A Contemporary Report of Low-Dose-Rate Brachytherapy for Prostate Cancer Using MRI for Risk Stratification: Disease Outcomes and Patient-Reported Quality of Life.

PURPOSE: We examined a prospective consecutive cohort of low dose rate (LDR) brachytherapy for prostate cancer to evaluate the efficacy of monotherapy for unfavorable-intermediate risk (UIR) disease, and explore factors associated with toxicity and quality of life (QOL). METHODS: 149 men with prostate cancer, including 114 staged with MRI, received Iodine-125 brachytherapy alone (144-145 Gy) or following external beam radiation therapy (110 Gy; EBRT). Patient-reported QOL was assessed by the Expanded Prostate Index Composite (EPIC) survey, and genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively recorded (CTC v4.0). Global QOL scores were assessed for decline greater than the minimum clinically important difference (MCID). Univariate analysis (UVA) was performed, with 30-day post-implant dosimetry covariates stratified into quartiles. Median follow-up was 63 mo. RESULTS: Men with NCCN low (n = 42) or favorable-intermediate risk (n = 37) disease were treated with brachytherapy alone, while most with high-risk disease had combined EBRT (n = 17 of 18). Men with UIR disease (n = 52) were selected for monotherapy (n = 42) based on clinical factors and MRI findings. Freedom from biochemical failure-7 yr was 98%. Of 37 men with MRI treated with monotherapy for UIR disease, all 36 men without extraprostatic extension were controlled. Late Grade 2+/3+ toxicity occurred in 55/3% for GU and 8/2% for GI, respectively. Fifty men were sexually active at baseline and had 2 yr sexual data; 37 (74%) remained active at 2 yr. Global scores for urinary incontinence (UC), urinary irritation/obstruction (UIO), bowel function, and sexual function (SF) showed decreases greater than the MCID (p < 0.05) in UC at 2 mo, UIO at 2 and 6 mo, and SF at 2-24 mo, and >5 yr. Analysis did not reveal any significant associations with any examined rectal or urethral dosimetry for late toxicity or QOL. CONCLUSION: Disease outcomes and patient-reported QOL support LDR brachytherapy, including monotherapy for UIR disease.

"Robotic fatigue?" - The impact of case order on positive surgical margins in robotic-assisted laparoscopic prostatectomy.

PURPOSE: Multiple robotic-assisted surgeries are often performed within a single operating day; however, the impact of this practice on patient outcomes has not been examined. We aim to determine whether outcomes for robotic-assisted laparoscopic prostatectomy (RALP) differed when performed sequentially. MATERIALS AND METHODS: A multi-institutional, retrospective cohort study was conducted involving a total of 8 academic centers between years 2015 and 2018. Participants were adult males undergoing RALP for localized prostate cancer on operative days in which 2 RALP cases were performed sequentially by the same resident-attending team. The primary outcome of the study was presence of positive surgical margin (PSM). Secondary outcomes were lymph node yield, operative time, and estimated blood loss. The primary analysis was a random effects meta-analysis model for PSM. RESULTS: Overall, 898 RALP cases (449 sequential pairs) were included in the study. There was no significant difference in PSM rate (27.2% vs. 30.3%, P= 0.338) between first and second case groups, respectively. Utilizing random effects meta-analysis, the second case cohort had no increased risk of PSM (OR 0.761.231.97, P= 0.40). Higher blood loss was noted in the second case cohort (186.7 ml vs. 221.7 ml, P = 0.002). Additionally, factors associated with PSM were increasing prostate specific antigen, higher percent tumor involvement, extraprostatic extension, and seminal vesicle invasion. CONCLUSION: Case sequence was not associated with PSM, lymph node yield, or operative time for RALP. Disease specific factors and institutional experience are associated with increased risk for positive surgical margin which can aid providers in scheduling of patients.

Setting up a pediatric robotic urology program: A USA institution experience.

