Radical prostatectomy findings in patients predicted to have low-volume/low-grade prostate cancer diagnosed by extended-core biopsies: an analysis of volume and zonal distribution of tumour foci.

OBJECTIVE: To measure total tumour volume (TTV) and dominant TV (DTV) in radical prostatectomy (RP) specimens from patients predicted to have low-volume, low-grade (LV/LG) prostate cancer, as this entity can be predicted from biopsy findings and prostate-specific antigen (PSA) level, but tumour under-sampling remains a challenge in active surveillance programmes. PATIENTS AND METHODS: This was a retrospective study from an academic centre, of men with prostate cancer treated from 2000 to 2007, with a PSA level of <10 ng/mL and one core of cancer from an extended scheme showing either Gleason score (GS) 3 + 3 of <3.0 mm or 3 + 4 of <2.0 mm. All men had RP, and the TTV, DTV, tumour location, pathological GS and stage were measured. RESULTS: Of 3055 RPs, 66 (2.1%) met the inclusion criteria. The core with cancer was from a sextant and alternative site in 26 (39%) and 40 (61%) patients, respectively. A pathological GS 3 + 3 or 3 + 4 was assigned to 94%, while 6% were GS > or = 4 + 3; all 66 tumours were organ-confined. The median (range) TTV and DTV were 0.15 (0.0008-5.06) and 0.14 (0.0008-5.04) mL, respectively. The median number of tumour foci was 3 (1-7), being unifocal in 17/66 (26%) and multifocal in 49/66 (74%). The transition zone was involved in 29% of unifocal and 71% of multifocal tumours. Of all 66 patients, the TTV was <0.5 mL in 47 (71%), and of 59 patients with biopsy GS 3 + 3, 33 (56%) had a TTV of <0.5 mL and pathological GS 3 + 3. Of 19 patients with a TTV of > or =0.5 mL, the median TTV was 1.06 (0.51-5.05) mL, with tumour foci of transition zone origin in 16 (84%). The study was limited by its retrospective design and small sample size. CONCLUSIONS: Using conservative selection criteria for predicting LV/LG cancer, RP specimens showed organ-confined disease in all cases, upgrading to GS > or = 4 + 3 in 6%, and TTV <0.5 mL in 71% of cases. The transition zone is a common location of under-sampled disease.

Cancer ablation with regional templates applied to prostatectomy specimens from men who were eligible for focal therapy.

OBJECTIVE: To assess the totality of prostate cancer eradication in radical prostatectomy (RP) specimens from men with a unilaterally positive prostate biopsy, and who would currently qualify for subtotal prostate ablation with controlled thermal energy such as cryoablation or high-intensity focused ultrasound. MATERIALS AND METHODS: Therapies for prostate cancer hold the promise of individualized treatment that selectively ablates the tumour while minimizing treatment-associated morbidity, but as prostate cancer is multifocal there are concerns about untreated residual disease. RP specimens (180) from men with a unilaterally positive prostate biopsy were examined to characterize the location, volume and grade of each tumour focus. Two treatment templates (hemiprostate and 'hockey-stick') were applied to every prostate cross-section. The nature of the in-field and out-of-field tumours was assessed and described for each treatment template. RESULTS: A single focus of cancer was the only tumour in 31 (17%) of the patients (contralateral cancer was present in 149, 83%, of specimens despite a unilateral positive biopsy). Hemiprostate and hockey-stick treatment templates covered all tumour foci in 17% and 47% of men, respectively. Most out-of-field cancers were clinically insignificant tumours not identified by prostate biopsy (low-volume, 0.5 mL; and low grade, Gleason score < or =6). Regional ablation would have successfully treated all clinically significant prostate tumours in 64% and 81% of patients using the hemiprostate or hockey-stick template, respectively. The hockey-stick template encompassed all dominant tumours (largest volume). CONCLUSIONS: Regionally targeted prostate ablation is capable of eradicating all dominant tumours and the vast majority of clinically significant tumours in men with unilateral disease by biopsy. The study of focally ablative therapy should proceed under the auspices of an approved protocol.

Prediction of extraprostatic extension in men with biopsy Gleason score of 8 or greater.

