Preoperative Prostate-specific Antigen Research Articles

Infected Pelvic Lymphocele after Robot-Assisted Radical Prostatectomy

The aim of this study is to clarify the incidences of infected pelvic lymphocele (IPL) after robot-assisted radical prostatectomy (RARP). From 2016 to 2017, we evaluated 173 consecutive patients who underwent RARP. The transperitoneal approach was used for the RARPs. Limited lymph node dissection was performed in the pelvic lymphoceles region surrounding the obturator nerve. Patients with IPL were defined as those with infected pelvic lymphoceles classified as Clavien-Dindo (CD) classification system grade II or greater and a fever over 38 degrees Celsius. All other cases were defined as nonIPL. IPL was observed in 5 cases (2.9%) that were classified as CD grade II in 2 cases, IIIa in 2 cases, and IVa in 1 case. The most severe case (CD grade IVa) required temporary dialysis for acute renal failure during conservative treatment. While the dissected lymph nodes in the IPL group were sificantly greater than those in the nonlPL group (20.8 ± 7.1 vs 10.3 ± 6.0, P = 0.0298) and the preoperative prostate specific antigen in the IPL group was significantly higher than that in the nonIPL group (15.6 ± 21.7 ng/ml vs 9.0 ± 6.1 ng/ml, P = 0.0359), there were no significant differences in the other background factors between the two groups. In the multivariate analysis, the number of dissected lymph nodes was an independent predictive factor for IPL. While the incidences of IPL after RARP were low, the number of dissected lymph nodes was related to IPL.

Interrelationship Between Health Insurance Status and Prostate Cancer Grade Can Have Critical Impact on Prostate Cancer Disease Control: A Retrospective Cohort Study.

The extent to which prostate cancer (PCa) pathology interacts with health insurance to predict PCa outcomes remains unclear. This study will assess the overall association of health insurance on PCa disease control and analyze its interrelationship PCa pathology. A total of 674 PCa patients, treated with prostatectomy from 1987 to 2015, were included in the study. Freedom from biochemical failure (FFbF) was used as a measure of PCa disease control. Methods of categorical and survival analysis were used to analyze the relationships between health insurance, PCa pathology, and FFbF. A total of 63.3% patients were privately insured, 27.1% were publicly insured, and 9.5% were uninsured. In a multivariable model, privately (hazard ratio [HR] = 0.64, 95% confidence interval [CI]: 0.42-0.97, P = .03) and publicly (HR = 0.65, 95% CI: 0.41-1.04, P = .07) insured patients showed improvement in FFbF compared to uninsured patients. The association of health insurance was significantly stronger for the patients with pathologically low grade PCa (pathologic Gleason Score 3+3 & preoperative prostate-specific antigen ≤10 ng/mL), likelihood ratio P = .009. Privately (HR = 0.22, 95% CI: 0.10-0.46) or publicly (HR = 0.26, 95% CI: 0.11-0.60) insured patients with low grade PCa demonstrated favorable association with FFbF. Patients with private and public insurance were more likely to experience favorable treatment. The association of health insurance on PCa disease control is significantly stronger among patients with pathologically low grade PCa. This study identifies health insurance status as pretreatment surrogate for PCa disease control.

Adjuvant hormone therapy after radical prostatectomy in high-risk localized and locally advanced prostate cancer: First multicenter, observational study in China.

ObjectivePotential of combined androgen blockade (CAB) has not been explored extensively in Chinese males with prostate cancer (PCa). Therefore, this study evaluated the 2-year prostate-specific antigen (PSA) recurrence rate and quality of life (QoL) in patients with high-risk localized and locally advanced PCa receiving adjuvant hormone therapy (HT) after radical prostatectomy (RP).MethodsThis prospective, multicenter, observational study conducted in 18 centers across China enrolled patients with high-risk factor (preoperative PSA>20 ng/mL or Gleason score >7) or locally advanced PCa. Different adjuvant HT were administered after RP according to investigator’s decision in routine clinical practice. Relationship of baseline and postoperative characteristics was assessed with recurrence rate. PSA recurrence rate and Functional Assessment of Cancer Therapy-Prostate (FACT-P) QoL scores were recorded at 12 months and 24 months. Kaplan-Meier analysis was used to construct the PSA recurrence rate during follow-up.ResultsA total of 189 patients (mean age: 66.9±6.5 years) were recruited, among which 112 (59.3%) patients showed serum PSA>20 ng/mL preoperatively. The highest postoperative pathological advancement noticed was from clinical T2 (cT2) to pathological T3 (pT3) (43.9%) stage. The majority of the patients (66.1%) received CAB as adjuvant HT, for a median duration of 20.0 months. The least recurrence (15.2%) was noticed in patients treated with CAB, followed by those treated with luteinizing hormone-releasing hormone agonist (LHRHa) (16.1%), and antiandrogen (19.0%), with non-significant difference noted among the groups. None of the baseline or postoperative characteristics was related with PSA recurrence in our study. The 24-month FACT-P QoL score of 119 patients treated for >12 months showed significant improvement above baseline compared with those treated for ≤12 months.ConclusionsAdjuvant CAB therapy after RP showed reduction trend in 2-year PSA recurrence rate in high-risk Chinese patients with localized and locally advanced PCa, compared with adjuvant anti-androgens (AA) or LHRHa therapy. Further long-term therapy (>12 months) significantly improved QoL compared to short-term HT therapy, suggesting the beneficial effect of long-term CAB therapy in improving QoL.

