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Purpose: An increase in the pretreatment neutrophil-to-lymphocyte ratio is associated with poor prognosis for various cancers, including renal cell carcinoma. However, the clinical implication of a posttreatment change in the neutrophil-to-lymphocyte ratio in patients with cancer remains unclear., Materials and Methods: We reviewed the records of 250 patients with nonmetastatic clear cell renal cell carcinoma and analyzed associations among clinicopathological variables, the preoperative and postoperative neutrophil-to-lymphocyte ratio, and recurrence-free survival., Results: The 10-year recurrence-free survival rate for patients with a preoperative neutrophil-to-lymphocyte ratio of 2.7 or greater was significantly lower than that for those with a ratio of less than 2.7 (64.4% vs 83.7%, p = 0.0004). When combined with the postoperative ratio, patients with a preoperative ratio of 2.7 or greater could be further divided into 2 groups with a significantly different prognosis. The 10-year recurrence-free survival rate for patients with a preoperative neutrophil-to-lymphocyte ratio of 2.7 or greater and postoperative ratio of less than 2.7 was significantly lower than that for those with a preoperative and postoperative ratio of 2.7 or greater (52.0% vs 83.5%, p = 0.0487). The latter was similar to the 83.7% for patients with a preoperative ratio of less than 2.7. In patients with recurrence the ratio at recurrence was significantly increased compared with the postoperative ratio (mean ± SD 2.82 ± 1.63 vs 2.00 ± 0.90, p = 0.0090). Multivariate analysis showed that tumor size, pathological tumor stage and the neutrophil-to-lymphocyte ratio change (a combination of the preoperative and postoperative ratios) were independent predictors of recurrence. Using these 3 significant variables patients were stratified into low, intermediate and high risk groups, among which the recurrence-free survival rate significantly differed., Conclusions: The posttreatment neutrophil-to-lymphocyte ratio change was a significant prognostic factor for recurrence as well as tumor size and pathological tumor stage in patients with clear cell renal cell carcinoma., (Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: From the perspective of oncological and functional outcomes partial nephrectomy is considered standard surgery for small renal tumors 4 cm or less. However, radical nephrectomy is commonly done for small tumors. It is important to predict postoperative renal function in patients to choose the most optimal surgical procedure., Materials and Methods: We retrospectively reviewed the records of 271 patients treated with radical nephrectomy for renal cell carcinoma. Associations of tumor size and clinical variables with renal function were analyzed., Results: Preoperatively the mean ± SD glomerular filtration rate was 74.38 ± 17.70 ml per minute/1.73 m(2) and 56 patients (20%) had renal insufficiency (glomerular filtration rate less than 60 ml per minute/1.73 m(2)). The mean decrease in the glomerular filtration rate after radical nephrectomy was 24.2 ± 12.40 ml per minute/1.73 m(2) (31.5% ± 15%). Of 215 patients with a preoperative glomerular filtration rate of 60 ml per minute/1.73 m(2) or greater 165 (77%) had new onset renal insufficiency. Age, tumor size, preoperative glomerular filtration rate and hypertension were significantly associated with new onset renal insufficiency. Multivariate analysis revealed that age 60 years or greater, tumor size 7 cm or less and the preoperative glomerular filtration rate were independent risk factors for new onset renal insufficiency (p <0.05). Finally, we developed a predictive model for new onset renal insufficiency after radical nephrectomy., Conclusions: Tumor size 7 cm or less, age 60 years or greater and a decreased preoperative glomerular filtration rate were significant risk factors for new onset renal insufficiency in patients treated with radical nephrectomy. Partial nephrectomy might be considered an option according to the risk of postoperative renal insufficiency, especially in elderly patients with a tumor of 7 cm or less., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We investigated the prognostic significance of the neutrophil-to-lymphocyte ratio to predict recurrence in patients with nonmetastatic renal cell carcinoma., Materials and Methods: We retrospectively reviewed the records of 192 patients with nonmetastatic renal cell carcinoma (T1-4N0M0) who underwent nephrectomy between 1986 and 2000. Mean followup was 93 months (range 6 to 232) months. We assessed the prognostic value of the pretreatment neutrophil-to-lymphocyte ratio, and other clinical and laboratory parameters on univariate and multivariate analysis., Results: Presentation mode, tumor stage, C-reactive protein, lymphocyte count and the neutrophil-to-lymphocyte ratio significantly correlated with recurrence-free survival on univariate analysis. The recurrence-free survival rate in patients with a neutrophil-to-lymphocyte ratio of less than 2.7 was 93.7% at 5 years and 79.8% at 10 years, significantly higher than the 77.9% and 58.4%, respectively, in patients with a ratio of 2.7 or greater (p = 0.0205). Multivariate analysis revealed that T stage and the neutrophil-to-lymphocyte ratio were independent predictors of recurrence. The 10-year survival rate in patients at low risk (T2 or less and neutrophil-to-lymphocyte ratio less than 2.7), intermediate risk (T2 or less and ratio 2.7 or greater, or T3 or greater and ratio less than 2.7) and high risk (T3 or greater and ratio 2.7 or greater) was 82.0%, 63.6% and 33.0%, respectively, which were significantly different., Conclusions: An increased pretreatment neutrophil-to-lymphocyte ratio is an independent predictor of recurrence. The combination of T stage and the neutrophil-to-lymphocyte ratio can be used to stratify recurrence risk in patients with nonmetastatic renal cell carcinoma., (2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The prognostic significance of positive surgical margins (PSM) in radical prostatectomy (RP) specimens remains unclear. While most studies have concluded that a PSM is an independent adverse prognostic factor, others report that surgical margin status has no effect on prognosis. One reason for these discordant conclusions is the variable number of patients with a PSM who receive adjuvant therapy and the differing statistical methods used to account for the effects of the time course of adjuvant treatment on recurrence. We evaluated the prognostic significance of PSMs using multiple methods of analysis accounting for patients who received adjuvant therapy., Materials and Methods: We analyzed 1,389 consecutive patients with clinical stage T1-3 prostate cancer treated with RP by 2 surgeons from 1983 to 2000. Of 179 patients with a PSM, 37 received adjuvant therapy (AT), 29 radiation therapy and 8 received hormonal therapy. Because the method used to account for men receiving AT can affect the outcome of the analysis, data were analyzed by the Cox proportional hazards technique accounting for patients receiving AT using 5 methods: 1) exclusion, 2) inclusion (AT ignored), 3) censoring at time of AT, 4) failing at time of AT and 5) considering AT as a time dependent covariate., Results: Overall 179 patients (12.9%) had a PSM, including 6.8% of 847 patients with pT2 and 23% of 522 patients with pT3 disease. A PSM was a significant predictor of cancer recurrence when analyzed using methods 1, 3, 4 and 5 (p=0.005, p=0.014, p=0.0005, p=0.002, respectively). However, it was not a predictor of recurrence using method 2 in which AT was ignored (p=0.283). Using method 5 multivariate analysis demonstrated that a PSM (p=0.002) was an independent predictor of 10-year progression-free probability (PFP) along with Gleason score (p=0.0005), extracapsular extension (p=0.0005), seminal vesicle invasion (p <0.0005), positive lymph nodes (p <0.0005) and preoperative serum prostate specific antigen (p <0.0001). Using method 5 the 10-year PFP was 58% +/- 12% and 81% +/- 3% for patients with and without a PSM, respectively (p <0.00005). The relative risk of recurrence in men with a PSM using method 5 was 1.52 (95% confidence interval 1.06-2.16)., Conclusions: We confirm that a PSM has a significant adverse impact on PFP after RP in multivariate analysis using multiple statistical methods to account for patients who received AT. While prostate cancer screening strategies have resulted in a majority of men having organ confined disease at RP, surgeons should continue to strive to reduce the rate of positive surgical margins to improve cancer control outcomes.

