Nomogram Predicting Bladder Cancer-specific Mortality After Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-invasive Bladder Cancer: Results of an International Consortium.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) is associated with improved overall and cancer-specific survival. The post-NAC pathological stage has previously been reported to be a major determinant of outcome. OBJECTIVE: To develop a postoperative nomogram for survival based on pathological and clinical parameters from an international consortium. DESIGN, SETTING, AND PARTICIPANTS: Between 2000 and 2015, 1866 patients with MIBC were treated at 19 institutions in the USA, Canada, and Europe. Analysis was limited to 640 patients with adequate follow-up who had received three or more cycles of NAC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A nomogram for bladder cancer-specific mortality (BCSM) was developed by multivariable Cox regression analysis. Decision curve analysis was used to assess the model's clinical utility. RESULTS AND LIMITATIONS: A total of 640 patients were identified. Downstaging to non-MIBC (ypT1, ypTa, and ypTis) occurred in 271 patients (42 %), and 113 (17 %) achieved a complete response (ypT0N0). The 5-yr BCSM was 47.2 % (95 % confidence interval [CI]: 41.2-52.6 %). On multivariable analysis, covariates with a statistically significant association with BCSM were lymph node metastasis (hazard ratio [HR] 1.90 [95% CI: 1.4-2.6]; p < 0.001), positive surgical margins (HR 2.01 [95 % CI: 1.3-2.9]; p < 0.001), and pathological stage (with ypT0/Tis/Ta/T1 as reference: ypT2 [HR 2.77 {95 % CI: 1.7-4.6}; p < 0.001] and ypT3-4 [HR 5.9 {95 % CI: 3.8-9.3}; p < 0.001]). The area under the curve of the model predicting 5-yr BCSM after cross validation with 300 bootstraps was 75.4 % (95 % CI: 68.1-82.6 %). Decision curve analyses showed a modest net benefit for the use of the BCSM nomogram in the current cohort compared with the use of American Joint Committee on Cancer staging alone. Limitations include the retrospective study design and the lack of central pathology. CONCLUSIONS: We have developed and internally validated a nomogram predicting BCSM after NAC and radical cystectomy for MIBC. The nomogram will be useful for patient counseling and in the identification of patients at high risk for BCSM suitable for enrollment in clinical trials of adjuvant therapy. PATIENT SUMMARY: In this report, we looked at the outcomes of patients with muscle-invasive bladder cancer in a large multi-institutional population. We found that we can accurately predict death after radical surgical treatment in patients treated with chemotherapy before surgery. We conclude that the pathological report provides key factors for determining survival probability.

Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. PATIENTS AND METHODS: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. RESULTS: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the 'CIS' versus 'no-CIS' groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63-1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01-1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23-2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34-0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82-1.35; p = 0.70). CONCLUSION: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.

Spurious elevation of serum PSA after curative treatment for prostate cancer: clinical consequences and the role of heterophilic antibodies.

BACKGROUND: Various interferences can cause spurious results for common laboratory tests. Although rare, heterophilic antibodies may produce false elevations in PSA that could prompt unnecessary therapy in men previously treated for prostate cancer. The aim of this study was to determine the prevalence of small, spurious PSA elevations, and the role of heterophilic antibodies. METHODS: Phase I: all PSA tests drawn and measured between 27 October 2008 and 26 October 2010 at Vanderbilt University Medical Center were analyzed (n=17 133). Patients who had been treated for prostate cancer with PSA values that changed from undetectable to detectable were evaluated. Phase II: patients with a detectable PSA ≤0.5 ng ml(-1) measured between 24 October 2010 and 19 January 2011 were studied prospectively (n=1288). If any patient had a previously undetectable PSA value, their serum was tested for heterophilic antibody interference. RESULTS: Phase I: 11 men had a spuriously elevated PSA after curative treatment for prostate cancer (0.3%). Mean time to PSA elevation was 3.4±5.5 years, and mean elevation in PSA was 0.33±0.28 ng ml(-1). Each patient's PSA was undetectable after being repeated, and no patient went on to unnecessary treatment. Phase II: 10 men had a newly detectable PSA, 9 of whom had a history of prostate cancer. Each tested negative for interfering heterophilic antibodies when their PSA test was repeated with a heterophilic antibody-blocking reagent. CONCLUSIONS: In a large cohort, we estimate the prevalence of spuriously elevated PSA values in our population to be 0.3%. No patient with a prostate cancer history was subjected to unnecessary diagnostic evaluation or treatment. On prospective evaluation of PSA conversion to low detectable levels, no patient had evidence of interfering heterophilic antibodies. When using PSA for post-treatment surveillance, it is crucial to confirm all concerning values and consider the presence of a spurious elevation in PSA if the value does not correlate with the clinical scenario.

