Oncological safety and functional outcomes of testosterone replacement therapy in symptomatic adult-onset hypogonadal prostate cancer patients following robot-assisted radical prostatectomy.

PURPOSE: Testosterone replacement therapy (TRT) remains controversial in men with treated prostate cancer. We assessed its safety and functional impacts in patients after definitive surgical treatment with robotic-assisted radical prostatectomy (RARP). METHODS: We performed a retrospective analysis of 1303 patients who underwent RARP during the years 2006-2019. We identified men with symptoms of andropause and low serum testosterone who received TRT post-RARP; then we divided the cohort into two groups accordingly for comparison. Biochemical recurrence (BCR) was the primary endpoint. Secondary endpoints included functional outcomes. Predictors of BCR, including the effect of TRT on BCR, were evaluated using univariable and multivariable logistic regression. RESULTS: Among the forty-seven men who received TRT, the mean age was 60.83 years with a median follow-up of 48 months. Three (6.4%) and 157 (12.56%) patients experienced BCR in TRT and non-TRT groups, respectively. Baseline characteristics were similar between both groups except for higher mean BMI in the TRT group (p = 0.03). In the multivariate analysis (MVA), higher pre-RARP prostate-specific antigen (PSA) (p = 0.043), higher International Society of Urological Pathology score (p < 0.001), seminal vesical invasion (p = 0.018) and positive surgical margin (p < 0.001) were predictors of BCR. However, TRT was not (p = 0.389). In addition, there was a significant change in the Sexual Health Inventory for Men (p = 0.022), and serum testosterone level (p < 0.001) before and 6 months after initiation of TRT. CONCLUSION: Our findings suggest that TRT, in well-selected, closely followed, symptomatic men post-RARP is an oncologically safe and functionally effective treatment in prostate cancer patients post-RARP.

Detectable Prostate-specific antigen value between 0.01 and 0.1 ng/ml following robotic-assisted radical prostatectomy (RARP): does it correlate with future biochemical recurrence?

PURPOSE: The aim of the study is to evaluate the impact of having a nadir and persistently detectable ultrasensitive prostate-specific antigen (uPSA) between 0.01 and 0.1 ng/ml post-robot-assisted radical prostatectomy (RARP), on future biochemical recurrence (BCR). METHODS: We conducted a retrospective analysis of a prospectively maintained cohort of 1359 men who underwent RARP, between 2006 and 2019. Patients were followed with uPSA at 1, 3, 6, 9, 12, 18, 24, 30, 36 months and annually thereafter. We included patients with PSA nadir values between 0.01 and 0.1 ng/ml within 6 months of surgery and with at least 2 follow-up measurements within the same range. We divided patients based on their BCR status and analyzed uPSA changes. Multivariable Cox-regression models (CRMs) were used to analyze variables predicting BCR-free survival (BCR-FS). RESULTS: We identified 167 (12.3%) patients for analyses, with a mean follow-up time of 60.2 ± 31.4 months. In our cohort, 5-year BCR-FS rate was 86%. Overall, 32 (19.1%) patients had BCR, with a mean time to BCR of 43.7 ± 24.3 months. BCR-free patients had stable mean uPSA values ≤ 0.033 ng/ml, while patients who developed BCR showed a slowly rising trend over time, with a significant difference between groups starting at 9 months (p < 0.02). In multivariable CRMs, a rising uPSA starting at 9 months was an independent predictor of BCR (HR: 2.7; 95% CI 1.6-3.82; p = 0.013). CONCLUSION: In the present cohort, our results demonstrated that a considerable number of men have detectable uPSA values ranging between 0.01 and 0.1 ng/ml post-RARP. They can still be followed regularly to avoid patients' anxiety and salvage radiotherapy. Close follow-up is still required.

Pre-radiotherapy PSA progression is a negative prognostic factor in prostate cancer patients using 5­alpha-reductase inhibitors.