Can Robot-assisted Radical Prostatectomy Improve Functional Outcomes Compared to Laparoscopic Radical Prostatectomy? Experience at a Laparoscopic Center

Purpose: This study compared the perioperative parameters and early functional outcomes between robot-assisted radical prostatectomy (RARP) and laparoscopic radical prostatectomy (LRP) at a urological laparoscopic center. Materials and Methods: Between January 2006 and May 2017, 242 patients underwent endoscopic radical prostatectomy (LRP for 208 cases; RARP for 34 cases). Patients who were followed up > 12 months were included in the study. Propensity score-matched groups of patients who underwent LRP or RARP were created based on age, body mass index, history of diabetes mellitus, history of smoking, preoperative prostate-specific antigen level, clinical T status, risk group classification, American Society of Anesthesiologists score, and whether the nerve-sparing technique was performed. Results: There were no significant differences in the blood transfusion rate, surgical margin status, length of stay, catheterization time, or days to oral intake for both procedures. Although RARP is more time-consuming, it provided significant benefits regarding the yield of dissected lymph nodes (19 vs. 9; P < 0.001) and early urinary continence recovery (i.e., continence rates after 1 month [56.2% vs. 21.9%; P = 0.006] and after 3 months [84.4% vs. 53.1%; P = 0.001]). No difference was observed for early complications, although the RARP group had more late complications. Conclusion: Our experience indicated that RARP could provide less blood loss and faster recovery of urinary continence and yield more dissected lymph nodes compared to LRP. Further studies are needed to determine whether the long-term clinical, functional, and oncological outcomes are superior.

Stromal androgen receptor expression in prostate cancer in relation to clinicopathological parameters

Background Prostate cancer (PCa) is one of the most commonly diagnosed male tumors all over the world. Most studies have concentrated upon the established role of epithelial androgen receptor (AR) expression in PCa, but the role of stromal AR expression is still not completely understood. Aim To assess immunohistochemical expression of stromal AR and investigate its relation to the PCa grade (according to the new contemporary advances in Gleason score/grading system) and other clinicopathological parameters. Materials and methods This is a retrospective study performed on 65 cases of PCa. All cases were immunohistochemically stained for AR to assess its stromal expression using the Allred score applied for estrogen receptor (ER) and progesterone receptor (PR) in the breast. The results were recorded for statistical analysis. Results Stromal AR was significantly related to the percentage of PCa in the specimen (P=0.003), tumor grade (P=0.001), perineural invasion (P=0.041), and cancer stage (P=0.001). On the contrary, stromal AR expression showed statistically insignificant relation with patients’ age (P=0.231), diabetes mellitus status (P=0.073), preoperative prostate-specific antigen level (P=0.202), digital rectal examination result (P=0.421), weight of the prostate (P=0.083), tumor size (P=0.209), and lymph node metastasis (P=0.411). Moreover, using Spearman’s correlation, there was a highly statistically significant correlation between stromal AR score and both Gleason grade/score (P Conclusion AR expression in prostatic cancer stroma may have protective value against cancer progression.

Does seminal vesicle-sparing robotic radical prostatectomy influence postoperative prostate-specific antigen measured with an ultrasensitive immunoassay?

PURPOSE Sparing of the seminal vesicles during robotic radical prostatectomy (SVRP) is an attempt to reduce potential damage to the hypogastric pelvic nerves. However, the seminal vesicles are known to express prostate-specific antigen (PSA) and it is unknown whether SVRP influences oncological outcome measured with ultrasensitive PSA immunoassays. In a retrospective study we analysed whether SVRP affects oncological outcome in terms of ultrasensitive PSA nadir and biochemical recurrence as compared with standard robotic assisted laparoscopic radical prostatectomy (sRALP). METHODS Overall, 102 patients underwent robotic prostatectomy. Patients were non-randomly allocated to the following surgical techniques: a SVRP group of 39 patients who underwent robotic radical prostatectomy sparing the tips of the seminal vesicles; a standard group of 63 patients who were treated with sRALP. Inclusion criteria were histologically proven negative margins (R0) and negative lymph node status (pN0). PSA was measured with an ultrasensitive assay. The Mann-Whitney U-test was used to compare the differences in PSA nadir and follow-up PSA. Biochemical recurrence was diagnosed if PSA rose to ≥0.2 mg/ml. RESULTS Median (range) follow-up was 31.4 (16.4–43.8) months. Preoperative PSA was 5.8 (0.13–15.29) ng/ml in the SVRP group and 7.1 (0.8–46) ng/ml in the sRALP group. Two cases of biochemical recurrence occurred in the sRALP group during follow-up. One of these two patients presented with locally advanced prostate carcinoma diagnosed from the definitive pathological specimen (pT3b). No patient of the SVRP group had seminal vesicle invasion or biochemical recurrence. No significant between-group difference in terms of PSA nadir and follow-up PSA was recorded. However, the percentage of patients who did not reach PSA nadir values of <0.01 ng/ml was higher in the SVRP group (10 vs 5% in the sRALP group). CONCLUSIONS Compared with sRALP, SVRP had no clinical impact on oncological outcome in terms of PSA nadir or biochemical recurrence measured with an ultrasensitive PSA immunoassay. A slightly higher PSA nadir after SVRP seems to be expected, which needs to be mentioned during follow-up of these patients.

