Peri-operative, functional and early oncologic outcomes of salvage robotic-assisted radical prostatectomy after high-intensity focused ultrasound partial ablation.

BACKGROUND: Partial ablation of the prostate using high-intensity focussed ultrasound (HIFU-PA) is a treatment option for localised prostate cancer. When local recurrence occurs, salvage robot-assisted radical prostatectomy is a treatment option for selected patients, but there is a paucity of data on the peri-operative safety, functional and oncologic outcomes of sRARP.. The objective of this study was therefore to describe peri-operative safety, functional and early oncologic outcomes following salvage robot-assisted radical prostatectomy (sRARP) for local recurrence after HIFU-PA. METHODS: Retrospective analysis of a prospective database of 53 consecutive men who underwent sRARP after HIFU-PA from 2012 to 2018. Continence and erectile-function were reported pre-HIFU, pre-sRARP, 3-months post-sRARP and 12-months post-sRARP. Complications, PSMs and need for subsequent ADT/radiotherapy were assessed. RESULTS: 45 men were suitable for inclusion and had sufficient data for analyses. Median duration from HIFU to sRARP was 30.0 months and median follow-up post-sRARP was 17.7 months. Median age, PSA and ISUP group were 63.0 yrs., 7.2 ng/mL and 2; 88.9% were cT2. Median operative-console time, blood loss and hospital stay were 140 min, 200 ml and 1 day respectively. Clavien-Dindo grade 1, 2 and 3 complications < 90 days occurred in 8.9, 6.7 and 2.2%; late (>90d) complications occurred in 13.2%. At sRARP pathology, ISUP 3-5 occurred in 51.1%, pT3a/b in 64.5%, and PSMs in 44.4% (37.5% for pT2, 48.3% for pT3). Of men with > 3-months follow-up after sRARP, 26.3% underwent adjuvant radiotherapy/ADT for residual disease or adverse pathologic features; 5.3% experienced BCR requiring salvage ADT/radiotherapy. Freedom from ADT/radiotherapy was 66.7% at 12-months. Pad-free rates were 100% pre-HIFU, 95.3% post-HIFU, 29.4% 3-months post-sRARP, and 65.5% 12-months post-sRARP. Median IIEF-5 scores pre-HIFU, post-HIFU, 3- and 12-months post-sRARP were 23.5, 16, 5 and 5, respectively. Potency rates were 81.8, 65.5, 0 and 0%, respectively. Bilateral/unilateral nerve sparing were feasible in 7%/22%. CONCLUSION: Salvage RARP was safe with acceptable but sub-optimal continence and poor sexual-function and poor oncologic outcomes. One in three men required additional treatment within 12-months. This information may aid men and urologists with treatment selection and counselling regarding primary HIFU-PA vs primary RARP and when considering salvage RARP.

Pathological Findings and Magnetic Resonance Imaging Concordance at Salvage Radical Prostatectomy for Local Recurrence following Partial Ablation Using High Intensity Focused Ultrasound.

PURPOSE: We describe the pathological characteristics of recurrence following high intensity focused ultrasound partial ablation in men treated with salvage robot-assisted radical prostatectomy. We assessed the sensitivity of magnetic resonance imaging before salvage robot-assisted radical prostatectomy in these men. MATERIALS AND METHODS: A total of 35 men underwent salvage robot-assisted radical prostatectomy after high intensity focused ultrasound partial ablation from 2012 to 2018. We compared clinicopathological characteristics before ultrasound and before salvage prostatectomy after ultrasound to histopathology on salvage prostatectomy. We assessed infield recurrence, out of field disease, positive surgical margins and magnetic resonance imaging sensitivity before salvage robot-assisted radical prostatectomy. RESULTS: Before high intensity focused ultrasound 55.9% of men had multifocal disease and 47.1% had Gleason 3 + 3 disease outside the treatment field. Median time to salvage prostatectomy was 16 months (IQR 11-26). Indications for salvage prostatectomy were infield recurrence in 55.8% of cases, out of field recurrence in 20.6%, and infield and out of field recurrence in 23.5%. On salvage prostatectomy histopathology revealed significant cancer, defined as ISUP (International Society of Urological Pathology) 2 or greater, infield in 97.1% of cases, out of field in 81.3%, and infield and out of field in 79.4%. Of the cases 82.4% were adversely reclassified at salvage prostatectomy compared to 67.6% before ultrasound. The positive surgical margin rate was 40.0%. Of the positive margins 84.6% were in the region of previous ultrasound despite wide excision, including pT2 in 28.6%, pT3 in 47.6% and size 3 mm or greater, pT3 or multifocal (ie significant) in 31.4%. After ultrasound the sensitivity of magnetic resonance imaging for infield and out of field recurrence was 81.8% and 60.7%, respectively. CONCLUSIONS: Salvage robot-assisted radical prostatectomy may confer a higher risk of positive surgical margins, upgrading and up-staging than primary robot-assisted radical prostatectomy. High intensity focused ultrasound carries a risk of recurrence inside and outside the ablation zone. This information may inform salvage surgical planning and patient counseling regarding the choice of initial therapy and salvage treatment after high intensity focused ultrasound.