Complications of pelvic lymph node dissection for prostate cancer.

Pelvic lymph node dissection (PLND) represents the standard for detection of occult pelvic nodal metastases from prostate cancer, and may be performed separately from or at the time of radical prostatectomy. In addition to its potential for diagnostic staging, a PLND may be therapeutic in some patients. However, considerable debate centers on the appropriate candidates for the procedure, the extent and proper boundaries of dissection, optimal surgical approach, and absolute oncologic benefit. Several series suggest that there likely is limited benefit of PLND in low-risk patients and that PLND can be safely omitted in a high percentage of men undergoing contemporary radical prostatectomy. Furthermore, the value of PLND in patients with intermediate- and high-risk disease must be balanced against the potential morbidity of the procedure. In the setting of this debate, concern over morbidity directly attributable to this procedure is of paramount importance. This review focuses on the complications associated with PLND, including lymphocele, thromboembolic events, ureteral injury, nerve injury, vascular injury, and lymphedema.

Association between prostate-specific antigen and leptin, adiponectin, HbA1c or C-peptide among African-American and Caucasian men.

Prior studies report slightly lower prostate-specific antigen (PSA) levels among obese men. To understand this effect, we investigated the association between PSA and blood HbA1c, C-peptide, leptin and adiponectin levels in African-American (AA) (n=121) and Caucasian (CA) (n=121) men. Among AA men, PSA levels decreased with increasing C-peptide levels (PSA=0.99, 0.93, 0.75 and 0.53 ng ml(-1) across quartiles of C-peptide, respectively; P(trend)=0.005). Among CA men, PSA levels decreased with increasing HbA1c (PSA=0.84, 0.73, 0.77 and 0.45 ng ml(-1) across quartiles of HbA1c, respectively; P(trend)=0.005). This may suggest that metabolic disturbances related to metabolic syndrome or diabetes affect the ability to detect early-stage prostate cancer.

The association between body size, prostate volume and prostate-specific antigen.

Increasing prostate volume contributes to urinary tract symptoms and may obscure prostate cancer detection. We investigated the association between obesity and prostate volume, prostate-specific antigen (PSA) and PSA density among 753 men referred for prostate biopsy. Among men with a negative biopsy, prostate volume significantly increased approximately 25% from the lowest to highest body mass index (BMI), waist or hip circumference or height categories. PSA was 0.7 ng/ml lower with a high waist-to-hip ratio. These associations were less consistent among subjects diagnosed with high-grade prostatic intraepithelial neoplasia or cancer. Our data suggest that obesity and height are independently associated with prostate volume..

Estimated blood loss and transfusion requirements of radical cystectomy.

PURPOSE: Radical cystectomy has been associated with significant blood loss and/or transfusion requirement. We defined and characterized blood loss and transfusion parameters in this population. MATERIALS AND METHODS: We reviewed the records of 304 consecutive patients who underwent radical cystectomy and urinary diversion between October 1995 and July 2000. Charts were examined, and univariate and multivariate logistic regression analysis was performed to evaluate estimated blood loss and the transfusion requirement. RESULTS: Complete blood loss data were available in 297 cases. Overall 45% of patients had anemia preoperatively. Median estimated blood loss was 600 ml. (range 100 to 3,000). On univariate analysis increased estimated blood loss was related to patient age, American Society of Anesthesiologists score, longer operative time and paralytic ileus. Overall transfusion was done in 88 of 297 cases (30%) with a median requirement of 2 units (range 1 to 10). The transfusion rate in male and female patients was 26% and 40%, respectively (p <0.05). On univariate analysis female gender, ileal conduit diversion and lower preoperative hematocrit correlated with transfusion need (p = 0.04, <0.001 and <0.001, respectively). On multivariate logistic regression analysis lower preoperative hematocrit, increased estimated blood loss, major complications and ileal conduit diversion type correlated with a higher transfusion rate (odds ratio 8.34, 5.88 and 4.60, respectively). CONCLUSIONS: Acute blood loss anemia is common in patients undergoing radical cystectomy, and predicting blood loss and transfusion requirements remains difficult. These data indicate the need for continued refinement in surgical techniques to decrease blood loss as well as for strategies designed to decrease the need for blood transfusion.

