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Purpose: Survivors of surgically managed prostate cancer may experience urinary incontinence and erectile dysfunction. Our aim was to determine if 68 Ga-prostate-specific membrane antigen-11 positron emission tomography CT (PSMA-PET) in addition to multiparametric (mp) MRI scans improved surgical decision-making for nonnerve-sparing or nerve-sparing approach., Materials and Methods: We prospectively enrolled 50 patients at risk for extraprostatic extension (EPE) who were scheduled for prostatectomy. After mpMRI and PSMA-PET images were read for EPE prediction, surgeons prospectively answered questionnaires based on mpMRI and PSMA-PET scans on the decision for nerve-sparing or nonnerve-sparing approach. Final whole-mount pathology was the reference standard. Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic curves were calculated and McNemar's test was used to compare imaging modalities., Results: The median age and PSA were 61.5 years and 7.0 ng/dL. The sensitivity for EPE along the posterior neurovascular bundle was higher for PSMA-PET than mpMRI (86% vs 57%, P = .03). For MRI, the specificity, positive predictive value, negative predictive value, and area under the curve for the receiver operating characteristic curves were 77%, 40%, 87%, and 0.67, and for PSMA-PET were 73%, 46%, 95%, and 0.80. PSMA-PET and mpMRI reads differed on 27 nerve bundles, with PSMA-PET being correct in 20 cases and MRI being correct in 7 cases. Surgeons predicted correct nerve-sparing approach 74% of the time with PSMA-PET scan in addition to mpMRI compared to 65% with mpMRI alone ( P = .01)., Conclusions: PSMA-PET scan was more sensitive than mpMRI for EPE along the neurovascular bundles and improved surgical decisions for nerve-sparing approach. Further study of PSMA-PET for surgical guidance is warranted in the unfavorable intermediate-risk or worse populations., Clinicaltrials.gov Identifier: NCT04936334.

Introduction: We sought to update our experience of oncologic and functional outcomes of robot-assisted radical prostatectomy (RARP) for prostate cancer in patients with history of holmium laser enucleation of the prostate (HoLEP). Patients and Methods: Twenty-seven patients with previous HoLEP who underwent RARP were matched 1:1 with RARP patients with no history of transurethral surgery. Demographic, operative, oncologic, continence, and erectile function outcomes were analyzed. Results: Median time between HoLEP and RARP was 31 months with a mean prostate-specific antigen doubling time of 4.28 ng/mL/year. Operative times were significantly longer with higher bladder neck reconstruction rates and similarly low complication rates. Biochemical recurrence was relatively low (7%) in the HoLEP group, identical to the comparative group. Continence at last follow-up was not statistically significant between groups, although time to continence favored the non-HoLEP cohort. Erectile function recovery was generally poor in the post-HoLEP cohort (11%), although bilateral nerve sparing was rarely performed (11%). Compared with our initial experience, there were significant improvements in time to continence (16 vs 36 weeks). No T2 post-HoLEP RARP since 2010 has had a positive surgical margin. Conclusions: Post-HoLEP prostatectomy remains feasible with similar perioperative and oncologic outcomes compared with matched cohorts. Functional recovery remains slowed yet may continue to improve with technical familiarity.

Objectives: To evaluate the impact of obesity on patients developing wound complications within 30 days of open and robotic radical prostatectomy using the National Surgical Quality Improvement Program (NSQIP)., Methods: Patients undergoing radical prostatectomy in 2011 to 2012 were identified from NSQIP, which is a multi-institutional database of comprehensive 30-day postoperative outcomes. Wound complication included superficial surgical site infections (SSIs), deep SSI, organ space infections, and dehiscence. Descriptive statistics and multiple logistic regression examined the relationship between obesity and wound complications in open and robotic radical prostatectomy., Results: Of the 12,454 radical prostatectomy cases reported in the study period, 9248 were robotic (74%), 2244 (18%) patients were normal weight (body mass index [BMI] <25), 5836 (47%) were overweight (BMI 25-30), and 4374 (35%) were obese (BMI >30). Wound complications occurred in 134 (4%) of open and 114 (1%) of robotic radical prostatectomies. After adjusting for age, history of smoking, history of diabetes, history of chronic steroid use, and operative time, it was determined that obese patients were at 71% increased odds of developing a wound complication after open prostatectomy (p = 0.034), while there was no difference in the odds of a wound complication after robotic radical prostatectomy (odds ratio 1.14, p = 0.665)., Conclusions: Obese patients are at increased risk of developing wound complications when undergoing open vs robotic radical prostatectomy. Obese patients likely benefit from robotic radical prostatectomy whenever feasible.

