A decision aid versus shared decision making for prostate cancer screening: results of a randomized, controlled trial.

INTRODUCTION: Shared decision making (SDM) is widely encouraged by both the American Urological Association and Choosing Wisely for prostate cancer screening. Implementation of SDM is challenging secondary to time constraints and competing patient priorities. One strategy to mitigate the difficulties in implementing SDM is to utilize a decision aid (DA). Here we evaluate whether a DA improves a patient's prostate cancer knowledge and affects prostate-specific antigen (PSA) screening rates. MATERIALS AND METHODS: Patients were randomized to usual care (UC), DA, or DA + SDM. Perception of quality of care was measured using the Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey. Outcomes were stratified by long term provider relationship (LTPR, > 3 years) versus short term provider relationship (STPR, < 3 years). Knowledge of prostate cancer screening and the decision regarding screening were assessed. Groups were compared using ANOVA and logistic regression models. RESULTS: A total of 329 patients were randomized. Patients in the DA + SDM arm were significantly more likely to report discussing the implication of screening (33% DA + SDM, 22% UC, 16% DA, p = 0.0292) and answered significantly more knowledge questions correctly compared to the UC arm (5.03 versus 4.46, p = 0.046). However, those in the DA arm were significantly less likely to report that they always felt encouraged to discuss all health concerns (72% DA, 78% DA + SDM, 87% UC, p = 0.0285). Interestingly, STPR patients in the DA arm were significantly more likely to undergo PSA-based prostate cancer screening (41%) than the UC arm (8%, p = 0.019). This effect was not observed in the LTPR group. CONCLUSIONS: Providing patients a DA without a personal interaction resulted in a greater chance of undergoing PSA-based screening without improving knowledge about screening or understanding of the consequences of this decision. This effect was exacerbated by a shorter term provider relationship. With complex issues such as the decision to pursue PSA-based prostate cancer screening, tools cannot substitute for direct interaction with a trusted provider.

Functional reprogramming of human prostate cancer to promote local attraction of effector CD8(+) T cells.

BACKGROUND: Local infiltration of CD8(+) T cells (CTLs) in tumor lesions predicts overall clinical outcomes and the clinical benefit of cancer patients from immune checkpoint blockade. In the current study, we evaluated local production of different classes of chemokines in prostate cancer lesions, and the feasibility of their modulation to promote selective entry of CTLs into prostate tumors. METHODS: Chemokine expression in prostate cancer lesion was analyzed by TaqMan-based quantitative PCR, confocal fluorescence microscopy and ELISA. For ex vivo chemokine modulation analysis, prostate tumor explants from patients undergoing primary prostate cancer resections were cultured for 24 hr, in the absence or presence of the combination of poly-I:C, IFNα, and celecoxib (PAC). The numbers of cells producing defined chemokines in the tissues were analyzed by confocal microscopy. Chemotaxis of effector CD8(+) T cells towards the untreated and PAC-treated tumor explant supernatants were evaluated in a standard in vitro migration assays, using 24 well trans-well plates. The number of effector cells that migrated was enumerated by flow cytometry. Pearson (r) correlation was used for analyzing correlations between chemokines and immune filtrate, while paired two tailed students t-test was used for comparison between treatment groups. RESULTS: Prostate tumors showed uniformly low levels of CTL/NK/Th1-recruiting chemokines (CCL5, CXCL9, CXCL10) but expressed high levels of chemokines implicated in the attraction of myeloid derived suppressor cells (MDSC) and regulatory T cells (Treg ): CCL2, CCL22, and CXCL12. Strong positive correlations were observed between CXCL9 and CXCL10 and local CD8 expression. Tumor expression levels of CCL2, CCL22, and CXCL12 were correlated with intratumoral expression of MDSC/Treg markers: FOXP3, CD33, and NCF2. Treatment with PAC suppressed intratumoral production of the Treg -attractant CCL22 and Treg /MDSC-attractant, CXCL12, while increasing the production of the CTL attractant, CXCL10. These changes in local chemokine production were accompanied by the reduced ability of the ex vivo-treated tumors to attract CD4(+) FOXP3(+) Treg cells, and strongly enhanced attraction of the CD8(+) Granzyme B(+) CTLs. CONCLUSIONS: Our data demonstrate that the chemokine environment in prostate cancer can be reprogrammed to selectively enhance the attraction of type-1 effector immune cells and reduce local attraction of MDSCs and Tregs . Prostate 76:1095-1105, 2016. © 2016 Wiley Periodicals, Inc.

