Development and external validation of an extended repeat biopsy nomogram

PURPOSE: We hypothesized that the outcome of repeat biopsy could be accurately predicted. We tested this hypothesis in a contemporary cohort from 3 centers. MATERIALS AND METHODS: The principal cohort of 1,082 men from Hamburg, Germany was used for nomogram development as well as for internal 200 bootstrap validation in 721 and external validation in 361. Two additional external validation cohorts, including 87 men from Milan, Italy and 142 from Seattle, Washington, were also used. Predictors of prostate cancer on repeat biopsy were patient age, digital rectal examination, prostate specific antigen, percent free prostate specific antigen, number of previous negative biopsy sessions and sampling density. Multivariate logistic regression models were used to develop the nomograms. RESULTS: The mean number of previous negative biopsies was 1.5 (range 1 to 6) and the mean number of cores at final repeat biopsy was 11.1 (range 10 to 24). Of the men 370 (30.2%) had prostate cancer. On multivariate analyses all predictors were statistically significant (p < or =0.028). After internal validation the nomogram was 76% accurate. External validation showed 74% (Hamburg), 78% (Milan) and 68% (Seattle) accuracy. CONCLUSIONS: Relative to the previous nomograms (10 predictors or 71% accuracy) our tool relies on fewer variables (6) and shows superior accuracy in European men. Accuracy in American men is substantially lower. Racial, clinical and biochemical differences may explain the observed discrepancy in predictive accuracy.     

Validation of a nomogram for predicting positive repeat biopsy for prostate cancer

PURPOSE: We reported a nomogram and subsequently a corrected version for predicting the probability of positive biopsy in men with 1 or more prior negative biopsies. In this study we assessed the validity of this nomogram when applied to an external dataset. MATERIALS AND METHODS: There were 230 patients from the Brooklyn Veterans Administration Medical Center who underwent 1 or more repeat biopsies after initial negative biopsy from January 1993 to June 2003. Predictor variables studied in the nomogram were patient age, family history of prostate cancer, digital rectal examination, serum prostate specific antigen, prostate specific antigen slope, months from initial negative biopsy session, months from previous negative biopsy session, cumulative number of negative cores previously taken and history of high grade intraepithelial neoplasm or atypical small acinar proliferation. We calculated the nomogram predicted probability in each patient. These predicted outcomes were compared with actual biopsy results. Area under the ROC curve was calculated as a measure of discrimination. Calibration was assessed graphically. RESULTS: We evaluated a total of 356 repeat biopsies in 230 patients (mean 2.56 total biopsies per patient). The mean number of total cores per patient was 17.9. There were 78 positive biopsies. The area under the ROC curve was 0.71, which was greater than any single risk factor. Nomogram calibration appeared to be good. CONCLUSIONS: Our corrected nomogram for predicting positive repeat biopsy performed well when applied to a sample of men at the Brooklyn Veterans Administration Medical Center. This nomogram can provide important additional information to aid the urologist and patient with a negative biopsy in evaluating clinical options.     

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.     

Diagnostic value of systematic biopsy methods in the investigation of prostate cancer: a systematic review

PURPOSE: Several new extended prostate biopsy schemes (greater than 6 cores) have been proposed. We compared the cancer detection rates and complications of different extended prostate biopsy schemes for diagnostic evaluation in men scheduled for biopsy to identify the optimal scheme. MATERIALS AND METHODS: In a systematic review we searched 13 electronic databases, screened relevant urological journals and the reference lists of included studies, and contacted experts. We included studies that compared different systematic prostate biopsy methods using sequential sampling or a randomized design in men scheduled for biopsy due to suspected prostate cancer. We pooled data using a random effects model when appropriate. RESULTS: We analyzed 87 studies with a total of 20,698 patients. We pooled data from 68 studies comparing a total of 94 extended schemes with the standard sextant scheme. An increasing number of cores were significantly associated with the cancer yield. Laterally directed cores increased the yield significantly (p = 0.003), whereas centrally directed cores did not. Schemes with 12 cores that took additional laterally directed cores detected 31% more cancers (95% CI 25 to 37) than the sextant scheme. Schemes with 18 to 24 cores did not detect significantly more cancers. Adverse events for schemes up to 12 cores were similar to those for the sextant pattern. Adverse event reporting was poor for schemes with 18 to 24 cores. CONCLUSIONS: Prostate biopsy schemes consisting of 12 cores that add laterally directed cores to the standard sextant scheme strike the balance between the cancer detection rate and adverse events. Taking more than 12 cores added no significant benefit.     