Purpose: Urinary continence is a driver of quality of life after radical prostatectomy. In this study we evaluated the impact of a biological bladder neck sling on the return of urinary continence after robot-assisted radical prostatectomy., Materials and Methods: This study compared early continence in patients undergoing robot-assisted radical prostatectomy with a sling and without a sling in a 2-group, 1:1, parallel, randomized controlled trial. Patients were blinded to group assignment. The primary outcome was defined as urinary continence (0 to 1 pad per day) at 1 month postoperatively. Inclusion criteria were organ confined prostate cancer and a prostate specific antigen less than 15 ng/ml. Exclusion criteria were any prior surgery on the prostate, a history of neurogenic bladder and history of pelvic radiation. A chi-squared test was used for the primary outcome., Results: A total of 147 patients were randomized (control 74, sling 73) and 92% were available for primary end point analysis at 1 month. There were no significant differences in baseline or perioperative data except that operating room time was 20.1 minutes longer for the sling group (p=0.04). The continence rate was similar between the control and sling groups at 1 month (47.1% vs 55.2%, p=0.34) and 12 months (86.7% vs 94.5%, p=0.15), respectively. Adverse events were similar between the control and sling groups (10.8% vs 13.7%, p=0.59)., Conclusions: The application of an absorbable urethral sling at robot-assisted radical prostatectomy was well tolerated with no increase in obstructive symptoms in this randomized trial. However, the sling failed to show a significant improvement in continence., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate outcomes of post-holmium laser enucleation of the prostate (HoLEP) robot-assisted radical prostatectomy (RARP)., Patients and Methods: Using an institutional database, we identified 11 HoLEP patients who subsequently underwent RARP. These were matched 1:2 to RARP patients without a previous transurethral surgical procedure. Variables matched were age, pre-RARP prostate-specific antigen level, and biopsy Gleason score. Urinary continence and sexual function were evaluated by physician questioning, American Urological Association symptom score, and Sexual Health in Men (SHIM) scores. Descriptive statistics were used to compare cohorts., Results: RARP pathologic outcomes were similar between cases and controls. Twenty-seven percent of previous HoLEP patients reached strict urinary continence (leak free, pad free) at last follow-up compared with 64% of matched controls (P=0.071). The average (range) SHIM score at last follow-up was 2.6 (1-5) for previous HoLEP patients compared with 13.9 (5-20) (P<0.001). The posterior bladder neck and apical dissections were significantly more challenging in the setting of previous HoLEP and necessitated a low threshold for wider resection to minimize positive surgical margins., Conclusions: Post-HoLEP RARP is challenging but preliminarily appears safe and feasible when performed by an experienced robotic surgeon. Patients should be counseled regarding expectations of urinary continence and sexual function in this setting.

Objective: To explore the relationship between operative time, approach, and length of stay (LOS) in partial nephrectomy (PN), radical prostatectomy (RP), and adrenalectomy (AD)., Materials and Methods: Using the National Surgical Quality Improvement Program database, we identified all PN, RP, and AD from 2010 to 2012. Non-prostate cancer RP were excluded. The primary outcome was LOS. Descriptive comparisons were drawn between open and minimally invasive surgery (MIS) for each surgery. Multiple linear regression assessed the impact of open versus MIS and operative time on LOS when controlling for confounders., Results: We identified 3760 PN (60% MIS), 12,081 RP (82% MIS), and 1684 AD (76% MIS) cases for inclusion. Differences in operative time were identified. In PN and RP, MIS mean operative time was 10 to 23 minutes longer (p<0.001 each); while for AD, open was 35 minutes longer (p<0.001). Open procedures had consistently longer median LOS (p<0.001 all). Results of the linear regression are given next., Conclusions: Operative time and surgical approach are directly associated with LOS, independent of complications and patient comorbidities.

Objective: To compare the impact surgical technique has on clinicopathologic and oncologic outcomes among patients undergoing radical prostatectomy for clinically localized prostate cancer., Materials and Methods: Utilizing the experience of a single surgeon and pathologist, a retrospective review of 1,041 patients undergoing open (RRP) and robotic-assisted (RALP) radical prostatectomy between 1999 and 2010 with pathologic evaluation using whole-mount sectioning techniques and tumor mapping was performed from our prospective database. Differences in the incidence, location, and linear length of positive surgical margins were compared. Additionally, rates of biochemical relapse-free survival according to technique were assessed., Results: A total of 357 RRP and 669 RALP patients were evaluated. The overall incidence of surgical margin positivity when stratified by stage of disease and location of positive margins was nearly identical between groups for organ confined disease. The apex and posterior surfaces represented the 2 most common locations for positive margins. RALP had notably fewer positive margins in pathologic T3 disease and a statistically shorter linear length of margin positivity among all patients. Short and intermediate-term biochemical-free survival rates were identical between groups., Conclusions: RALP is associated with operative oncologic control rates that compare very favorably to RRP. The data suggest that in the hands of an experienced surgeon, RALP has oncologic outcomes that are at least as good if not better than RRP., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Pelvic lymphadenectomy for prostate cancer is an important tool in the prognostication of the disease in selected patients who are at risk of occult lymph node metastases. This procedure, usually performed in conjunction with radical prostatectomy, had progressed successfully from an open approach to the current robot-assisted approach. The following article and accompanying video describe the surgical technique of robot-assisted pelvic lymphadenectomy for prostate cancer. We also discuss the indications, patient selection, preparation, complications, and tips to avoid the major pitfalls in the procedure.

