Two-stage classifiers that minimize PCA3 and the PSA proteolytic activity testing in the prediction of prostate cancer recurrence after radical prostatectomy.

INTRODUCTION: Early biochemical recurrence after prostate cancer surgery is associated with higher risk of aggressive disease and cancer specific death. Many new tests are being developed that will predict the presence of indicators of aggressive disease like early biochemical recurrence. Since recurrence occurs in less than 10% of patients treated for prostate cancer, validation of such tests will require expensive testing on large patient groups. Moreover, clinical application of the validated test requires that each new patient be tested. In this report we introduce a two-stage classifier system that minimizes the number of patients that must be tested in both the validation and clinical application of any new test for recurrence. MATERIALS AND METHODS: Expressed prostatic secretion specimens were prospectively collected from 450 patients prior to robot-assisted radical prostatectomy for prostate cancer. Patients were followed for 2.5 years for evidence of biochemical recurrence. Standard clinical parameters, the levels proteolytic activity of prostate specific antigen (PSA) and the levels of PCA3 RNA, PSA RNA and TMPRSS2:ERG fusion RNA were determined in each prospective patient specimen for subsequent correlation with biochemical recurrence. RESULTS: While levels of PCA3 and PSA proteolytic activity (PPA) in prostatic secretions provided an effective pre-surgical predictor of early biochemical recurrence in prostate cancer, application of the two-stage classifier shows that only 60% of the patients need these tests. CONCLUSION: Two-stage classifiers can provide a parsimonious approach to both the validation and clinical application of biomarker-based tests. Adoption of the two-stage neutral zone classifier can reduce unnecessary testing in prostate cancer treatment.

NCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer Early Detection provide recommendations for prostate cancer screening in healthy men who have elected to participate in an early detection program. The NCCN Guidelines focus on minimizing unnecessary procedures and limiting the detection of indolent disease. These NCCN Guidelines Insights summarize the NCCN Prostate Cancer Early Detection Panel's most significant discussions for the 2016 guideline update, which included issues surrounding screening in high-risk populations (ie, African Americans, BRCA1/2 mutation carriers), approaches to refine patient selection for initial and repeat biopsies, and approaches to improve biopsy specificity.

Prostate Cancer, Version 1.2016.

The NCCN Guidelines for Prostate Cancer address staging and risk assessment after an initial diagnosis of prostate cancer and management options for localized, regional, and metastatic disease. Recommendations for disease monitoring, treatment of recurrent disease, and systemic therapy for metastatic castration-recurrent prostate cancer also are included. This article summarizes the NCCN Prostate Cancer Panel's most significant discussions for the 2016 update of the guidelines, which include refinement of risk stratification methods and new options for the treatment of men with high-risk and very-high-risk disease and progressive castration-naïve disease.

NCCN Clinical Practice Guidelines Prostate Cancer Early Detection, Version 2.2015.

Prostate cancer represents a spectrum of disease that ranges from nonaggressive, slow-growing disease that may not require treatment to aggressive, fast-growing disease that does. The NCCN Guidelines for Prostate Cancer Early Detection provide a set of sequential recommendations detailing a screening and evaluation strategy for maximizing the detection of prostate cancer that is potentially curable and that, if left undetected, represents a risk to the patient. The guidelines were developed for healthy men who have elected to participate in the early detection of prostate cancer, and they focus on minimizing unnecessary procedures and limiting the detection of indolent disease.

Prostate cancer early detection, version 1.2014. Featured updates to the NCCN Guidelines.

The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for men choosing to participate in an early detection program for prostate cancer. These NCCN Guidelines Insights highlight notable recent updates. Overall, the 2014 update represents a more streamlined and concise set of recommendations. The panel stratified the age ranges at which initiating testing for prostate cancer should be considered. Indications for biopsy include both a cutpoint and the use of multiple risk variables in combination. In addition to other biomarkers of specificity, the Prostate Health Index has been included to aid biopsy decisions in certain men, given recent FDA approvals.

Prostate cancer, version 2.2014.

Prostate cancer has surpassed lung cancer as the most common cancer in men in the United States. The NCCN Guidelines for Prostate Cancer provide multidisciplinary recommendations on the clinical management of patients with prostate cancer based on clinical evidence and expert consensus. NCCN Panel guidance on treatment decisions for patients with localized disease is represented in this version. Significant updates for early disease include distinction between active surveillance and observation, a new section on principles of imaging, and revisions to radiation recommendations. The full version of these guidelines, including treatment of patients with advanced disease, can be found online at the NCCN website.

Prostate cancer, version 1.2014.