Purpose: We investigated whether repeat prostate biopsies are associated with more favorable prognoses, less extensive disease or higher rates of IC in patients who are ultimately diagnosed with prostate cancer and treated with RRP., Materials and Methods: We examined standard clinical and pathological data on 1,357 patients treated with RRP from 1983 to 2001. In addition, we noted the rate of IC in a subgroup of 847 patients in whom tumor volume was measured., Results: Cancer was found in 1,042 patients (77%) at the first biopsy, in 227 (17%) at the second biopsy, in 59 (4%) at the third biopsy and in 29 (2%) at the fourth or later biopsy. Patients with 2 or greater biopsies had a higher rate of clinical T1c stage cancer and larger prostates than patients with only 1 biopsy (each p < 0.0001). After RRP patients with 1 biopsy had a lower rate of organ confined tumors (61% vs 75%, p < 0.0001), and a higher rate of extracapsular extension, seminal vesicle invasion, lymph node metastases and Gleason sum 7 or greater than other patients. IC was found in 10% of patients with 1 biopsy and 18% of those with 2 or greater biopsies (p = 0.018). Despite these more favorable pathological outcomes there was no difference in biochemical recurrence rate., Conclusions: Although we found that a greater number of biopsies was related to a better pathological outcome after RRP, the number of biopsies did not predict disease recurrence. The increasing number of biopsies currently being performed, especially in patients with larger prostates, likely results in higher rates of IC.