Cross‐cultural validation of a prognostic tool: example of the Kattan preoperative nomogram as a predictor of prostate cancer recurrence after radical prostatectomy

OBJECTIVE

To establish the predictive accuracy of the Kattan preoperative nomogram by comparing predictions at 5 years with actual progression in patients who had a radical prostatectomy (RP).

MATERIALS AND METHODS

We reviewed the data for 928 patients treated by RP as a first‐line treatment for localized prostate cancer, between 1994 and 2005. Recurrence was defined as one prostate‐specific antigen (PSA) level of >0.4 ng/mL. The 5‐year progression‐free probability (PFP) rate was evaluated on censured data using the Kaplan‐Meier method. Relationships between all predictor variables included in the Kattan nomogram (PSA level, biopsy Gleason scores and clinical stage) and survival were evaluated by Cox proportional‐hazards regression analysis. The discriminating ability of the nomogram was assessed by the concordance index (c‐index). Bootstrapping was used to assess confidence intervals (CIs), and then the calibration was assessed.

RESULTS

The median follow‐up was 60 months. Overall, 177 (19%) patients had a recurrence; the 5‐year PFP rate (95% CI) was 80.9 (78–83)%. Of the three variables included in the nomogram, all were associated with recurrence in a multivariate analysis (P < 0.001). The c‐index (95% CI) was only 0.664 (0.584–0.744). In general, the nomogram was not well calibrated.

CONCLUSIONS

There was a discrepancy between the predicted PFP as estimated by the Kattan nomogram and actual relapse in this group of patients. Clinicians should be aware that the nomogram is less accurate when used outside the population used to formulate the nomogram. Although more accurate tools are needed, the Kattan nomogram is still the best choice for urologists so far.     

Predicting the presence and side of extracapsular extension: a nomogram for staging prostate cancer

PURPOSE: We developed a model to predict the side specific probability of extracapsular extension (ECE) in radical prostatectomy (RP) specimens based on the clinical features of the cancer. MATERIALS AND METHODS: We studied 763 patients with clinical stage T1c-T3 prostate cancer who were diagnosed by systematic needle biopsy and subsequently treated with RP. Candidate predictor variables associated with ECE were clinical T stage, the highest Gleason sum in any core, percent positive cores, percent cancer in the cores from each side and serum prostate specific antigen (PSA). Receiver operating characteristic (ROC) analyses were performed to assess the predictive value of each variable alone and in combination. We constructed and internally validated nomograms to predict the side specific probability of ECE based on logistic regression analysis. RESULTS: Overall 30% of the patients and 17% of 1,526 prostate lobes (left or right) had ECE. The areas under the ROC curves (AUC) of the standard features in predicting side specific probability of ECE were 0.627 for PSA, 0.695 for clinical T stage on each side and 0.727 for Gleason sum on each side. When these features were combined predictive accuracy increased to 0.788. The highest value (0.806) was achieved by adding the percent positive cores and the percent cancer in the biopsy specimen to the standard features. The resulting nomograms were internally validated and had excellent calibration and discrimination accuracy. CONCLUSIONS: Standard clinical features of prostate cancer in each lobe-PSA, palpable induration and biopsy Gleason sum-can be used to predict the side specific probability of ECE in RP specimens. The predictive accuracy is increased by adding information from systematic biopsy results. The predictive nomograms are sufficiently accurate for use in clinical practice in decisions such as wide versus close dissection of the cavernous nerves from the prostate.     

Significant upgrading affects a third of men diagnosed with prostate cancer: predictive nomogram and internal validation

OBJECTIVE: To explore the rate of significant upgrading from biopsy to radical prostatectomy (RP) specimens in a contemporary cohort, and to develop a prognostic model capable of predicting the probability of significant upgrading, as previous reports indicate that up to 43% of men with low-grade prostate cancer at biopsy will be diagnosed with high-grade cancer at RP. PATIENTS AND METHODS: The study cohort comprised 4789 men (median age 63 years, range 39-82) treated with RP, with available clinical stage, prostate-specific antigen levels, biopsy and RP Gleason sum values. These variables were used as predictors in multivariate logistic regression models (LRMs) addressing the rate of significant Gleason sum upgrading, defined as a Gleason sum increase either from < or = 6 to > or = 7 or from 7 to > or = 8 between the biopsy and RP specimens. Regression coefficients were used to develop and validate (200 bootstrap re-samples) a nomogram predicting significant biopsy Gleason sum upgrading. RESULTS: Significant biopsy Gleason sum upgrading was recorded in 1349 (28.2%) patients. In multivariate LRMs, all predictors were highly significant (all P < 0.001). The bootstrap-corrected accuracy of the nomogram predicting the probability of significant Gleason sum upgrading between biopsy and RP specimens was 75.7%. CONCLUSION: Our nomogram might prove highly useful when the possibility of a more aggressive Gleason variant could change the treatment options.     