The NCCN Guidelines for Prostate Cancer provide multidisciplinary recommendations on the clinical management of patients with prostate cancer. This report highlights notable recent updates. Radium-223 dichloride is a first-in-class radiopharmaceutical that recently received approval for the treatment of patients with symptomatic bone metastases and no known visceral disease. It received a category 1 recommendation as both a first-line and second-line option. The NCCN Prostate Cancer Panel also revised recommendations on the choice of intermittent or continuous androgen deprivation therapy based on recent phase III clinical data comparing the 2 strategies in the nonmetastatic and metastatic settings.

Prostate cancer, Version 3.2012: featured updates to the NCCN guidelines.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer provide multidisciplinary recommendations for the clinical management of patients with prostate cancer. These NCCN Guidelines Insights highlight notable recent updates. Abiraterone acetate is a first-in-class hormonal agent that represents a new standard of care for patients with metastatic castration-recurrent prostate cancer who have previously received docetaxel (category 1 recommendation). Abiraterone acetate also received category 2B recommendations in the prechemotherapy setting for asymptomatic patients or symptomatic patients who are not candidates for docetaxel. The NCCN Prostate Cancer Panel also added new indications for existing agents, including the option of sipuleucel-T as second-line therapy. In addition, brachytherapy in combination with external beam radiation therapy with or without androgen deprivation therapy is now an alternative for patients with high-risk localized tumors or locally advanced disease.

Controlling the dorsal venous complex during robotic prostatectomy.

INTRODUCTION: The objective of our study was to determine whether dorsal venous complex (DVC) control technique influences positive apical margins following robotic assisted laparoscopic radical prostatectomy (RALRP). MATERIALS AND METHODS: One thousand fifty-eight patients who underwent RALRP at City of Hope from June 2007 to October 2009 were assessed. Endoscopic stapling and suture ligature of the DVC were compared. Positive apical margins were identified and compared based on DVC-control technique. Recurrence probability was estimated using the Kaplan-Meier method, and logistic regression analysis was used to predict the odds of positive apical margins. RESULTS: Of 1058 patients, 633 (60%) underwent endoscopic stapling, and 425 (40%) had suture ligature. The groups had similar baseline characteristics including age and body mass index. We observed a statistically different PSA (5.4 ng/mL versus 5.2 ng/mL, p = 0.03) and operative time (2.8 hours versus 2.7 hours, p = 0.02) between stapling and suture groups, but the actual difference was small. Operative time, Gleason score, pathologic stage, and overall positive margin rates were not significantly different between groups. Positive apical margins were observed in 39 (6%) and 27 (6%) patients in the staple and suture groups, respectively. Multivariate analysis showed that the positive apical margin rate was greater in patients with higher pathologic stage and final pathological Gleason score. CONCLUSIONS: During RALRP, there is no difference in positive apical margin rate when the DVC is controlled using either endoscopic stapling or suture ligature. However, patients with a higher pathologic stage and final pathologic Gleason score are at higher risk for positive apical surgical margins.

Robotic assisted laparoscopic salvage prostatectomy for radiation resistant prostate cancer.

PURPOSE: We report on outcomes of robotic assisted laparoscopic radical prostatectomy as salvage local therapy for radiation resistant prostate cancer. MATERIALS AND METHODS: We retrospectively reviewed the charts of all patients who underwent robotic assisted laparoscopic radical prostatectomy for biopsy proven prostate cancer after primary radiation treatment. Patient characteristics, intraoperative and perioperative data, and oncological and functional outcomes were assessed. RESULTS: A total of 18 patients were identified with a median followup of 18 months (range 4.5 to 40). Primary treatment was brachytherapy in 8 patients and external beam radiation in 8, while 2 underwent proton beam therapy. Median age at salvage robotic assisted laparoscopic radical prostatectomy was 67 years (range 53 to 76). Median preoperative prostate specific antigen was 6.8 ng/ml (range 1 to 28.9) and median time to surgery after primary treatment with radiation was 79 months (range 7 to 146). Median operative parameters for estimated blood loss, surgery length and hospital stay were 150 ml, 2.6 hours and 2 days, respectively. No patient required conversion to open surgery or a blood transfusion, or experienced a rectal injury. Perioperative complications occurred in 7 patients (39%) of which the most common was urine leak identified by postoperative cystogram. Five patients (28%) had a positive surgical margin. Although some patients had limited followup, 6 (33%) were continent and 67% were free of biochemical progression. CONCLUSIONS: Robotic assisted laparoscopic radical prostatectomy can be performed safely as salvage local therapy after failed radiation therapy. Outcomes are comparable to those of large series of open salvage prostatectomy.