Correction: Development and validation of a novel risk score for the detection of insignificant prostate cancer in unscreened patient cohorts.

Since the publication of this paper, the authors noticed that Amar Ahmad was not credited as contributing equally to the paper. He should be considered as a joint first author with Lorenzo Dutto. In addition, the author Ashwin Sridhar was incorrectly listed as Ashwin Shridhar, and the author Gregory L. Shaw was incorrectly listed as Gregory Shaw. The correct names are listed above.

PEOPLE: PatiEnt prOstate samPLes for rEsearch, a tissue collection pathway utilizing magnetic resonance imaging data to target tumor and benign tissue in fresh radical prostatectomy specimens.

BACKGROUND: Over 1 million men are diagnosed with prostate cancer each year worldwide, with a wide range of research programs requiring access to patient tissue samples for development of improved diagnoses and treatments. A random sampling of prostate tissue is sufficient for certain research studies; however, there is growing research need to target areas of the aggressive tumor as fresh tissue. Here we set out to develop a new pathway "PEOPLE: PatiEnt prOstate samPLes for rEsearch" to collect high-quality fresh tissue for research use, using magnetic resonance imaging (MRI) to target areas of tumor and benign tissue. METHODS: Prostate tissue was sampled following robotic radical prostatectomy, using MRI data to target areas of benign and tumor tissue. Initially, 25 cases were sampled using MRI information from clinical notes. A further 59 cases were sampled using an optimized method that included specific MRI measurements of tumor location along with additional exclusion criteria. All cases were reviewed in batches with detailed clinical and histopathological data recorded. For one subset of samples, DNA was extracted and underwent quality control. Ex vivo culture was carried out using the gelatin sponge method for an additional subset. RESULTS: Tumor was successfully fully or partially targeted in 64% of the initial cohort and 70% of the optimized cohort. DNA of high quality and concentration was isolated from 39 tumor samples, and ex vivo culture was successfully carried out in three cases with tissue morphology, proliferation, and apoptosis remaining comparable before and after 72 hours culture. CONCLUSION: Here we report initial data from the PEOPLE pathway; using a method for targeting areas of tumor within prostate samples using MRI. This method operates alongside the standard clinical pathway and minimizes additional input from surgical, radiological, and pathological teams, while preserving surgical margins and diagnostic tissue.

Development and validation of a novel risk score for the detection of insignificant prostate cancer in unscreened patient cohorts.

BACKGROUND: Active surveillance is recommended for insignificant prostate cancer (PCa). Tools exist to identify suitable candidates using clinical variables. We aimed to develop and validate a novel risk score (NRS) predicting which patients are harbouring insignificant PCa. METHODS: We used prospectively collected data from 8040 consecutive unscreened patients who underwent radical prostatectomy between 2006 and 2016. Of these, data from 2799 patients with Gleason 3 + 3 on biopsy were used to develop a multivariate model predicting the presence of insignificant PC at radical prostatectomy (ERSPC updated definition3: Gleason 3 + 3 only, index tumour volume < 1.3 cm3 and total tumour volume < 2.5 cm3). This was used to develop a novel risk score (NRS) which was validated in an equivalent independent cohort (n = 441). We compared the accuracy of existing predictive tools and the NRS in these cohorts. RESULTS: The NRS (incorporating PSA, prostate volume, age, clinical T Stage, percent and number of positive biopsy cores) outperformed pre-existing predictive tools in derivation and validation cohorts (AUC 0.755 and 0.76, respectively). Selection bias due to analysis of a surgical cohort is acknowledged. CONCLUSIONS: The advantage of the NRS is that it can be tailored to patient characteristics and may prove to be valuable tool in clinical decision-making.

Urine-derived lymphocytes as a non-invasive measure of the bladder tumor immune microenvironment.

