Preoperative parameters, including percent of positive biopsy cores, in predicting pathological findings after radical prostatectomy

OBJECTIVES: We investigated whether preoperative parameters predict pathological stage at radical prostatectomy for patients with clinically localized prostatic cancer. MATERIALS AND METHODS: We studied a total of 160 men with clinically localized prostatic cancer (less than or equal to clinical T2) who underwent radical rertropubic prostatectomy at Wakayama Medical University. Clinical Ts patients are not included in this study. Preoperative parameters include patient age, Body Mass Index, preoperative serum PSA value, biopsy Gleason score, clinical stage, the percent of positive biopsy cores (%PosBx) and the percent of positive biopsy cores on the dominant side (%DomPosBx). Univariate and multivariate analysis were performed to examine the prognostic significance of these preoperative parameters. Significant independent factors were combined to create a table to predict pathologically organ confined disease. RESULTS: Univariate analysis showed preoperative serum PSA value (p< 0.001), biopsy Gleason score (p =0.001), clinical stage (p = 0.026), %PosBx (p= 0.002) and %DomPosBx (p=0.003) were significantly related to the pathological stage. On multivariate analysis, serum PSA value (p< 0.01), biopsy Gleason score (p<0.05) and %DomPosBx (p<0.05) were significant independent predictors of pathological stage. CONCLUSION: We provide two model combinations using preoperative clinical factors, one is a combination of serum PSA and biopsy Gleason score and the other is a combination of serum PSA and %DomPosBx, which define a new preoperative model for predicting pathological organ confined prostatic cancer. These combinations are useful and provide important information for urologists to determine the appropriate treatment strategy for clinically localized prostatic cancer.     

Percent of cancer in the biopsy set predicts pathological findings after prostatectomy

PURPOSE: The ability to use pretreatment variables to identify patients with organ confined prostate cancer continues to challenge physicians. We examined information available preoperatively, including prostate needle biopsy, clinical stage and preoperative prostate specific antigen (PSA), and evaluated these data based on pathological variables after radical retropubic prostatectomy. MATERIALS AND METHODS: We reviewed results in 135 consecutive patients who underwent radical retropubic prostatectomy at a single institution. Needle biopsy information, such as the number of cores, percent of tumor per biopsy set, laterality of positive cores and Gleason sum, were compared with pathological data on the radical retropubic prostatectomy specimen, including pathological stage, Gleason sum and tumor volume. Clinical data, including biopsy information and pathological findings, were compared using univariate and multivariate models. RESULTS: Overall total PSA, percent of tumor in the biopsy and bilateral positive cores directly correlated with tumor volume (p <0.01). Also, increasing PSA, increasing percent of tumor in the biopsy and bilateral positive cores were associated with increased risks of extracapsular extension (p <0.01). CONCLUSIONS: From the information readily available from prostate needle biopsy these results suggest that percent of tumor in the biopsy is a useful predictor of pathological stage and tumor volume. Furthermore, including percent of tumor in the biopsy set and bilateral disease with traditional variables such as serum PSA and clinical stage may improve pretreatment tumor staging. This finding adds additional credence to the inclusion of percent of tumor in the biopsy set in models for the preoperative prediction of pathological stage and should be factored into discussions with patients on treatment options.     

Percent of prostate needle biopsy cores with cancer is significant independent predictor of prostate specific antigen recurrence following radical prostatectomy: results from SEARCH database

