Delineating patient errors in an intracavernosal injection program.

BACKGROUND: Intracavernosal injection therapy (ICI) is a well-established therapeutic strategy for men with erectile dysfunction. Complications are often related to patient error when performong ICI. AIM: The objective of this study was to examine patient errors in an established patient training program for performing ICI and identify factors that could predict major errors. METHODS: Patients enrolled in our ICI program are trained on technical aspects, and dose titration is begun. Patients are given explicit instructions during training, both verbally and in written form. Records were reviewed for men using ICI for ≥6 months. Multivariable analysis was used to define predictors of major errors. OUTCOMES: Errors were listed as minor (zero-response injection, penile bruising, expired medication) and major (errors potentially leading to priapism: dose self-titration, double injecting). RESULTS: Overall, 1368 patients met the inclusion criteria and were included in the analysis. The mean patient age was 66 ± 22 (range 29-91) years. Regarding education, 41% of patients had graduate-level education, 48% had college education, and 11% high school education. Mean follow-up was 3.2 ± 7.6 (range 0.5-12) years. The agents used were trimix (62%), bimix (35%), papaverine (2%), and prostaglandin E1 monotherapy (1%). At least 1 error occurred during self-administration in 42% of patients during their time in the program. Errors included zero response to medication due to technical error (8% of patients), penile bruising (34%), use of an expired bottle (18%), self-titration (5%), and double injecting (4% of patients); 12% of men committed ≥1 error during their time in the program. On multivariable analysis, independent predictors of the occurrence of a major error included: young age, graduate-level education, and <12 months of injection use. CLINICAL IMPLICATIONS: To the best of our knowledge, this is the first reported study to investigate ICI errors and risk factors. The identification of factors predictive of major errors allows for more tailored and intensive training in this subset of patients. STRENGTHS AND LIMITATIONS: Strengths of this study include a large patient population (1386 men) with a considerable follow-up time. Additionally, the rigorous training, education, and monitoring of the participants, as well as the use of formal definitions, enhances the accuracy and reliability of the results. Despite the strengths of the study, recall bias may be a limitation concern. CONCLUSION: The majority of patients were error free, and the majority of the errors were minor in nature. Major errors occurred in <10% of patients. Younger age, graduate-level education, and less experience with ICI were independent predictors of major errors.

Corrigendum to "RPN (Radius, Position of tumour, iNvasion of renal sinus) Classification and Nephrometry Scoring System: An Internationally Developed Clinical Classification To Describe the Surgical Difficulty for Renal Masses for Which Robotic Partial Nephrectomy Is Planned" [Eur. Urol. Open Sci. 54 (2023) 33-42].

[This corrects the article DOI: 10.1016/j.euros.2023.05.007.].

Are systematic prostate biopsy still necessary in biopsy naive men?

PURPOSE: Multiparametric MRI and the transperineal approach have become standard in the diagnostic pathway for suspected prostate cancer. Targeting of MRI lesions is performed at most centers, but the routine use of systematic cores is controversial. We aim to assess the value of obtaining systematic cores in patients undergoing cognitive fusion targeted double-freehand transperineal prostate biopsy. MATERIALS AND METHODS: Patients who underwent a cognitive fusion, freehand TPB at a single tertiary urology service (Perth, Australia) between November 2020 and November 2021 were retrospectively reviewed. Patients were included if they were biopsy naive and had a clinical suspicion of prostate cancer, based on their mpMRI results. Both targeted and systematic cores were taken at the time of their biopsy. RESULTS: One hundred forty patients suited the selection criteria. Clinically significant cancer was identified in 63% of patients. Of those that had clinically significant cancer, the target lesion identified 91% of the disease, missing 9% of patients whom the target biopsy detected non-clinically significant cancer but was identified in the systematic cores. Higher PI-RADS category patients were also found to be associated with an increasing likelihood of identifying clinically significant cancer within the target. CONCLUSIONS: In patients with PI-RADS 3 and higher, the target biopsy can miss up to 9% of clinically significant cancer. Systematic cores can add value as they can also change management by identifying a high-risk disease where only intermediate cancer was identified in the target. A combination of targeted and systematic cores is still required to detect cancer.

The Use of Prophylactic Ureteric Stents in Major Abdomino-Pelvic Sarcoma Surgery: Risks, Benefits, and Potential Complications.