Expression and clinical significance of Caveolin-1 in prostate Cancer after transurethral surgery

BackgroundProstate cancer is a common malignancy of the male genitourinary system that occurs worldwide. The current research aims to investigate caveolin-1 expression in prostate cancer tissue and its relationship with pathological grade, clinical pathologic staging, and preoperative prostate-specific antigen (PSA) levels.MethodsFrom January 2012 to December 2014, samples from 47 patients with prostate cancer who had received transurethral prostatic resection (TURP) and 20 patients with benign prostatic hyperplasia were collected at the First Affiliated Hospital of Guangxi Medical University. Caveolin-1 was detected by streptavidin-perosidase (SP) immunohistochemical staining in pathological tissue slices. The results were statistically analyzed for pathological grade, clinical stage, and preoperative PSA level.ResultsThe expression of caveolin-1 was significantly higher in prostate cancer samples than in benign prostatic hyperplasia samples (P < 0.05), and caveolin-1 expression was significantly different among the pathological grades of poorly, moderately and well-differentiated prostate cancer (P < 0.05). The difference in caveolin-1 expression was significant for different clinical stages (T1-T2 and T3-T4) of prostate cancer (P < 0.05). The difference in caveolin-1 expression was not significant among samples with different preoperative PSA levels (0–10, 10–100 and > 100 μg/L) (P > 0.05).ConclusionsCaveolin-1 is closely related to the pathological grade and clinical stage of prostate cancer after transurethral surgery, and it may be a novel tumor marker for prostate cancer. The expression of caveolin-1 is not associated with preoperative serum PSA levels.

Predictors of biochemical recurrence after Retzius-sparing robot-assisted radical prostatectomy: Analysis of 359 cases with a median follow-up period of 26months.

Our aim was to evaluate the predictors of biochemical recurrence after Retzius-sparing robot-assisted radical prostatectomy. The study cohort consisted of 359 consecutive non-metastatic prostate cancer patients who underwent Retzius-sparing robot-assisted radical prostatectomy between November 2012 and January 2016. According to the National Comprehensive Cancer Network prostate cancer risk classification, 164 patients (45.7%) had high- or very high-risk prostate cancer. No patient received adjuvant therapy until documented biochemical recurrence. Biochemical recurrence-free survival was estimated using the Kaplan-Meier method. Univariable and multivariable Cox proportional hazards regression models were used to determine variables predictive of biochemical recurrence. The median follow-up period was 26months (interquartile range 19-38months). The overall biochemical recurrence rate was 14.8%, and the median time to biochemical recurrence was 11months (interquartile range 6-22months). The 3-year biochemical recurrence-free survival probability was 71.2%, 72.1%, 88.7%, 82.3% and 95.7% in very high-, high-, intermediate-, low- and very low-risk prostate cancer, respectively (log-rank, P<0.001). On multivariable analysis, preoperative prostate-specific antigen (hazard ratio 1.03, 95% confidence interval 1.02-1.04; P<0.0001), percentage of maximum core involvement on biopsy (hazard ratio 1.02, 95% confidence interval 1.01-1.03; P=0.029) and clinical stage ≥T3a (hazard ratio 2.12, 95% confidence interval 1.02-4.39; P=0.043) were predictors of biochemical recurrence, whereas pathological Gleason score ≥8 (hazard ratio 5.63, 95% confidence interval 1.62-19.61; P=0.007) and pathological tumor volume (hazard ratio 1.08, 95% confidence interval 1.04-1.20; P<0.001) were the main pathological predictors of biochemical recurrence. Retzius-sparing robot-assisted radical prostatectomy confers effective biochemical recurrence control at the mid-term follow-up period. Preoperative prostate-specific antigen, advanced clinical stage and higher Gleason score were important predictors of biochemical recurrence after Retzius-sparing robot-assisted radical prostatectomy. Long-term oncological safety still needs to be established.

Holmium Laser Enucleation of the Prostate Provides Similar Incidental Prostate Cancer Detection Rates as Open Prostatectomy: A Matched Pair Analysis

Introduction: Whereas the excellent functional outcomes after Holmium laser enucleation of the prostate (HoLEP) and its equivalency to open prostatectomy (OP) have been studied in detail in the past years, the oncological equivalency has yet to be investigated. Therefore, we conducted a matched pair analysis to evaluate and compare incidental prostate cancer detection rates after HoLEP and OP. Patients and methods: Preoperative patient age, total prostate-specific antigen (PSA), and prostate volume were used as primary matching criteria. Descriptive statistics were used to confirm matching quality. Statistical analyses were performed using Fisher´s exact test and T-test or Mann-Whitney U-test for dichotomous and continuous variables, respectively. Results: After the matching procedure, 72 out of 145 patients after HoLEP and 72 out of 477 patients after OP were included. Mean patient age (70 vs. 71 years), median prostate volume (106 vs. 107 mL), and median preoperative total PSA (4.32 vs. 4.36 ng/mL) were almost identical. The amount of removed tissue did not differ between HoLEP and OP. Incidental prostate cancer detection rate was similar with 9.7% after HoLEP and 8.3% after OP (p = 1.000). Conclusion: This first matched pair analysis shows that HoLEP does not have a disadvantage regarding cancer detection rate during desobstructive surgery for large prostates.