Prostate Needle Biopsy Outcomes in the Era of the U.S. Preventive Services Task Force Recommendation against Prostate Specific Antigen Based Screening.

PURPOSE: We determined whether the characteristics of patients undergoing prostate needle biopsies and prostate needle biopsy results changed after the U.S. Preventive Services Task Force recommendation in 2012 against prostate specific antigen based screening for prostate cancer for men of any age. MATERIALS AND METHODS: A prospective database of patients undergoing prostate needle biopsies at Virginia Mason from 2004 to 2014 was reviewed. Welch's t-test and chi-square tests were used to compare patients seen before to those seen after the USPSTF recommendation. Relative risks and corresponding confidence intervals were estimated by general linear regression. RESULTS: Patients in the post-USPSTF group (310) had a higher prostate specific antigen (p <0.001), were more likely to be diagnosed with higher clinical stage (2b, p=0.003; 2c-3a, p=0.027) and D'Amico high risk prostate cancer (p=0.036), with an adjusted relative risk for high risk prostate cancer of 1.25 (95% CI 1.02-1.52) compared to those in the pre-USPSTF group (1,416). Limiting the pre-USPSTF group to the 30 months before the draft guidelines (448 patients) yielded similar results. The absolute number of biopsies performed decreased by 31%, with the majority of the decrease occurring in the detection of intermediate risk tumors. CONCLUSIONS: In the 2 and a half years after the USPSTF recommendation against prostate specific antigen based screening, patients undergoing prostate needle biopsies were significantly more likely to be diagnosed with high risk disease. However, a reduction in the number of prostate needle biopsies performed occurred concomitantly with a decrease in the detection of intermediate risk, potentially curable prostate cancer. Future focus on informed application of screening techniques may prevent the reversal of decades of improvement in the prostate cancer mortality rate.

Phase II trial of neoadjuvant docetaxel and CG1940/CG8711 followed by radical prostatectomy in patients with high-risk clinically localized prostate cancer.

BACKGROUND: Prostate cancer (PC) is the most commonly diagnosed noncutaneous malignancy in American men. PC, which exhibits a slow growth rate and multiple potential target epitopes, is an ideal candidate for immunotherapy. GVAX for prostate cancer is a cellular immunotherapy, composed of PC-3 cells (CG1940) and LNCaP cells (CG8711). Each of the components is a prostate adenocarcinoma cell line that has been genetically modified to secrete granulocyte-macrophage colony-stimulating factor. Hypothesizing that GVAX for prostate cancer could be effective in a neoadjuvant setting in patients with locally advanced disease, we initiated a phase II trial of neoadjuvant docetaxel and GVAX. For the trial, the clinical effects of GVAX were assessed in patients undergoing radical prostatectomy (RP). METHODS: Patients received docetaxel administered at a dose of 75 mg/m(2) every 3 weeks for 4 cycles. GVAX was administered 2-3 days after chemotherapy preoperatively for four courses of immunotherapy. The first dose of GVAX was a prime immunotherapy of 5×10(8) cells. The subsequent boost immunotherapies consisted of 3×10(8) cells. After RP, patients received an additional six courses of immunotherapy. Pathologic complete response, toxicity, and clinical response were assessed. The primary endpoint of the trial was a pathologic state of pT0, which is defined as no evidence of cancer in the prostate. RESULTS: Six patients completed neoadjuvant docetaxel and GVAX therapy. No serious drug-related adverse events were observed. Median change in prostate-specific antigen (PSA) following neoadjuvant therapy was 1.47 ng/ml. One patient did not undergo RP due to the discovery of positive lymph nodes during exploration. Of the five patients completing RP, four had a downstaging of their Gleason score. Undetectable PSA was achieved in three patients at 2 months after RP and in two patients at 3 years after RP. CONCLUSIONS: Neoadjuvant docetaxel/GVAX is safe and well tolerated in patients with high-risk locally advanced PC. No evidence of increased intraoperative hemorrhage or increased length of hospital stay postoperatively was noted. These results justify further study of neoadjuvant immunotherapy.