PURPOSE: Recent studies have suggested that the percent of positive cores in the prostate needle biopsy is a significant predictor of outcome among men undergoing radical prostatectomy or radiation therapy for prostate cancer. We evaluate whether either percent of cores with cancer or percent of cores positive from the most and least involved side of the prostate needle biopsy was associated with a worse outcome among men treated with radical prostatectomy. MATERIALS AND METHODS: A retrospective survey of 1,094 patients from the SEARCH Database treated with radical prostatectomy at 4 different equal access medical centers in California between 1988 and 2002 was undertaken. We used multivariate analysis to examine whether total percent of prostate needle biopsy cores with cancer, percent of cores positive from each side of the prostate and other clinical variables were significant predictors of adverse pathology and time to prostate specific antigen (PSA) recurrence following radical prostatectomy. RESULTS: On multivariate analysis serum PSA and percent of positive cores were significant predictors of positive surgical margins, nonorgan confined disease and seminal vesicle invasion. Percent of positive cores (p <0.001), serum PSA (p = 0.008) and biopsy Gleason score (p = 0.014) were significant independent predictors of time to biochemical recurrence. On a separate multivariate analysis that included the variables of total percent of positive cores, percent of positive cores from the most involved side of the biopsy, percent of positive cores from the least involved side of the biopsy and whether the biopsy was positive unilaterally or bilaterally, only the percent of positive cores from the most involved side of the biopsy was a significant independent predictor of PSA failure following radical prostatectomy. Percent of positive cores was used to separate patients into a low risk (less than 34%), intermediate risk (34% to 50%) and high risk (greater than 50%) groups, which provided significant preoperative risk stratification for PSA recurrence following radical prostatectomy (p <0.001). Percent of positive cores cut points were able to further risk stratify men who were at low (p = 0.001) or intermediate (p = 0.036) but not high (p = 0.674) risk for biochemical failure based on serum PSA and biopsy Gleason score. CONCLUSIONS: Percent of positive cores in the prostate needle biopsy was a significant predictor of adverse pathology and biochemical failure following radical prostatectomy, and the cut points of less than 34%, 34% to 50% and greater than 50% can be used to risk stratify patients preoperatively. The finding that percent of positive cores from the most involved side of the biopsy was a stronger predictor of PSA failure than the total percent of cores involved suggests that multiple positive biopsies from a single side might be a better predictor of a larger total cancer volume and thus correlate with clinical outcome.     

Gleason score 7 prostate cancer on needle biopsy: is the prognostic difference in Gleason scores 4 + 3 and 3 + 4 independent of the number of involved cores?

PURPOSE: We addressed whether Gleason score 3 + 4 = 7 and 4 + 3 = 7 cancers on needle biopsy behave differently and whether this behavior is independent of the number of cores involved by cancer. If it is not an independent predictor of prognosis, one may report Gleason score 7 cancer with the number of positive cores without regard to whether the primary pattern was 3 or 4. This practice would remove a source of poor interobserver reproducibility when grading prostate cancer on needle biopsy. MATERIALS AND METHODS: We identified 537 patients with Gleason score 7 tumors on biopsy. The results of patient preoperative digital rectal examination, serum prostate specific antigen (PSA) measurement and age were used to predict 4 outcomes based on assessment of the corresponding radical prostatectomy specimens, including 1) pathological stage (organ confined, focal extraprostatic extension, nonfocal extraprostatic extension or seminal vesicle-lymph node involvement), 2) organ confinement (yes/no), 3) Gleason score and 4) surgical margin status (positive/negative) RESULTS: Multivariate regression of postoperative Gleason score groups against all 5 input variables (3 + 4 versus 4 + 3, number of positive cores, PSA, age and digital rectal examination) yielded a statistically significant positive correlation with preoperative PSA (p <0.001) and preoperative Gleason scores of 4 + 3 versus 3 + 4 on biopsy (p <0.001). Pathological stage correlated with preoperative PSA (p <0.001), Gleason score 4 + 3 disease (p = 0.016), positive digital rectal examination (p <0.001) and 3 or more positive cores (p = 0.016). Positive surgical margins were predicted only by preoperative PSA (p = 0.001). CONCLUSIONS: Because the biological behavior of biopsy Gleason score 3 + 4 or 4 + 3 of Gleason score 7 cancer differs regardless of the number of cores involved, future nomograms predicting pathological stage would benefit from examining 3 + 4 and 4 + 3 disease separately.     