Purpose: The prognostic significance of positive surgical margins (PSM) in radical prostatectomy (RP) specimens remains unclear. While most studies have concluded that a PSM is an independent adverse prognostic factor, others report that surgical margin status has no effect on prognosis. One reason for these discordant conclusions is the variable number of patients with a PSM who receive adjuvant therapy and the differing statistical methods used to account for the effects of the time course of adjuvant treatment on recurrence. We evaluated the prognostic significance of PSMs using multiple methods of analysis accounting for patients who received adjuvant therapy., Materials and Methods: We analyzed 1,389 consecutive patients with clinical stage T1-3 prostate cancer treated with RP by 2 surgeons from 1983 to 2000. Of 179 patients with a PSM, 37 received adjuvant therapy (AT), 29 radiation therapy and 8 received hormonal therapy. Because the method used to account for men receiving AT can affect the outcome of the analysis, data were analyzed by the Cox proportional hazards technique accounting for patients receiving AT using 5 methods: 1) exclusion, 2) inclusion (AT ignored), 3) censoring at time of AT, 4) failing at time of AT and 5) considering AT as a time dependent covariate., Results: Overall 179 patients (12.9%) had a PSM, including 6.8% of 847 patients with pT2 and 23% of 522 patients with pT3 disease. A PSM was a significant predictor of cancer recurrence when analyzed using methods 1, 3, 4 and 5 (p=0.005, p=0.014, p=0.0005, p=0.002, respectively). However, it was not a predictor of recurrence using method 2 in which AT was ignored (p=0.283). Using method 5 multivariate analysis demonstrated that a PSM (p=0.002) was an independent predictor of 10-year progression-free probability (PFP) along with Gleason score (p=0.0005), extracapsular extension (p=0.0005), seminal vesicle invasion (p <0.0005), positive lymph nodes (p <0.0005) and preoperative serum prostate specific antigen (p <0.0001). Using method 5 the 10-year PFP was 58% +/- 12% and 81% +/- 3% for patients with and without a PSM, respectively (p <0.00005). The relative risk of recurrence in men with a PSM using method 5 was 1.52 (95% confidence interval 1.06-2.16)., Conclusions: We confirm that a PSM has a significant adverse impact on PFP after RP in multivariate analysis using multiple statistical methods to account for patients who received AT. While prostate cancer screening strategies have resulted in a majority of men having organ confined disease at RP, surgeons should continue to strive to reduce the rate of positive surgical margins to improve cancer control outcomes.