PURPOSE: Recent data have shown that high grade prostate cancer is a potentially surgically curable disease in properly selected patients. We assessed the ability of preoperative variables to predict extraprostatic extension in men with biopsy Gleason score 8 or greater. MATERIALS AND METHODS: We identified 159 patients who underwent prostatectomy without neoadjuvant therapy for biopsy proven Gleason score 8 or greater T1c-T2N0M0 cancer between 1996 and 2006. Univariate and multivariate analyses were performed to predict extraprostatic extension using side specific data, including clinical features and biopsy findings. RESULTS: Organ confined cancer was pathologically confirmed in 84 of 159 patients (52.8%). Side specific analysis was practicable on 124 sides (124 men) and side specific extraprostatic extension was found on 48 of the 124 sides (38.7%). Gleason grade 5 element, maximum tumor length, percent of positive cores, positive basal cores and side specific palpable disease were significantly associated with side specific extraprostatic extension. On multivariate analysis maximum tumor length and a positive basal core were independent predictors of side specific extraprostatic extension (p <0.001 and 0.033, respectively). When maximum tumor length was less than 7 mm and the basal core was negative for cancer, the incidence of side specific extraprostatic extension was low (2 of 35 cases or 5.7%). In contrast, the risk of side specific extraprostatic extension was 56.8% (25 of 44 cases) when maximum tumor length was 7 mm or greater and the basal core was positive for cancer. CONCLUSIONS: Applying our criteria for prostatectomy could significantly decrease the risk of inadequate cancer control and increase the probability of maintaining potency in patients with prostate cancer with biopsy Gleason score 8 or greater.

PCA3 molecular urine assay correlates with prostate cancer tumor volume: implication in selecting candidates for active surveillance.

PURPOSE: Prostate cancer gene 3 (PCA3) has shown promise as a molecular marker in prostate cancer detection. We assessed the association of urinary PCA3 score with prostatectomy tumor volume and other clinical and pathological features. MATERIALS AND METHODS: Urine specimens were collected after digital rectal examination from 59 men scheduled for prostate biopsy and 83 men scheduled for radical prostatectomy. Prostatectomy findings were evaluable for 96 men. PCA3 and prostate specific antigen mRNAs were quantified with Gen-Probe DTS 400 System. The PCA3 score was defined as the ratio of PCA3 mRNA/prostate specific antigen mRNA x10(3). RESULTS: The PCA3 score in men with negative biopsies (30) and positive biopsies (29) were significantly different (median 21.1 and 31.0, respectively, p = 0.029). The PCA3 score was significantly correlated with total tumor volume in prostatectomy specimens (r = 0.269, p = 0.008), and was also associated with prostatectomy Gleason score (6 vs 7 or greater, p = 0.005) but not with other clinical and pathological features. The PCA3 score was significantly different when comparing low volume/low grade cancer (dominant tumor volume less than 0.5 cc, Gleason score 6) and significant cancer (p = 0.007). On multivariate analysis PCA3 was the best predictor of total tumor volume in prostatectomy (p = 0.001). Receiver operating characteristic curve analysis showed that the PCA3 score could discriminate low volume cancer (total tumor volume less than 0.5 cc) well with area under the curve of 0.757. CONCLUSIONS: The PCA3 score appears to stratify men based on prostatectomy tumor volume and Gleason score, and may have clinical applicability in selecting men who have low volume/low grade cancer.

Circulating tumor cells in peripheral blood samples from patients with increased serum prostate specific antigen: initial results in early prostate cancer.

PURPOSE: We evaluated the hypothesis that circulating tumor cells as determined using the CellSearch System would correlate with tumor volume, pathological stage and Gleason score in men with localized prostate cancer. MATERIALS AND METHODS: Samples of blood (30 ml) were drawn from 97 men with localized prostate cancer before radical prostatectomy, on postoperative days 2 to 3 and at 6 weeks. A control group consisted of 25 men with an increased prostate specific antigen and no tumor detected on extended prostate biopsy. Samples were analyzed for circulating tumor cells using the CellSearch System. RESULTS: Circulating tumor cells were detected in 21% of patients with cancer and 20% of controls (p = 0.946). At 6 weeks after prostatectomy circulating tumor cells were detected in 16% and 11% (p = 0.51) of the men positive and negative for circulating tumor cells at baseline, respectively. Of the 20 patients with cancer who had circulating tumor cells at baseline 18 showed no circulating tumor cells after surgery. Circulating tumor cell values did not correlate with tumor volume, pathological stage or Gleason score. Only 3.1% of the men with cancer and 8% of the control group had 3 or more circulating tumor cells per 22.5 ml blood at baseline. CONCLUSIONS: In metastatic breast, prostate and other cancers more than 5 circulating tumor cells are often detected using the CellSearch System, and may correlate with prognosis. However, in the setting of localized prostate cancer the number of detectable circulating tumor cells was low, with findings comparable to those in men who were biopsy negative for cancer. We found no correlation between the number of circulating tumor cells and known prognostic factors in this population.