OBJECTIVE: To investigate the impact of 5­alpha-reductase inhibitor (5-ARI) use on radiotherapy outcomes for localized prostate cancer. PATIENTS AND METHODS: We included 203 patients on a 5-ARI from our institutional database comprising over 2500 patients who had been treated with either external beam radiotherapy (EBRT) or brachytherapy for localized prostate cancer. Patients received a 5-ARI for urinary symptoms or active surveillance. Cancer progressions at the time of definitive treatment were analyzed according to the following criteria: (a) progression of Gleason score or increase in cancer volume on biopsy, (b) first biopsy positive for cancer after being treated for urinary symptoms with a 5-ARI, and (c) prostate-specific antigen (PSA) progression with or without a previous cancer diagnosis. Biochemical failure (BF) was defined by the Phoenix definition. Log-rank test was used for survival analysis. RESULTS: At a median follow-up of 38.2 months (standard deviation 22.2 months), 10 (4.9%) patients experienced BF. Concerning prostate cancer progression criteria, 52% of men demonstrated none, 37% showed only one criterion, and 11% showed two. Using univariate analysis, PSA progression (p = 0.004) and appearance of a positive biopsy (p < 0.001) were significant predictive factors for BF, while Gleason progression (p = 0.3) was not. In multivariate analysis adjusted for cancer aggressiveness, rising PSA (hazard ratio, HR, 5.7; 95% confidence interval, CI, 1.1-28.8; p = 0.04) and the number of cancer progression factors (HR 2.9, 95% CI 1.2-7.0, p = 0.02) remained adverse risk factors. CONCLUSION: PSA progression experienced during 5­ARI treatment before radiotherapy is predictive of worse biochemical outcome. Such details should be considered when counseling men prior to radiation therapy.

Functional outcomes of robot-assisted radical prostatectomy in patients eligible for active surveillance.

OBJECTIVE: To assess the outcome of low risk prostate cancer (PCa) patients who were candidates for active surveillance (AS) but had undergone robot-assisted radical prostatectomy (RARP). METHOD: We reviewed our prospectively collected database of patients operated by RARP between 2006 and 2014. Low D'Amico risk patients were selected. Oncological outcomes were reported based on pathology results and biochemical failure. Functional outcomes on continence and potency were reported at 12 and 24 months. Continence was assessed by the number of pads per day. With respect to potency, it was assessed using the Sexual Health Inventory for Men (SHIM) and Erectile Hardness Scale (EHS). RESULTS: Out of 812 patients, 237 (29.2%) patients were D'Amico low risk and were eligible for analysis. 44 men fit Epstein's criteria. 134 (56.5%) men had pathological upgrading. Age and clinical stage were predictors of upgrading on multivariate analysis. 220 (92.8%) patients had available follow-up for biochemical recurrence, potency, and continence for 2 years. The mean and median follow-up was 34.8 and 31.4 months, respectively. Only 5 (2.3%) men developed BCR, all of whom had pathological upgrading. Extra capsular extension and positive surgical margins were observed in 14.8 and 19.1%, respectively. 0 pad was achieved in 86.7 and 88.9% at 1 and 2 years, respectively. Proportion of patients with SHIM > 21 at 1 and 2 years was 24.8 and 30.6%, respectively. Moreover, patients having erections adequate for intercourse (EHS ≥ 3) were seen in 69.6 and 83.1% at 1 and 2 years, respectively. Functional outcomes of patients fitting Epstein's criteria (n = 44) and patients with no upgrading on final pathology (n = 103) were not significantly different compared to the overall low risk study group. CONCLUSION: This retrospective study showed that RARP is not without harm even in patients with low risk disease. On the other hand, considerable rate of upgrading was noted.

Does surgical delay for radical prostatectomy affect biochemical recurrence? A retrospective analysis from a Canadian cohort.

AIM: We sought to explore the impact of surgical wait time (SWT) to robot-assisted radical prostatectomy (RARP) on biochemical recurrence (BCR). METHOD: Retrospective review of a prospectively collected database between 2006 and 2015 was conducted on all RARP cases. SWT was defined as period from prostate biopsy to surgery. Primary outcome was the impact on BCR, which was defined as two consecutive PSA ≥ 0.2 ng/dl, or salvage external beam radiation therapy and/or salvage androgen deprivation therapy. Patients were stratified according to D'Amico risk categories. Univariable analysis (UVA) and multivariable analyses (MVA) with a Cox proportional hazards regression model were used to evaluate the effect of SWT and other predictive factors on BCR, in each D'Amico risk group and on the overall collective sample. RESULTS: Patients eligible for analysis were 619. Mean SWT was 153, 169, 150, and 125 days, for overall, low-, intermediate-, and high-risk patients, respectively. Multivariate analysis on the overall cohort did not show a significant relation between SWT and BCR. On subgroup analysis of D'Amico risk group, SWT was positively correlated to BCR for high-risk group (p = 0.001). On threshold analysis, cut-off was found to be 90 days. SWT did not significantly affect BCR on UVA and MVA in the low- and intermediate-risk groups. CONCLUSION: Increased delay to surgery could affect the BCR, as there was a positive association in high-risk group. Further studies with longer follow-up are necessary to assess the impact of wait time on BCR, cancer specific survival and overall survival.