Comparison of lymph node dissection and short-term efficacy of laparoscopic radical operation in patients with different grades of prostate cancer

Objective To investigate and compare pelvic lymph node dissection and the short-term efficacy of laparoscopic radical operation in patients with different Gleason grades of prostate cancer. Methods The medical records of 98 patients with prostate cancer treated by laparoscopic radical operation in our hospital were analyzed retrospectively. According to the preoperative Gleason score, the patients were divided into group A (Gleason score ≤ 6 points, 37 cases), group B (Gleason score of 3+ 4=7 points or 4+ 3=7 points, 42 cases) and group C (Gleason score≥ 8 points, 19 cases). The situation of operation, the incidence of postoperative complications, preoperative and postoperative prostate specific antigen (PSA) levels and the probability of postoperative PSA level > 0.2 ng/mL were compared among the 3 groups. All patients were followed up to August 2017, and the biochemical recurrence rates of two groups were recorded. Results There was no patient undergoing lymph node dissection in group A, 38 patients undergoing pelvic lymph node dissection in group B, and all patients undergoing pelvic lymph node dissection in group C. There was no significant difference between group B and group C in the number of dissected lymph nodes (P>0.05). The operation time and intraoperative blood loss of group A were shorter or less than those of group B or group C (P 0.05). The positive rates of incisal margin in group A and group B (0% and 2.38%) were lower than that in group C (15.79%) (P 0.05). PSA levels in the 3 groups at 1 month after operation were lower than those before operation (P 0.05). The odds of PAS level > 0.2 ng/mL in group A and group B (0 and 2.38%) were significantly lower than that in group C (15.79%) (P<0.05). The biochemical recurrence rates of group A and group B (2.70% and 7.14%) were lower than that of group C (26.32%) (P<0.013). Conclusions Lymph node dissection should be carried out after evaluating the risk of pelvic lymph node dissection in patients with prostate cancer before laparoscopic radical operation. The lower the Gleason score is, the lower the positive margin rate of incisal margin and biochemical recurrence rate are. Key words: Prostatic Neoplasms; Laparoscopy; Lymph Node Excision

Robot-Assisted Radical Prostatectomy in a Post−Kidney Transplant Patient: An Initial Case Report in China

ObjectiveOur aim was to evaluate the general applicability, feasibility, and safety of robot-assisted radical prostatectomy (RARP) in Chinese renal allograft patients for prostate cancer removal. Patients and MethodsA 62-year-old patient diagnosed as having biopsy-proven localized prostate cancer in March 2016 who had undergone renal transplant 12 years ago was studied. The preoperative prostate-specific antigen value was determined to be 11.82 ng/mL and the Gleason score was determined to be 3 + 3. The RARP was carried out using a transperitoneal and posterior approach with 5 ports in May 2016. The most important technique was ensuring that the transplanted kidney and ureter remained untouched during the surgery. Only the right obturator lymph nodes were dissected because the renal allograft was overlying the iliac vessels. ResultsThe RARP was successfully concluded following 230 minutes with an estimated blood loss of 200 mL. There were no postoperative complications. Final pathology was T2cN0M0, Gleason 3 + 3. Following catheter removal, the patient was completely continent and was discharged with no change in serum creatinine or glomerular filtration rate levels. During a 21-month follow-up, unobstructed urination, no incontinence, no biochemical recurrence, and normal kidney function were observed. ConclusionRARP in Chinese renal allograft patients is a feasible method that can be accomplished with no injuries to the transplanted kidney or ureter and is achieved with favorable oncological and functional outcomes. In addition, post−kidney transplant male patients are recommended to have routine prostate-specific antigen screening for the early detection of prostate cancer.

13q deletion is linked to an adverse phenotype and poor prognosis in prostate cancer.

Deletions of chromosome arm 13q belong to the most frequent molecular alterations in prostate cancer. To better understand the role of 13q deletion in prostate cancer we took advantage of our large prostate cancer tissue microarray comprising more than 12 000 cancer samples with full pathological and clinical follow-up data. Fluorescence in situ hybridization with probes for ENOX1 (13q14.11) and the retinoblastoma gene (RB1, 13q14.2) was employed. A 13q deletion was found in 21% of 7375 analyzable cancers. Deletions were always heterozygous and associated with high Gleason grade (P < .0001), advanced tumor stage (P < .0001), high preoperative prostate-specific antigen (PSA) levels (P = .0125), lymph node metastasis (P = .0377), positive resection margin (P = .0064), and early biochemical recurrence (P < .0001). 13q deletions were marginally more frequent in prostate cancers with negative ERG status (22.9%) than in ERG-positive tumors (18.7%; P < .0001). Loss of 13q predicted patient prognosis independently from established prognostic parameters that are available at the time of biopsy (P = .0004), including preoperative PSA level, clinical tumor stage, and biopsy Gleason grade. In summary, the results of our study identify 13q deletion as a frequent event in prostate cancer, which is linked to an adverse phenotype and poor prognosis in this disease.