Implementing a robotic urological surgery program requires institutional support, and necessitates a comprehensive, detail-oriented plan that accounts for training, oversight, cost and case volume. Given the prevalence of robotic surgery in adult urology, in many instances it might be feasible to implement a pediatric robotic urology program within the greater context of adult urology. This involves, from an institutional standpoint, proportional distribution of equipment cost and operating room time. However, the pediatric urology team primarily determines goals for volume expansion, operative case selection, resident training and surgical innovation within the specialty. In addition to the clinical model, a robust economic model that includes marketing must be present. This review specifically highlights these factors in relationship to establishing and maintaining a pediatric robotic urology program. In addition, we share our data involving robot use over the program's first nine years (December 2007-December 2016).

Extraprostatic Extension Is Extremely Rare for Contemporary Gleason Score 6 Prostate Cancer.

BACKGROUND: A significant proportion of men with Gleason score 6 (GS6) prostate cancer undergo treatment with radiation or surgery. OBJECTIVE: To assess pathologic stage of pure GS6 at radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: In the period 2003-2014, 7817 patients underwent RP at two institutions. Of 2502 patients with GS6 at surgery, 60 were identified as stage pT3a-b on initial pathologic review, 55 with pT3a (extraprostatic extension, EPE), and five with pT3b (seminal vesicle invasion; SVI). All cases of GS6 with pT3 disease underwent contemporary pathologic evaluation for Gleason grade, stage, and extent of EPE. At one institution, all GS≥7 pT3b cases were re-reviewed for downgrading. The 2014 International Society of Urological Pathology (ISUP) Gleason grading criteria and 2009 ISUP recommendations on pT3 staging were applied. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Calculated incidence (%) of pT3a, pT3b, pT4, and lymph node-positive disease. RESULTS AND LIMITATIONS: Of the 60 GS6 pT3a-b cases identified in the period 2003-2014, seven (0.28% of entire GS6 cohort) with GS6 and pT3a were identified after re-review, all focal EPE. Among the re-examined cohort, no cases of GS6 with pT3b were observed. None of the 132 GS≥7 pT3b cases were downgraded to GS6. Limitations include partial embedding of specimens and separate pathologic review at each institution. CONCLUSIONS: In a large prostatectomy cohort, GS6 never had seminal vesicle invasion (0%) and was very rarely (0.28%) associated with extraprostatic extension. PATIENT SUMMARY: GS6 prostate cancer rarely spreads outside the prostate. A new finding in this study was that GS6 prostate cancer never spread to the seminal vesicles.

Robotic­assisted pelvic lymph node dissection for prostate cancer: frequency of nodal metastases and oncological outcomes

Purpose Limited data are available regarding the oncologic efficacy of pelvic lymph node dissection (PLND) performed during robotic-assisted laparoscopic prostatectomy (RALP) for prostate cancer. We aimed to determine the frequency of pelvic lymph node metastasis and oncological outcomes following RALP with PLND in patients who did not receive adjuvant androgen deprivation therapy (ADT). Methods We retrospectively reviewed the records of 1740 consecutive patients who underwent RALP and extended PLND. The primary endpoint was biochemical recurrence (BCR). The estimated BCR probability was obtained using the Kaplan­Meier method. Cox proportional hazard regression models were used to assess for predictors of BCR. Results One hundred and eight patients (6 pertcent) with positive LNs were identified. The median number of LNs removed was 17 (IQR 11­24), and median follow-up was 26 months (IQR 14­43). Ninety-one (84 pertcent) patients did not receive adjuvant ADT of whom 60 pertcent had BCR with a median time to recurrence of 8 months. The 1- and 3-year BCR-free probability was 42 and 28 pertcent, respectively. Patients with ≤2 LN+ had significantly better biochemicalfree estimated probability compared to those with >2 LN+ (p = 0.002). The total number of LN+ (HR = 1.1; 95 pertcent CI 1.01­1.2, p = 0.04) and Gleason 8­10 (HR = 1.96; 95 perrtcent CI 1.1­3.4, p = 0.02) were predictors of BCR on multivariate analysis. Conclusion Among men with positive lymph nodes at time of robotic prostatectomy, those with two or fewer positive nodes and Gleason <8 exhibited favorable biochemical-free survival without adjuvant therapy.(AU) Cerrar

Prognostic Significance of Percentage and Architectural Types of Contemporary Gleason Pattern 4 Prostate Cancer in Radical Prostatectomy.