Despite the advances in cancer immunotherapy, only a fraction of patients with bladder cancer exhibit responses to checkpoint blockade, highlighting a need to better understand drug resistance and identify rational immunotherapy combinations. However, accessibility to the tumor prior and during therapy is a major limitation in understanding the immune tumor microenvironment (TME). Herein, we identified urine-derived lymphocytes (UDLs) as a readily accessible source of T cells in 32 patients with muscle invasive bladder cancer (MIBC). We observed that effector CD8+ and CD4+ cells and regulatory T cells within the urine accurately map the immune checkpoint landscape and T cell receptor repertoire of the TME. Finally, an increased UDL count, specifically high expression of PD-1 (PD-1hi) on CD8+ at the time of cystectomy, was associated with a shorter recurrence-free survival. UDL analysis represents a dynamic liquid biopsy that is representative of the bladder immune TME that may be used to identify actionable immuno-oncology (IO) targets with potential prognostic value in MIBC.

In-depth Critical Analysis of Complications Following Robot-assisted Radical Cystectomy with Intracorporeal Urinary Diversion.

BACKGROUND: Robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) is an attractive option to open cystectomy, but the benefit in terms of improved outcomes is not established. OBJECTIVE: To evaluate the early postoperative morbidity and mortality of patients undergoing iRARC and conduct a critical analysis of complications using standardised reporting criteria as stratified according to urinary diversion. DESIGN, SETTING, AND PARTICIPANTS: A total of 134 patients underwent iRARC for bladder cancer at a single centre between June 2011 and July 2015. INTERVENTION: Radical cystectomy with iRARC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patient demographics, pathologic data, and 90-d perioperative mortality and complications were recorded. Complications were reported according to the Clavien-Dindo (CD) classification and stratified according to urinary diversion type and either surgical or medical complications. The chi-square test and t test were used for categorical and continuous variables respectively. Multivariable logistic regression was performed on variables with significance in univariate analysis. RESULTS AND LIMITATIONS: The 90-d all complication rate following ileal conduit and continent diversion was 68% and 82.4%, and major complications were 21.0% and 20.6% respectively. The 90-d mortality was 3% and 2.9% for ileal conduit and continent diversion patients, respectively. On multivariate analysis, the blood transfusion requirement was independently associated with major complications (p=0.002) and all 30-d (p=0.002) and 90-d (p=0.012) major complications. Male patients were associated with 90-d major complications (p=0.015). Critical analysis identified that surgical complications were responsible for 39.4% of all 90-d major complications. The incidence of surgical complications did not decline with increasing number of iRARC cases performed (p=0.742, r=0.31). Limitations of this study include its retrospective nature, limited sample size, and limited multivariate analysis due to the low number of major complications events. CONCLUSIONS: Although complications following iRARC are common, most are low grade. A critical analysis identified surgical complications as a cause of major complications. Addressing this issue could have a significant impact on lowering the morbidity associated with iRARC. PATIENT SUMMARY: We looked at the surgical outcomes in bladder cancer patients treated with minimally invasive robotic surgery. We found that surgical complications account for most major complications and previous surgical experience may be a confounding factor when interpreting results from a different centre even in a randomised trial setting.

A comprehensive guide to perioperative management and operative technique for robotic cystectomy with intracorporeal urinary diversion.

Robotic-assisted radical cystectomy (RARC) represents an evolution of open radical cystectomy (ORC) with the aim of reducing patient morbidity and improving return to normal function, whilst maintaining oncological equivalence. RARC is gaining popularity, especially in high-volume centres, although there remains a lack of level 1 evidence to demonstrate any superiority of RARC over ORC. All previously reported studies that randomised ORC and RARC have utilised a technique for RARC requiring a conversion to open surgery for urinary diversion. Conversion to open surgery invariably masks the benefits of a truly minimally invasive approach. Moreover, such studies tend to report a small sample size, likely reflecting early surgical experience that may contribute to the lack of observed benefit. Nonetheless, it is established that short-term oncological outcomes following RARC are comparable to those after ORC. It is likely that the benefits of RARC are only observed in cases wherein intracorporeal urinary diversion (iRARC) is performed by a surgical team with high volume experience, which will minimise morbidity and maximise early return to normal function. In this review, we will discuss a holistic approach to iRARC, including patient selection, perioperative optimisation, the surgical technique for iRARC with urinary diversion reconstruction, the use of enhanced recovery protocol, oncological outcomes and perioperative complications.

Blood Transfusion Requirement and Not Preoperative Anemia Are Associated with Perioperative Complications Following Intracorporeal Robot-Assisted Radical Cystectomy.