An analysis of leukapheresis and central venous catheter use in the randomized, placebo controlled, phase 3 IMPACT trial of Sipuleucel-T for metastatic castrate resistant prostate cancer.

PURPOSE: Sipuleucel-T is an autologous cellular immunotherapy. We review the safety of the leukapheresis procedure required for sipuleucel-T preparation and complications related to venous catheter use in the randomized, placebo controlled phase 3 IMPACT (IMmunotherapy for ProstAte Cancer Trial) study (NCT 00065442). MATERIALS AND METHODS: A total of 512 patients with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer were enrolled in the study. All patients were scheduled to undergo 3 standard 1.5 to 2.0 blood volume leukapheresis procedures at 2-week intervals. Leukapheresis related adverse events and those related to venous catheter use were reviewed. Immune cell counts were examined throughout the treatment course. RESULTS: Of 512 enrolled patients 506 underwent 1 or more leukapheresis procedures and were included in this analysis. Adverse events were comparable between the sipuleucel-T and control arms. Leukapheresis related adverse events were primarily associated with transient hypocalcemia (39.3%). Most leukapheresis related adverse events (97%) were of mild/moderate intensity. Median white blood cell count and absolute monocyte and lymphocyte counts were stable and within normal ranges throughout the treatment course. Of all patients 23.3% had a central venous catheter placed primarily for leukapheresis. Patients with vs without a central venous catheter had a higher risk of infection potentially related to catheter use (11.9% vs 1.3%, p <0.0001) and a trend toward a higher incidence of venous vascular events potentially related to catheter use, excluding the central nervous system (5.9% vs 2.1%, p = 0.06). CONCLUSIONS: Adverse events related to leukapheresis are manageable and quickly reversible. The majority of patients can undergo leukapheresis without a central venous catheter. Central venous catheters are associated with an increased risk of infections and venous vascular events. Peripheral intravenous access should be used when feasible.

Feasibility of injected indocyanine green for ureteral identification during robotic left-sided colorectal resections.

BACKGROUND: Ureteral identification is essential to performing safe colorectal surgery. Injected immunofluorescence may aid with ureteral identification, but feasibility without ureteral catheterization is not well described. METHODS: Case series of robotic colorectal resections where indocyanine green (ICG) injection with or without ureteral catheter placement was performed. Imaging protocol, time to ureteral identification, and factors impacting visualization are reported. RESULTS: From 2019 to 2020, 83 patients underwent ureteral ICG injection, 20 with catheterization and 63 with injection only. Main indications were diverticulitis (52%) and cancer (36%). Median time to instill ICG was faster with injection alone than with catheter placement (4min vs 13.5min, p < 0.001). Median time [IQR] to right ureter (0.3 [0.01-1.2] min after robot docking) and left ureter (5.5 [3.1-8.8] min after beginning dissection) visualization was not different between injection alone and catheterization. CONCLUSION: ICG injection alone is faster than with indwelling catheter placement and equally reliable at intraoperative ureteral identification.

Opioid-Limiting Pain Control After Transurethral Resection of the Prostate: A Randomized Controlled Trial.