The International Society of Urological Pathology (ISUP) 2014 consensus meeting recommended a novel grade grouping for prostate cancer that included dividing Gleason score (GS) 7 into grade groups 2 (GS 3+4) and 3 (GS 4+3). This division of GS 7, essentially determined by the percent of Gleason pattern (GP) 4 (< or >50%), raises the question of whether a more exact quantification of the percent GP 4 within GS 7 will yield additional prognostic information. Modifications were also made by ISUP regarding the definition of GP 4, now including 4 main architectural types: cribriform, glomeruloid, poorly formed, and fused glands. This study was conducted to analyze the prognostic significance of the percent GP 4 and main architectural types of GP 4 according to the 2014 ISUP grading criteria in radical prostatectomies (RPs). The cohort included 585 RP cases of GS 6 (40.2%), 3+4 (49.0%), and 4+3 (10.8%) prostate cancers. Significantly different 5-year biochemical recurrence (BCR)-free survival rates were observed among GS 6 (99%, 95% confidence interval [CI]: 97%-100%), 3+4 (81%, 95% CI: 76%-86%), and 4+3 (60%, 95% CI: 45%-71%) cancers (P<0.01). Dividing the GP 4 percent into quartiles showed a 5-year BCR-free survival of 84% (95% CI: 78%-89%) for 1% to 20%, 74% (95% CI: 62%-83%) for 21% to 50%, 66% (95% CI: 50%-78%) for 51% to 70%, and 32% (95% CI: 9%-59%) for >70% (P<0.001). Among the GP 4 architectures, cribriform was the most prevalent (43.7%), and combination of architectures with cribriform present was more frequently observed in GS 4+3 (60.3%). Glomeruloid was mostly (67.1%) seen combined with other GP 4 architectures. Unlike the other GP 4 architectures, glomeruloid as the sole GP 4 was observed only as a secondary pattern (ie, 3+4). Among patients with GS 7 cancer, the presence of cribriform architecture was associated with decreased 5-year BCR-free survival when compared with GS 7 cancers without this architecture (68% vs. 85%, P<0.01), whereas the presence of glomeruloid architecture was associated with improved 5-year BCR-free survival when compared with GS 7 cancers without this architecture (87% vs. 75%, P=0.01). However, GS 7 disease having only the glomeruloid architecture had significantly lower 5-year BCR-free survival than GS 6 cancers (86% vs. 99%, P<0.01). Multivariable Cox proportional hazards regression model for factors associated with BCR among GS 7 cancers identified age (hazard ratio [HR] 0.95, P<0.01), preoperative prostate-specific antigen (HR 1.07, P<0.01), positive surgical margin (HR 2.70, P<0.01), percent of GP 4 (21% to 50% [HR 2.21], 51% to 70% [HR 2.59], >70% [HR 6.57], all P<0.01), presence of cribriform glands (HR 1.78, P=0.02), and presence of glomeruloid glands (HR 0.43, P=0.03) as independent predictors. In conclusion, our study shows that increments in percent of GP 4 correlate with increased risk for BCR supporting the ISUP recommendation of recording the percent of GP 4 in GS 7 prostate cancers at RP. However, additional larger studies are needed to establish the optimal interval for reporting percent GP 4 in GS 7 cancers. Among the GP 4 architectures, cribriform independently predicts BCR, whereas glomeruloid reduces the risk of BCR. Distinction should be made between cribriform and glomeruloid architectures, despite glomeruloid being considered as an early stage of cribriform, as cribriform confers a higher risk for poorer outcome.

The impact of days off between cases on perioperative outcomes for robotic-assisted laparoscopic prostatectomy.