Abstract B083: Disease marker-specific disseminated tumor cells in bone are rare at the time of radical prostatectomy

Abstract Introduction: In prostate cancer (PCa), DTCs are cells that have escaped the primary lesion and enter the metastatic site, most commonly the bone marrow (BM). The pelvis is a common metastatic site for prostate cancer metastases. However, it is unclear when PCa cells leave the prostate and travel to bone in clinically localized disease. Thus, we studied whether PCa DTCs can be detected at the time of radical prostatectomy (RP) by performing a bone marrow aspiration (BMA) from the anterior iliac crest (AIC) at the time of surgery. Methods: The study protocol was approved by the institutional review board at the Johns Hopkins Medical Institutions. Informed consent to perform BMA was obtained from 94 clinically localized PCa patients undergoing a robotic-assisted laparoscopic prostatectomy (RALP). In the supine position, patients underwent general anesthesia and were prepped and draped in a normal sterile fashion. Aspiration was performed by the attending surgeon prior to first incision and obtained percutaneously from the AIC using a BM biopsy needle (11G x 100 mm Hospital Trapsystem, HS Hospital Service S.p.A.). 8-20 mL of BM were aspirated into 1 or 2 10-mL syringes (BD) and transferred into collection tubes through an 18-gauge needle (PrecisionGlide, BD). Samples were distributed among 7 different principal investigators within 24 hours of collection for DTC analyses. One type of analysis included the AdnaTest, which first involved collecting 8 mL of BM from 43/77 (56%) patients. 5 mL of whole cell extract was then assayed with the AdnaTest ProstateCancerSelect kit (Qiagen) to enrich for epithelial-marker, EpCAM, positive cells using immunomagnetic beads. Reverse transcription (SensiScript RT kit, Qiagen) and real-time qPCR quantified the expression of RPL13A (control, ribosomal protein), EPCAM (epithelial), NKX3.1, prostate-specific antigen (PSA), androgen receptor full length (AR), and HOXB13 (prostate-specific). DTC detection was defined as positive prostate-specific marker expression in the BM. Quality control was performed with Sanger sequencing. Results: BM was successfully obtained from 77/94 (82%) patients. The median (range) age was 62 (43-76) years and the median (range) preoperative PSA was 6 (1.3-62.6) ng/mL. 8/77 (10%) patients had RP Gleason Score 6 disease, 37/77 (48%) were Gleason 3+4, 18/77 (23%) were 4+3, and 13/77 (17%) were Gleason 8-10. One patient had an undetermined RP Gleason due to effects from neoadjuvant chemotherapy. 65/77 (85%) had PSA &amp;lt;10, 8/77 (10%) had PSA 10-20, and 4/77 (5%) had PSA &amp;gt;20. 50/77 (65%) had pT2, 21/77 (27%) had pT3a, and 6/77 (8%) had pT3b diseases. 3/77 (4%) had lymph node metastasis as confirmed in their pathology. The average time to collect BM and transfer into tubes was 2.5 minutes. The median volume collected was 10.5 mL. RALP was performed without BMA-associated complication and there were no reports of BMA-induced postoperative complications including discomfort at the BMA site. Patients were discharged on postoperative day one. For the AdnaTest, 1/43 (2%) BM expressed PSA and 43/43 (100%) expressed EpCAM. Conclusions: We demonstrated an efficient percutaneous approach to BMA from the AIC with 77/94 (82%) successful attempts to obtain BMA and an average collection time of 2.5 minutes. This technique is feasible and safe with no BMA-associated surgical complications or patient discomfort postoperatively. Samples are utilized to study PCa dissemination to bone. Putative PSA positive DTCs can be identified at the time of RP. Citation Format: Emily A. Caruso, Stephanie Glavaris, Heather J. Chalfin, Kenneth C. Valkenburg, Mohamad E. Allaf, Misop Han, Kenneth Pienta. Disease marker-specific disseminated tumor cells in bone are rare at the time of radical prostatectomy [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B083.

Predictors of Rectourethral Fistula Formation After Primary Whole-Gland Cryoablation for Prostate Cancer: Results from the Cryo On-Line Database Registry.