Delivery of human mesenchymal adipose-derived stem cells restores multiple urological dysfunctions in a rat model mimicking radical prostatectomy damages through tissue-specific paracrine mechanisms.

Urinary incontinence (UI) and erectile dysfunction (ED) are the most common functional urological disorders and the main sequels of radical prostatectomy (RP) for prostate cancer. Mesenchymal stem cell (MSC) therapy holds promise for repairing tissue damage due to RP. Because animal studies accurately replicating post-RP clinical UI and ED are lacking, little is known about the mechanisms underlying the urological benefits of MSC in this setting. To determine whether and by which mechanisms MSC can repair damages to both striated urethral sphincter (SUS) and penis in the same animal, we delivered human multipotent adipose stem cells, used as MSC model, in an immunocompetent rat model replicating post-RP UI and ED. In this model, we demonstrated by using noninvasive methods in the same animal from day 7 to day 90 post-RP injury that MSC administration into both the SUS and the penis significantly improved urinary continence and erectile function. The regenerative effects of MSC therapy were not due to transdifferentiation and robust engraftment at injection sites. Rather, our results suggest that MSC benefits in both target organs may involve a paracrine process with not only soluble factor release by the MSC but also activation of the recipient's secretome. These two effects of MSC varied across target tissues and damaged-cell types. In conclusion, our work provides new insights into the regenerative properties of MSC and supports the ability of MSC from a single source to repair multiple types of damage, such as those seen after RP, in the same individual.

Network meta-analysis of second-line treatment in metastatic renal cell carcinoma: efficacy and safety.

This paper aims to compare the approved second-line treatment options in metastatic renal cell carcinoma. A network meta-analysis (NMA) using the frequentist approach and generalized pairwise modeling was computed for the approved drugs in this setting. The results of this NMA showed that the combination of lenvatinib and everolimus yielded the lowest hazard ratio (HR) for progression-free survival (HR: 0.4; 95% CI: 0.21-0.75) and overall survival (HR: 0.55; 95% CI: 0.30-1.00). The great efficacy of this combination is limited by the prevalence of grade 3-4 adverse events (70.6%) leading to treatment discontinuation in 17.6%. This NMA is to the best of our knowledge, the first analysis of the approved regimens for the second-line treatment of metastatic renal cell carcinoma.

180W-LBO GreenLight XPS laser vaporization for benign prostatic hyperplasia: our experience with current markers of surgical proficiency for durable and reproducible outcomes.

INTRODUCTION: This study aims at analyzing the impact of reaching current markers of proficiency on intra and postoperative clinical outcomes of laser vaporization with 180W GreenLight XPS in the treatment of benign prostatic hyperplasia. MATERIALS AND METHODS: A retrospective analysis was conducted on a prospectively collected database of 328 consecutive patients who underwent photoselective vaporization of the prostate (PVP) using Greenlight XPS performed by a single experienced laser surgeon. A logarithmic model was used to evaluate the case number to attain benchmark criteria for durable treatment. We compared clinical outcomes before and after current markers of proficiency, defined as either an energy density of 4kJ/cm³ or a 6 month prostate-specific antigen (PSA) drop of = 50%, were attained. RESULTS: Energy delivered per prostate volume increased significantly with experience. The published benchmark values of 4kJ/cm³ and 6 month PSA drop of 50% were attained after 190 and 155 cases, respectively. There were no significant differences between groups in intraoperative complications or postoperative functional outcomes. However, the number of Clavien-Dindo category I adverse events significantly decreased with experience. Sub-analysis evaluating prostate volumes ≤ 80 cm³ and > 80 cm³ demonstrated comparable clinical outcomes before and after technical proficiency. CONCLUSION: In our experience, the case volume required to achieve consistent reference values related to durable clinical outcomes and surgical proficiency was > 150 cases. However, desirable clinical outcomes were attained before reaching current markers of proficiency, regardless of preoperative prostate size. This suggests that current thresholds of technical proficiency may not be a good predictor of satisfying clinical outcomes.