A streamlined three-dimensional volume estimation method accurately classifies prostate tumors by volume.

Prostate tumor volume has been suggested to be an important pathologic variable that predicts for clinical significance and outcome. However, the determination of tumor volume using standard methods such as computerized planimetry or image analysis is labor intensive. We studied whether length (L), width (W), and height (number of cross sections x sectional thickness, CST) of a tumor focus could be used to estimate prostate tumor volume. We studied 1091 tumor foci from 365 selected serially sectioned radical prostatectomy specimens. We randomly divided the specimens into evaluation (182 specimens) and validation (183 specimens) groups. After analyzing the evaluation group, we derived the formula 0.4 (slope of the regression line) x L x W x CST to estimate volume. We then tested whether our three-dimensional volume estimation formula could accurately classify tumor volume for specimens in the validation set as insignificant (0.5 cm3), and also into a five-category tumor volume scheme. Our three-dimensional estimate accurately classified tumors into insignificant and significant total volume categories in 94.0% of cases and into the five-category scheme in 85.8% cases. These accuracy rates were significantly better than rates for other methods. The three-dimensional estimate is an accurate and straightforward method for assessing prostate tumor volume.

Randomized phase II trial evaluation of erectile function after attempted unilateral cavernous nerve-sparing retropubic radical prostatectomy with versus without unilateral sural nerve grafting for clinically localized prostate cancer.

BACKGROUND: Nonrandomized studies of unilateral nerve-sparing (UNS) radical prostatectomy (RP) have reported improved recovery of erectile function if the sacrificed cavernous nerve is reconstructed with a sural nerve graft (SNG). OBJECTIVE: To determine whether UNS RP plus SNG results in a 50% relative increase in potency at 2 yr compared to UNS RP alone. DESIGN, SETTING, AND PARTICIPANTS: The study enrolled patients from October 2001-May 2006 from a single academic center and was randomized, open label. Participants were men with localized prostate cancer recommended for UNS RP, less than 66 yr old, normal baseline erectile function, and willing to participate in early erectile dysfunction (ED) therapy. Patients were followed up to 2 yr. INTERVENTION: Patients underwent UNS RP and ED therapy starting at 6 wk: oral prostaglandin type-5 (PDE5) inhibitor, vacuum erection device (VED), and intracavernosal injection therapy. In the SNG group, a plastic surgeon performed the procedure at the time of RP. MEASUREMENTS: The ability to have an erection suitable for intercourse with or without a PDE5 inhibitor at 2 yr. The hypothesis was that SNG would result in a 60% potency rate compared to 40% for controls (80% power, 5% two-way significance). RESULTS AND LIMITATIONS: The trial planned to enroll 200 patients, but an interim analysis at 107 patients met criteria for futility and the trial was closed. For patients completing the protocol to 2 yr, potency was recovered in 32 of 45 (71%) of SNG and 14 of 21 (67%) of controls (p=0.777). By intent-to-treat analysis, potency recovered in 32 of 66 (48.5%) of SNG and 14 of 41 (34%) of controls (p=0.271). No differences were seen in time to potency or quality of life scores for ED and urinary function. Limitations included slower-than-expected accrual and poor compliance with ED therapy: <65% for VED and <40% for injections. CONCLUSIONS: The addition of SNG to a UNS RP did not improve potency at 2 yr following surgery. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT00080808, http://www.clinicaltrials.gov/ct2/show/NCT00080808?term=NCT00080808&rank=1.

Natural history of biochemical progression after radical prostatectomy based on length of a positive margin.