Intrarectal lidocaine during transrectal prostate biopsy: results of a prospective double-blind randomized trial.

PURPOSE: Recent reports have indicated the benefit of anesthesia during prostate biopsy. To assess this finding objectively we performed a prospective randomized double-blind study to compare patient pain with and without local anesthesia during transrectal ultrasound guided prostate biopsies. MATERIALS AND METHODS: Between August 2000 and March 2001, 108 men undergoing transrectal ultrasound guided biopsy of the prostate were randomized in double-blind fashion to receive intrarectal 2% lidocaine gel or intrarectal lubricant alone. No patient received pre-procedure narcotics or sedation. Pain associated with biopsy was determined using a horizontal linear visual analog pain scale. Pain scores in the 2 treatment groups were compared and possible predictors of increased pain were examined. RESULTS: The 2 groups were similar in demographic characteristics. There was no significant difference in pain score in the 2% lidocaine and lubricant alone groups (28.3 versus 28.9 mm., p = 0.88). Previous biopsy, time since previous biopsy, physician, number of biopsies and prostate volume did not correlate with pain score, while age correlated negatively with the score (r = -0.27, p = 0.005). A single complication involving a vasovagal episode resolved spontaneously. CONCLUSIONS: Intrarectal lidocaine gel provides no significant therapeutic or analgesic benefit compared with lubricant alone for transrectal ultrasound guided biopsy of the prostate. In younger patients more discomfort is associated with this procedure.

Health related quality of life assessment after radical prostatectomy in men with prostate specific antigen only recurrence.

PURPOSE: The health related quality of life assessment is becoming increasingly important among patients with prostate cancer. Meanwhile, treatment of patients with increasing prostate specific antigen (PSA) after radical retropubic prostatectomy remains controversial. We attempt to define the impact of PSA recurrence on the health related quality of life of patients after radical retropubic prostatectomy. MATERIALS AND METHODS: Of 604 consecutive patients who underwent radical retropubic prostatectomy between March 1991 and September 1998, 510 (84%) were available for followup. Each patient was mailed the RAND 36-Item Health Survey and University of California, Los Angeles, Prostate Cancer Index questionnaire. A total of 348 (70%) questionnaires were returned. Health related quality of life scores were then compared between patients with and without PSA recurrence. A multivariate analysis was also performed to elucidate further the cause of differences between the groups. RESULTS: Overall, 88 (25%) patients had PSA recurrence. In regard to health related quality of life there were small (less than 10%) but statistically significant differences in 2 of 4 physical health domains (RAND 36-Item Health Survey). There was a significant decrease in only 1 category of the mental health domain for patients with PSA recurrence. Only sexual function was statistically lower on the University of California, Los Angeles, Prostate Cancer Index. This result reflects the lower incidence of nerve sparing in these patients, as confirmed by the multivariate analysis. Overall patient satisfaction was similar between those with and without PSA recurrence (76% and 79%, respectively). CONCLUSIONS: Our study demonstrates small health related quality of life differences in patients with biochemical PSA recurrence versus those without. These findings provide a baseline assessment of general and disease specific health related quality of life domains among these patients. Future studies should focus on differences in the measure of cancer anxiety before and after administration of adjuvant therapy in these asymptomatic patients.

Radical cystectomy is safe in elderly patients at high risk.

PURPOSE: Radical cystectomy is standard treatment for bladder cancer in healthy individuals. We determined the safety of radical cystectomy in elderly patients at high risk. MATERIALS AND METHODS: We reviewed the records of all patients who underwent radical cystectomy at our institution between January 1994 and June 2000. Of these 382 patients we identified 44 who were elderly and at high risk, as defined by age 75 years or greater and American Society of Anesthesiologists classification 3 or greater. We examined postoperative care, perioperative minor/major complications, the mortality rate and the need for rehospitalization. RESULTS: Median age of the 44 patients was 77.5 years (range 75 to 87). American Society of Anesthesiologists class was 3 in 40 patients and 4 in 4. Median hospitalization was 7 days (range 4 to 20). Postoperatively 31 of the 44 patients (70%) were transferred directly to the general urology floor, while cardiac monitoring was required postoperatively in 30%. Nine of these patients were transferred to a step-down unit and the remaining 4 required surgical intensive care unit admission. Minor and major complications developed in 10 (22.7%) and 2 (4.5%) cases, respectively. No patients died in the perioperative period and 4 patients were hospitalized within 6 months of discharge home. CONCLUSIONS: Our results support the safety of radical cystectomy in elderly patients at high risk. Acceptable perioperative morbidity and mortality may be achieved without routine intensive monitoring postoperatively.