Long-term urinary functional outcome of vesicourethral anastomosis with bidirectional poliglecaprone (Monocryl®) vs. barbed polyglyconate suture (V-LocTM 180) in robot-assisted radical prostatectomy.

INTRODUCTION: We aimed to evaluate urinary continence recovery following robot-assisted radical prostatectomy (RARP) using monofilament poliglecaprone (Monocryl®) suture vs. barbed suture (V-LocTM 180) during vesicourethral anastomosis (VUA). METHODS: In this prospective, observational cohort, data were collected on 322 consecutive patients. All patients underwent continuous, bidirectional, single-layer running anastomosis with either 3.0 monofilament suture (n=141) or 3.0 barbed suture (n=181). The primary outcome was continence recovery defined as time to 0 pad at one, three, six, 12, and 24 months following surgery. RESULTS: Continence rates were significantly better with monofilament VUA at all followup time points up to one year. Median time to continence was one month vs. five months in the monofilament group vs. barbed group, respectively (p<0.001). Continence rates in monofilament suture vs. barbed group at one, three, six, 12, and 24 months were 56% vs. 26% (p<0.001), 73% vs. 36.4% (p<0.001), 84.4% vs. 60.2% (p<0.001), 90.8% vs. 71.9% (p<0.001), and 93.5% vs.87.1% (p=0.1), respectively. Anastomosis time was shorter in the barbed group, with a median of 23 vs. 30 minutes (p<0.001). Patients anastomosed with Monocryl suture had smaller prostate weight (median 42.5 g vs. 50 g; p<0.001) and harbored less advanced disease (T2a-c 76.6 vs. 74%; p=0.01) relative to patients treated with V-Loc 180 suture. However, in a multivariate Cox logistic regression analyses, independent predictors of continence recovery were suture type (hazard ratio [HR] 53; 95% confidence interval [CI] 0.41-0.68; p=0.02] and prostate size (HR 0.99; 95% CI 0.98-0.99; p<0.001). CONCLUSIONS: Barbed VUA contributed to delayed continence recovery compared to monofilament poliglecaprone suture during the first year post-RARP. However, no statistically significant difference was recorded at two years post-RARP. These results warrant special attention, especially with the widespread use of barbed suture in recent years.

Perioperative predictors for post-prostatectomy urinary incontinence in prostate cancer patients following robotic-assisted radical prostatectomy: Long-term results of a Canadian prospective cohort.

INTRODUCTION: We aimed to report the impact of perioperative factors that have not been well-studied on continence recovery following robotic-assisted radical prostatectomy (RARP). METHODS: We analyzed data of 322 men with localized prostate cancer who underwent RARP between October 2006 and May 2015 in a single Canadian centre. All patients were assessed at one, three, six, 12, and 24 months after surgery. We evaluated risk factors for post-prostatectomy urinary incontinence from a prospectively collected database in multivariate Cox regression analysis. The primary endpoint was continence, defined as 0 pad usage per day. RESULTS: 0-pad continence rates were 126/322 (39%), 187/321 (58%), 222/312 (71%), 238/294 (80%), and 233/257 (91%) at one, three, six, 12, and 24 months, respectively. Bladder neck preservation (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.5-0.99; p=0.04), and prostate size (HR 0.99; 95% CI 0.98-0.99; p=0.02) were independent predictors of continence recovery after RARP. Smoking at time of surgery predicted delayed continence recovery on multivariate analysis (HR 1.42; 95% CI 1.01-1.99; p=0.04). Neurovascular bundles preservation was associated with continence recovery after 24 months. No statistically significant correlation was found with other variables, such as age, body mass index, Charlson comorbidity index, preoperative oncological baseline parameters, presence of median lobe, or thermal energy use. CONCLUSIONS: Our results confirmed known predictors of postprostatectomy incontinence (PPI), namely bladder neck resection and large prostate volume. Noteworthy, cigarette smoking at the time of RARP was found to be a possible independent risk factor for PPI. This study is hypothesis-generating.

The risk of urinary retention following robot-assisted radical prostatectomy and its impact on early continence outcomes.