OBJECTIVE: To assess whether a multimodal opioid-limiting protocol and patient education intervention can reduce postoperative opioid use following transurethral resection of the prostate. METHODS: This prospective, non-blinded, single-institution, randomized controlled trial (NCT04102566) assigned 50 patients undergoing a transurethral resection of the prostate to either a standard of care control (SOC) or multimodal experimental group (MMG). The intervention included adding ibuprofen to the postoperative pain regimen, promoting appropriate opioid use while hospitalized, an educational intervention, and discharging without opioid prescription. Data regarding demographics, operative data, opioid use, pain scores, and patient satisfaction were compared. RESULTS: A total of 47 patients were included, n = 23 (MMG) and n = 24 (SOC). Demographic and operative findings were similar. Statistical analysis for noninferiority demonstrated non-inferior inpatient pain control (mean pain score 2.5 MMG vs 2.4 SOC, P = 0.0003). The multimodal group used significantly fewer morphine milligram equivalents after discharge (0 vs 4.1, P = 0.04). Inpatient use was reduced but did not reach statistical significance (6.0 vs 9.8, P = 0.2). Mean satisfaction scores with pain control were similar (9.6 MMG vs 9.2 SOC, P = 0.32). No opioid prescriptions were requested after discharge. Adverse events and medication side effects were infrequent and largely similar between groups. CONCLUSION: Implementation of an opioid-limiting postoperative pain protocol and patient education resulted in no outpatient opioid use while maintaining patient satisfaction with pain control. Eliminating opioids following a common urologic procedure will decrease risk of opioid-related adverse events and have a positive downstream impact.

Type and Screen Prior to Radical Prostatectomy for Prostate Cancer- Time for a Change?

PURPOSE: Despite low rates of transfusion associated with robotic prostatectomy, surgeons routinely obtain preoperative blood typing. Here we aim to understand the cost savings associated with eliminating blood typing prior to prostatectomy. MATERIALS AND METHODS: A retrospective review of our single surgeon radical prostatectomy database was performed. Patients receiving blood transfusions within 3 days of prostatectomy were identified and clinical characteristics were recorded. Cost information was obtained, and descriptive statistical analysis performed. RESULTS: 1,581 patients underwent prostatectomy from 2000 to 2019. Thirty-two patients (2.02%) received a transfusion within 3 days of surgery. The transfusion rate for open prostatectomy was 3.21% vs 1.37% for robotic prostatectomy. The cost of preoperative blood typing for all radical prostatectomies was $113,832, or about $5,812.70 per year. CONCLUSIONS: Transfusion rates for prostatectomy are low and decline with experience. Significant cost savings is possible by avoiding routine preoperative blood typing in most patients undergoing radical prostatectomy.

Does a perioperative belladonna and opium suppository improve postoperative pain following robotic assisted laparoscopic radical prostatectomy? Results of a single institution randomized study.

INTRODUCTION: Robotic assisted laparoscopic radical prostatectomy (RALP) is a common treatment for localized prostate cancer. Despite a primary advantage of improved postoperative pain, patients undergoing RALP still experience discomfort. Belladonna, containing the muscarinic receptor antagonists atropine and scopolamine, in combination with opium as a rectal suppository (B & O) may improve post-RALP pain. This study evaluates whether a single preoperative B & O results in decreased postoperative patient-reported pain and analgesic requirements. MATERIALS AND METHODS: Patients undergoing RALP at Virginia Mason Medical Center between November 2008 and July 2009 were offered the opportunity to enter a randomized, double-blind, placebo-controlled trial. Exclusion criteria included: glaucoma, bronchial asthma, convulsive disorders, chronic pain, chronic use of analgesics, or a history of alcohol or opioid dependency. Surgeons were blinded to suppository placement which was administered after induction of anesthesia. All patients underwent a standardized anesthesia regimen. Postoperative pain was assessed by a visual analog scale (VAS) and postoperative narcotic use was calculated in intravenous morphine equivalents. RESULTS: Ninety-nine patients were included in the analysis. The B & O and control groups were not significantly different in terms of age, body mass index, operative time, nerve sparing status or prostatic volume. Postoperative pain was significantly improved during the first two postoperative hours in the B & O group. Similarly, 24-hour morphine consumption was significantly lower in patients who received a B & O. No adverse effects secondary to suppository placement were identified. CONCLUSION: Preoperative administration of B & O suppository results in significantly decreased postoperative pain and 24-hour morphine consumption in patients undergoing RALP.

Erectile function following unilateral cavernosal nerve replacement.