To define the incidence and risk factors associated with rectourethral fistula (RUF) formation following primary whole-gland cryosurgery using a multicenter centralized registry. The Cryo On-Line Data (COLD) registry was queried for men undergoing primary whole-gland cryotherapy between 1990 and 2014 who developed a RUF. Patient factors and disease parameters were correlated with RUF using chi-square and the t-test. Variables with p < 0.25 were entered into a binary logistic regression with stepwise backward elimination to determine the factors associated with RUF formation. A total of 4102 men underwent primary whole-gland cryotherapy in the COLD registry at the time of analysis. Postoperative RUF was documented in 50 out of 4102 cases (1.2%). Patients with RUF had similar demographic data, prostate volume, preoperative prostate-specific antigen level, and clinical stage in comparison to those without fistula. On both univariate and multivariate analyses, postoperative urinary retention (odds ratio [OR]: 6.30; confidence interval [95% CI] 3.43-11.58, p < 0.001), preoperative Gleason score of ≥7 (OR: 1.92; 95% CI 1.08-3.43, p = 0.027), and preoperative incontinence (OR: 2.95; 95% CI 1.12-7.76, p = 0.028) were the most significant risk factors associated with RUF formation. Primary whole-gland cryotherapy for prostate cancer is associated with a historically low rate (1.2%) of postoperative RUF formation. The rate decreased further to 0.55% over the last several years, suggesting better patient selection and technical improvement. Postoperative urinary retention, Gleason score ≥7, and preoperative urinary incontinence were the key demographic, clinical, and pathologic features associated with RUF formation in this study.

Tailored postoperative treatment of prostate cancer: final results of a phase I/II trial

BackgroudThe European Organization for Research and Treatment of Cancer (EORTC) trial 22,911 reported 74% 5-year biochemical disease-free survival (bDFS) in patients with prostate carcinoma treated with radical prostatectomy (RP) followed by postoperative radiotherapy (RT). This study aimed to improve these outcomes by using a combined-intensified-modulated-adjuvant treatment, including RT and hormone therapy (HT) after RP.Materials and methodsThis phase I/II trial treatment was designed to improve 5-year bDFS from ~ 75 to 90%. Patients were consecutively enrolled using the following inclusion criteria: age < 80 years, histological diagnosis of prostate adenocarcinoma without known metastases, stage pT2-4N0-1, and Eastern Cooperative Oncology Group performance status of 0–2. All patients had at least one of these pathologic features: capsular perforation, positive surgical margins, seminal vesicle invasion, and pelvic lymph nodes involvement. A minimum dose of 64.8 Gy to the tumor bed was delivered in all patients. Depending on tumor characteristics at diagnosis, patients received a higher dose (70.2 Gy; 85.4%) and/or prophylactic pelvic lymph nodes irradiation (57.7%) and/or HT (69.1%). Biochemical relapse was defined as two consecutive rising prostate-specific antigen (PSA) values > 0.2 ng/ml.ResultsA total of 123 patients were enrolled in the study and completed the scheduled treatment. Median preoperative and postoperative PSA were: 8.8 and 0.06 ng/mL, respectively. The percentages of patients with pathologically involved nodes and positive resection margins were: 14.6% and 58.5%, respectively. With a median follow-up of 67 months (range: 37–120 months), the actuarial 5-year bDFS, local control, metastasis-free survival, and overall survival (OS) were: 92.9%, 98.7%, 96.1%, and 95.1%, respectively.ConclusionA higher 5-year bDFS (92.9%) was recorded compared to studies based on standard adjuvant RT, even though patients with nodal disease and detectable postoperative PSA were enrolled. Clinical end points, as long-term disease-free survival and OS, will require further assessments. (ClinicalTrials.gov: NCT03169933)

Prognostic utility of neutrophil-to-lymphocyte and platelets-to-lymphocyte ratio in predicting biochemical recurrence post robotic prostatectomy.

Utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting biochemical recurrence (BCR) in patients with localized prostate cancer. Retrospective analysis of patients operated by robot-assisted radical prostatectomy. Variables included were: NLR, PLR pre-operative prostate specific antigen, pathological Gleason score, surgical margins status, extracapsular extension, seminal vesical invasion, and lymph node status. Out of 321 patients, no association between NLR or PLR and BCR was detected. Predictors of BCR were pathological Gleason score, extracapsular extension and positive surgical margins. On multivariate analysis, the Gleason Score, extracapsular extension and positive surgical margins remained the only predictors of BCR. Neither elevated NLR nor PLR predicted an increased risk of BCR.

Application of pubovesical complex preserving technique during laparoscopic radical prostatectomy