INTRODUCTION: We aimed to evaluate the risk factors of acute urinary retention (AUR) following robot-assisted radical prostatectomy (RARP), as well as the relationship of AUR with early continence outcomes. METHODS: The records of 740 consecutive patients who underwent RARP by two experienced surgeons at our institution were retrospectively reviewed from a prospectively collected database. Multiple factors, including age, body mass index (BMI), international prostate symptom score (IPSS), prostate volume, presence of median lobe, nerve preservation status, anastomosis time, and catheter removal time (Day 4 vs. 7), were evaluated as risk factors for AUR using univariate and multivariate analysis. The relation between AUR and early return of continence (one and three months) post-RARP was also evaluated. RESULTS: The incidence of clinically significant vesico-urethral anastomotic (VUA) leak and AUR following catheter removal were 0.9% and 2.2% (17/740), respectively. In men who developed AUR, there was no significant relationship with regards to age, BMI, IPSS, prostatic volume, median lobe, nerve preservation, or anastomosis time; however, the incidence of AUR was significantly higher for men with catheter removal at Day 4 (4.5% [16/351]) vs. Day 7 (0.2% [1/389]) (p=0.004). Moreover, patients with early removal of the catheter (Day 4) who developed AUR had an earlier one-month return of 0-pad continence 87.5% (14/16) compared to patients without AUR 45.6% (153/335), with no significant difference at three months. CONCLUSIONS: While AUR is an uncommon complication of RARP, its incidence is much higher than VUA leakage. Further, it is often not well-discussed during patient counselling preoperatively. Moreover, earlier return of urinary continence was observed in patients experiencing AUR following RARP exclusively with catheter removal at Day 4. Future studies are warranted to validate the long-term impact of AUR on continence outcomes.

Indocyanine green fluorescence-guided sentinel lymph node identification in urologic cancers: a systematic review and meta-analysis.

INTRODUCTION: To date, bilateral pelvic lymph node dissection (PLND) represents the most accurate and reliable staging procedure for the detection of lymph node invasion in prostate cancer and bladder cancer. However, the procedure is not devoid of complications. In this field, Indocyanine green fluorescence-guided sentinel lymph node (SLN) identification is an emerging and promising technique, as accurate staging of urologic cancer could be enhanced by a thorough evaluation of the sentinel lymph nodes. Aim of the present review is to analyze available evidence and perform a metanalysis on ICG-guided SLN detection for urologic malignancies. EVIDENCE ACQUISITION: A systematic review to assess the clinical value of Indocyanine green for the identification of sentinel lymphatic drainage for bladder, prostate, kidney and penile cancers was undertaken, with a meta-analysis to generate pooled detection rate concerning patients (clinical sensitivity) and nodes basin (technical sensitivity) separately. Studies reporting on the use of Indocyanine green for the detection of SLNs from the bladder, prostate and penile cancers were included. EVIDENCE SYNTHESIS: A total of 10 clinical trials were included. Using the fixed effects model and the random effects model, the pooled patient detection rates and their 95% confidence intervals (95% CI) were 0.88 (0.82-0.92) and 0.92 (0.84-0.96), respectively. The pooled nodes detection rates were 0.71 (95% CI: 0.68-0.74) using the fixed effect model and 0.75 (95% CI: 0.56-0.87) using the random effect model. Significant heterogeneities existed among studies for patients and for nodes (I2=0.66, P<0.001 and I2=0.96, P<0.001, respectively). Significant publication bias was found in patient detection rate (P<0.001) and in nodes detection rate (P<0.001). CONCLUSIONS: SLN mapping in bladder and prostate cancer is a method with a high detection rate, although its specificity to predict LN invasion remains poor. Large, well-constructed trails are needed to assess the impact of ICG-fluorescence guided SLN dissection on uro-oncologic surgery.

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

AIM: Utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting biochemical recurrence (BCR) in patients with localized prostate cancer. MATERIALS & METHODS: 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. RESULTS: 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. CONCLUSION: Neither elevated NLR nor PLR predicted an increased risk of BCR.

Monopolar Transurethral Enucleo-Resection of the Prostate Versus Holmium Laser Enucleation of the Prostate: A Canadian Novel Experience.