INTRODUCTION: With nerve-sparing techniques, patients undergoing a radical prostatectomy may avoid the morbidity of erectile dysfunction. Certain patients who are not candidates for nerve-sparing procedures may be eligible for nerve interposition grafts. While bilateral cavernosal nerve grafting after radical prostatectomy has shown efficacy, the effect of unilateral nerve grafting following prostatectomy remains unclear. We evaluate a large group of patients who underwent a unilateral cavernosal nerve replacement. METHODS: Forty patients underwent unilateral nerve sparing surgery with concomitant contralateral cavernosal nerve replacement. Patients were selected for this procedure based upon preoperative nomogram risk assessment, endorectal MRI evidence of extra capsular disease (ECE) or intraoperative histology demonstrating margin positivity. Age, demographic data, Gleason score, clinical and pathologic stage and pre and post operative IIEF data was collected and prospectively analyzed. RESULTS: Median follow-up was 19 months. Median change in IIEF scores was 7.5. Twenty-one of 29 patients (72%) report being able to penetrate after prostatectomy. Sixteen of those 21 (76%) continue to require PDE-5 inhibitors to facilitate penetration. Four of the 6 patients (67%) who were unable to have intercourse following cavernosal nerve replacement received adjuvant hormonal and/or radiation therapy. Twenty-eight patients (97%) reported numbness at the graft harvest site. One patient experienced a graft site infection. Two of 29 (7%) patients reported pain at the harvest site. CONCLUSION: Unilateral sural nerve grafting is a feasible and well-tolerated approach for patients who must undergo wide resection of a NVB. While men do show a decrease in their IIEF score, 76% are able to achieve penetration following surgery. The majority of men continue to require PDE-5 inhibitors to facilitate intercourse.

Post-operative drain output as a predictor of bladder neck contracture following radical prostatectomy.

BACKGROUND: Bladder neck contracture (BNC) following prostatectomy has been reported in 0.5-32% of cases. While the etiology of a BNC is unclear, several factors have been associated with this complication, including blood loss, devascularization of bladder neck tissue, poor mucosal apposition and urinary extravasation. To study the impact of urinary extravasation on BNC formation, we used postoperative drain output as a surrogate measure for anastomotic leakage. METHODS: All patients undergoing a radical retropubic prostatectomy (RRP) or a robotic assisted radical prostatectomy (RARP) from January 2000 to April 2006 have been entered into a prospective review board-approved database. All RRP patients had their anastomosis performed in an interrupted fashion using six monofilament 2-0 sutures. All robotic-assisted radical prostatectomy anastomoses were performed in a running fashion using 2-0 monofilament sutures. A single, closed suction Jackson Pratt drain was placed over the surgical bed at the conclusion of the case. Post-operative drain outputs were recorded. All patients were evaluated at 3, 6, 9, 12 and 24 months post-operatively. All patients who reported a diminished urinary stream or incontinence were evaluated by office cystoscopy. The inability to navigate an 18 French cystoscope through the bladder neck was defined as a bladder neck contracture. RESULTS: A total of 576 patients underwent a radical prostatectomy over this time span. Complete records were available for 535 (93%) of these patients. There were 21 bladder neck contractures (3.9%) overall. The post-operative drain output ranged from 5-5,465 ml (median 119 ml). Eight patients who had drain outputs less than 119 ml developed a BNC while 13 BNC developed in patients with Jackson Pratt drain output > 119 ml (P = 0.343). In patients who underwent an open RRP, 19/424 (4.5%) developed contractures while 2/108 (1.9%) RARP patients developed a BNC (P = 0.105). CONCLUSION: The amount of post-operative drain output is not statistically associated with the development of a bladder neck contracture.

Increasing Adherence to an AUA Guideline: A Durable Impact on Immediate Postoperative Mitomycin C Use.