Purpose: We characterized prostate cancer focality in regard to clinicopathological features, prognostic value and impact on biochemical outcome., Materials and Methods: We retrospectively reviewed the records of 1,366 patients in our prospective database who underwent radical prostatectomy between 1999 and 2010 for clinically localized prostate cancer with pathological evaluation using whole mount sectioning techniques and tumor mapping. Unifocal disease was defined as the identification of a solitary cancer focus in the prostate without additional tumor foci or satellite lesions, ie multifocal disease, on histopathological evaluation. Cox regression modeling was used to identify predictors of biochemical progression among groups., Results: A total of 184 patients (13%) fulfilled our unifocal tumor criteria. Unifocal tumors tended to be smaller in volume and in greatest diameter than multifocal tumors (p<0.0001 and <0.005, respectively). Of patients with pathologically insignificant disease the relative proportion with unifocal tumors increased to 28% from 13% in the overall cohort (p<0.0005). Also, tumor focality failed to predict biochemical recurrence in univariate and multivariate models. Accordingly we noted no significant differences in 5-year biochemical recurrence-free survival for unifocal and multifocal tumors (66% and 61%, respectively, p=0.76). Limitations of this study include its retrospective nature., Conclusions: In this study tumor focality failed to predict patients likely to experience biochemical failure. Tumor characteristics were similar regardless of focality. However, unifocal tumors had smaller volume and were more commonly seen as clinically insignificant compared to multifocal tumors., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: • To characterize the anatomical distribution and pathological features of unifocal cancers, which have been reported to occur in 17-33% of men undergoing radical prostatectomy (RP), in whole- mount prostatectomy specimens., Patients and Methods: • Between 1999 and 2008, a retrospective review of 1274 patients undergoing RP for clinically localized prostate cancer with pathological evaluation using whole-mount sectioning techniques and tumour mapping was performed from our prospective database. • The study cohort comprised those patients who were found to have unifocal tumours., Results: • A total of 176 (14%) patients fulfilled our criteria for having unifocal tumours. The median age at time of surgery was 61 years. The mean preoperative PSA level was 8.6 ng/mL. • In all, 28% of patients were identified as having extracapsular extension (ECE) and 11% had seminal vesicle invasion (SVI). • Of 98 patients undergoing pelvic lymph dissection, six (6%) had positive lymph nodes; 49% of tumours had Gleason score ≥7 and 60% had Gleason pattern 4 or 5 found within the tumour. • Mean tumour volume and maximum diameter were 3.3 mL and 1.7 cm, respectively. Overall, 89 (51%) tumours qualified as localized, organ-confined and low-grade cancers, possibly amenable to focal ablative approaches. • The limitations of the present study include its descriptive and retrospective nature., Conclusions: • While unifocal prostate cancers were most commonly localized to the prostate, half of these patients were associated with intermediate- or high-grade disease. • High-risk features including ECE, SVI, lymph node invasion (LNI), and large tumour volume were identified in a third of patients. • Further studies assessing predictors beyond focality will be needed to determine whether patients can be identified before surgery who might be suitable candidates for lesion-ablative therapies., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Objective: To report the long-term outcome of high-grade prostate cancer treated with radical prostatectomy (RP) as initial monotherapy, analyse the effect of clinical and pathological variables on survival, and report cancer-related symptoms., Patients and Methods: A retrospective chart review was conducted to identify patients with Gleason 8-10 prostate cancer found on pathological review in men undergoing RP as initial therapy for clinically localized disease between 1988 and 2005. Kaplan-Meier analysis was used to calculate event-free survival. Univariable and multivariable analyses were used to assess the effects of clinical and pathological variables on prostate-specific antigen (PSA) recurrence., Results: After excluding 20 patients, 119 were identified with pathologically confirmed high-grade cancers at the time of RP. The overall median (interquartile range) follow-up was 73 (41-113) months. Twenty-four (20%) patients had organ-confined cancer, 60 (50%) had specimen-confined cancer, and 14 (12%) had nodal metastasis. Kaplan-Meier analysis showed overall survival rates at 5 and 10 years, respectively, of 90% and 75%, cancer-specific survival of 92% and 82%, and a PSA recurrence-free follow-up at 5 years of 31%. Using univariable analysis, preoperative PSA level, pathological Gleason score, pathological stage, surgical margin status and tumour volume were found to significantly affect the PSA recurrence-free follow-up. No variables were significant on multivariable analysis. Cancer-related symptoms were reported by only 14 patients, with a median time from surgery to first symptom of 43 months., Conclusion: High-grade prostate cancer can be treated with RP as initial monotherapy with an acceptable 10-year cancer-specific survival (82%). The PSA recurrence-free follow-up is poor (31% at 5 years). However, few patients progress to symptomatic recurrence after PSA relapse within the first 5 years.

Background: Morphologic and clinical heterogeneity within tumor grades is well recognized in prostate cancer. The objective of the current study was to determine whether the combined percentage of Gleason patterns 4 and 5 in radical prostatectomy specimens is an independent predictor of cancer-specific survival in prostate cancer patients., Methods: The radical prostatectomy specimens were analyzed from 504 consecutive prostate cancer patients who were treated at Indiana University Medical Center between 1990 and 1998. Various clinical and pathologic characteristics were analyzed., Results: A higher combined percentage of Gleason patterns 4 and 5 was associated with older age, higher preoperative serum prostate-specific antigen level, higher pathologic stage, positive surgical margins, extraprostatic extension of tumor, higher Gleason score, perineural invasion, and lymph node metastasis. In the multivariate Cox regression model, the combined percentage of Gleason patterns 4 and 5 was found to be an independent predictor of cancer-specific survival (P = .04)., Conclusions: The combined percentage of Gleason patterns 4 and 5 is a powerful predictor of prostate cancer-specific survival. Assessment of high-grade cancer amounts may allow for better stratification of patients into appropriate prognostic groups and treatment protocols.

The presence of positive surgical margins is a negative prognostic indicator in patients undergoing prostatectomy for prostate cancer; whether the extent of the positive margins affects the clinical outcome with regards to prostate-specific antigen (PSA) recurrence remains uncertain. We evaluated the linear extent of margin positivity as a prognostic indicator in a series of radical prostatectomy specimens. One hundred seventy-four consecutive margin-positive prostatectomy specimens were evaluated. The linear extent of margin positivity was measured with an ocular micrometer and ranged from 0.05 to 75.0 mm (mean, 8.94; median, 5.0). The linear extent of margin positivity was associated with tumor volume (P = .03) but was not associated with patients' age at surgery, preoperative PSA level, prostate weight, pathologic stage, Gleason score, extraprostatic extension, seminal vesicle invasion, perineural invasion, high-grade prostatic intraepithelial neoplasia, or PSA recurrence. In the full model multiple Cox regression, significant predictors for PSA recurrence were Gleason score (P = .001) and preoperative PSA (P = .01); extent of margin positivity was not predictive of PSA recurrence (hazard ratio, 1.00; 95% confidence interval, 0.98-1.02; P = .97) nor was tumor volume a significant factor when adjusted for other covariates (P = .27). Preoperative PSA, tumor stage, and Gleason score remained significant prognostic factors in evaluating the likelihood of PSA recurrence in patients with positive surgical margins; the extent of margin positivity, however, is not a prognostic factor for PSA recurrence and should, therefore, not necessarily be included in the final report for radical prostatectomy specimens.