OBJECTIVE: To study the functional outcome of patients undergoing transurethral enucleation and resection of the prostate (TUERP) vs patients undergoing holmium laser enucleation of the prostate (HoLEP) in men with bladder outlet obstruction. MATERIALS AND METHODS: We retrospectively analyzed our prospectively collected database of two groups of patients. Twenty-four patients underwent TUERP (group 1), and 27 underwent HoLEP (group 2). Preoperative characteristics, intervention parameters, postoperative functional outcomes, uroflowmetry, and complications were collected. RESULTS: Mean prostate size in groups 1 and 2 were 87.2 and 93.5 cc, respectively. The mean duration of surgery was 110 minutes in group 1 and 136 minutes in group 2. In group 1, prostate-specific antigen (PSA) dropped from 4.4 to 1.2 ng/cc after 12 months. International Prostate Symptom Score (IPSS) was 3.75 at 12 months with a preoperative value of 20.9. With respect to maximum urinary flow rate (Qmax), it increased to 21.8 mL/s from a preoperative value of 6.4 mL/s. In group 2, the PSA dropped from 7.6 to 1.3 ng/cc. IPSS dropped from 22.3 to 3.8, Qmax increased from 7.7 to 22.5 mL/s. Hemoglobin, complications, and all studied parameters were not statistically significant between both groups. CONCLUSION: In this study, TUERP was safe and efficacious in benign prostatic hyperplasia patients with large glands. Modifications can be implemented on the standard transurethral resection of the prostate technique to treat patients with prostate sizes >70 cc.

Functional and oncological outcomes of salvage external beam radiotherapy following robot-assisted radical prostatectomy in a Canadian cohort.

INTRODUCTION: We sought to determine the impact of salvage radio-therapy (SRT) on oncological and functional outcomes of patients with prostate cancer after biochemical recurrence (BCR) following robot-assisted radical prostatectomy (RARP). METHODS: Data of 70 patients with prostate cancer treated with SRT after developing BCR were retrospectively analyzed from a prospectively collected RARP database of 740 men. Oncological (prostate-specific antigen [PSA]) and functional (pads/day, International Prostate Symptom Score [IPSS], and Sexual Health Inventory for Men [SHIM]) outcomes were reported at six, 12, and 24 months after RT and adjusted for pre-SRT status. RESULTS: Men who underwent SRT had a mean age, PSA, and time from radical prostatectomy (RP) to RT of 61.8 years (60.1-63.6), 0.5 ng/ml (0.2-0.8), and 458 days (307-747), respectively. Freedom from biochemical failure (FFBF) post-SRT, defined as a PSA nadir <0.2 ng/mL, was observed in 89%, 93%, and 81%, at six, 12, and 24 months, respectively. Undetectable PSA was observed in 14%, 35%, and 40% at the same time points, respectively. There was no significant difference in urinary continence post-SRT (p=0.56). Rate of strict continence (0 pads/day) was 71% at 24 months compared to 78% pre-SRT. Mean IPSS at six, 12, and 24 months was 3.4, 3.6, and 3.6, respectively compared to pre-RT score of 3.3 (p=0.61). The mean SHIM score pre-SRT was comparable at all time points following treatment (p=0.86). CONCLUSIONS: In this unique Canadian experience, it appears that early SRT is highly effective for the treatment of BCR following RARP with little impact on urinary continence and potency outcomes.

Innovations in imaging modalities for recurrent and metastatic prostate cancer: a systematic review.

INTRODUCTION: The last decade has witnessed tremendous changes in the management of advanced and metastatic castration resistant prostate cancer. In the current systematic review, we analyze novel imaging techniques in the setting of recurrent and metastatic prostate cancer (PCa), exploring available data and highlighting future exams which could enter clinical practice in the upcoming years. EVIDENCE ACQUISITION: The National Library of Medicine Database was searched for relevant articles published between January 2012 and August 2017. A wide search was performed including the combination of following words: "Prostate" AND "Cancer" AND ("Metastatic" OR "Recurrent") AND "imaging" AND ("MRI" OR "PET"). The selection procedure followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) principles and is presented using a PRISMA flow chart. EVIDENCE SYNTHESIS: Novel imaging techniques, as multiparametric magnetic resonance imaging (MRI), whole-body MRI and Choline and prostate-specific membrane antigen (PSMA) PET imaging techniques are currently revolutioning the treatment planning in patients with advanced and metastatic PCa, allowing a better characterization of the disease. Multiparametric MRI performs well in the detection of local recurrences, with sensitivity rates of 67-98% and overall diagnostic accuracy of 83-93%, depending on the type of magnetic field strength (1.5 vs. 3T). Whole body MRI instead shows a high specificity (>95%) for bone metastases. PET imaging, and in particular PSMA PET/CT, showed promising results in the detection of both local and distant recurrences, even for low PSA values (<0.5 ng/mL). Sensitivity varies from 77-98% depending on PSA value and PSA velocity. CONCLUSIONS: Whole body-MRI, NaF PET, Choline-PET/CT and PSMA PET/CT are flourishing techniques which find great application in the field of recurrent and metastatic PCa, in the effort to reduce treatment of "PSA only" and rather focus our therapies on clinical tumor entities. Standardization is urgently needed to allow adequate comparison of results and diffusion on a large scale.