INTRODUCTION: In this quality initiative we assessed whether providing surgeons with the American Urological Association guideline regarding intravesical mitomycin C at the time of surgery scheduling impacts compliance. Furthermore, we examined the durability of the intervention and the influence of surgeon volume on guideline adherence. METHODS: All patients (105) undergoing transurethral bladder tumor resection from July 2015 to February 2016 at Virginia Mason Medical Center were included prospectively. At the scheduling of surgery urologists were provided with a preoperative tool that included the relevant guideline. Mitomycin C use during the study period was compared to historical and subsequent year's use. Additionally, we stratified results by high and low volume resectionists. RESULTS: Before this study mitomycin C was used in 17.1% (25 of 146) of all resections. During the intervention period its use nearly tripled to 43% (28 of 65), an increase of 25.9%. The year after the intervention its use decreased to 32.7% (36 of 110). Durability was strongest for high volume surgeons and trended toward significance for low volume surgeons. CONCLUSIONS: Providing surgeons with a copy of the guideline at the time of surgery scheduling resulted in a threefold increase in guideline compliance. This change is durable and most impactful for higher volume surgeons. We believe this model can be used to ensure adherence and consideration for many guidelines.

Evolution of the Ureteral Stent: The Pivotal Role of the Gibbons Ureteral Catheter.

OBJECTIVE: To review the pioneering contributions of Dr. Robert Gibbons of Virginia Mason Medical Center to the evolution and development of the modern ureteral stent. METHODS: We reviewed Dr. Gibbons' extensive work through primary sources, including interviews, projector slides, radiology images, stent prototypes, his personal writings, and archived documents. In addition, we performed a review of historical texts and manuscripts describing important innovations in the development of the ureteral stent. RESULTS: In 1972, motivated by a desire to provide his patients with a long-term alternative to open nephrostomy and inspired by Drs. David Davis and Paul Zimskind, who in 1967 had described the use of indwelling ureteral silicone tubing, Dr. Gibbons began to experiment with modifications to improve upon existing stents. To address distal migration, Dr. Gibbons added "wings" that collapsed as the stent was advanced and expanded once in proper position to secure the stent in place. Barium was embedded into the proximal tip to facilitate radiographic visualization. A flange was added to the distal end, preventing proximal migration and minimizing trigonal irritation, and a tail was attached to aid in stent removal. The result was the original Gibbons stent, the first commercially available ureteral stent, and the establishment of Current Procedural Terminology code 52332, still used today. CONCLUSION: The ureteral stent is a fundamental component of urologic practice. In developing the Gibbons stent, Dr. Gibbons played a pivotal role in addressing the challenge of internal urinary diversion particularly for those who needed long-term management. Urologists and the patients they serve owe Dr. Gibbons and other surgeon-inventors a debt of gratitude for their innovative work.

Mechanical failure rate of da Vinci robotic system.

INTRODUCTION: Robotic-assisted laparoscopic radical prostatectomy (RLRP) is playing an increasing role in the surgical management of prostate cancer. The benefits of minimally invasive surgery, enhanced surgeon familiarity with the instrumentation, and increased patient demand has led to the popularity of this surgical technique. There are, however, shortcomings specifically associated with this technology. Notably, instrumentation failure associated with robotic procedures represents a new and unique problem in urological surgery. We examine the rate of mechanical failure of the da Vinci robotic system and its impact on our prostate cancer program. MATERIALS AND METHODS: We reviewed our prospective, institutional review board-approved database of the first 350 RLRP procedures that were scheduled for surgery at our institution. We identified all cases in which mechanical failure of the da Vinci robotic system resulted in surgery being cancelled, postponed, or converted to a conventional laparoscopic or an open radical prostatectomy. RESULTS: Nine of the 350 (2.6%) scheduled RLRPs were unable to be completed robotically secondary to device malfunction. Six of the malfunctions were detected prior to anesthesia induction and surgery was rescheduled. Three other malfunctions occurred intraoperatively and were converted either to a conventional laparoscopic (1 case) or an open surgical approach (2 cases). The etiology of the malfunctions included the following: set-up joint malfunction (2), arm malfunction (2), power error (1), monocular monitor loss (1), camera malfunction (1), metal fatigue/ break of surgeon's console hand piece (1) and software incompatibility (1). CONCLUSIONS: Although uncommon, malfunction of the da Vinci robotic system does occur and may lead to psychological, financial, and logistical burdens for patients, physicians, and hospitals. Patients should be carefully counseled preoperatively regarding the possibility of robotic mechanical failure.