Objective: To investigate the relationship of preoperative prostate-specific antigen (PSA) level and PSA density with several clinical and pathological variables, including biochemical recurrence after radical prostatectomy (RP), and to compare the preoperative PSA level and PSA density as prognostic factors in prostate cancer., Patients and Methods: The study included 348 patients who had a RP at one institution, with whole-mount specimens of the prostate examined by one pathologist. Univariate and multivariate analyses were used to assess the relationship of the preoperative PSA level and PSA density with clinical and pathological variables, and by receiver operating characteristic (ROC) analysis to evaluate the relative usefulness of the two factors as predictors for biochemical recurrence., Results: The PSA level before RP was significantly correlated (Spearman's rank correlation) with patient age (P = 0.003), prostate weight (P < 0.001), cancer volume (P < 0.001) and Gleason score (P = 0.033), and with surgical margin status and pathological stage (both P < 0.001) in the RP specimen. In the multivariate analysis controlling for tumour stage, surgical margin status, and Gleason score, both PSA level and PSA density were significant predictors of PSA recurrence (P = 0.027 and 0.01, respectively). ROC analysis showed no statistical difference between the PSA level and PSA density in predicting PSA recurrence after RP (P = 0.40)., Conclusions: These results show a significant correlation of the preoperative PSA level with other established prognostic factors for prostate cancer. In the multivariate analysis, both PSA level and PSA density were independent predictors of PSA recurrence. Because the PSA level is as effective as PSA density in predicting PSA recurrence, the extra effort required to calculate PSA density may not be warranted. We recommend that the PSA level before RP be considered in stratifying patients into different prognostic groups, and in determining the optimum management.

Purpose: Gleason grade and tumor stage are well established prognostic factors in prostate cancer. Histological demonstration of tumor in lymphovascular spaces has been associated with poor prognosis in many tumor types but it is not included in current prostate cancer grading and staging schemes. Whether lymphovascular invasion is an independent prognostic factor for disease progression in prostate cancer is uncertain. We retrospectively investigated lymphovascular invasion as a predictive factor for biochemical failure and cancer specific survival following radical prostatectomy., Materials and Methods: The records of 504 patients with prostatic adenocarcinoma undergoing radical prostatectomy were reviewed for lymphovascular invasion. Clinical followup data were available on 459 cases. Mean followup was 44 months (range 1.5 to 144). Multivariate analysis was performed using the Cox model., Results: Lymphovascular invasion was identified in 106 cases (21%). Univariate analysis showed a significant association between lymphovascular invasion and higher preoperative serum prostate specific antigen (PSA), advanced pathological stage, higher Gleason score, positive surgical margins, extraprostatic extension, seminal vesicle invasion, lymph node metastasis and perineural invasion (each p <0.001). No association was observed between lymphovascular invasion and patient age at surgery, prostate weight or high grade prostatic intraepithelial neoplasia. Lymphovascular invasion was an independent predictor of PSA recurrence (HR 1.6, 95% CI 1.12 to 2.38, p = 0.01) and cancer specific survival (HR 2.75, 95% CI 1.04 to 2.28, p = 0.041) after controlling for tumor stage, surgical margins and Gleason grade on multivariate analysis. Five-year cancer specific survival was 90% in men with lymphovascular invasion compared to 98% in those without lymphovascular invasion (p <0.001)., Conclusions: Lymphovascular invasion can be identified in approximately 20% of prostate cancer cases. Lymphovascular invasion is an independent risk factor for PSA recurrence and cancer death in patients with prostate cancer.

The aim of this article is to evaluate wide primary perirectal dissection (WR) during the course of radical prostatectomy as a technique to decrease positive surgical margin rates and improve subsequent biochemical outcomes. A retrospective review of a single surgeon's series of 320 patients, including 61 who underwent WR, from 1998 to the present was performed. Patients were stratified into risk groups based on preoperative data known to predict time to prostate cancer mortality. Pathologic outcomes were tabulated and biochemical outcomes were analyzed at follow-up. Comparisons were made between WR and radical retropubic prostatectomy (RRP) with or without nerve sparing based on these parameters within each risk group. Kaplan-Meier, multivariate, and propensity score analyses were used to evaluate the impact of surgical technique on biochemical recurrence. Urinary morbidity was compared using a retrospective review of University of California-Los Angeles Prostate Cancer Symptom Index self-questionnaires. No increase in urinary or rectal morbidity was noted using the WR technique. A statistically significant decrease in positive surgical margins was noted in the high-risk population (55% vs 16%, P = 0.010) in favor of WR. Biochemical failure was similar between groups (WR vs RRP), and no biochemical survival advantage could be documented. Thus, the WR technique may successfully decrease the rate of positive surgical margins in a high-risk group without any increased urinary morbidity. This technique may affect only local control because biochemical recurrence rates were not statistically different. This finding implies the presence of occult metastatic disease at the time of surgery. A larger population with better-matched subjects is needed to clarify the potential role of WR in an intermediate-risk population.