Clinical under staging of high risk nonmuscle invasive urothelial carcinoma treated with radical cystectomy.

PURPOSE: The role of radical cystectomy in patients with nonmuscle invasive urothelial carcinoma of the bladder remains controversial. The risk of overtreatment must be balanced against the potential benefit of aggressive therapy. We reviewed our results in these patients with a particular emphasis on clinical under staging. MATERIALS AND METHODS: We reviewed the records of 214 consecutive patients who underwent radical cystectomy for urothelial carcinoma between April 1995 and August 1999, focusing on those with nonmuscle invasive, stages T1 or less disease. We assessed clinical and pathological data as well as outcomes based on pathological disease extent. RESULTS: A total of 78 patients (36%) underwent radical cystectomy for clinical stages T1 or less disease. Indications included disease refractory to intravesical therapy in 29 cases (37%), pathological findings reflective of high grade stage T1 or multifocal disease in 26 (33%), radiographic suspicion of invasive disease in 15 (20%) and severe symptoms in 8 (10%). Cancer was clinically under staged with stages pT2 or greater disease in 31 patients (40%) according to final pathology results. Under staging was most pronounced in the 10 patients (67%) with suspicious radiography and in the 18 (64%) with absent muscle in the biopsy specimen. Of the 78 patients with pathological stages pT1 disease or less 98% had no evidence of disease compared to 65% with stages pT2 or greater disease (p <0.01). CONCLUSIONS: Despite the intent to perform early cystectomy a significant percent of patients harbored occult muscle invasive and/or metastatic disease. In clinical and pathological, superficial stages T1 or less cases disease-free survival was excellent. Due to these results, the selection of high risk superficial transitional cell carcinoma cases for continued bladder sparing treatment should include uninvolved muscle on biopsy and absent radiographic suspicion of invasion.

Ratio of free-to-total prostate specific antigen correlates with tumor volume in patients with increased prostate specific antigen.

PURPOSE: We evaluated the relationship between the ratio of free-to-total prostate specific antigen (PSA) and prostate pathology, including grade, stage and tumor volume, among patients with prostate cancer who underwent radical prostatectomy. MATERIALS AND METHODS: We prospectively analyzed 54 consecutive patients with prostate cancer who underwent radical prostatectomy and in whom frozen serum was available for assessment of free-to-total PSA ratio. Pathological review was done with whole mount sections, and total tumor volume was determined by planimetry. Comparison between free-to-total PSA ratio and pathological parameters was performed using the Pearson correlation coefficient. RESULTS: Among the 54 patients mean total and free-to-total PSA ratio were 5.81 and 14.2 ng./ml., respectively, and free-to-total PSA ratio directly correlated with prostate volume (p = 0.037), and inversely correlated with Gleason score (p = 0.012) and extracapsular disease (p = 0.0074). Furthermore, there was a significant relationship between free-to-total PSA ratio and pathological stage pT2a/b in 39 cases versus pT3a/b in 15 (p = 0.005). Overall, there was no correlation between free-to-total PSA ratio and tumor volume. However, among 37 patients with an increased PSA, defined as greater than 4.0 ng./ml., a significant inverse relationship between free-to-total PSA ratio and tumor volume was identified (p = 0.01). Among this subset there was only a weak correlation with prostate volume (p = 0.049). CONCLUSIONS: Our findings suggest that free-to-total PSA ratio may be predictive of tumor biology among those patients with a total PSA of greater than 4 ng./ml. as evidenced by good correlation with tumor grade and volume. This finding appears to be independent of prostate volume. These preliminary results suggest the need for additional studies among patients with an increased PSA designed to evaluate the potential role of free-to-total PSA ratio in combination with traditional clinical variables in the prediction of prostate cancer pathology.

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.

Update on transrectal ultrasound-guided needle biopsy of the prostate.