PURPOSE: To examine the effect of days off between cases on perioperative outcomes for robotic-assisted laparoscopic prostatectomy (RALP). METHODS: We analyzed a single-surgeon series of 2036 RALP cases between 2003 and 2014. Days between cases (DBC) was calculated as the number of days elapsed since the surgeon's previous RALP with the second start cases assigned 0 DBC. Surgeon experience was assessed by dividing sequential case experience into cases 0-99, cases 100-249, cases 250-999, and cases 1000+ based on previously reported learning curve data for RALP. Outcomes included estimated blood loss (EBL), operative time (OT), and positive surgical margins (PSMs). Multiple linear regression was used to assess the impact of the DBC and surgeon experience on EBL, OT, and PSM, while controlling for patient characteristics, surgical technique, and pathologic variables. RESULTS: Overall median DBC was 1 day (0-3) and declined with increasing surgeon case experience. Multiple linear regression demonstrated that each additional DBC was independently associated with increased EBL [ß = 3.7, 95% CI (1.3-6.2), p < 0.01] and OT [ß = 2.3 (1.4-3.2), p < 0.01], but was not associated with rate of PSM [ß = 0.004 (-0.003-0.010), p = 0.2]. Increased experience was also associated with reductions in EBL and OT (p < 0.01). Surgeon experience of 1000+ cases was associated with a 10% reduction in PSM rate (p = 0.03) compared to cases 0-99. CONCLUSIONS: In a large single-surgeon RALP series, DBC was associated with increased blood loss and operative time, but not associated with positive surgical margins, when controlling for surgeon experience.

Contemporary Population-Based Comparison of Localized Ductal Adenocarcinoma and High-Risk Acinar Adenocarcinoma of the Prostate.

OBJECTIVE: To compare pathological characteristics, treatment patterns, and survival in patients with ductal adenocarcinoma (DC) compared to those with acinar adenocarcinoma (AC). MATERIALS AND METHODS: Using the National Cancer Database, we identified patients diagnosed with clinically localized (cN0, cM0) pure DC (n = 1328) and AC (n = 751,635) between 1998 and 2011. High-risk AC was defined as Gleason 8-10. Demographic, treatment, pathological, and survival characteristics of patients were compared. RESULTS: Compared to patients with Gleason 8-10 AC, those with DC presented with lower mean prostate-specific antigen (10.3 vs 16.2 ng/mL, P <.001), had similar rates (11.7% vs 11.5%, P = .8) of clinical extra-capsular extension (stage ≥ cT3), and were more likely to undergo prostatectomy (54% vs 36%, P <.001). Compared to patients with Gleason 8-10 AC undergoing prostatectomy, those with DC had more favorable pathology: stage ≥ T3 (39% vs 52%, P <.001), fewer positive lymph nodes (4% vs 11%, P <.001), and fewer positive margins (25% vs 33%, P <.001). On Kaplan-Meier analysis, patients with DC had similar 5-year survival (75.0%, 95% confidence interval [CI] [71.7-78.9]) compared to those with Gleason 8-10 AC (77.1%, 95% CI [76.6%-77.6%], P = .2). On Cox multivariable analysis, patients with Gleason 8-10 AC had a similar risk of death compared to those with DC (hazards ratio = 0.92, 95% CI [0.69-1.23], P = 6). CONCLUSION: In this large contemporary population-based series, patients with DC of the prostate presented with lower prostate-specific antigen, had more favorable pathological features, and similar overall survival compared to men with Gleason 8-10 AC.

Bloody otorrhea after robotically assisted laparoscopic prostatectomy.

Bilateral bloody otorrhea is a rare complication of surgery and to our knowledge a previously unpublished event. We review the case of a 50-year-old male who underwent robotic-assisted laparoscopic radical prostatectomy (RALP) with bilateral lymphadenectomy for Gleason's Score 4 + 4 = 8 prostate cancer. Bloody discharge from bilateral auditory canals was noted upon removal of the surgical drapes. Otolaryngologic examination revealed bilateral anterior auditory canal hematomas without any loss of hearing. Steep Trendelenburg position in combination with perioperative anticoagulants may have contributed to this complication. Given the rarity of this event no specific risk factors are identified.

Robotic-assisted pelvic lymph node dissection for prostate cancer: frequency of nodal metastases and oncological outcomes.