Experience improves staging accuracy of endorectal magnetic resonance imaging in prostate cancer: what is the learning curve?

INTRODUCTION: Accurate clinical staging is critical in guiding treatment for patients with prostate adenocarcinoma. Endorectal magnetic resonance imaging (MRI) has been advocated to improve staging accuracy. In order to assess the learning curve for endorectal MRI interpretation, we compared two cohorts of patients with high-risk prostate who underwent endorectal MRI at a center with limited prior exposure to this imaging modality. MATERIALS AND METHODS: Data for all patients who received a preoperative endorectal MRI followed by radical prostatectomy were prospectively collected. MRI was performed in patients with a high level of suspicion for extracapsular disease based on biopsy Gleason score, prostate specific antigen level, and digital rectal examination or if the Memorial Sloan-Kettering nomogram predicted a greater than 30% likelihood of extracapsular disease. The MRI results of our first 40 patients (group 1) and our second 40 patients (group 2) were compared to assess for improvement. RESULTS: Between October 2003 and September 2005, 80 patients underwent an endorectal MRI followed by radical prostatectomy. Mean age and median PSA were 58.4 (range 43 - 74) and 6.4 (range 0.048 -115.0), respectively. MRI findings were compared to the pathological findings from the radical prostatectomy specimen. Sensitivity, specificity, positive predictive value, and negative predictive value for detection of extracapsular disease were 31.3% versus 64.7%, 70.8% versus 78.3%, 41.7% versus 68.8%, and 60.7% versus 75.0%, respectively in group 1 versus group 2. The accuracy of MRI for detecting extracapsular extension was 52.5% in group 1 compared to 72.5% in group 2. CONCLUSIONS: In our series, endorectal MRI initially did not accurately predict tumor stage in patients with prostatic adenocarcinoma. With further experience, the accuracy of MRI substantially improved and approached the results from centers with significant experience in the interpretation of endorectal prostate MRI.

Cytologic persistence of malignant cells after transurethral resection of bladder tumors: Implications for concomitant manipulation of the urinary tract at the time of endoscopic resection.

BACKGROUND: The current study was conducted to determine the feasibility of cytologically clearing the bladder of tumor cells after transurethral resection of bladder tumor (TURBT) and aggressive serial bladder washing. METHODS: A prospective pilot sample of 20 patients with known bladder masses was enrolled before undergoing TURBT. Preoperative cytology and 4 postoperative cytology specimens were assessed for malignant cells between serial bladder washes. Surgeons assessed tumor grade visually at the time of TURBT. RESULTS: Surgeons were able to differentiate high-grade disease with limited accuracy (75% sensitivity, 92% specificity, 85% negative predictive value, and 86% positive predictive value). For patients with low-grade disease (12 patients), cytology was atypical in 25% of patients immediately before TURBT and was negative after serial washings in all patients. In patients with high-grade disease (8 patients), approximately 75% had cytology consistent with high-grade urothelial carcinoma immediately before TURBT and only 1 patient was cleared cytologically after serial bladder washings. CONCLUSIONS: In patients with high-grade disease, serial bladder washing after TURBT does not appear to clear malignant cells as detected by cytology. This theoretical oncologic risk should be weighed when considering concomitant upper tract procedures such as retrograde pyelography. Future work is needed to quantify risk. Cancer Cytopathol 2017;125:114-119. © 2016 American Cancer Society.

Sequencing of Sipuleucel-T and Androgen Deprivation Therapy in Men with Hormone-Sensitive Biochemically Recurrent Prostate Cancer: A Phase II Randomized Trial.