Photoselective vaporization of the prostate with the 180-W XPS-Greenlight laser: Five-year experience of safety, efficiency, and functional outcomes.

INTRODUCTION: Transurethral resection of the prostate (TURP) is still considered the gold standard surgical treatment for symptomatic benign prostatic hyperplasia (BPH). However, photoselective vaporization of the prostate (PVP) has gained widespread global acceptance in national guidelines as a safe and effective alternative option. Nevertheless, further evidence is required to assess the durability of Greenlight PVP. Herein, we report our five years of PVP experience with the Greenlight 180W XPS laser system. METHODS: A retrospective analysis was conducted on a prospectively gathered database of 370 consecutively included patients who underwent PVP using Greenlight XPS-180 W laser system (Boston Scientific, Boston, MA, U.S.) performed by a single experienced laser surgeon between 2011 and 2016. Preoperative characteristics, intervention parameters, postoperative functional, uroflowmetry outcomes, and complications were collected. Outcomes are reported over a period of five years. RESULTS: Mean age was 68 years, with a mean prostate volume of 78.8 cc (95% confidence interval [CI] 70.9-78.7]). The mean followup was 59.4 months (55.4-63.5). Mean energy, operative time, and energy/cc were 270.2 kJ (255.2-285.2), 62.7 minutes (59.6-65.7), and 3.7 kJ/cc (3.6-3.9), respectively. Compared to preoperative values, International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), and post-void residual (PVR) parameters were significantly improved and sustained over the five postoperative years. Of note, only 66 patients (out of 370) had a complete five-year followup. Prostate-specific antigen (PSA) reached nadir at one year, with a drop of 67% from the mean preoperative value of 6.2 ng/mL. Mean IPSS nadir was reached at three years, with a drop of 80.4% (-21.1 points). Similarly, mean quality of life (QoL) score dropped by 82.8% after three years (preoperative mean of 4.7). With respect to mean Qmax, there was an increase by 72.7% (+14.7 mL/s) at one year, reaching the value of 19.9 mL/s. Moreover, mean PVR was 32.8 mL at four years compared to 345 mL preoperatively. At five years followup, PSA, IPSS, QoL, and PVR dropped by 59.7% (3.7 ng/mL), 75.2% (19.7 points), 78.72% (3.7 points), and 84.4% (291.3 mL), respectively. Qmax increased by 12.9 mL/s. Clavien complication rates were low, with bladder neck stenosis observed in seven (1.6%) men. During the five-year followup, only four patients (1%) required BPH surgical re-intervention. CONCLUSIONS: This is the first long-term reporting of Greenlight XPS-180W laser system. In experienced hands, the observed outcomes appear to demonstrate that Greenlight XPS-180 W laser system is safe, efficacious, and durable for the treatment of bladder outlet obstruction (BOO) secondary to BPH.

External validation of the novel International Society of Urological Pathology (ISUP) Gleason grading groups in a large contemporary Canadian cohort.