PURPOSE: Limited data are available regarding the oncologic efficacy of pelvic lymph node dissection (PLND) performed during robotic-assisted laparoscopic prostatectomy (RALP) for prostate cancer. We aimed to determine the frequency of pelvic lymph node metastasis and oncological outcomes following RALP with PLND in patients who did not receive adjuvant androgen deprivation therapy (ADT). METHODS: We retrospectively reviewed the records of 1740 consecutive patients who underwent RALP and extended PLND. The primary endpoint was biochemical recurrence (BCR). The estimated BCR probability was obtained using the Kaplan-Meier method. Cox proportional hazard regression models were used to assess for predictors of BCR. RESULTS: One hundred and eight patients (6 %) with positive LNs were identified. The median number of LNs removed was 17 (IQR 11-24), and median follow-up was 26 months (IQR 14-43). Ninety-one (84 %) patients did not receive adjuvant ADT of whom 60 % had BCR with a median time to recurrence of 8 months. The 1- and 3-year BCR-free probability was 42 and 28 %, respectively. Patients with ≤2 LN+ had significantly better biochemical-free estimated probability compared to those with >2 LN+ (p = 0.002). The total number of LN+ (HR = 1.1; 95 % CI 1.01-1.2, p = 0.04) and Gleason 8-10 (HR = 1.96; 95 % CI 1.1-3.4, p = 0.02) were predictors of BCR on multivariate analysis. CONCLUSION: Among men with positive lymph nodes at time of robotic prostatectomy, those with two or fewer positive nodes and Gleason <8 exhibited favorable biochemical-free survival without adjuvant therapy.

Early removal of urethral catheter with suprapubic tube drainage versus urethral catheter drainage alone after robot-assisted laparoscopic radical prostatectomy.

PURPOSE: Retrospective single institution data suggest that postoperative pain after robot-assisted laparoscopic radical prostatectomy is decreased by early removal of the urethral catheter with suprapubic tube drainage. In a randomized patient population we determined whether suprapubic tube drainage with early urethral catheter removal would improve postoperative pain compared with urethral catheter drainage alone. MATERIALS AND METHODS: Men with a body mass index of less than 40 kg/m(2) who had newly diagnosed prostate cancer and elected robot-assisted laparoscopic radical prostatectomy were included in analysis. Block randomization by surgeon was used and randomization assignment was done after completing the urethrovesical anastomosis. In patients assigned to suprapubic tube drainage the urethral catheter was removed on postoperative day 1 and all catheters were removed on postoperative day 7. Visual analog pain scale and satisfaction questionnaires were administered on postoperative days 0, 1 and 7. RESULTS: A total of 29 patients were randomized to the urethral catheter vs 29 to the suprapubic tube plus early urethral catheter removal at the time of interim futility analysis. Mean visual analog pain scale scores did not differ between the groups at any time point and a similar percent of patients cited the catheter as the greatest bother with nonsignificant differences in treatment related satisfaction. Complications during postoperative week 1 did not vary between the groups. Based on interim results the trial was terminated due to lack of effect. CONCLUSIONS: Patients randomized to suprapubic tube vs urethral catheter drainage for the week after prostatectomy had similar pain, catheter related bother and treatment related satisfaction in the perioperative period. We no longer routinely offer suprapubic tube drainage with early urethral catheter removal at our institution.

How accurate is our clinical prediction of "minimal prostate cancer"?