Preoperative p27 status is an independent predictor of prostate specific antigen failure following radical prostatectomy

PURPOSE: p27 is an important cell cycle regulator, and decreased expression in radical prostatectomy specimens is associated with an increased risk of prostate specific antigen (PSA) failure. To our knowledge no prior study has shown that preoperative p27 status independently predicts recurrence after radical prostatectomy. MATERIALS AND METHODS: The prostate needle biopsy specimens of 161 men treated with radical prostatectomy were examined for p27 expression using immunohistochemistry. Various p27 cut points were examined for their ability to separate patients into groups with different risk for time to biochemical recurrence following radical prostatectomy. The best p27 cut point was compared to other clinical variables (PSA, clinical stage, age, biopsy Gleason score and percent of prostate needle biopsy with cancer) on multivariate analysis to determine which variables independently predicted biochemical failure. RESULTS: A p27 cut point of less than 45% positive staining cells resulted in significant preoperative risk stratification for time to PSA failure (HR 2.41, p = 0.010). On multivariate analysis serum PSA (HR 1.04, p = 0.011), biopsy Gleason score (HR 1.51, p = 0.011), percent of biopsy tissue with cancer (HR 10.01, p = 0.001) and less than 45% p27 positive cells (HR 2.44, p = 0.014) were all independent predictors of biochemical recurrence. CONCLUSIONS: Preoperative p27 expression is an independent predictor of time to biochemical recurrence following radical prostatectomy. Patients with less than 45% p27 positive cells in the prostate needle biopsy specimen have almost a 2.5-fold increased risk of biochemical recurrence. To our knowledge this study is the first to show that p27 status of the prostate needle biopsy specimen can be used before radical prostatectomy to predict biochemical failure.     

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.     

Under staging and under grading in a contemporary series of patients undergoing radical prostatectomy: results from the Cancer of the Prostate Strategic Urologic Research Endeavor database

PURPOSE: We determined the prevalence of under staging and under grading in contemporary patients undergoing radical prostatectomy in academic and community based urology practices, and defined important predictors of under staging in this population. MATERIALS AND METHODS: We compared clinical T stage and biopsy Gleason score with pathological T stage and prostatectomy Gleason score in 1,313 patients enrolled in the Cancer of the Prostate Strategic Urologic Research Endeavor database, a longitudinal registry of patients with prostate cancer, who underwent radical prostatectomy, including 53% since 1995. Under grading was determined for the primary and secondary Gleason patterns and defined as a biopsy Gleason pattern of 1 to 3 that became pathological Gleason pattern 4 or 5. Under staging was defined as a clinically organ confined tumor that was extraprostatic stages pT3 to 4 or N+ at radical prostatectomy. Univariate and multivariate analysis was performed to determine important risk factors for under staging and significant risk factors were used to identify the likelihood of under staging in clinically relevant patient subgroups. The importance of the percent of positive biopsies in regard to the likelihood of under staging was determined by assigning patients to previously described risk groups based on serum prostate specific antigen (PSA) at diagnosis and biopsy Gleason score. RESULTS: Under grading of primary and secondary Gleason patterns occurred in 13% and 29% of patients, respectively, while under staging occurred in 24%. Univariate and multivariate analysis revealed that PSA at diagnosis, biopsy Gleason score and the percent of positive biopsies were significant predictors of under staging. The percent of positive biopsies appeared to be most important for predicting the likelihood of extraprostatic disease extension in intermediate or high risk disease based on serum PSA at diagnosis and biopsy Gleason grade. CONCLUSIONS: The prevalence of under grading and under staging in contemporary patients undergoing radical prostatectomy may be lower than previously reported. PSA at diagnosis, biopsy Gleason score and the percent of positive biopsies are important predictors of under staging. The percent of positive biopsies should be incorporated into risk assessment models of newly diagnosed prostate cancer.     

Percent of cores positive for cancer is a better preoperative predictor of cancer recurrence after radical prostatectomy than prostate specific antigen