Performance of a single assay for both type III and type VI TMPRSS2:ERG fusions in noninvasive prediction of prostate biopsy outcome.

BACKGROUND: TMPRSS2:ERG fusions are promising prostate cancer biomarkers. Because they can occur in multiple forms in a single cancer specimen, we developed a quantitative PCR test that detects both type III and type VI TMPRSS2:ERG fusions. The assay is quantified from a standard curve determined with a plasmid-cloned type III TMPRSS2:ERG fusion target. METHODS: We collected expressed prostatic secretion (EPS) under an institutional review board-approved, blinded, prospective study from 74 patients undergoing transrectal ultrasound-guided biopsy for prostate cancer. We compared the characteristic performance of the test for type III and type VI TMPRSS2:ERG fusions in predicting biopsy outcome and distinguishing between high and low Gleason scores with similar tests for the expression of PCA3 and DNA methylation levels of the APC, RARB, RASSF1, and GSTP1 genes. We used logistic regression to analyze the effects of multiple biomarkers in linear combinations. RESULTS: Each test provided a significant improvement in characteristic performance over baseline digital rectal examination (DRE) plus serum prostate-specific antigen (PSA); however, the test for type III and type VI TMPRSS2:ERG fusions yielded the best performance in predicting biopsy outcome [area under the curve (AUC) 0.823, 95% CI 0.728-0.919, P < 0.001] and Gleason grade >7 (AUC 0.844, 95% CI 0.740-0.948, P < 0.001). CONCLUSIONS: Although each test appears to have diagnostic value, PSA plus DRE plus type III and type VI TMPRSS2:ERG provided the best diagnostic performance in EPS specimens.

The impact of prostate gland weight in robot assisted laparoscopic radical prostatectomy.

PURPOSE: We determined whether prostate weight has an impact on the pathological and operative outcomes of robot assisted laparoscopic radical prostatectomy. MATERIALS AND METHODS: We reviewed the records of 1,847 consecutive patients who underwent robot assisted laparoscopic radical prostatectomy at our institution. Variables were compared across quartile distributions of prostate size as defined by weight, including group 1-less than 30 gm, group 2-30 to 49.9, group 3-50 to 69.9 and group 4-70 or greater. Factors assessed in this analysis were patient age, body mass index, prostate specific antigen, Gleason score, pathological stage, margin status, operative time, blood loss, transfusion rate, length of stay and rehospitalization rate. RESULTS: Patients with a larger prostate (group 4) were older (mean age 66.2 years), had higher pretreatment prostate specific antigen (median 6.5 ng/ml), lower Gleason score (mean 6.3), longer operative time (mean 3.2 hours), higher estimated blood loss (median 250 cc) and longer hospital stay (p = 0.0002). There was a trend toward higher risk disease based on D'Amico risk stratification and positive margin status in group 1, although evidence of extracapsular extension was more common in groups 2 and 3. There was no association between prostate size and body mass index, lymph node status, blood transfusion rate, seminal vesicle involvement and rehospitalization rate. CONCLUSIONS: Robot assisted laparoscopic radical prostatectomy in patients with an enlarged prostate is feasible with slightly longer operative time, urinary leakage rates and hospital stay. Pathologically larger prostates are generally associated with lower Gleason score and risk group stratification. One-year continence rates and biochemical recurrence rates are similar across all groups.

Counterpoint: robot-assisted laparoscopic prostatectomy: perhaps the surgical gold standard for prostate cancer care.

Robot-assisted laparoscopic prostatectomy (RALP) has gained immense popularity. This article examines the most critical outcome measures in prostate cancer surgery and shows the reasons why this technique is gaining in popularity. Operative time, length of stay, blood loss, transfusions, postoperative pain, continence, potency, and cancer control all favor or tend toward improvement and benefit in RALP compared with traditional radical retropubic prostatectomy. In addition, as even greater experience and technological improvements are incorporated, further outcome improvements will be appreciated. RALP is now an accepted treatment option for prostate cancer and may soon be the most desirable treatment of prostate cancer patients.

Perioperative complications of laparoscopic and robotic assisted laparoscopic radical prostatectomy.