OBJECTIVES: To assess the effect of length of positive margin on prognosis in men after radical prostatectomy. METHODS: The positive surgical margin without either seminal vesicle invasion or lymph node metastases was identified in 117 men undergoing prostatectomy between 1991 and 1999. The length of positive margin was obtained by adding together the lengths of all areas of the tumor in contact with the inked surface. Biochemical failure was defined as a serum prostate specific antigen level 0.1 ng/mL or greater. Statistical analyses were performed to compare times with progression and to determine factors for progression. RESULTS: The median follow-up duration was 43 months, and the overall 5-year progression-free survival (PFS) rate was 74.6%. The differences in prognoses between men with a positive margin 1 mm or less and those with a margin 1.1 to 3 mm was not significant; however, there was a significant difference in prognosis between men with a margin 3 or less and those with a margin greater than 3 mm (P <0.01). Multivariate analyses revealed that both Gleason score 8 or greater and a margin 3 mm or greater were independent predictors. The prognoses in men with neither of these risk factors was statistically better than that of men with either or both of these risk factors (5-year PFS rates 93% versus 57%, respectively; P <0.0001). CONCLUSIONS: The length of positive margin is significantly associated with disease progression. The Gleason score and the extent of positive margin can be used to stratify the risk for recurrence in patients with positive margin.

The relationship between serum prostate specific antigen level and tumor volume persists in the current era.

PURPOSE: We compared the relationships of serum prostate specific antigen to tumor volume and to noncancerous prostate tissue volume using multivariate analysis in men undergoing prostatectomy during 2 periods. MATERIALS AND METHODS: From our prostatectomy database we randomly selected 200 men from 1991 to 1994 (early group) and 200 from 2000 to 2003 (recent group) who underwent radical prostatectomy without neoadjuvant therapy. The variables analyzed were patient age, log prostate specific antigen, pathological stage, Gleason score, log total tumor volume and log noncancerous prostate tissue volume. Univariate correlation and multiple regression analyses were performed to assess the linearity of the relationships among the variables. RESULTS: There was a significant difference between the early and recent groups in age (median 64 years, IQR 58-67 vs 59, IQR 53-65; p<0.001), prostate specific antigen (8.3 ng/ml, IQR 5.7-12.5 vs 5.8, IQR 4.4-7.8; p<0.001), total tumor volume (2.0 cc, IQR 1.0-3.6 vs 1.4, IQR 0.6-2.9; p<0.001), Gleason score (7, IQR 7-8 vs 7, IQR 7-7; p<0.001) and the incidence of extraprostatic disease (39% vs 18.5%, p<0.001) but not in noncancerous prostate tissue volume (35.7 cc, IQR 28.6-46.5 vs 37.1, IQR 28.9-50.1). There was a relationship between log prostate specific antigen and log total tumor volume (r=0.486, p<0.001 and r=0.237, p<0.01), and between log prostate specific antigen and log noncancerous prostate tissue volume (r=0.179, p<0.05 and r=0.138, p=0.051) in the early and the recent groups, respectively. Multiple regression analyses revealed that log total tumor volume, log noncancerous prostate tissue volume and Gleason score were significant independent variables for predicting log prostate specific antigen in the 2 groups. In the recent group log noncancerous prostate tissue volume had the most significant association with log prostate specific antigen (p<0.001), whereas in the early group log total tumor volume had the most significant association (p<0.001). CONCLUSIONS: Although the relationship between serum prostate specific antigen and tumor volume decreased from early treatment years to recent years, the association remained at a significant level. In recent years noncancerous prostate tissue volume had the most significant association with prostate specific antigen.

Is there a role for serum human tissue kallikrein in detection of prostate cancer?

OBJECTIVES: To retrospectively evaluate the diagnostic performance of a serum human tissue kallikrein 11 (hK11) assay to predict the presence of prostate cancer in a screened population of men with a total prostate-specific antigen (PSA) level between 2.5 and 10.0 ng/mL. METHODS: Frozen serum samples from 114 men with a total PSA level between 2.5 and 10.0 ng/mL who had undergone transrectal prostate ultrasound-guided biopsy with at least 10 cores were retrospectively analyzed for hK11. The performance characteristics of hK11, PSA, hK11/PSA ratio, and hK11 density (hk11/prostate volume) were analyzed for their ability to differentiate cancer from noncancer. The results obtained were analyzed using the Mann-Whitney U test, chi-square test, and receiver operating characteristic curves. RESULTS: Prostate cancer was diagnosed in 36 (32%) of the 114 men whose serum samples were analyzed. No significant differences were found in hK11 (median 0.71 ng/mL versus 0.69 ng/mL), PSA level (median 3.9 ng/mL versus 4.1 ng/mL), hK11/PSA ratio (median 0.15 versus 0.17), or hK11 density (median 0.015 versus 0.016) between men with and without prostate cancer. A comparison of the areas under the curve for hK11 (0.491), PSA (0.540), hK11/PSA ratio (0.505), and hK11 density (0.589) showed no significant differences. CONCLUSIONS: In this retrospective study, hK11, hK11/PSA ratio, and hK11 density showed no diagnostic advantage compared with PSA in differentiating cancer from noncancer in men whose total PSA level was in the range of 2.5 to 10.0 ng/mL.