PURPOSE: We examined the prognostic significance of clinical and pathological variables on outcome following radical retropubic prostatectomy (RRP) in a cohort of patients in the post-prostate specific antigen (PSA) era. MATERIALS AND METHODS: We reviewed the clinical and pathological data on a cohort of 476 patients who underwent RRP for localized prostate cancer between January 1990 and July 2001 by 1 urologist (WCD). Median age, preoperative PSA and followup were 61 years, 5.8 ng/ml and 49 months, respectively. We used Cox proportional hazard modeling to evaluate the prognostic significance of clinical and pathological variables for cancer recurrence, defined as 2 successive PSA determinations 0.3 ng/ml or greater. RESULTS: Of the 476 patients 53 (11%) had recurrence. Estimated cancer nonprogression probability was 86% (95% CI 83 to 90) and 76% (95% CI 68 to 86) at 5 and 10 years, respectively. Two multivariate analyses were performed. The first analysis, using only preoperative indicators, found that the percent of biopsy cores positive for cancer and biopsy Gleason score were the best predictive indicators of recurrence. The second multivariate analysis, using preoperative and postoperative indicators, found that the percent of biopsy cores positive for cancer, RRP Gleason score and the combined pathological stage/margin status variable were the best predictive indicators of recurrence. PSA was not found to be an important predictor of recurrence on either multivariate analysis. Patients with a percent of biopsy cores in the upper half of the distribution (greater than 28% positive) were at significantly increased risk for recurrence compared with those in the lower half of the distribution (28% or less positive) (HR 3.86, p <0.001). CONCLUSIONS: The percent of cores positive for cancer was a better predictor of cancer recurrence than PSA in this post-PSA era RRP series. In addition, surgical Gleason score and pathological stage/surgical margins were also independent predictors of cancer recurrence after RRP. These 3 predictors are displayed in a nomogram-type format to summarize estimated 5 and 10-year recurrence-free probabilities.     

Prognostic significance of tumor volume after radical prostatectomy: a multivariate analysis of pathological prognostic factors

OBJECTIVES: To analyze the association between Gleason score, stage and status of surgical margins with tumor volume in prostate cancer progression after radical prostatectomy. METHODS: 200 consecutive radical prostatectomy specimens were analyzed. Preoperative clinical stage, PSA, results of prostate biopsies as well as pathological results were noted. A biochemical recurrence was defined as a single, postoperative detectable PSA level (>0.2 ng/ml). Tumor volume was compared to postoperative staging, Gleason score, and surgical margin status to predict tumor progression. Univariate and multivariate analysis using stepwise logistic regression were used to identify parameters with additional prognostic value. RESULTS: Pathological results of the prostatectomy specimens showed 149 (74.5%) pT2a-b, 29 (14.5%) pT3a and 22 (11%) pT3b tumors. Tumor volume was 0.57 cc for pT2a, 1.2cc for pT2b, 1.7cc for pT3a and 2.9cc for pT3b, respectively (p<0.05). Taken together, mean volume for pT2 and pT3 were 1.06 and 2.2 cc, respectively (p<0.0001). Five-year progression-free actuarial survival was 69.7%. Using univariate analysis, tumor progression correlated with final Gleason score (p<0.0007), positive surgical margins (p=0.02), tumor volume (p=0.009) and stage (p<0.0001). In a multivariate analysis, tumor progression correlated only with the final Gleason score (p=0.04) and stage (p=0.0002). CONCLUSION: Gleason score and pathological stage are independent factors to predict prostate cancer progression after radical prostatectomy. When these parameters are known, tumor volume does not provide additional information.     

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.     

The extent of biopsy involvement as an independent predictor of extraprostatic extension and surgical margin status in low risk prostate cancer: implications for treatment selection

