the patients who were treated expectantly. RESULTS: Treatments chosen for 136 patients with favorable biopsy features were radical prostatectomy alone for 48 and with preoperative androgen deprivation for 30, radiation to the prostate for 12, androgen deprivation therapy for 21, and watchful waiting for 25. Of 48 patients who underwent radical prostatectomy without androgen deprivation therapy, 25% had nonorgan-confined cancers. Seven cancers (14.6%) were Gleason score of 7, but no cancers were 8 or greater. Among 42 prostatectomy specimens for which cancer volume was measured, 22 (52.4%) had cancer volume >0.5 cm(3). Pretreatment serum PSA levels were correlated neither with the Gleason score, tumor extension nor cancer volume. There was only one nonorgan-confined cancer in the 23 cancers for which PSA density was <0.2 ng/ml/g. The ability of PSA density to predict cancer volume <0. 5 cm(3) was 0.61 using a cut-off of 0.2 ng/ml/g. Of the 25 patients treated expectantly, the PSA doubling time was less than 2 years for 3 patients, while it was stable or fluctuated for 13. CONCLUSIONS: Tumor extension can be predicted based on PSA density in nonpalpable prostate cancer with favorable biopsy features, but predictability of cancer volume based on PSA or PSA density is not satisfactorily high. New parameters or biomarkers that complement needle biopsy findings are needed to predict clinical significance of T1c prostate cancer with favorable biopsy features.