Purpose: There continues to be debate regarding the prognostic significance of tumor volume (TV) in radical prostatectomy (RP) specimens. We assessed the prognostic significance of TV in a large series of patients followed for a long time to discover whether the effect of TV has changed with earlier detection of smaller tumors., Materials and Methods: TV was measured planimetrically in 1,302 consecutive RP specimens with clinical stage T1-3 prostate cancer from 1983 to 2000. We correlated TV with standard clinical and pathological features, and determined the prostate specific antigen nonprogression rate. Median followup was 46 months (range 1 to 202)., Results: TV was weakly associated with other clinical and pathological features. Median TV decreased significantly over time (2.16 cm3 before 1995 vs 1.25 cm3 after 1995, p <0.001) and this decrease was also found within each clinical stage. In univariate analysis TV correlated strongly with the probability of progression. However, in multivariate analysis TV was not a significant independent predictor of prognosis, either in the whole cohort of patients or in those with peripheral zone cancer only. Even in univariate analysis TV had no effect on prognosis for patients in whom cancer was either confined to the prostate or was Gleason score 2 through 6., Conclusions: TV provides no independent prognostic information when considered in multivariate analysis with Gleason score and pathological stage. Measurement of TV before treatment is less likely to characterize prostate cancer accurately than assessment of tumor grade and extent. There seems to be little reason to measure TV routinely in RP specimens.

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.

Purpose: We examined whether the year in which radical prostatectomy (RP) was performed is a predictor of treatment outcome after controlling for standard prognostic factors., Materials and Methods: We examined the association between RP year and outcome in 6,556 patients from 7 centers using preoperative and pathological features. Patients underwent surgery between 1985 and 2000. The variables analyzed were RP year, clinical stage, pretreatment prostate specific antigen, biopsy Gleason sum, RP Gleason sum, margin status, level of extracapsular extension, seminal vesicle status, lymph node status, neoadjuvant hormones and adjuvant therapy. Median followup was 23 months (maximum 166). Separate Cox multivariate regression analyses were performed to analyze preoperative and postoperative factors., Results: RP year was a predictor of outcome on preoperative analysis (p = 0.006) but not on postoperative analysis (p = 0.130). Patient outcome steadily improved with surgery through the mid 1990s and then it appeared to level off., Conclusions: When controlling for preoperative features, the year in which RP was performed is a predictor of outcome on multivariate analysis. This effect could not be explained by stage migration.

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.

Purpose: Men diagnosed with clinically localized prostate cancer have a number of treatment options available, including watchful waiting, radical prostatectomy and radiation therapy. With the widespread use of serum prostate specific antigen (PSA) testing, prostate cancers are being diagnosed earlier in their natural history, with many tumors being small and of little health risk to the patient, at least in the short term. To better counsel men diagnosed with prostate cancer, we developed a statistical model that accurately predicts the presence of small moderately differentiated, confined cancer based on clinical variables (serum PSA, clinical stage, prostate biopsy Gleason grade and ultrasound volume) and variables derived from the analysis of systematic biopsies., Materials and Methods: The analysis included 409 patients diagnosed by systematic needle biopsy with clinical stages T1c or T2a N0 or NX and M0 or MX prostate cancer who were treated solely with radical prostatectomy at 1 of 2 institutions. Additional biopsy features included number and percentage of biopsy cores involved with cancer and high grade cancer, in addition to total length of biopsy cores involved. Indolent cancer was defined as pathologically organ confined cancer 0.5 cc or less in volume and without poorly differentiated elements. Logistic regression was used to construct several prediction models and the resulting nomograms., Results: Overall 80 (20%) of the patients had indolent cancer. The nomogram predicted the presence of an indolent cancer with discrimination (area under the receiver operating characteristics curves) for various models ranging from 0.64 to 0.79. Calibration of the models appeared good., Conclusions: Nomograms incorporating pretreatment variables (clinical stage, Gleason grade, PSA and the amount of cancer in a systematic biopsy specimen) can predict the probability that a man with prostate cancer has an indolent tumor. These nomograms have good discriminatory ability and calibration, and may benefit the patient and clinician when the various treatment options for prostate cancer are being considered.