PURPOSE: We identify predictors of extraprostatic extension and positive surgical margins in patients with low risk prostate cancer (prostate specific antigen [PSA] 10 ng./ml. or less, biopsy Gleason score 7 or less and clinical stage T1c-2b). MATERIALS AND METHODS: From August 1997 to January 1999, 143 previously untreated patients underwent radical retropubic prostatectomy for clinically localized prostate cancer. A total of 62 patients were low risk, with PSA 10 ng./ml. or less, biopsy Gleason score 7 or less and clinical stage T1c-2b, and had sextant biopsy with separate pathological evaluation of each sextant cores. PSA, clinical stage, biopsy Gleason score, average percentage of cancer in the entire biopsy specimen, maximum percentage of cancer on the most involved core, number of cores involved and bilaterality were evaluated for association with extraprostatic extension, seminal vesicle involvement and positive surgical margins. RESULTS: Of the 62 patients 13 (21%) had extraprostatic extension, 6 (10%) seminal vesicle involvement and 20 (32%) positive surgical margins. Average percentage greater than 10% and maximum percentage greater than 25% were associated with extraprostatic extension (p = 0.01 and 0.004, respectively). Average percentage greater than 10%, maximum percentage greater than 25%, more than 2 cores involved and bilaterality were associated with positive surgical margins (p = 0.007, 0.01, 0.002 and 0.03, respectively). On multivariate analysis maximum percentage remained the only independent predictor of extraprostatic extension (p = 0.03), and the number of cores involved remained an independent predictor of positive surgical margins (p = 0.01). Biopsy Gleason score, PSA and clinical stage did not correlate with extraprostatic extension or positive surgical margins in this patient population. CONCLUSIONS: In low risk prostate cancer the extent of biopsy involvement significantly correlates with the risk of extraprostatic extension and positive surgical margins. Biopsy information should be considered when selecting and modifying treatment modalities.     

Serum leptin and pathological findings at the time of radical prostatectomy

PURPOSE: Obesity has been associated with a higher risk of progression following radical prostatectomy (RP). Obese men have higher serum leptin, a hormone produced by adipocytes, which has also been shown to be an in vitro prostate cancer growth factor. We examined whether serum leptin correlates with advanced pathological findings at RP. MATERIALS AND METHODS: Preoperative serum from 225 men treated with RP between 1998 and 1999 was examined for serum leptin. Multivariate logistic regression analysis was used to determine whether serum leptin was predictive of extraprostatic extension (pT3a). RESULTS: Serum leptin highly correlated with body mass index (Spearman r = 0.602, p <0.001). Serum leptin was not associated with total or percent free prostate specific antigen (PSA), biopsy or prostatectomy Gleason score, age or height. On multivariate analysis with total and percent free PSA, clinical stage, age, biopsy Gleason score, body mass index, serum leptin, and height as variables considered for entry into the model, serum PSA (p = 0.009), clinical stage (p = 0.019) and serum percent free PSA (p = 0.041) were the only variables predictive of extraprostatic extension. Serum leptin was not significantly associated with pathological stage (pT3a). CONCLUSIONS: In the current study of predominantly white men with mainly low risk disease there was no statistically significant association between serum leptin and pathological stage (pT3a) at RP. In this cohort serum leptin was not a good biomarker for predicting advanced stage at RP.     

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.     

Prediction of tumour volume and pathological stage in radical prostatectomy specimens is not improved by taking more prostate needle-biopsy cores

OBJECTIVE: To determine what, if any, additional prognostic information is available from the prostate needle biopsy by comparing the number of biopsy cores obtained with the pathology assessed from the radical retropubic prostatectomy (RRP) specimen. PATIENTS AND METHODS: The results from 135 consecutive patients who underwent RRP at a single institution were reviewed. Needle biopsy information (number of cores, percentage of positive cores, laterality of the positive cores, and Gleason sum) were compared with the pathological data of the RRP specimen, including stage, Gleason sum and tumour volume. Patients were further stratified into those with six or fewer cores (96 men) or more than six cores (39 men). Clinical data, including biopsy information and pathological findings, were compared using univariate and multivariate models. RESULTS: Overall, univariate analysis showed that the total prostate-specific antigen (PSA) level, number of positive cores, bilateral positive cores and percentage of positive cores were directly correlated with tumour volume (P=0.01). Also, PSA and percentage of positive cores were directly correlated with extracapsular extension (P=0.008 and P=0.01, respectively). In the multivariate model, the most important independent predictors of RRP tumour volume and pathological stage were the preoperative PSA level and percentage of cancer in the biopsy (P<0.01). There was no significant relationship between the number of cores obtained and the predicted pathology of the RRP specimen. There were no differences in the number of positive cores, bilateral positive cores or percentage tumour in the cores between men with more or less than six biopsies. In men with more than six core biopsies, there was no significant increase in prognostic information for tumour volume and extracapsular extension, or a correlation between the Gleason sum on biopsy and the RRP specimen. Taking more than six biopsies did not result in a significantly greater detection of potentially indolent tumours (defined as a tumour volume of <0.5 mL). CONCLUSIONS: While taking more prostate needle biopsy cores seems to improve the detection of prostate cancer, there appears to be no major improvement in prognostic information over that gained from traditional sextant biopsies. Furthermore, the results suggest that the percentage of positive cores is the best predictor of both pathological stage and tumour volume, from among the information readily available from prostate needle biopsy. Given the variability in the number of cores obtained for diagnosis in clinical practice, these results add credence to the use of the percentage of positive cores in the biopsy set, with known predictors such as PSA and Gleason score, into future models that attempt to predict tumour biology.     