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

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

A nomogram for predicting low-volume/low-grade prostate cancer: a tool in selecting patients for active surveillance.

BACKGROUND: The authors reported previously that assessment of the number of positive biopsy cores, maximum tumor length in a core, Gleason score, and prostate volume in an extended biopsy enhanced the accuracy of predicting low-volume/low-grade prostate cancer. On the basis of those findings, they developed a nomogram to predict the probability of low-volume/low-grade prostate cancer specifically for men with a single positive biopsy core. METHODS: The study cohort comprised 258 men who underwent radical prostatectomy without neoadjuvant therapy. Prostate cancer was diagnosed in only 1 core of an extended biopsy scheme. Low-volume/low-grade cancer was defined as pathologic organ-confined disease and a tumor volume<0.5 cc with no Gleason grade 4 or 5 cancer. Patient age, prostate-specific antigen (PSA) level, prostate volume, PSA density (PSAD), and tumor length in a biopsy core were examined as variables. A fitted multiple logistic regression model was used to establish the nomogram. RESULTS: One hundred thirty-three patients (51.6%) had low-volume/low-grade cancer. To establish the nomogram, age, PSAD, and tumor length were adopted as variables. The fitted model suggested that older age, higher PSAD values, and greater tumor length would reduce the probability of low-volume/low-grade cancer. The nomogram predicted low-volume/low-grade cancer with good discrimination (an area under the receiver operating characteristic curve of 0.727). Calibration of this nomogram showed good predicted probability. CONCLUSIONS: The authors established a nomogram with which to predict low-volume/low-grade cancer in men with 1 positive biopsy core in an extended biopsy scheme, and they recommend this nomogram for use in selecting men for active surveillance.

The detection and potential economic value of complexed prostate specific antigen as a first line test.

PURPOSE: Prostate cancer detection is subject to a number of variables that can lead to unnecessary biopsies and associated costs. Measuring cPSA has been proposed as an alternative to tPSA for the early detection of prostate cancer. MATERIALS AND METHODS: Between November 1998 and April 2000, 1,362 men underwent transrectal ultrasound guided biopsies at 7 institutions. Of 1,243 evaluable men 467 with tPSA between 2.5 and 6.0 ng/ml, and normal digital rectal examination were analyzed. Statistical analysis used to compare cancer detection rates between PSA assays was performed using the Mann-Whitney U test. A separate group of 2,807 men who participated in a free cancer detection program was used to determine the current tPSA distribution and assess the economic impact of cPSA. RESULTS: Cancer was detected in 31.5% of the men (147 of 467) with tPSA between 2.5 and 6.0 ng/ml. Using a 2.2 ng/ml cPSA cutoff point detected 93.9% of cancers and would have avoided 20.3% of unnecessary biopsies in men with tPSA between 2.5 and 4.0 ng/ml. A 2.2 ng/ml cPSA cutoff point achieved an 11.9% overall decrease in the number of unnecessary biopsies in the tPSA range of 2.5 to 6.0 ng/ml with accompanying 98% sensitivity. The decrease in unnecessary biopsies is potentially associated with substantial health care cost savings. CONCLUSIONS: In the clinically relevant sensitivity ranges a 2.2 ng/ml cPSA cutoff point decreases the number of unnecessary biopsies and maintains higher specificity than a tPSA threshold of 2.5 ng/ml, illustrating the potential value of cPSA as a first line diagnostic test.

Influence of anthropometric measurements, age, and prostate volume on prostate-specific antigen levels in men with a low risk of prostate cancer.