Objective To describe a novel pubovesical complex preserving technique for laparoscopic radical prostatectomy and to evaluate its postoperative outcomes. Methods From January 2011 to May 2017, 168 patients who underwent laparoscopic radical prostatectomy were enrolled and analyzed retrospectively. Their mean age were 62.8 (46-74) years, preoperative PSA 11.3ng/ml, Gleason score 6.7, preoperative prostate volume 46.5 ml. They all got preoperative potency (IIEF-5 score ≥15 score). TNM clinical stage: cT1 123 cases, 45 cases cT2. There were 59 patients with pubovesical complex preserving technique for laparoscopic radical prostatectomy(group A): without pelvic fascia cut and deep vein complex suture. The preservation of the periprostatic anatomy was kept by preserving the pubovesical complex, including detrusor apron with pubovesical ligaments, DVC and NVB. There were 46 patients with conventional intrafascial laparoscopic radical prostatectomy(group B) and 63 patients with interfascial laparoscopic radical prostatectomy(group C). No differences were found between the three groups in terms of preoperative age, clinical staging, prostate-specific antigen (PSA) values, Gleason score at biopsy and preoperative good potency (IIEF-5 score)(P>0.05). Continence was defined as zero to one security pad per day. The three groups were compared for perioperative variables, PSM(positive surgical margin, PSM)rate, postoperative urinary continence functional and potency (IIEF-5 score). Biochemical recurrence-free survival was by Kaplan-Meier and log-rank. Results No differences were found in the three groups in terms of operative times, blood loss, catheterization time and postoperative stay and histologic status (PSM was similar to that of the groups (8.5% in group A, 13.0% in group B vs. 11.1% in group C). Urinary incontinence: group A, the continence rate was 71%, 82%, 92% and 100% at 1, 3 and 6 months after catheter removal, respectively; group B, the continence rate was 63%, 80%, 89% and 96% respectively; group C, it was 24%, 54%, 79% and 86% respectively. The group A showed a significantly earlier recovery from incontinence compared with that in the group C at immediately after catheter removal and 1 month after catheter remove(χ2=27.47, P 0.05). Regarding sexual function, at the postoperative 1, 3, 6 months, median IIEF-score was 10, 11, 16 in the group A, respectively, 8, 9, 13 in the group B respectively, and 7, 8, 12 in the group C respectively. No differences were found in the three groups in potency (IIEF-5 score). Baseline IIEF-score was reached by 53%, 35% and 21% at postoperative 6 months. There were significant differences between the A and the C groups.(χ2=13.45, P 0.05). Follow-up was 31.6(6-69) months. Biochemical recurrence-free survival at 3 years was 79.3%, 76.3% and 76.4% by A, B and C group, respectively. Conclusions The pubovesical complex preserving technique for laparoscopic radical prostatectomy provides early recovery from incontinence, faster recovery of sexual function preoperative levels. Key words: Laparoscopic surgery; Prostate cancer; Sexual function; Urinary incontinence

Abstract B72: DNA methylation and genetic alterations contribute to aggressive prostate cancer in African American men

Abstract Background: African-American (AA) men are more often diagnosed with early-onset aggressive prostate cancer than European American (EA) men. Prostate cancer health disparities between AA and EA men are attributed to socioeconomic as well as biologic differences existing between the two groups. The purpose of this study is to investigate how genetic and epigenetic alterations, specifically DNA methylation, contribute to early-onset aggressive prostate cancer in AA men. Methods: We performed 450K methylation array and RNA-sequencing on radical prostatectomy specimens from AA (n=32) and EA (n=5) men treated at Roswell Park Cancer Institute (RPCI). To increase analytical power, we included AA (n=22) and EA (n=172) patients from The Cancer Genome Atlas (TCGA) database. We found no significant difference in the average age between EA and AA men in the RPCI cohort, but the TCGA cohort consisted of AA men who had significantly lower average and median age compared to EA men (57 and 56 vs 61 and 62; p=0.019). We assessed baseline androgen receptor (AR) protein levels in matched benign and malignant AA (n=95) and EA (n=93) radical prostatectomy tissues from RPCI using immunohistochemistry. Gleason score &amp;lt;3+4 and &amp;gt;4+3 were classified as low and high aggressive tumors, respectively. Results: Unsupervised hierarchical clustering of DNA methylation levels in prostate cancers revealed 9 clusters. We focused on the 2 largest clusters, Cluster 1 (n=133) and Cluster 3 (n=73). Cluster 1 consisted predominantly of low aggressive disease (p=0.00002) with lower serum prostate specific antigen (PSA) values (8.97 vs 13.35 ng/ml) compared to Cluster 3. Following this trend, AA patients, but not EA patients, in Cluster 1 had better overall (57 vs 50 months, p=0.48) and disease-free time (47 vs 22 months, p=0.01) as compared to Cluster 3. ERG (ETS-related gene) fusion-positive prostate cancer is believed to be more aggressive than fusion-negative prostate cancer due to increased ERG gene transcription. We did not observe a difference in fusion status between the two DNA methylation clusters. However, overall DNA methylation was higher in fusion-negative samples as compared to fusion-positive samples in the TCGA dataset. ERG is known to bind to and reduce PSA, a direct downstream AR target. In the TCGA dataset, AA fusion-negative patients had higher average and median preoperative PSA values (18.38, 20.15 ng/ml) as compared with AA fusion-positive (7.51, 6.70 ng/ml), EA fusion-positive (9.43, 7.00 ng/ml), and EA fusion-negative patients (11.47, 7.50 ng/ml). There was no significant difference in the AR transcript and AR protein levels between fusion-positive and -negative AA and EA men. AR protein expression in RPCI cohort tissue microarrays showed that adjacent nontumor tissues from AA men had higher percent AR positive nuclei (p&amp;lt;0.05) compared to adjacent nontumor tissues from EA men. Conclusions: Analysis of the RPCI and TCGA cohorts indicated that DNA methylation separated low and high aggressive prostate cancer in AA men. Further analysis will include more patients as well as identify differences in specific CpG loci between Cluster 1 and Cluster 3. Our results suggest that DNA methylation alterations can be important in patients with ERG fusion-negative disease since these prostate cancers exhibit higher levels of overall DNA methylation. Lastly, our observations of higher AR expression in adjacent nontumor tissues suggest that there are underlying genetic variations that contribute to early-onset high aggressive prostate cancer in AA men compared to EA men. Citation Format: Swathi Ramakrishnan, Xuan Peng, Qianya Qi, Qiang Hu, Gissou Azabdaftari, Elena Pop, James Mohler, Kristopher Attwood, Li Yan, Jianmin Wang, Anna Woloszynska-Read. DNA methylation and genetic alterations contribute to aggressive prostate cancer in African American men [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B72.