Purpose: The detection of low volume and early stage prostate cancer has increased with the widespread use of prostate specific antigen screening for prostatic adenocarcinoma. This increased detection has led to efforts to stratify patient risk and the potential benefits of various treatments based on preoperative clinical and biopsy data. We examined various clinical parameters and prostate biopsy features to determine which variables are most predictive of small volume (less than 0.5 ml) cancer at prostatectomy., Materials and Methods: We studied 336 patients who underwent prostatectomy for prostate cancer. Radical prostatectomy specimens were completely embedded and whole mounted. Final tumor volume in the radical prostatectomy specimens was determined by the grid method. Clinical data were gathered by a review of patient charts. Various preoperative clinical and biopsy findings were analyzed to determine factors predictive of small volume cancer at prostatectomy., Results: A total of 55 patients (16%) were found to have small volume cancer (less than 0.5 ml). On univariate logistic regression certain variables were significant predictors of small volume cancer, namely the highest Gleason score from all positive biopsy sites (p = 0.001), the Gleason score from the biopsy site with the highest percent of adenocarcinoma (p = 0.006), the highest percent of adenocarcinoma at any biopsy site (p <0.0001), the percent of adenocarcinoma at the biopsy site with the highest Gleason score (p <0.0001), the highest percent of cores positive for adenocarcinoma at any biopsy site (p = 0.001), the percent of cores with carcinoma at the site with the highest Gleason score (p = 0.002), the number of positive sites (p <0.0001) and tumor bilaterality (p <0.0001). None of the clinical parameters that we studied, including preoperative prostate specific antigen (p = 0.52), clinical stage (p = 0.62) or patient age (p = 0.94), was predictive of small volume cancer. On multivariate analysis the highest percent of adenocarcinoma at any site (adjusted OR 0.95, 95% CI 0.92 to 0.97, p <0.0001) and the number of positive biopsy sites (adjusted OR 0.97, 95% CI 0.96 to 0.99, p <0.0001) were significant predictors of small volume cancer., Conclusions: The number of positive biopsy sites and the highest percent of adenocarcinoma at any biopsy site are significant predictors of small volume cancer in radical prostatectomy specimens.

Some investigators consider small-volume prostate cancer (0.5 ml or less) without Gleason pattern 4/5 elements as clinically insignificant. The objective of this study was to characterize the anatomic distribution and pathologic features of small tumors (aggregate volume of 0.5 ml or less) in whole-mount prostatectomy specimens. Between 1999 and 2003, 371 consecutive patients underwent radical prostatectomy at the Indiana University Hospitals for localized prostate cancer. Patients who received hormonal or radiation therapy prior to the surgery were excluded from the study. A total of 62 specimens with total tumor volume of 0.5 ml or less were identified and included in this study. All specimens were embedded and whole-mounted. Tumor volume was measured using the grid method. The mean age at the time of surgery was 59 years (median, 61 years; range, 37-72 years). The mean preoperative prostate-specific antigen (PSA) was 6.5 ng/ml (range: 0.3-18 ng/ml). The mean prostate weight was 53 g (range: 16-132 g). The mean tumor volume was 0.29 ml (median, 0.35 ml; range, 0.02-0.48 ml). Tumor multifocality and bilaterality were present in 69 and 37% of cases, respectively. Three (5%) had positive surgical margins. The largest tumor was located in the peripheral zone, transitional zone, and central zone in 79, 16, and 5% of cases, respectively. The largest tumor was located in the anterior prostate in 10 cases (16%) and in the posterior prostate in 52 cases (84%). The distribution of Gleason scores was 5 (12 cases, 19 %), 6 (40 cases, 65 %), and 7 (10 cases, 16 %). One case had a primary Gleason pattern 4. None had extraprostatic extension, seminal vesicle invasion, or lymph node metastasis. Small-volume prostate cancers are often multifocal and bilateral, with predilection for the peripheral zone. Of these small-volume cases, 16% had Gleason pattern 4 and might, therefore, be clinically significant.

Purpose: Clinical outcome is variable in prostate cancer patients treated with radical prostatectomy. The Gleason histologic grade of prostatic adenocarcinoma is one of the strongest predictors of biologic aggressiveness of prostate cancer. We evaluated the significance of the relative proportion of high-grade cancer (Gleason patterns 4 and/or 5) in predicting cancer progression in prostate cancer patients treated with radical prostatectomy., Patients and Methods: Radical prostatectomy specimens from 364 consecutive prostate cancer patients were totally embedded and whole mounted. Various clinical and pathologic characteristics were analyzed. All pathologic data, including Gleason grading variables, were collected prospectively., Results: A multiple-factor analysis was performed that included the combined percentage of Gleason patterns 4 and 5, Gleason score, tumor stage, surgical margin status, preoperative prostate-specific antigen (PSA), extraprostatic extension, and total tumor volume. Using Cox regression analysis with bootstrap resampling for predictor selection, we identified the combined percentage of Gleason patterns 4 and 5 (P < .0001) and total tumor volume (P = .009) as significant predictors of PSA recurrence., Conclusion: The combined percentage of Gleason patterns 4 and 5 is one of the most powerful predictors of patient outcome, and appears superior to conventional Gleason score in identifying patients at increased risk of disease progression. On the basis of our results, we recommend that the combined percentage of Gleason patterns 4 and 5 be evaluated in radical prostatectomy specimens. The amount of high-grade cancer in a prostatectomy specimen should be taken into account in therapeutic decision making and assessment of patient prognosis.

Complete removal of the tumor by surgery offers the best chance for cancer cure; however, many prostate cancer patients who have negative surgical margins at radical prostatectomy will still experience local and distant tumor recurrence. In other organs, the closest distance between tumor and resection margin has prognostic significance. This has not been adequately studied in prostatectomy specimens. We undertook a prospective study of 278 consecutive margin-negative whole-mount prostatectomy cases. The anatomic location and closest distance between tumor and resection margin, measured with an ocular micrometer, were analyzed. All the slides were reviewed by a single pathologist, and data were collected prospectively. The closest distance between tumor and resection margin ranged from 0.02 to 5.0 mm (mean, 0.7 mm; median, 0.5 mm) and correlated with patient age (P = 0.03), prostate weight (P = 0.002), Gleason score (P = 0.001), pathologic stage (P = 0.01), tumor volume (P < 0.001), and perineural invasion (P < 0.001). The closest distance between tumor and resection margin was not a significant predictor of PSA recurrence in univariate or multivariate logistic regression; and we do not, therefore, advocate reporting the closest distance between tumor and resection margin as a standard part of the surgical pathology report on prostatectomy specimens.