OBJECTIVES: To assess the correlation between age, height, body weight, body mass index, body surface area (BSA), prostate volume, and prostate-specific antigen (PSA) level, and to determine the significant factors for predicting the PSA level in men with a low risk of having prostate cancer. METHODS: Men who had undergone at least one ultrasound-guided extended prostate biopsy at the M.D. Anderson Cancer Center from 1998 to 2003 and were proven, on pathologic examination, to be without cancer were included in this study. All patients underwent clinical evaluations, including digital rectal examination, serum PSA determination, transrectal ultrasound examination, and anthropometric measurements. The relationship between the clinical parameters and PSA level was examined by the Mann-Whitney U test and determination of the Pearson correlation coefficient. RESULTS: A total of 653 men were eligible for analysis in our study. The median age was 62.0 years; the median prostate volume was 48.3 cm3; and the median PSA level was 5.5 ng/mL. The PSA level correlated with age (P < 0.001) and prostate volume (P < 0.001), but not with height, body weight, body mass index, or BSA. The prostate volume correlated with age (P < 0.001), body weight (P < 0.001), body mass index (P < 0.01), and BSA (P < 0.01), but not with height. Multivariate analysis revealed that prostate volume and BSA were significant factors for predicting the PSA level. CONCLUSIONS: Of the variables tested, prostate volume was most significantly related to the PSA level. The anthropometric parameters were not directly associated with the PSA level, but were associated with the prostate volume. Our findings suggest that differences in the PSA level may be influenced by body size, if the prostate volume is held constant in men with a low risk of having prostate cancer.

The relationship between tumor volume and the number of positive cores in men undergoing multisite extended biopsy: implication for expectant management.

PURPOSE: We assessed the relationship between the number of positive cores obtained at extended biopsy and tumor volume in radical prostatectomy specimens as a tool for predicting the biological significance of prostate cancer from biopsy data. MATERIALS AND METHODS: The study group included 207 men who were treated with radical prostatectomy without neoadjuvant therapy at our cancer center. All patients were diagnosed by systematic extended biopsy (10 or 11 cores) performed between 1997 and 2003. The variables analyzed were patient age, prostate specific antigen, clinical stage, biopsy Gleason score, maximum tumor length in a core, greatest percent of tumor in a core, total tumor length, total percent of tumor in all cores, positive core location, initial or repeat biopsy and prostate volume in subgroups based on the number of positive cores, that is group 1-1, group 2-2 and group 3-3 or more cores. Bivariate correlation analysis and multiple logistic regression analysis were used to determine the predictors of insignificant cancer. RESULTS: The number of positive cores was significantly related to total tumor volume (r = 0.433, p <0.001). Insignificant prostate cancer (volume less than 0.5 cc and Gleason score 6 or less) was found in 21.7% of patients (45 of 207). The incidence of insignificant cancer was 42.5% (31 of 73 patients) in group 1, 16.4% (10 of 61) in group 2 and 5.5% (4 of 73) in group 3. There was a significant difference in the incidence of insignificant cancer among the subgroups (group 1 vs 2 p <0.001, group 1 vs 3 p <0.0001 and group 2 vs 3 p <0.05). The best model for predicting insignificant cancer in group 1 was the combination of tumor length less than 2 mm, Gleason score 3 + 4 or less and prostate volume greater than 50 cc with 83.9% sensitivity (26 of 31 patients) and 61.9% specificity (26 of 42). CONCLUSIONS: The probability of insignificant cancer was directly related to the number of positive cores. Tumor length in a core, Gleason score and prostate volume significantly enhanced the prediction model for insignificant cancer in men with 1 positive core who underwent extended biopsy.

Validation of criteria used to predict extraprostatic cancer extension: a tool for use in selecting patients for nerve sparing radical prostatectomy.

PURPOSE: We have previously reported that a prostate biopsy core specimen with a tumor length of at least 7 mm plus any positive basal biopsy core is the best predictor of extraprostatic extension (EPE) in radical prostatectomy (RP) specimens. We present prospectively collected data to validate our results. MATERIALS AND METHODS: The study included 270 patients who underwent RP for localized prostate cancer between January 2002 and December 2003 by a single surgeon. We correlated side specific biopsy data, pretreatment prostate specific antigen, clinical stage and RP type using pathological specimen data. RESULTS: Mean patient age was 59.6 years and median prostate specific antigen was 8.24 ng/ml. Of the patients 94 (35%) underwent unilateral and 114 (42%) underwent bilateral nerve sparing RP. The overall incidence of EPE was 16%. The incidence of EPE was 33% in patients who met our criteria vs 4.6% in those who did not. Of 538 evaluable sides 7.2% were positive at the surgical margin. The incidence of ipsilateral positive margins was 2.5% when the neurovascular bundle was spared according to our criteria vs 11.8% when the bundle was resected according to criteria. CONCLUSIONS: This series validates our finding that a prostate biopsy core with a tumor length of at least 7 mm plus a positive basal biopsy core of any length and tumor grade is predictive of ipsilateral EPE. In the absence of these criteria the incidence of ipsilateral positive margins is low. Thus, these criteria are valuable for predicting EPE and selecting patients for nerve sparing RP.