Predicting pathological stage of localized prostate cancer using volume weighted mean nuclear volume

PURPOSE: With the use of prostate specific antigen (PSA) and transrectal ultrasound guided biopsy of the prostate, increasing numbers of clinically localized prostate cancers have recently been detected. Presently, approximately 60% of men newly diagnosed with prostate cancer are believed to have organ confined disease but at the time of surgery less than 50% are ultimately found to have organ confined disease on final pathological analysis. Prediction of pathological stage before surgery using various prognostic factors is needed to determine whether radical prostatectomy is indicated. We have reported that estimates of volume weighted mean nuclear volume can accurately predict the prognosis of clinically localized prostate cancer treated with androgen ablation. In this study we examine whether estimates of mean nuclear volume can predict the pathological stage of cases treated with radical prostatectomy. MATERIALS AND METHODS: A retrospective, prognostic study of 52 patients with clinically localized prostate cancer (21 cases T1c, 27 T2, 4 T3) diagnosed at Kobe City General Hospital between January 1996 and December 1999 and treated with radical prostatectomy was performed. Unbiased estimates of mean nuclear volume measured from transrectal biopsy specimens were compared with PSA at diagnosis, clinical stage, estimated tumor volume and Gleason score with regard to prediction of pathological stage. RESULTS: Univariate analysis revealed that estimates of mean nuclear volume (p <0.0001), PSA at diagnosis (p = 0.0148) and estimated tumor volume (p = 0.0005) significantly correlated with pathological stage but Gleason score did not (p = 0.2011). In addition, multivariate logistic regression analysis demonstrated that estimates of mean nuclear volume (p = 0. 0073), PSA at diagnosis (p = 0.0277) and estimated tumor volume (p = 0.0197) were significantly independent predictors of pathological stage. CONCLUSIONS: The results of our study suggest that combining PSA and estimated tumor volume with estimates of mean nuclear volume can significantly contribute to the prediction of pathological stage of prostate cancer. We recommend use of these 3 factors to predict pathological stage of prostate cancer before surgery.     

Multivariate models to predict clinically important outcomes at prostatectomy for patients with organ-confined disease and needle biopsy Gleason scores of 6 or less

The objective of this study was to determine the clinical and biopsy features associated with outcomes at radical retropubic prostatectomy (RRP) in patients with clinically organ-confined prostate cancers and biopsy Gleason scores (GS) of 6 or less. We reviewed 274 biopsies with GS 6 or less cancers from patients with clinically organ-confined disease between 1995 and 1998 to determine statistically significant predictors for the following outcomes at RRP: tumor volume, small (<0.5 cc), confined (pT2) tumors with RRP GS of 6 or less (potentially “insignificant” tumors), and extraprostatic extension (EPE). Clinical and pathologic features evaluated included age, serum prostate specific antigen (PSA), clinical stage, percent biopsy cores and surface area positive for cancer (tumor extent), perineural invasion, MIB-I proliferation, and DNA ploidy by digital image analysis (DIA). Multivariate analyses showed that biopsy tumor extent (median percent surface area positive 3.3%; P < 0.001 and median biopsy cores positive 28.6%; P = 0.001) and PSA (median 5.5 ng/mL; P = 0.009) predicted tumor volume (median 1.4 cc). Biopsy tumor extent (P = 0.002), PSA (P = 0.002), and percent S-phase nuclei (P = 0.050) predicted potentially “insignificant” tumors at RRP (n = 76, 28%). Percent surface area positive for cancer (P = 0.003) predicted EPE (n = 22, 8%). DNA ploidy (n = 211, 79% diploid) and MIB-I proliferation (median 1.4%) did not add information to predict these RRP outcomes. Biopsy tumor extent and serum PSA were significantly associated with tumor volume. Biopsy tumor extent, serum PSA, and percent S-phase nuclei by DIA were predictive of potentially insignificant tumors. Patients with clinically confined disease, <5% biopsy surface area positive for cancer, <20% biopsy cores positive for cancer, and GS 6 or less, had a 48% chance of having a potentially insignificant tumor at diagnosis if the serum PSA was <10 ng/mL. Percent surface area predicted EPE at RRP. DNA ploidy and MIB-I proliferation by DIA did not provide additional information.     