INTRODUCTION: We sought to test the discriminatory ability of the 2014 International Society of Urological Pathology (ISUP) Gleason grading groups (GGG) for predicting biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP) in a large, contemporary, Canadian cohort. METHODS: A total of 621 patients who underwent RARP in two major Canadian centres were identified in a prospectively maintained Canadian database between 2006 and 2016. Followup endpoint was BCR. Log-rank test, univariable, and multivariable Cox regression analyses were used. RESULTS: Mean followup was 27.9 months. All five ISUP GGG independently predicted BCR. Statistically significant differences in BCR rates were found between GGG 2 and GGG 3 strata (p<0.001). No statistically significant differences in BCR rates were found between GGG 4 and GGG 5 strata (p=0.3). Relative to GGG 1, the GGG 2, GGG 3, GGG 4, and GGG 5 yielded a 1.10-, 3.44-, 4.18-, and 4.74-fold hazard ratio (HR) increment in BCR, respectively. CONCLUSIONS: This population-based Canadian cohort study confirms the added discriminatory property of the novel ISUP grading, specifically for GGG 2 and GGG 3 strata. No difference, however, was observed between GGG 4 and GGG 5, likely due to the lower number of patients in these groups. As such, after external validation, the 2014 ISUP GGG appears to retain clinical prognostic significance in a Canadian population.

Comparing conventional laparoscopic to robotic-assisted extended pelvic lymph node dissection in men with intermediate and high-risk prostate cancer: a matched-pair analysis.

BACKGROUND: In intermediate and high-risk prostate cancer patients, a robotic-assisted approach is increasingly being used for prostatectomy and extended pelvic lymph node dissection (ePLND). This is reducing the number of conventional laparoscopic radical prostatectomies (LR P) and laparoscopic ePLNDs for prostate cancer in Europe. Aim of this study is to compare laparoscopic ePLND to robotic-assisted ePLND in a cohort of patients with intermediate and high risk prostate cancer. METHODS: We performed a matched-pair analysis matching 1:1 70 patients who underwent LRP+ePLND (2004-2009) to 70 who underwent RAR P+ePLND (2010-2014). All patients presented with intermediate or high-risk prostate cancer according to D'Amico classification. Patients were retrospectively analyzed. Differences in pathologic characteristics and postoperative complications across the two groups were assessed using Wilcoxon Rank sum or χ2 Test. RESULTS: LRP was associated with shorter OR times and decreased blood loss (P<0.001). However, in the robotic-assisted arm, more lymph nodes were retrieved (18 vs. 12; P<001). No significant difference in positive surgical margins was found across the two techniques (P=0.9). Lymphocele formation and prolonged lymphorrea were specifically addressed as complications, with no significant difference emerging from our analyses (P>0.74). CONCLUSIONS: In this matched-pair analysis comparing patients with intermediate and high-risk prostate cancer, a robotic-assisted approach was associated to a higher lymph node yield compared to conventional laparoscopy. However, this increase in node yield was balanced with longer OR times, increased blood loss, similar postoperative complications and similar oncologic outcomes. Larger and prospective studies in patients at high risk are necessary to validate these findings.

Does surgical delay for radical prostatectomy affect patient pathological outcome? A retrospective analysis from a Canadian cohort.

INTRODUCTION: We sought to assess the impact of surgical wait time (SWT) to robot-assisted radical prostatectomy (RARP) on final pathological outcome. METHODS: A retrospective review of RARP patient records operated between 2006 and 2015 was conducted. SWT was defined as period from prostate biopsy to surgery. Primary outcome was the impact on postoperative Cancer of the Prostate Risk Assessment (CAPRA-S) score. Patients were stratified according to D'Amico risk categories. Univariate analysis (UVA) and multivariable (MVA) analysis with a generalized linear model was used to evaluate the effect of SWT and other predictive factors on pathological outcome in individual risk group and on the overall sample. RESULTS: A total of 835 patients were eligible for analysis. Mean SWT was significantly different between the three D'Amico groups, with mean SWT of 180.22 days (95% confidence interval [CI] 169.03; 191.41), 159.14 days (95% CI 152.38; 165.90), and 138.96 days (95% CI 124.60; 153.33) for low-, intermediate-, and high-risk groups, respectively (p<0.001). After stratification by D'Amico risk group, no significant association was observed between SWT and CAPRA-S score in the three risk categories on UVA and MVA. Predictors of higher CAPRA-S score in the multivariable model in the overall cohort were: older age (p=0.014), biopsy Gleason score (p<0.001), percentage of positive cores (p<0.001), and clinical stage (p<0.001). CONCLUSIONS: In the present study evaluating SWT for RARP in a Canadian socialized system, increased delay for surgery does not appear to impact the pathological outcome. Further studies are required to evaluate the impact of wait time on biochemical recurrence-free survival, cancer-specific survival, and overall survival.