BACKGROUND: Recommendations for active surveillance versus immediate treatment for low risk prostate cancer are based on biopsy and clinical data, assuming that a low volume of well-differentiated carcinoma will be associated with a low progression risk. However, the accuracy of clinical prediction of minimal prostate cancer (MPC) is unclear. OBJECTIVES: To define preoperative predictors for MPC in prostatectomy specimens and to examine the accuracy of such prediction. METHODS: Data collected on 1526 consecutive radical prostatectomy patients operated in a single center between 2003 and 2008 included: age, body mass index, preoperative prostate-specific antigen level, biopsy Gleason score, clinical stage, percentage of positive biopsy cores, and maximal core length (MCL) involvement. MPC was defined as < 5% of prostate volume involvement with organ-confined Gleason score < or = 6. Univariate and multivariate logistic regression analyses were used to define independent predictors of minimal disease. Classification and Regression Tree (CART) analysis was used to define cutoff values for the predictors and measure the accuracy of prediction. RESULTS: MPC was found in 241 patients (15.8%). Clinical stage, biopsy Gleason's score, percent of positive biopsy cores, and maximal involved core length were associated with minimal disease (OR 0.42, 0.1, 0.92, and 0.9, respectively). Independent predictors of MPC included: biopsy Gleason score, percent of positive cores and MCL (OR 0.21, 095 and 0.95, respectively). CART showed that when the MCL exceeded 11.5%, the likelihood of MPC was 3.8%. Conversely, when applying the most favorable preoperative conditions (Gleason < or = 6, < 20% positive cores, MCL < or = 11.5%) the chance of minimal disease was 41%. CONCLUSIONS: Biopsy Gleason score, the percent of positive cores and MCL are independently associated with MPC. While preoperative prediction of significant prostate cancer was accurate, clinical prediction of MPC was incorrect 59% of the time. Caution is necessary when implementing clinical data as selection criteria for active surveillance.

Short (≤ 1 mm) positive surgical margin and risk of biochemical recurrence after radical prostatectomy.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: It has been suggested that a very short positive margin does not confer additional risk of BCR after radical prostatectomy. This study shows that even very short PSM is associated with increased risk of BCR. OBJECTIVE: To re-evaluate, in a larger cohort with longer follow-up, our previously reported finding that a positive surgical margin (PSM) ≤ 1 mm may not confer an additional risk for biochemical recurrence (BCR) compared with a negative surgical margin (NSM). PATIENTS AND METHODS: Margin status and length were evaluated in 2866 men treated with radical prostatectomy (RP) for clinically localized prostate cancer at our institution from 1994 to 2009. We compared the BCR-free survival probability of men with NSMs, a PSM ≤ 1 mm, and a PSM < 1 mm using the Kaplan-Meier method and a Cox regression model adjusted for preoperative prostate-specific antigen (PSA) level, age, pathological stage and pathological Gleason score (GS). RESULTS: Compared with a NSM, a PSM ≤ 1 mm was associated with 17% lower 3-year BCR-free survival for men with pT3 and GS ≥ 7 tumours and a 6% lower 3-year BCR-free survival for men with pT2 and GS ≤ 6 tumours (log-rank P < 0.001 for all). In the multivariate model, a PSM ≤ 1 mm was associated with a probability of BCR twice as high as that for a NSM (hazard ratio [HR] 2.2), as were a higher PSA level (HR 1.04), higher pathological stage (HR 2.7) and higher pathological GS (HR 3.7 [all P < 0.001]). CONCLUSION: In men with non-organ-confined or high grade prostate cancer, a PSM ≤ 1 mm has a significant adverse impact on BCR rates.

Predictors of serum vitamin D levels in African American and European American men in Chicago.

Vitamin D deficiency is epidemiologically linked to prostate, breast, and colon cancer. When compared with European American (EA) men, African American (AA) men have increased risk of prostate cancer, but few studies evaluate vitamin D status in AA men. The authors evaluate the biological and environmental predictors of vitamin D deficiency in AA and EA men in Chicago, Illinois, a low ultraviolet radiation environment. Blood samples were collected from 492 men, aged between 40 and 79 years, from urology clinics at three hospitals in Chicago, along with demographic and medical information, body mass index, and skin melanin content using a portable narrow-band reflectometer. Vitamin D intake and ultraviolet radiation exposure were assessed using validated questionnaires. The results demonstrated that Black race, cold season of blood draw, elevated body mass index, and lack of vitamin D supplementation increase the risk of vitamin D deficiency. Supplementation is a high-impact, modifiable risk factor. Race and sunlight exposure should be taken into account for recommended daily allowances for vitamin D intake.