The predictors of pelvic lymph node metastasis at radical retropubic prostatectomy.

PURPOSE: We studied preoperative variables in a contemporary series of patients who underwent radical retropubic prostatectomy (RRP) to determine which variables were associated with lymph node metastasis. MATERIALS AND METHODS: Between January 1995 and November 1999, 1,091 men underwent RRP, 695 of whom underwent bilateral pelvic lymph node dissection without any prior therapy. We evaluated biopsy Gleason score, maximum tumor length and maximum percentage of tumor in the positive core(s), location and number of positive cores, and total prostate specific antigen before surgery in 295 of these patients. We also developed a classification and regression tree analysis algorithm to segregate the risk of positive lymph node metastasis. Stepwise logistic regression analyses were used to determine independent predictors of lymph node metastasis. RESULTS: Of the 695 patients 19 (2.7%) had lymph node metastasis. Clinical stage, Gleason score, positive basal core, greatest percentage of tumor on positive cores and maximum tumor length in positive core were significant predictors of lymph node metastasis in the Mann-Whitney U test and chi-square test. Classification and regression trees analysis revealed that 4 or more positive cores with any Gleason grade 4 or 5, serum prostate specific antigen 15.0 ng/ml or greater, or the presence of dominant Gleason 4 or 5 were independent predictors of lymph node metastasis. Our algorithm had a significantly higher diagnostic performance than the Hamburg algorithm (p = 0.002). CONCLUSIONS: Our algorithm may be a valid tool for the prediction of lymph node metastasis and may help to select men who do not need to undergo bilateral pelvic lymph node dissection with RRP.

Update on prostate biopsy technique.

PURPOSE OF REVIEW: Over the past decade, a considerable number of modifications have been made to the techniques for prostate cancer biopsy. In this review, we discuss the developments reported in the literature since January 2003. RECENT FINDINGS: The addition of laterally directed biopsies has enhanced the diagnostic performance of the conventional sextant biopsy approach. Several models of the extended biopsy technique have been introduced that increase the number of cores by combining sextant and lateral biopsies to enhance the cancer detection rate. Several reports have shown that the cancer detection rate decreases as prostate volume increases, compared with an increasing cancer detection rate on repeat biopsy in men with large prostate gland volumes. Other studies have shown that the percentage of positive cores and the total percentage of tumor found at biopsy are significant independent predictors of pathological outcome on multivariate analysis. In randomized, double-blind studies, infiltration of the neurovascular bundles with lidocaine significantly reduces pain associated with extended biopsies. SUMMARY: Current reports have suggested that: (1) extended biopsy schemes decrease the false-negative rate compared with conventional sextant biopsy; (2) laterally directed biopsies from the anterior horn should be included in extended biopsy protocols; and (3) local anesthesia reduces pain associated with extended biopsy.

A comparison of extended biopsy and sextant biopsy schemes for predicting the pathological stage of prostate cancer.

PURPOSE: We compared the performance of the extended multisite directed biopsy strategy to the sextant component of this strategy for predicting the pathological stage and Gleason score of the radical prostatectomy specimen. MATERIALS AND METHODS: We studied 157 men in whom prostate cancer was diagnosed by extended multisite directed biopsy and who underwent radical retropubic prostatectomy. The pretreatment variables of serum prostate specific antigen, prostate specific antigen density, biopsy specimen Gleason score, the location, number and percent of cancer containing cores, greatest tumor length in a single core and greatest percent of tumor in a single core were determined and compared with the pathological features of prostate cancer in the radical prostatectomy specimens. A comparison of the information obtained from sextant component cores of the extended biopsy strategy with that from all cores of the extended biopsy strategy was performed using chi-square statistics and ROC curve analysis. RESULTS: When comparing the areas under the ROC curves, the extended multisite directed biopsy strategy was found to have greater predictive power for extraprostatic extension than the sextant core component of this biopsy scheme, although the difference was not significantly different. The sextant component was equivalent to the extended biopsy strategy for predicting the prostatectomy specimen Gleason score. CONCLUSIONS: The extended biopsy strategy has better performance in the upper sensitivity ranges compared to the sextant technique for predicting extraprostatic extension.