前列腺癌分期方法的临床评价

目的 :探讨临床参数对前列腺癌分期的临床意义。　方法 :通过病理诊断、MRI检查及全身骨扫描对 112例经前列腺活检病理证实的前列腺癌进行分期 ,结合血清前列腺特异抗原 (PSA)、穿刺后Gleason评分、穿刺阳性针数百分率评价其临床意义。　结果 :112例前列腺癌中 ,血清PSA、Gleason评分、穿刺阳性针数百分率对前列腺癌分期有显著相关性 (r=0 .6 98,r=0 .6 74 ,r=0 .6 71,P均 <0 .0 0 1) ,但对B期和C期前列腺癌的诊断差异无显著性 (χ2=2 .6 75 ,P =0 .0 96 ;χ2 =0 .70 4 ,P =0 .4 0 1) ,血清PSA较Gleason评分和穿刺阳性针数百分率对D期的诊断差异有显著性 (χ2 =5 .135 ,P =0 .0 2 3;χ2 =4 .5 93,P =0 .0 32 )。血清PSA、Gleason评分和穿刺阳性针数百分率的敏感性分别为 76 .7%、83.3%和 77.8% ,特异性为 5 0 %、77.3%和 5 4 .5 % ,准确性为 71.4 %、82 .1%和 73.2 %。　结论 :血清PSA、Gleason评分、穿刺阳性针数百分率可预测前列腺癌的分期 ,穿刺后Gleason评分对前列腺癌分期的预测较血清PSA和穿刺阳性针数百分率更准确。血清PSA对远处转移性前列腺癌的预测更有意义     

RELATIONSHIP BETWEEN SYSTEMATIC BIOPSIES AND HISTOLOGICAL FEATURES OF 222 RADICAL PROSTATECTOMY SPECIMENS: LACK OF PREDICTION OF TUMOR SIGNIFICANCE FOR MEN WITH NONPALPABLE PROSTATE CANCER

PURPOSE: Because of the recent increase in nonpalpable prostate cancer (clinical stage T1c) in men, preoperative needle biopsy findings have had an important role for treatment decisions. We examine the correlation among histopathological features of 6 systematic biopsies and radical prostatectomy specimens in which 1 investigator reviewed all histological sections. MATERIALS AND METHODS: We studied a total of 450 men with clinical stage T1c prostate cancer from whom needle biopsies were matched with radical prostatectomy specimens, and selected 222 patient biopsies that were obtained from 6 or more separate regions of the prostate. The pretreatment parameters of serum prostate specific antigen (PSA), PSA density, number of positive needle biopsies, distribution of positive cores, linear cancer length, and percent Gleason grade 4/5 on the biopsy were determined and compared with histopathological features of prostate cancer in the radical prostatectomy specimens. All biopsies and radical prostatectomies were evaluated morphologically at the department of urology. RESULTS: Of the 222 men the largest cancer was clinically insignificant in 23 (10%), as measured by a cancer volume of less than 0.5 cc. Cancer volume in the prostatectomy specimen was significantly related to all parameters in the biopsy, with the surprising exception of cancer distribution in the positive biopsies. However, all of these correlations with cancer volume were weak, with Pearson's correlation squared (R(2)) multiplied by 100 less than 10%. Unfortunately, tumor grade on the biopsy agreed with the prostatectomy specimen in only 81 of 222 (36%) cases. Grade assessment with needle biopsy underestimated the tumor grade in 102 (46%) cases and overestimated it in 39 (18%). No single parameter in the biopsy was a predictor of tumor significance, as measured by a cancer volume of greater than 0.5 cc. However, the best model to predict a tumor less than 0.5 cc in volume was the combination of a single positive core with cancer length less than 3 mm. that contained no Gleason grade 4/5. The use of PSA or PSA density in combination with needle biopsy findings did not enhance prediction of tumor significance. CONCLUSIONS: These results indicate a weak and disappointing correlation among all pathological features of 6 systematic biopsies and radical prostatectomy specimens. The combination of 1 positive core with cancer length less than 3 mm. that contains no Gleason grade 4/5 is probably the best predictor of prostate cancer less than 0.5 cc in men with nonpalpable tumors, a cancer volume that occurred in only 10% of the 222 (23) men.     