Purpose: The prognostic significance of perineural invasion in radical prostatectomy specimens is uncertain. We evaluated the relationship between perineural invasion and other pathological characteristics in whole mount radical retropubic prostatectomy specimens as well as prostate specific antigen (PSA) recurrence postoperatively., Materials and Methods: Between 1999 and 2003, 364 consecutive patients were treated with radical prostatectomy for localized prostate cancer. Radical prostatectomy specimens were processed by the whole mount technique. The relationship of perineural invasion and various clinicopathological characteristics to PSA recurrence was analyzed., Results: Perineural invasion was present in 287 specimens (79%). Specimens with perineural invasion were associated with smaller prostate weight (p <0.0001), greater pathological stage (p <0.0001), larger tumor volume (p <0.0001), higher Gleason score (p <0.0001), a higher incidence of extraprostatic extension (p <0.0001) and seminal vesicle invasion (p = 0.02), and a higher positive surgical margin rate (p = 0.01). Perineural invasion did not correlate with preoperative PSA (p = 0.96), lymph node metastases (p = 0.35), multifocality (p = 0.21), high grade prostatic intraepithelial neoplasia (p = 0.12) or PSA recurrence (p = 0.24)., Conclusions: While perineural invasion in the radical prostatectomy specimen significantly correlated with multiple adverse pathological factors, it did not predict which patients will have early PSA recurrence following radical prostatectomy.

Purpose: We examine the complication and continence rates with early catheter removal (day 3 or 4) after radical retropubic prostatectomy., Materials and Methods: A total of 365 patients with localized prostate cancer underwent radical retropubic prostatectomy at Indiana University Hospital with planned urethral catheter removal before discharge home. Low pressure cystograms were performed on postoperative day 3 or 4 to determine if catheter removal was possible. A subset of patients were analyzed using a validated prostate cancer specific questionnaire (University of California, Los Angeles Prostate Cancer Symptom Index) to determine quality of life outcomes., Results: The catheter was removed on postoperative day 3 or 4 in 263 patients (72%). The reasons for leaving the catheter indwelling were significant leak on cystogram or excessive suprapubic drainage (21%), extensive bladder neck reconstruction (1%) and prolonged hospitalization because of an ileus or other complicating factor (6%). Thirteen patients (3.6%) were either unable to void after catheter removal or presented with retention (not associated with hematuria or clots) after hospital discharge, requiring reinsertion of the Foley catheter. A total of 41 patients (11%) had either an early or late complication (excluding incontinence). There were 3 complications (0.8%) that were considered major because they were potentially life threatening or required a return to the operating room. A pelvic abscess developed in 2 patients and a lymphocele in 1, which required percutaneous drainage. After at least 6 months (mean 20.9 months) 140 patients (89.2%) and 14 (8.9%) reported excellent and good continence, respectively. The patient questionnaire demonstrated bother scores to be minimal to no bother for 95% to 98% of patients at 6 and 12 months., Conclusions: This study confirms that it is safe to remove catheters in most patients 3 to 4 days after prostatectomy if a cystogram demonstrates no extravasation. Complication rates and continence rates with this approach compare favorably with series in which catheters are left indwelling for longer periods.

Background: A wide range of disorders can be detected in the urine. Tumor-modifying proteins in the urine may serve as a diagnostic tool for cancer patients and the alterations in their profiles may indicate efficacies of chemotherapy, radiotherapy, and surgery. Methods: We focused on urinary proteomes of patients with prostate cancer and identified tumor-modifying proteins in the samples before and after prostatectomy. Protein array analysis was conducted to evaluate a differential profile of tumor-promoting cytokines, while mass spectrometry-based global proteomics was conducted to identify tumor-suppressing proteins. Results: The result revealed striking differences by prostatectomy. Notably, the urine from the post-prostatectomy significantly decreased the tumorigenic behaviors of prostate tumor cells as well as breast cancer cells. We observed that angiogenin, a stimulator of blood vessel formation, was reduced in the post-prostatectomy urine. By contrast, the levels of three cell-membrane proteins such as prostasin (PRSS8), nectin 2 (PVRL2), and nidogen 1 (NID1) were elevated and they acted as extracellular tumor-suppressing proteins. These three proteins, given extracellularly, downregulated tumorigenic genes such as Runx2, Snail, and transforming growth factor beta and induced apoptosis of tumor cells. However, the role of NID1 differed depending on the location, and intracellular NID1 was tumorigenic and reduced the percent survival. Conclusions: This study demonstrated that prostatectomy remarkably altered the profile of urinary proteomes, and the post-prostatectomy urine provided tumor-suppressive proteomes. The result sheds novel light on the dynamic nature of the urinary proteomes and a unique strategy for predicting tumor suppressors. [ABSTRACT FROM AUTHOR]

With the advancement of early detection tools for prostate cancer and ability to better localize disease, there has been increased interest in focal or targeted therapies that carry less morbidity than traditional whole-gland treatments. The Sonablate® high-intensity focused ultrasound (HIFU) device has Food and Drug Administration (FDA) 510(K) clearance in the United States for ablation of prostate tissue. HIFU utilizes an ultrasound (US) transducer that focuses US beams on a preset point as much as 4 cm from the energy source without injuring intervening tissue. The Sonablate system guides the surgeon step-by-step to perform effective ablation of a target lesion. The surgeon can assess treatment effect with tissue change monitoring, and care is taken to prevent rectal wall injury. We believe hemiablation is the most favorable focal HIFU treatment to optimize cancer control and minimize the side effects associated with whole gland therapy. We recommend considering HIFU ablation as an extension of active surveillance rather than definitive treatment. Further research on long-term oncologic and functional outcomes is warranted. [ABSTRACT FROM AUTHOR]