A Multicentre Study of 5-year Outcomes Following Focal Therapy in Treating Clinically Significant Nonmetastatic Prostate Cancer

BackgroundClinically significant nonmetastatic prostate cancer (PCa) is currently treated using whole-gland therapy. This approach is effective but can have urinary, sexual, and rectal side effects. ObjectiveTo report on 5-yr PCa control following focal high-intensity focused ultrasound (HIFU) therapy to treat individual areas of cancer within the prostate. Design, setting, and participantsThis was a prospective study of 625 consecutive patients with nonmetastatic clinically significant PCa undergoing focal HIFU therapy (Sonablate) in secondary care centres between January 1, 2006 and December 31, 2015. A minimum of 6-mo follow-up was available for599 patients. Intermediate- or high-risk PCa was found in 505 patients (84%). InterventionDisease was localised using multiparametric magnetic resonance imaging (mpMRI) combined with targeted and systematic biopsies, or transperineal mapping biopsies. Areas of significant disease were treated. Follow-up included prostate-specific antigen (PSA) measurement, mpMRI, and biopsies. Outcome measurements and statistical analysisThe primary endpoint, failure-free survival (FFS), was defined as freedom from radical or systemic therapy, metastases, and cancer-specific mortality. Results and limitationsThe median follow-up was 56 mo (interquartile range [IQR] 35–70). The median age was 65 yr (IQR 61–71) and median preoperative PSA was 7.2 ng/ml (IQR 5.2–10.0). FFS was 99% (95% confidence interval [CI] 98–100%) at 1 yr, 92% (95% CI 90–95%) at 3 yr, and 88% (95% 85–91%) at 5 yr. For the whole patient cohort, metastasis-free, cancer-specific, and overall survival at 5 yr was 98% (95% CI 97–99%), 100%, and 99% (95% CI 97–100%), respectively. Among patients who returned validated questionnaires, 241/247 (98%) achieved complete pad-free urinary continence and none required more than 1 pad/d. Limitations include the lack of long-term follow-up. ConclusionsFocal therapy for select patients with clinically significant nonmetastatic prostate cancer is effective in the medium term and has a low probability of side effects. Patient summaryIn this multicentre study of 625 patients undergoing focal therapy using high-intensity focused ultrasound (HIFU), failure-free survival, metastasis-free survival, cancer-specific survival, and overall survival were 88%, 98%, 100%, and 99%, respectively. Urinary incontinence (any pad use) was 2%. Focal HIFU therapy for patients with clinically significant prostate cancer that has not spread has a low probability of side effects and is effective at 5 yr.

Focal Treatment for Unilateral Prostate Cancer Using High-Intensity Focal Ultrasound: A Comprehensive Study of Pooled Data.

Focal therapy for prostate cancer (PCa) remains experimental. Aim of the current study is to review available evidence and perform a pooled analysis exploring oncologic and functional results of high intensity focus ultrasound (HIFU) focal therapy for the treatment of unilateral PCa. The National Library of Medicine Database was searched for relevant articles. A wide search was performed, including the combination of following words: "HIFU," "prostate," "cancer," and "focal." Overall, 167 articles were reviewed. Of these, seven articles were identified and eligible for the pooled analysis. Data on HIFU hemiablation or focal prostate ablation, oncologic and functional results were pooled from these seven studies that included 366 men with unilateral PCa. In the 366 analyzed cases, mean age was 67 years (95% confidence interval 66-69), and mean preoperative prostate-specific antigen was 6.4 ng/cc (5.5-7.4). Three studies included PCa up to Gleason 7 (3 + 4), three studies did include also Gleason 7 (4 + 3), whereas one study had no limitation in terms of Gleason score. Regarding early complications, low-grade Clavien-Dindo I-II were reported in 26% (16-37), whereas high-grade Clavien-Dindo ≥III were found in 3.8% (0-8.6). Analyzing oncologic outcomes mean follow-up was 26 months (23-31): at one year after HIFU, negative biopsy rate for clinically significant PCa was 87% (79-96), whereas salvage treatment-free survival rate was 92% (85-98). Regarding functional outcomes, reported potency rates were 74% (64-84), and continence 96% (91-100), although definitions of potency and continence were not homogenous across studies. This pooled analysis of the results of focal HIFU treatment of PCa shows promising oncologic and functional outcomes. Well-selected patients may be candidates for such a conservative partial treatment of the gland. Well-designed trials are awaited to compare HIFU focal treatment with current standard of care.