Prediction of pathological stages before prostatectomy in prostate cancer patients: Analysis of 12 systematic prostate needle biopsy specimens

OBJECTIVE: To identify the most reliable predictor of the pathological stage among multiple parameters obtained by performing systematic biopsies and to assess the predictive value of any identified parameters in combination with the prostate specific antigen and the Gleason scores. METHODS: We examined 5 biopsy parameters from 12 systematic needle biopsy results in 104 consecutive prostate cancer patients who underwent prostatectomy: the number of cores positive for cancer, percentage of positive biopsy cores, total linear cancer length (absolute sum of tumor length at each core), percentage cancer length (total cancer length divided by total length of cores obtained x100), and maximum cancer core length. The predictive values of these parameters were assessed using multivariate logistic analysis and receiver operating characteristic analysis. We evaluated whether the most reliable biopsy parameter in combination with traditional variables show better predictability of the pathological stage than traditional variables alone by receiver operating characteristic analysis. RESULTS: Of 104 patients, 85 (82.9%) had organ confined cancer and 19 (17.1%) showed extraprostatic extension. Of the five parameters examined, maximum cancer length was found to best predict pathological staging. Although insignificant, adding results of maximum cancer length to prostate specific antigen and Gleason scores improved predictability. Of 41 patients with a maximum cancer length of <0.9 cm, PSA of <16 ng/mL, and Gleason score of <7, none showed extraprostatic extension. CONCLUSIONS: The maximum cancer length was found to be the most reliable predictor of disease staging. The findings of a maximum cancer length of <0.9 cm, PSA of <16 ng/mL, and a Gleason score of <7 can suggest an organ-confined disease.     

Assessment of the enhancement in predictive accuracy provided by systematic biopsy in predicting outcome for clinically localized prostate cancer

PURPOSE: Current localized prostate cancer treatment outcome nomograms rely on prostate specific antigen (PSA), tumor stage and grade. We investigated whether the addition of prostate biopsy features may enhance the accuracy of a nomogram predicting recurrence after radical prostatectomy (RP). MATERIALS AND METHODS: Clinical data from 1,152 patients who underwent RP were used and included PSA, clinical stage, biopsy Gleason grade and systematic biopsy information that quantified the amount of cancer and high grade cancer. Predictive accuracy for freedom from recurrence after RP was assessed with and without tumor quantification in the biopsy by the area under the receiver operating characteristics curve (AUC). RESULTS: Percentage and number of cores with cancer, and percentage and number of cores with high grade cancer were predictors of outcome when added to models that included PSA, Gleason grade and clinical stage (all p <0.0001). Nomogram accuracy with 3 traditional variables (AUC 0.790) was minimally enhanced with the addition of percentage or number of positive cores (AUC 0.804 and 0.800, respectively), or percentage or number of cores with high grade cancer (AUC 0.802 and 0.800, respectively). Maximum predictive accuracy of 0.811 was achieved after supplementing the traditional 3-variable nomogram with various combinations of additional pathological predictors. CONCLUSIONS: The information provided by systematic biopsies substantially improves the ability to predict outcome following RP. However, some incremental predictive accuracy was achieved by adding systematic biopsy features.