Purpose: STAND, a randomized, phase II, open-label trial (NCT01431391), assessed sequencing of sipuleucel-T (an autologous cellular immunotherapy) with androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BRPC) patients at high risk for metastasis.Experimental Design: Men with BRPC following prostatectomy and/or radiotherapy, a PSA doubling time ≤12 months, and no metastasis were enrolled. Patients were randomized (34/arm) to sipuleucel-T followed by ADT (started 2 weeks after sipuleucel-T completion), or ADT followed by sipuleucel-T (started 12 weeks after ADT initiation); ADT continued for 12 months in both arms. The primary endpoint was PA2024-specific T-cell response [enzyme-linked immunospot (ELISPOT)] over time.Results: PA2024-specific ELISPOT responses over time were similar between groups, except at week 6, where responses were higher with sipuleucel-T→ADT versus ADT→sipuleucel-T (P = 0.013). PA2024-specific T-cell proliferation responses, averaged across time points, were approximately 2-fold higher with sipuleucel-T→ADT versus ADT→sipuleucel-T (P = 0.001). PA2024-specific cellular and humoral responses and prostatic acid phosphatase-specific humoral responses increased significantly versus baseline (P < 0.001) and were maintained for 24 months (both arms). Median time-to-PSA recurrence was similar between arms (21.8 vs. 22.6 months, P = 0.357). Development of a PA2024-specific humoral response correlated with prolonged time-to-PSA progression (HR, 0.22; 95% CI, 0.08-0.67; P = 0.007). Sipuleucel-T with ADT was generally well tolerated.Conclusions: Sipuleucel-T→ADT appears to induce greater antitumor immune responses than the reverse sequence. These results warrant further investigation to determine whether this sequence leads to improved clinical outcomes, as well as the independent contribution of ADT alone in terms of immune activation. Clin Cancer Res; 23(10); 2451-9. ©2016 AACR.

Endoscopic Management of Bladder Diverticula.

A 50-year-old man with benign prostatic hyperplasia and urinary retention had a very large diverticulum on the posterior wall of the bladder. The patient was managed with transurethral resection of the prostate and endoscopic fulguration of the bladder diverticulum mucosa using the Orandi technique. There was near-complete resolution of the bladder diverticulum following endoscopic management, obviating the need for bladder diverticulectomy. The patient now empties his bladder, with a postvoid residual < 50 mL and the absence of urinary tract infection after 6-month follow-up. We report the successful treatment of a large bladder diverticulum with endoscopic fulguration to near-complete resolution. This minimally invasive technique is a useful alternative in patients unfit for a more extensive surgical approach.

Quality of life after sipuleucel-T therapy: results from a randomized, double-blind study in patients with androgen-dependent prostate cancer.

OBJECTIVE: To collect and analyze quality-of-life (QOL) data from PROvenge Treatment and Early Cancer Treatment trial (PROTECT, NCT00779402), a phase III, randomized controlled trial of sipuleucel-T in patients with asymptomatic androgen-dependent prostate cancer. METHODS: Patients experiencing prostate-specific antigen relapse after radical prostatectomy entered a 3- to 4-month run-in phase of androgen-deprivation therapy (ADT), followed by 2:1 randomization to sipuleucel-T or control. QOL was assessed throughout the run-in and 26-week post-randomization phases using the Brief Fatigue Inventory (BFI), Linear Analog Self-Assessment (LASA) scale, Global Rating of Change (GRoC) scale, and an elicited symptoms list. RESULTS: One hundred seventy-six patients were randomized into 2 groups, the sipuleucel-T group (n = 117) or the control group (n = 59). The sample provided 80% power to detect a difference in fatigue interference score between treatment arms of 0.9 points. QOL declined predictably during ADT. At week 26, 26.2% of sipuleucel-T-treated patients and 21.6% of control-treated patients (P = .68) reported fatigue in the previous week, and the mean score for fatigue interference in the past 24 hours was 0.9 for both arms (P = .88). Results were comparable for usual fatigue (P = .91) and worst fatigue (P >.99). Mean LASA scores decreased in both groups (P = .26). The proportion of patients reporting better overall QOL on GRoC was similar (P = .62). CONCLUSION: There is no clinically significant negative impact on QOL after sipuleucel-T treatment compared with control after a period of ADT in patients with asymptomatic androgen-dependent prostate cancer.