BACKGROUND: Determining the optimal treatment for biochemical recurrence (BCR) after radical prostatectomy (RP) is challenging. OBJECTIVE:We evaluated the ability of CCP score (a prognostic RNA expression signature) to discriminate between systemic disease and local recurrence in patients with BCR after RP. METHODS: Sixty patients with BCR after RP were selected for analysis based on: 1) metastatic disease, 2) non-response to salvage external beam radiotherapy (EBRT), and 3) durable response to salvage EBRT. CCP scores were generated from the RNA expression of 46 genes. Logistic regression assessed the association between CCP score and patient group. RESULTS: Passing CCP scores were generated for 47 patients with complete clinical and pathologic data. CCP score predicted clinical status when comparing patients with metastatic disease or non-responders to salvage therapy to patients with durable response (p = 0.006). CCP score remained significantly predictive of clinical status after accounting for time to BCR, PSA level at BCR, and Gleason score (p = 0.0031). CONCLUSIONS: Elevated CCP score was associated with increased risk of systemic disease, indicating that CCP score may be useful in identifying patients with BCR who are most likely to benefit from salvage radiation therapy. [ABSTRACT FROM AUTHOR]

Purpose: We examined a retrospective cohort of patients with biochemical recurrence after prostatectomy to determine whether prostate specific antigen doubling time would remain stable with time. We also examined the relationship between other clinical parameters and the change in prostate specific antigen doubling time. Materials and Methods: We retrospectively reviewed the prostate cancer database from 1989 to 2008 to identify patients treated with radical prostatectomy for prostate cancer who experienced prostate specific antigen recurrence. Of the 2,237 patients identified 329 had biochemical recurrence. Prostate specific antigen doubling time was calculated at each visit and linear regression of prostate specific antigen doubling time with time was fit. Rate of change in prostate specific antigen doubling time was defined as the slope of the least squares regression line. Results: Median followup was 5 years (range 0.2 to 18). High Gleason score and local recurrence within 5 years were significantly associated with shorter 2-year prostate specific antigen doubling time and a decreased rate of change in doubling time (p = 0.0096, 0.0119, 0.0195 and 0.0258, respectively). Metastasis within 5 years was significantly associated with shorter 2 and 5-year doubling time (p = 0.0006 and 0.0014, respectively). Using all prostate specific antigen values within 5 years of initial biochemical recurrence yielded an overall median prostate specific antigen doubling time of 52.8 months (range 5.4 to 100.0). The median rate of change in doubling time was −1.05 (range −64.7 to 27.0). Median time to metastasis after biochemical recurrence was 12.9 years. Conclusions: Median prostate specific antigen doubling time decreases with time. This may influence the decision to offer secondary therapy to patients with biochemical recurrence sooner since initial prostate specific antigen doubling time is long and may not accurately reflect the biological nature of the disease. [Copyright &y& Elsevier]

The article focuses on a study on the effectiveness of combined percentage of Gleason patterns 4 and 5 in radical prostatectomy specimens in predicting cancer-specific survival among prostate cancer patients treated at Indiana University Medical Center in Indianapolis. The study analyzed various clinical and pathologic characteristics of the disease. It found that a higher combined percentage of Gleason patterns 4 and 5 was associated with older age, higher preoperative serum prostate-specific antigen level and lymph node metastasis.

Purpose: In radical prostatectomy specimens Gleason score 7 is among the most commonly assigned scores for prostate carcinoma accounting for 30% to 50% of cases. Gleason score 7 is different from other more differentiated prostate carcinomas (tumors of Gleason scores 5 and 6) with a significantly worse outcome and higher rate of recurrence. Nonetheless, Gleason score 7 tumors are heterogeneous. In this study we examined the differences in clinical outcome between primary Gleason grade 3 and 4 tumors in patients who underwent radical prostatectomy, and determined the influence of tertiary Gleason pattern 5 on patient outcome. Materials and Methods: A total of 504 patients underwent radical prostatectomy for prostate cancer and 228 of the patients (45%) had a Gleason score of 7. Cases were analyzed for a variety of clinical and pathological parameters. The influence of primary Gleason pattern and tertiary Gleason pattern 5 on patient outcome was assessed in the Cox regression model. Results: Among 228 patients with Gleason score 7 prostatic adenocarcinoma, 91 (40%) had a primary Gleason pattern 4 and 137 (60%) had primary Gleason pattern 3. Patients of the former group were more likely to have a higher pathological stage (p = 0.003), more likely to have PSA recurrence (p = 0.02) and more likely to have a tertiary Gleason pattern 5 (p <0.0001). A total of 37 (41%) patients with primary Gleason 4 had a tertiary Gleason pattern 5, whereas only 13 (9%) patients with primary Gleason 3 had a tertiary Gleason pattern 5. In the Cox regression model controlling for tumor stage and surgical margin status, the primary Gleason pattern was not an independent predictor of PSA recurrence (p = 0.80), whereas the presence of tertiary Gleason pattern 5 was a significant predictor of PSA recurrence (hazard ratio 2.10, 95% CI 1.24-3.55, p = 0.006). Five-year PSA recurrence-free survival was 70% for patients without a tertiary Gleason pattern 5 compared to 19% for those patients with a tertiary Gleason pattern 5. Conclusions: Among patients with Gleason score 7, primary Gleason grade 4 indicates a likelihood of higher tumor stage and higher probability of PSA recurrence than does primary pattern 3. However, it does not independently predict a worse outcome after controlling for other known prognostic parameters associated with disease progression. Regardless of whether the primary Gleason pattern is 3 or 4, a tertiary Gleason pattern 5 is the strongest predictor of a worse outcome in patients with Gleason grade 7 prostatic adenocarcinoma. Therefore, tertiary pattern 5 should be reported in radical prostatectomy specimens. [Copyright &y& Elsevier]