OBJECTIVES: To assess the prevalence of preoperative anemia and the impact of preoperative anemia and blood transfusion requirement on 30- and 90-day complications in a cohort of patients undergoing robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC). PATIENTS AND METHODS: IRARC was performed on 166 patients between June 2011 and March 2016. Prospective data were collected for patient demographics, clinical and pathologic characteristics, perioperative variables, transfusion requirements, and hospital length of stay. Thirty- and 90-day complications were classified according to the modified Memorial Sloan Kettering Cancer Center Clavien-Dindo system. RESULTS: Preoperative anemia was common (43.4%) and greatest in patients receiving neoadjuvant chemotherapy (48.6%) (p < 0.001). Patients with preoperative anemia were significantly more likely to have an Ileal conduit (p = 0.033), higher cystectomy stage (≥pT3) (p = 0.028), and a lower lymph node yield (p = 0.031). Preoperative anemia was not associated with increased perioperative morbidity but was associated with the requirement for blood transfusion (p = 0.001). Blood transfusion required in 20.4% of patients with intraoperative and postoperative blood transfusion rate was 10.2% and 13.9%, respectively. The 30-day all complication rate and 30-day major complication rate were 55.4% and 15.7%, respectively, while 90-day all complication rate and 90-day major complication rate were 65.7% and 19.3%, respectively. Intraoperative blood transfusion was not associated with increased complications, but postoperative blood transfusion requirement was independently associated with perioperative morbidity: all 30-day complications (p = 0.003), all 90-day complications (p = 0.009), and 90-day major complications (p = 0.004). CONCLUSION: The presence of preoperative anemia in patients undergoing iRARC is not associated with increased surgical risk, although preoperative anemic patients were significantly more likely to require blood transfusion. Blood transfusion requirement and specifically postoperative blood transfusion are independently associated with perioperative morbidity and are an important factor for the optimization of postoperative outcomes.

Recovery of Baseline Erectile Function in Men Following Radical Prostatectomy for High-Risk Prostate Cancer: A Prospective Analysis Using Validated Measures.

INTRODUCTION: Recovery of baseline erectile function (EF) after robotic radical prostatectomy in men with high-risk prostate cancer is under-reported. Published studies have selectively reported on low-risk disease using non-validated and poorly defined thresholds for EF recovery. AIM: To assess return to baseline EF in men after robotic radical prostatectomy for high-risk prostate cancer. MATERIALS: Five hundred thirty-one men underwent robotic radical prostatectomy for high-risk prostate cancer from February 2010 through July 2014. Pre- and postoperative EF was prospectively assessed using the International Index of Erectile Dysfunction (IIEF-5) questionnaire. Multivariate logistic regression analysis determined the effect of age, preoperative function, comorbidities, body mass index, prostate-specific antigen level, cancer stage or grade, nerve-sparing status, adjuvant therapy, and continence on EF return (defined as postoperative return to baseline EF with or without use of phosphodiesterase type 5 inhibitors). Kaplan-Meier analysis and log-rank test were used to analyze return over time. Mann-Whitney U-test was used to compare IIEF-5 scores. MAIN OUTCOME MEASURES: Pre- and postoperative EF was assessed using the IIEF-5 Sexual Health Inventory for Men at 3 months, 6 months, 1 year, 2 years, 3 years, and 4 years postoperatively. RESULTS: Overall, return of EF was seen in 23.5% of patients at 18 months. This was significantly increased in men no older than 60 years (P = .024), with a preoperative IIEF-5 score of at least 22 (P = .042), and after undergoing neurovascular bundle preservation (34.9% of patients, P < .001). There was no significant change in IIEF-5 scores from 3 to 36 months in patients who were treated with phosphodiesterase type 5 inhibitors in the non-neurovascular bundle preservation group (P = .87), although there was significant improvement in those receiving second- or third-line therapies (P = .042). Other than preoperative hypertension (P = .03), none of the other comorbidities predicted return of EF. CONCLUSION: In this study, 23.5% of men recovered to baseline EF. Of those who underwent bilateral neurovascular bundle preservation robotic radical prostatectomy, 70% recovered baseline EF; however, this accounted for only 9.6% of all patients. Only 4% of men who underwent non-neurovascular bundle preservation had baseline recovery with phosphodiesterase type 5 inhibitors up to 36 months. There was significant improvement after use of second- or third-line therapies, indicating the need for earlier institution of these treatment modalities.