Purpose: Although prostate cancer is found in about 30% of patients at the initial biopsy session, there is a need to identify those with a negative result but who are at high risk. Although individual risk factors have been found to be associated with cancer, patient counseling requires the integration of multiple risk factors to obtain a prediction for the individual., Materials and Methods: We studied 343 patients with at least 1 initial negative biopsy who were tested from August 1999 to September 2001. At each biopsy session we recorded patient age, family history of prostate cancer, serum prostate specific antigen (PSA), PSA slope, digital rectal examination findings, months from the initial biopsy session, cumulative number of negative cores previously obtained, and history of high grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. Through Cox regression analysis we determined the association of each variable with time to a positive biopsy. A nomogram was constructed using all variables and discrimination was calculated as the concordance index., Results: There were 661 biopsy sessions. A mean of 2.9 biopsy sessions were performed per patient and a mean of 9.15 cores were obtained per biopsy session for a mean of 25.2 per patient. Overall 20% of patients had cancer at the second biopsy session. The cumulative number of negative cores obtained, PSA slope, history of high grade prostatic intraepithelial neoplasia and history of atypical small acinar proliferation were associated with repeat biopsy findings (all p <0.05). A nomogram was constructed that had a concordance index of 0.70, which was greater than that of any single risk factor., Conclusions: We created a nomogram that predicts a positive biopsy after a previous negative biopsy session. It provides a wide range of probabilities for cancer and may improve clinical judgment before the decision to repeat biopsy.

Purpose: We determined whether systematic biopsy results increases the accuracy of standard clinical information in predicting seminal vesicle invasion (SVI)., Materials and Methods: We analyzed a retrospective cohort of 763 patients with clinical stages T1c-T3 prostate cancer who were diagnosed by systematic biopsy and treated with radical prostatectomy. We recorded the location of each biopsy core and measured the length of cancer and total length of each core. Using logistic regression analysis we constructed and internally validated a nomogram to predict SVI., Results: A total of 60 patients (7.9%) had SVI. Cancer was present in a biopsy core from the base in 437 patients, of whom 12.8% had SVI compared with only 1.2% of the 326 without cancer at the base. None of the 275 patients with prostate specific antigen (PSA) 10 ng/ml or less and no cancer at the base had SVI. On multivariate analysis serum PSA (p <0.0005), primary Gleason grade (p = 0.028) and percent cancer at the base (p <0.005) were the only significant predictors of SVI. The predictive accuracy of a standard model that included only stage, grade and PSA was maximally enhanced by including the percent cancer at the base (p = 0.0013). A nomogram that incorporated this variable produced probabilities of SVI that differed from the standard model by +/- 10% in 68% of the cases., Conclusions: The presence and amount of cancer in systematic needle biopsy cores from the base of the prostate strongly predicts the presence of SVI. Systematic biopsy results enhance the accuracy of nomograms to predict SVI.

Purpose: We evaluated in vivo magnetic resonance imaging (MRI) as a noninvasive method for early detection and quantitative measurements of superficial tumors in an orthotopic murine bladder tumor model., Materials and Methods: Murine bladder tumor cells were instilled into 25 mouse bladders and subsequently scanned with MRI 10, 14, 17 and 24 days after tumor inoculation. High quality T1-weighted spin-echo transverse images were obtained with 1.5 mm thick slices. Conditions for contrast agent instillation were optimized by evaluating varying concentrations of Gd-diethylenetetramine pentaacetic acid, water and air. Total tumor area in the largest bladder section on MRI was measured and compared quantitatively with actual tumor areas measured in whole mount bladder step sections., Results: Optimal MRI studies were obtained with intravesical instillation of 50 microl Gd-diethylenetetramine pentaacetic acid and 50 microl air. Overall 17 tumors in 11 mice were identified pathologically 10 days after tumor inoculation, of which 14 (82.4%) were identified by MRI with a largest mean diameter of 1.4 +/- 0.1 mm (range 1.0 to 2.2). Mean total tumor area on MRI 10, 14, 17 and 24 days after tumor inoculation was 0.024 +/- 0.005, 0.108 +/- 0.049, 0.165 +/- 0.020 and 0.318 +/- 0.023 cm2, respectively, which correlated well with actual tumor area (r2 = 0.977, p <0.001)., Conclusions: MRI is accurate and effective for noninvasively monitoring tumor growth in the orthotopic murine bladder cancer model. The improved resolution that we report compared with previous murine bladder studies highlights its potential for monitoring the therapeutic efficacy of antitumor agents for early superficial bladder tumors.