Improved detection of clinically significant, curable prostate cancer with systematic 12-core biopsy

PURPOSE: While systematic 12-core (S12C) biopsy detects more cancers than sextant biopsy, to our knowledge the clinical significance of these additionally detected tumors has not been established. We studied pathological parameters of prostatectomy specimens from patients undergoing radical prostatectomy for prostate cancer detected with a S12C biopsy to determine the clinical significance of these cancers in comparison with sextant detected cancers. MATERIALS AND METHODS: A total of 179 consecutive patients undergoing radical prostatectomy for clinically localized prostate cancer detected by S12C biopsy were studied. The groups compared consisted of the sextant core subset of the S12C and the entire S12C set. Total tumor volume, Gleason score, organ confined status, surgical margin status, seminal vesicle invasion, lymph node involvement, and clinical significance of tumors detected by sextant and by S12C templates were compared. RESULTS: S12C biopsy detected a greater number of cancers scored as moderate (Gleason score 2 to 6) or high (Gleason score 7 or greater) grade, and cancers of all sizes regardless of organ confined status than the sextant cores alone (all p <0.05). S12C biopsy identified a greater number of biologically significant and insignificant tumors regardless of how they were defined. CONCLUSIONS: Compared with the sextant set S12C biopsy detects a significantly greater number of surgically curable, biologically significant tumors as well as those that might be considered clinically insignificant.     

Prostate saturation biopsy in the reevaluation of microfocal prostate cancer

PURPOSE: We evaluated the ability of an extended, 32-core repeat transrectal ultrasound prostate biopsy protocol to improve the characterization of low volume, well differentiated disease in men with a diagnosis of potentially insignificant microfocal prostate cancer, as defined by 1 single focus positive core of 10 with less than 5 mm of Gleason score 6 or less tumor on primary biopsy. MATERIALS AND METHODS: A total of 35 consecutive patients, who were 62 to 75 years old, had a median serum prostate specific antigen of 8 ng/ml (range 0.5 to 14) and a diagnosis of minimal prostate cancer, and were willing to consider observation with delayed treatment at progression, were offered repeat saturation prostate biopsy with a median of 32 cores (range 18 to 36) under local anesthesia. This biopsy was to determine whether more extensive prostate sampling would confirm or disprove the initial diagnosis of microfocal, well differentiated prostate cancer. RESULTS: The procedure was aborted in 1 patient because of massive rectal hemorrhage. Another patient had acute prostatitis with gram-negative sepsis. Of 34 evaluable biopsy sets 11 (32%) were negative for cancer, suggesting that tumor detected at the primary biopsy was probably of low volume and amenable to observation with delayed treatment. Of the biopsies 23 (68%) were positive, 17 were at multiple sites and 7 were upgraded to Gleason score 7 or greater. These patients were then considered to have significant tumors and were offered active treatment. CONCLUSIONS: This study is to our knowledge the first to describe the clinical use of prostate saturation biopsies for re-evaluating potentially insignificant prostate cancer. Of patients with minimal disease on standard 10-core biopsy, results show that this technique may be helpful for distinguishing the 30% who probably have minimal disease based on negative repeat saturation biopsy from the 70% who almost certainly have a significant tumor, as characterized by multiple positive cores, with or without an increased Gleason score. The latter patients should be offered active therapy.     

Percent Gleason grade 4/5 as prognostic factor in prostate cancer diagnosed at transurethral resection