PURPOSE: While it remains controversial whether LRP or da Vinci RAP offers any advantages over radical retropubic prostatectomy, LRP and RAP are being used more frequently. We reviewed our experience with these minimally invasive techniques. MATERIALS AND METHODS: We reviewed intraoperative and early postoperative complications of 358 LRPs performed from October 2000 to January 2003 with those of 322 RAPs performed from June 2003 to June 2004. The transperitoneal approach with bilateral pelvic lymph node dissection was performed using each technique. Data acquisition was done independently of the 3 surgeons. RESULTS: The LRP and RAP groups had similar clinical characteristics in terms of patient race, body mass index, prostate specific antigen, risk group, and pathological tumor grade and stage. Median operative time and estimated blood loss for LRP and RAP were 4.1 and 3.1 hours, and 200 and 250 ml, respectively. No blood transfusions were given intraoperatively, although 8 patients with LRP (2.2%) and 5 with RAP (1.6%) were transfused postoperatively. Of the LRP and RAP patients 21 (5.9%) and 3 (0.3%), respectively, experienced intraoperative complications. Postoperatively 48 patients with LRP (13.4%) and 24 with RAP (6.8%) experienced urine leakage, while 19 with LRP (5.3%) and 9 with RAP (2.8%) had ileus. There were no deaths, myocardial infarctions, pulmonary emboli or cerebrovascular accidents. CONCLUSIONS: In our series surgeon experience derived from LRP may contribute to the lower complication rate and operative time of RAP. Dissemination of surgical technique and management of complications may lead to improved perioperative LRP and RAP morbidity. However, the morbidity of these 2 approaches compares favorably with that of radical retropubic prostatectomy.

Paint-only is equivalent to scrub-and-paint in preoperative preparation of abdominal surgery sites.

BACKGROUND: Antiseptic preoperative skin site preparation is used to prepare the operative site before making a surgical incision. The goal of this preparation is a reduction in postoperative wound infection. The most straightforward technique necessary to achieve this goal remains controversial. STUDY DESIGN: A prospective randomized trial was designed to prove equivalency for two commonly used techniques of surgical skin site preparation. Two hundred thirty-four patients undergoing nonlaparoscopic abdominal operations were consented for the trial. Exclusion criteria included presence of active infection at the time of operation, neutropenia, history of skin reaction to iodine, or anticipated insertion of prosthetic material at the time of operation. Patients were randomized to receive either a vigorous 5-minute scrub with povidone-iodine soap, followed by absorption with a sterile towel, and a paint with aqueous povidone-iodine or surgical site preparation with a povidone-iodine paint only. The primary end point of the study was wound infection rate at 30 days, defined as presence of clinical signs of infection requiring therapeutic intervention. RESULTS: Patients randomized to the scrub-and-paint arm (n = 115) and the paint-only arm (n = 119) matched at baseline with respect to age, comorbidity, wound classification, mean operative time, placement of drains, prophylactic antibiotic use, and surgical procedure (all p > 0.09). Wound infection occurred in 12 (10%) scrub-and-paint patients, and 12 (10%) paint-only patients. Based on our predefined equivalency parameters, we conclude equivalence of infection rates between the two preparations. CONCLUSIONS: Preoperative preparation of the abdomen with a scrub with povidone-iodine soap followed by a paint with aqueous povidone-iodine can be abandoned in favor of a paint with aqueous povidone-iodine alone. This change will result in reductions in operative times and costs.

Prostate cancer molecular markers GSTP1 and hTERT in expressed prostatic secretions as predictors of biopsy results.

OBJECTIVES: To develop noninvasive diagnostic tools for the early detection of prostate cancer (PCa). Current screening for PCa lacks sensitivity and specificity. Two molecular markers, telomerase activity and aberrant methylation of the glutathione S-transferase P1 (GSTP1) promoter, are found in more than 90% of PCa specimens. Additionally, these markers can be detected in bodily fluids such as urine and postprostatic massage urethral washes. METHODS: Expressed prostatic secretions (EPS) from men being evaluated for PCa were analyzed for human telomerase reverse transcriptase (hTERT) expression (the critical factor for telomerase activity) and GSTP1 methylation status. The results were compared with the prostate needle biopsy findings. RESULTS: EPS could be obtained from 86% of all subjects, and 90% of these samples yielded sufficient RNA and/or DNA for assaying. hTERT expression from EPS (n = 49) had 36% sensitivity and 66% specificity, and GSTP1 methylation from EPS (n = 58) had 46% sensitivity and 56% specificity for the detection of PCa. The combined analysis (n = 32) of hTERT and GSTP1 had 73% sensitivity and 43% specificity, giving a positive predictive value of 40% and a negative predictive value of 75%. CONCLUSIONS: These results demonstrate that EPS can be successfully obtained and easily tested for hTERT expression and GSTP1 methylation. Tests with a high negative predictive value, such as our combination assay results, could be useful in augmenting current PCa diagnostic procedures. For example, the examination of EPS for hTERT and GSTP1 methylation in patients with an elevated prostate-specific antigen level might be used in predicting which patients will have negative biopsies. The use of this assay could potentially eliminate up to 30% of costly and invasive needle biopsies.