Functional outcomes in African-Americans after robot-assisted radical prostatectomy.

BACKGROUND AND PURPOSE: Previous studies have demonstrated differences in surgical outcomes after radical prostatectomy based on ethnicity. We compared sexual and urinary outcomes in African-American (AA) patients 6 and 12 months after robot-assisted radical prostatectomy (RARP) with those of non-AA patients. PATIENTS AND METHODS: We reviewed our RARP database at our institution for patients with at least 12 months of follow-up. Erectile function was defined using the University of California, Los Angeles Prostate Cancer Index as erections "firm enough for masturbation and foreplay" or "firm enough for intercourse," while urinary continence was defined as being "pad free." Only patients who were potent and pad free preoperatively were included in the analysis. Multivariate logistic regression was used to compare postoperative potency and urinary pad-free status between AA and non-AA patients while controlling for pertinent demographic, clinical, and pathologic variables. RESULTS: In the urinary continence analysis, 140 AA patients and 576 non-AA patients were included, compared with 105 AAs and 500 non-AA patients who were included in the analysis of sexual function. At 12 months postoperatively, a smaller proportion of AA patients were potent compared with non-AA patients (60% vs 76.4%, P=0.001). Similarly, we found a lower incidence of pad-free status for AA patients at 12 months postoperatively (55.7% vs 69.8%, P=0.039). Similar functional results were found at 6 months postoperatively for both analysis groups. CONCLUSION: AA men appear to have worse urinary and sexual outcomes at 12 months after RARP compared with non-AA patients. At 6 months, there is no statistically significant difference. Further, longer-term studies are needed to validate these results.

Serum/glucocorticoid-regulated kinase 1 expression in primary human prostate cancers.

BACKGROUND: Serum/glucocorticoid-regulated kinase 1 (SGK1), a known target of the androgen receptor (AR) and glucocorticoid receptor (GR), is reported to enhance cell survival. This study sought to better define the role of SGK1 and GR in prostate cancer. METHODS: Immunohistochemistry was performed for AR, GR, and SGK1 on primary prostate cancers (n = 138) and 18 prostate cancers from patients treated with androgen deprivation therapy. Relative staining intensity was compared utilizing a Fisher's exact test. Univariate analyses were performed using log-rank and chi-squared tests to evaluate prostate cancer recurrence with respect to SGK1 expression. RESULTS: SGK1 expression was strong (3+) in 79% of untreated cancers versus 44% in androgen-deprived cancers (P = 0.003). Conversely, GR expression was present in a higher proportion of androgen-deprived versus untreated cancers (78% vs. 38%, P = 0.002). High-grade cancers were nearly twice as likely to have relatively low (0 to 2+) SGK1 staining compared to low-grade cancers (13.8% vs. 26.5%, P = 0.08). Low SGK1 expression in untreated tumors was associated with increased risk of cancer recurrence (adjusted log-rank test P = 0.077), 5-year progression-free survival 47.8% versus 72.6% (P = 0.034). CONCLUSIONS: SGK1 expression is high in most untreated prostate cancers and declines with androgen deprivation. However, these data suggest that relatively low expression of SGK1 is associated with higher tumor grade and increased cancer recurrence, and is a potential indicator of aberrant AR signaling in these tumors. GR expression increased with androgen deprivation, potentially providing a mechanism for the maintenance of androgen pathway signaling in these tumors. Further study of the AR/GR/SGK1 network in castration resistance.

Challenges and potential solutions to meeting accrual goals in a Phase II chemoprevention trial for prostate cancer.