Purpose: We assessed whether the appearance of cancer within the prostate on sonography is associated with different pathological features and/or prognoses compared with nonvisible impalpable cancers defined as stage T1c by the TNM staging system., Materials and Methods: We analyzed the clinical and pathological features, and progression rate in 323 patients with clinical stage T1cNX M0 cancer treated with radical prostatectomy between 1983 and 1998. Mean followup was 46.8 months (range 1 to 186)., Results: Of 323 impalpable stage T1c cancers 170 (53%) were visible and the remainder was not visible on ultrasound. There were no significant differences in clinical or pathological features of the cancers in these 2 groups. The prostate specific antigen nonprogression rate at 5 years was also similar for patients with impalpable cancer regardless of whether the lesion was or was not revealed by ultrasound (mean +/- SE 87% +/- 6% and 91% +/- 6%, respectively, p = 0.3767). Of the 170 visible cancers 55 patients had a hypoechoic lesion considered highly suspicious for cancer. These cancers were higher grade, more extensive, less likely to be confined to the prostate and the prognosis was significantly worse than that of impalpable cancer whether or not they were visible at a less suspicious level (IV or less, p = 0.011). However, such highly suspicious visible cancers are rarely visualized today. Initial serum prostate specific antigen more accurately predicts the pathological stage of impalpable cancer than transrectal ultrasound results., Conclusions: Impalpable cancers currently detected have similar pathological features and prognoses whether or not they are visible by ultrasound. Therefore, it is reasonable to categorize impalpable cancers as stage T1c and analyze the response to treatment regardless of the results of ultrasound.

Purpose: Bladder neck invasion by prostate cancer in radical prostatectomy specimens is uncommon and, thus, its influence on disease recurrence has not been well defined. Consequently the classification of bladder neck invasion in the TNM staging system is controversial. We studied our cohort of patients with stage pT4 disease and bladder neck invasion to clarify the true clinical behavior and prognostic significance of bladder neck invasion in radical prostatectomy specimens., Materials and Methods: The study group consisted of 4,090 consecutive patients treated with radical prostatectomy at one of our institutions between 1983 and 2001. Median followup was 53.1 months (range 1 to 189). After excluding from analysis patients treated with neoadjuvant androgen withdrawal or preoperative irradiation 72 of the remaining 2,571 (2.8%) with bladder neck invasion were classified with stage pT4 disease and their specimens were reviewed. Progression-free probability was determined by Kaplan-Meier analysis. Using the Cox proportional hazards model the independent prognostic significance of bladder neck invasion was assessed after controlling for pretreatment prostate specific antigen, final Gleason sum, extracapsular extension, surgical margins status, seminal vesicle invasion and lymph node involvement., Results: Of the 72 patients categorized with stage pT4 disease 14 (19%) had poorly differentiated Gleason sum 8 to 10 cancer, 38 (53%) had established extracapsular extension, 24 (33%) had seminal vesicle invasion and 8 (11%) had lymph node involvement. However, 26 patients (36%) had cancer confined to the prostate and 28 (39%) had negative surgical margins except for the bladder neck site. The mean 5-year progression-free probability plus or minus SD in all stage pT4 cases was 68% +/- 7%, which was better than in cases of seminal vesicle invasion (52% +/- 5%, log rank test p = 0.0156) but worse than in those of extracapsular extension (84% +/- 4.1%). Univariate analysis of the stage pT4 cohort revealed that higher prostatectomy Gleason sum, more extensive extracapsular extension and seminal vesicle invasion were significantly associated with an adverse prognosis. However, in a multivariate model that included all radical prostatectomy cases the finding of bladder neck invasion or stage pT4 disease did not independently predict prostate specific antigen recurrence., Conclusions: Stage pT4 disease comprises a heterogeneous group of tumors with various pathological features and inconsistent outcomes. Assigning the pT4 stage to cases of microscopic bladder neck invasion provides no independent ability for predicting disease progression after adjusting for other adverse disease features. Due to this and previously reported data the definition of stage pT4 disease should be modified in the next version of the TNM staging system.