OBJECTIVE To analyse tumour extent as a predictor of cancer progression after radical prostatectomy (RP), using a multivariate Cox regression model, as several variables (e.g. Gleason grade and tumour stage) are well-established prognostic factors in prostate cancer but it is uncertain if the visual estimation of tumour extent (percentage of carcinoma) is an independent predictor for prostate cancer recurrence. PATIENTS AND METHODS Tumour extent was estimated in the RP specimens from 504 men with clinically localized prostate cancer; clinical follow-up data were available for 459 men. The mean (range) follow-up was 44.3 (1.5–144) months. Cancer progression was defined by the development of biochemical recurrence, local recurrence, or distant metastasis. Multivariate analysis was used to assess tumour extent as a predictor of cancer progression. RESULTS Of the 459 patients, 157 had cancer progression; the mean tumour extent was 36% and 24% in those with and without cancer progression, respectively ( P < 0.001). Univariate analysis showed a significant association between the visual estimation of tumour extent and tumour stage, Gleason grade, surgical margins, extraprostatic extension, seminal vesicle invasion, lymph node metastasis, and preoperative serum prostate-specific antigen level (all P < 0.001). However, in a multivariate Cox regression model controlling for pathological stage, Gleason score, and surgical margin status, the visual estimation of tumour extent was no longer a significant predictor of cancer progression ( P = 0.84). CONCLUSION The visual estimation of tumour extent was associated with various established prognostic factors for prostate cancer, and with cancer progression in a univariate analysis, but it was not a significant predictor of cancer progression in the multivariate analysis controlling for pathological stage, Gleason score, and surgical margin status. [ABSTRACT FROM AUTHOR]

OBJECTIVE To test the hypothesis that prostate cancer patients with clinical stage cT1c and cT2 have similar outcomes and clinicopathological features, and should be grouped together. PATIENTS AND METHODS From a series of men with prostate cancer who had a radical retropubic prostatectomy (RP), we assessed those with cT1c (223) and cT2 (65) adenocarcinoma. All RP specimens were totally embedded and whole-mounted; tumour volume was measured using the grid method. Clinical and pathological characteristics were analysed. RESULTS Patients with cT2 tumours were more likely to have a higher Gleason score ( P = 0.04) and final pathological stage ( P = 0.05) than those with cT1c tumours. There was no significant difference in age ( P = 0.92), preoperative PSA level ( P = 0.17), prostate weight ( P = 0.34), tumour volume ( P = 0.16), surgical margin status ( P = 0.86), multifocality ( P = 0.92), the presence of perineural invasion ( P = 0.09), or high-grade prostatic intraepithelial neoplasia ( P = 0.99) between patients with clinical stage cT1c and those with cT2 tumours. There was no difference in PSA recurrence between patients with clinical stage T1c and those with cT2 tumours ( P = 0.27). CONCLUSIONS Patients with clinical stage cT2 tumours have a higher Gleason score and advanced pathological stage than tumours detected because of a high serum PSA level (cT1c). These results suggest that clinical stage cT1c tumours should be separated from clinical stage cT2 disease, but the PSA recurrence rate for both tumour stages is similar, indicating a need for further evaluation and refinement of the current clinical staging system. [ABSTRACT FROM AUTHOR]

Background: Incontinence and impotence occur following radical prostatectomy due to injury to nerves and sphincter muscle. Preserving nerves and muscle adjacent to prostate cancer risks positive surgical margins. Advanced imaging with MRI has improved cancer localization but limitations exist.Objective: To measure the accuracy for assessing extra-prostatic extension at nerve bundles for 2 PSMA-PET tracers and to compare the PET accuracy to standard-of-care predictors including MRI and biopsy results.Materials and Methods: We studied men with PSMA-targeted PET imaging, performed prior to prostatectomy in men largely with intermediate to high-risk prostate cancer, and retrospectively evaluated for assessment of extra-prostatic extension with whole-mount analysis as reference standard. Two different PSMA-PET tracers were included: 68Ga-PSMA-11 and 68Ga-P16-093. Blinded reviews of the PET and MRI scans were performed to assess extra-prostatic extension (EPE). Sensitivity and specificity for extra-prostatic extension were compared using McNemar's Chi2.Results: Pre-operative PSMA-PET imaging was available for 71 patients with either 68Ga-P16-093 (n = 25) or 68Ga-PSMA-11 (n = 46). There were 24 (34%) with pT3a (EPE) and 16 (23%) with pT3b (SVI). EPE Sensitivity (87% vs. 92%), Specificity (77% vs. 76%), and ROC area (0.82 vs. 0.84) were similar between P16-093 and PSMA-11, respectively (P = 0.87). MRI (available in only 45) found high specificity (83%) but low sensitivity (60%) for EPE when using a published grading system. MRI sensitivity was significantly lower than the PSMA-PET (60% vs. 90%, P = 0.02), but similar to PET when using a >5 mm capsular contact (76% vs. 90%, P = 0.38). A treatment change to "nerve sparing" was recommended in 21 of 71 (30%) patients based on PSMA-PET imaging.Conclusions: Presurgical PSMA-PET appeared useful as a tool for surgical planning, changing treatment plans in men with ≥4+3 or multi-core 3+4 prostate cancer resulting in preservation of nerve-bundles. [ABSTRACT FROM AUTHOR]