Over the past decade, the sextant biopsy technique has emerged as the standard of care in the detection of prostate cancer. This technique is easy to learn and well tolerated by patients and has a major complication rate of <1%. However, limitations in cancer detection have been appreciated, particularly a false-negative rate approaching 25%. This high failure rate has led investigators to refine biopsy techniques to improve cancer detection. Intuitively, increasing the total number of cores should improve cancer detection. However, the optimal core number has yet to be defined. Confounding factors include variability of prostate size, tumor volume, and tumor location. Currently, a new standard is emerging prescribing a minimum of eight cores, of which at least three are directed at the lateral aspect of the peripheral zone. These additional biopsies appear to enhance cancer detection by about 15%. The improved yield is most pronounced among patients with a serum prostate specific antigen concentration between 4 and 10 ng/mL and larger gland volume (>50 cc). These additional biopsies may decrease the need for repeat biopsies. In the meantime, strategies are being developed for the optimal technique of repeat biopsies among patients with persistent clinical suspicion in the setting of a prior negative biopsy. Currently, recommendations include increasing the biopsy number to a minimum of 10 cores, including sampling of the lateral peripheral and transition zones.

Bilateral ureteritis cystica with unilateral ureteropelvic junction obstruction.

Ureteritis cystica is a rare, benign, proliferative disorder characterized by multiple ureteral cysts and multiple filling defects noted on contrast ureteral imaging. A unique case of bilateral ureteritis cystica coincidental with chronic, congenital, unilateral ureteropelvic junction obstruction presenting with microscopic hematuria and lower urinary tract symptoms is described. The characteristic presentation as well as the diagnostic radiographic, ureteroscopic, and histologic features of pyeloureteritis cystica are reviewed.

Repeat transrectal ultrasound-guided prostate biopsy: a strategy to improve the reliability of needle biopsy grading in patients with well-differentiated prostate cancer.

OBJECTIVES: Gleason grade from prostate needle biopsy (PNB) specimens is important in guiding therapeutic decision making in patients with localized prostate cancer. Recent data from our institution suggest a significant discordance between Gleason grading from PNB versus the actual pathologic grade at radical prostatectomy (RRP). Of most concern is that a substantial proportion of patients with Gleason score of 6 or less from PNB actually have Gleason score of 7 or more at RRP. Under classic measurement theory, one useful way to improve the reliability of an inherently unreliable test is to repeat it. We investigated this strategy in an effort to reduce undergrading errors. METHODS: The control group of patients (n = 51) from our neoadjuvant androgen deprivation protocol was used as the test (two-biopsy) group in this study. These patients underwent two separate PNBs before RRP. We used the highest Gleason score from the two biopsies in these patients and compared the error rates with a concurrent group of patients treated at our institution (n = 226) who had only one set (single-biopsy group) of prostate biopsies. All pathologic slides were reviewed at our institution. Any PNB grade of 6 or less that was scored as 7 or more on final pathology was considered significant. RESULTS: Mean age, prostate-specific antigen levels, and stage distribution were not significantly different between these two groups. In the single-biopsy group, 165 patients had PNB Gleason score of 6 or less. Of these patients, 63 (38%) had final pathologic grade of 7 or more. In the two-biopsy group, 37 patients had PNB Gleason score of 6 or less. Of these patients, only 7 (19%) had final pathologic grade of 7 or more (P = 0.04). CONCLUSIONS: Prostate rebiopsy minimizes the inherent unreliability of PNB derived grade and should be considered for patients in whom watchful waiting or nomogram-based therapy has been selected.

Incidence and clinical significance of false-negative sextant prostate biopsies.

PURPOSE: Since most patients do not undergo repeat sextant prostate biopsies after a biopsy is positive for prostate cancer, the true incidence of false-negative biopsies is not well defined. We assess the incidence and clinical significance of false-negative sextant prostate biopsies in patients undergoing radical prostatectomy. MATERIALS AND METHODS: A total of 118 patients with biopsy proved prostate cancer underwent repeat sextant prostate biopsy before enrollment in a prospective randomized trial of radical prostatectomy with or without neoadjuvant hormonal therapy. Clinical parameters were assessed to determine potential sources of bias. Pathological parameters and prostate specific antigen relapse-free survival rates were compared to determine the clinical significance of false-negative biopsies. RESULTS: Of the 118 patients 27 (23%) had a negative repeat sextant biopsy. Except for initial clinical stage, no differences were noted in the clinical or pathological parameters, or prostate specific antigen relapse rates in patients with negative versus positive repeat biopsies. CONCLUSIONS: Our findings suggest that this 23% incidence of false-negative biopsies represents significant cancer. This relatively high incidence is important to consider in treatment modalities in which prostate biopsy may be performed to determine response to therapy.