PURPOSE: We investigated the value of percent Gleason grade 4/5 as a predictor of long-term outcome in men with prostate cancer diagnosed at transurethral resection who received deferred treatment. MATERIALS AND METHODS: A series of 305 men with prostate cancer diagnosed at transurethral resection from 1975 to 1990 who had subsequent expectancy was analyzed. Mean patient age at diagnosis was 74 years (range 52 to 95). Slides were reviewed, and the Gleason score, percent Gleason grade 4/5 and modified Gleason score (the sum of the dominant and worst grades) were assessed. RESULTS: At followup 271 men (89%) had died, including 110 (36%) of prostate cancer. Gleason score, percent Gleason grade 4/5 and modified Gleason score were significant predictors of disease specific survival (p <0.001). Of all men 34% had tumors without any grade 4/5 pattern, of whom only 8% died of prostate cancer compared with 52% with any grade 4/5 pattern (p <0.001). Gleason score 6 tumors with focal grade 4 (less than 5%) had a worse prognosis than pure Gleason score 3 + 3 = 6 tumors (p = 0.008). There was nonsignificantly shorter survival for Gleason score 4 + 3 = 7 than for Gleason score 3 + 4 = 7 disease (p = 0.19). In Cox models including all possible pairs of Gleason score, percent Gleason grade 4/5 and modified Gleason score the percent Gleason grade 4/5 and modified Gleason score were stronger than Gleason score, although all 3 were independently significant prognosticators. CONCLUSIONS: Percent Gleason grade 4/5, modified Gleason score and Gleason score are predictors of disease specific survival in patients with prostate cancer on deferred treatment. Our study indicates that any grade 4/5 pattern impairs the prognosis significantly.     

经直肠超声引导前列腺穿刺活检术诊断前列腺癌

目的　总结和评价经直肠超声引导下前列腺穿刺活检术对前列腺癌诊断的准确率。方法　222 例直肠指检阳性或 PSA>4μg/L的患者应用经直肠超声引导下前列腺6点系统穿刺活检以明确诊断。结果　222 例受检者中病理证实前列腺结节性增生41例、前列腺炎24例、前列腺肉瘤3例、前列腺癌 154 例,其中低分化癌 74 例、中分化癌 58 例、高分化癌 22 例。术后血尿15例、发热6例,其中高热1例,经抗生素治疗后体温恢复正常、尿检阴性。结论　经直肠超声引导下前列腺穿刺活检无需麻醉,患者痛苦小、安全性高,是诊断前列腺癌的可靠方法。     

Clinical value of prostate specific antigen based parameters for the detection of prostate cancer on repeat biopsy: the usefulness of complexed prostate specific antigen adjusted for transition zone volume

PURPOSE: To our knowledge the indications for repeat prostate needle biopsy in men whose previous transrectal ultrasound guided biopsy results revealed no evidence of cancer have not yet been defined. We identified the most effective method for detecting prostate cancer on repeat biopsy. MATERIALS AND METHODS: One or more systematic repeat prostate biopsies were performed in 144 consecutive patients, including 86 with prostate specific antigen (PSA) levels between 4 and 10 ng./ml. at repeat biopsy. Men in whom cancer was detected on repeat biopsies were compared with their counterparts in terms of digital rectal examination findings, PSA based parameters and an atypical prostate on initial prostate biopsy. RESULTS: Prostate cancer was detected on repeat biopsy in 39 of the 144 patients and in 19 on subset analysis of 86. Serum PSA levels at repeat biopsy did not differ significantly in patients with and without prostate cancer. According to receiver operating characteristics analysis the alpha1-antichymotrypsin-PSA complex adjusted for transition zone volume had the greatest area under the curve values, that is 0.756 for all 144 patients and 0.768 for the subset analysis of 86. Multiple logistic regression analysis of the subset of 86 patients showed that alpha1-antichymotrypsin-PSA complex adjusted for transition zone volume was the only significant independent predictor of cancer. CONCLUSIONS: alpha1-Antichymotrypsin-PSA complex adjusted for transition zone volume was the most powerful predictor of cancer in men who had undergone previous negative prostate biopsies. This parameter may be used to avoid more unnecessary repeat biopsies with an acceptable decrease in sensitivity.     

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.     

前列腺癌体积的临床预测及其意义

目的　研究以术前前列腺活检资料来推断前列腺癌体积及病理的价值。方法　以 3 3例因前列腺癌而行根治术的患者作为研究对象 ,将术前PSA、PSAD及前列腺 8点活检的结果与前列腺癌体积及病理进行相关分析研究。结果　 (1)前列腺癌体积与术前PSA、PSAD及前列腺活检的结果呈显著正相关 ,而与年龄、术前前列腺体积以及摘除标本的体积无明显相关关系 ;(2 )前列腺活检中阳性点数联合PSA与前列腺癌体积的回归模型预测前列腺癌体积最好 ;(3 )前列腺活检中阳性点数≤ 3点组的癌体积及精囊浸润率低于阳性点数≥ 4点组 ,两者有显著性差异。结论　前列腺 8点活检中阳性点数是预测前列腺癌体积及病理的一个重要参考指标 ,尤其是联合检测PSA ,更增加其预测前列腺癌体积的准确性