OBJECTIVE: The goal of this report is to describe the on going strategies, successes, challenges and solutions for recruitment in this multi-center, phase II chemoprevention trial targeting men at high risk for prostate cancer. METHODS: We developed and implemented a multi-center clinical trial in institutions with supportive infrastructure, lead by a recruitment team of experienced and committed physicians and clinical trial staff, implementing multi-media and community outreach strategies to meet recruitment goals. Screening logs were reviewed to identify trends as well as patient, protocol and infrastructure -related barriers impacting accrual and revisions to protocol implemented. RESULTS: Between January 2008 and February 2011 a total of 3547 individuals were prescreened with 94% (n=3092) determined to be ineligible based on diagnosis of cancer or benign biopsy results. Of these, 216 were considered eligible for further screening with 52% (n=113) declining to participate due to patient related factors and 14% (n=29) eliminated due to protocol-related criteria for exclusion. Ninety-four (94) subjects consented to participate with 34% of these subjects (n=74) meeting all eligibility criteria to be randomized to receive study agent or placebo. Across all sites, 99% of the recruitment of subjects in this clinical trial is via physician recruitment and referral with less than 1% responding to other recruitment strategies. CONCLUSION: A contemporary approach to subject recruitment and frequent evaluation is needed to assure responsiveness to emerging challenges to accrual and the evolving scientific literature. A focus on investing on improving systems for physician recruitment may be key to meeting recruitment target in chemoprevention trials.

Prostate Cancer Chemoprevention Targeting Men with High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) and Atypical Small Acinar Proliferation (ASAP): Model for Trial Design and Outcome Measures.

In spite of the large number of nutrient-derived agents demonstrating promise as potential chemopreventive agents, most have failed to prove effectiveness in clinical trials. Critical requirements for moving nutrient-derived agents to recommendation for clinical use include adopting a systematic, molecular-mechanism based approach and utilizing the same ethical and rigorous methods such as are used to evaluate other pharmacological agents. Preliminary data on a mechanistic rationale for chemoprevention activity as observed from epidemiological, in vitro and preclinical studies, phase I data of safety in suitable cohorts, duration of intervention based on time to progression of preneoplastic disease to cancer and the use of a valid panel of biomarkers representing the hypothesized carcinogenesis pathway for measuring efficacy must inform the design of phase II clinical trials. The goal of this paper is to provide a model for evaluating a well characterized agent- Polyphenon E- in a phase II clinical trial of prostate cancer chemoprevention.

Positive surgical margins after robotic assisted radical prostatectomy: a multi-institutional study.

PURPOSE: Positive surgical margins are an independent predictive factor for biochemical recurrence after radical prostatectomy. We analyzed the incidence of and associative factors for positive surgical margins in a multi-institutional series of 8,418 robotic assisted radical prostatectomies. MATERIALS AND METHODS: We analyzed the records of 8,418 patients who underwent robotic assisted radical prostatectomy at 7 institutions. Of the patients 323 had missing data on margin status. Positive surgical margins were categorized into 4 groups, including apex, bladder neck, posterolateral and multifocal. The records of 6,169 patients were available for multivariate analysis. The variables entered into the logistic regression models were age, body mass index, preoperative prostate specific antigen, biopsy Gleason score, prostate weight and pathological stage. A second model was built to identify predictive factors for positive surgical margins in the subset of patients with organ confined disease (pT2). RESULTS: The overall positive surgical margin rate was 15.7% (1,272 of 8,095 patients). The positive surgical margin rate for pT2 and pT3 disease was 9.45% and 37.2%, respectively. On multivariate analysis pathological stage (pT2 vs pT3 OR 4.588, p<0.001) and preoperative prostate specific antigen (4 or less vs greater than 10 ng/ml OR 2.918, p<0.001) were the most important independent predictive factors for positive surgical margins after robotic assisted radical prostatectomy. Increasing prostate weight was associated with a lower risk of positive surgical margins after robotic assisted radical prostatectomy (OR 0.984, p<0.001) and a higher body mass index was associated with a higher risk of positive surgical margins (OR 1.032, p<0.001). For organ confined disease preoperative prostate specific antigen was the most important factor that independently correlated with positive surgical margins (4 or less vs greater than 10 ng/ml OR 3.8, p<0.001). CONCLUSIONS: The prostatic apex followed by a posterolateral site was the most common location of positive surgical margins after robotic assisted radical prostatectomy. Factors that correlated with cancer aggressiveness, such as pathological stage and preoperative prostate specific antigen, were the most important factors independently associated with an increased risk of positive surgical margins after robotic assisted radical prostatectomy.