Here we present two cases of post-operative obstructive renal failure following major abdomino-pelvic sarcoma surgery. In both cases, prophylactic ureteric stents were inserted to aid the identification and protection of the ureters during resection of these complex retroperitoneal masses. In case one, obstructive renal failure occurred following ureteric stent removal on day 0 post-operatively. In case two, obstructive renal failure developed on day 1 post-operatively despite having a ureteric stent in situ. Here we propose that a combination of reflex anuria/ureteric edema and papillary sloughing led to the obstructive renal failure in both cases. Re-insertion of bilateral ureteric stents in case one, and replacement of a right ureteric stent in case two saw prompt excretion of urine and sloughy debris with rapid improvement of renal function. This article presents these cases in detail and further reviews the use of prophylactic ureteric stents in major abdomino-pelvic surgery along with the current guidelines for their usage.

ASTRA - An alternative approach for the posterior urethra

ABSTRACT Introduction: Access represents one of the main challenges in performing posterior urethroplasty (1, 2). Several approaches and tactics have been previously described (3). This video demonstrates the Anterior Sagittal Transrectal Approach (ASTRA), which allows better visualization of the deep perineum (4). Materials and Methods: Our patient was a 65-year-old man with post radical prostatectomy vesicourethral anastomotic stenosis. He failed repeated endoscopic interventions, eventually developing urinary retention and requiring a cystostomy. We offered a vesicourethral anastomotic repair through ASTRA. The patient was placed in the jackknife position and methylene blue instilled through the cystostomy. To optimize access to the bladder neck, an incision of the anterior border of the rectum is performed. Anastomosis is carried out with six 4-0 PDS sutures. These are tied using a parachute technique, after insertion of a 16F Foley. Results: The patient was discharged after 72 hours, and the Foley catheter was removed after 4 weeks. There were no access-related complications. Retrograde urethrogram 3 months after surgery confirmed patency of the anastomosis. Upon review 5 months after surgery the patient had urinary incontinence requiring 5 pads/day and was considered for an artificial urinary sphincter. Discussion: In our series of 92 patients who have undergone reconstructive procedure through ASTRA there have been no cases of fecal incontinence. Two patients with prior history of radiotherapy developed rectourethral fistulas. Urinary incontinence was observed in those patients with stenosis after radical prostatectomy. Conclusion: This video presents a step-by-step description of ASTRA, an approach that provides excellent visualization to the posterior urethra, representing an alternative access for repair of complex posterior urethral stenosis.

ASTRA - An alternative approach for the posterior urethra.

INTRODUCTION: Access represents one of the main challenges in performing posterior urethroplasty (1, 2). Several approaches and tactics have been previously described (3). This video demonstrates the Anterior Sagittal Transrectal Approach (ASTRA), which allows better visualization of the deep perineum (4). MATERIALS AND METHODS: Our patient was a 65-year-old man with post radical prostatectomy vesicourethral anastomotic stenosis. He failed repeated endoscopic interventions, eventually developing urinary retention and requiring a cystostomy. We offered a vesicourethral anastomotic repair through ASTRA. The patient was placed in the jackknife position and methylene blue instilled through the cystostomy. To optimize access to the bladder neck, an incision of the anterior border of the rectum is performed. Anastomosis is carried out with six 4-0 PDS sutures. These are tied using a parachute technique, after insertion of a 16F Foley. RESULTS: The patient was discharged after 72 hours, and the Foley catheter was removed after 4 weeks. There were no access-related complications. Retrograde urethrogram 3 months after surgery confirmed patency of the anastomosis. Upon review 5 months after surgery the patient had urinary incontinence requiring 5 pads/day and was considered for an artificial urinary sphincter. DISCUSSION: In our series of 92 patients who have undergone reconstructive procedure through ASTRA there have been no cases of fecal incontinence. Two patients with prior history of radiotherapy developed rectourethral fistulas. Urinary incontinence was observed in those patients with stenosis after radical prostatectomy. CONCLUSION: This video presents a step-by-step description of ASTRA, an approach that provides excellent visualization to the posterior urethra, representing an alternative access for repair of complex posterior urethral stenosis.

Painless penile periurethral polymicrobial abscess causing urinary retention.

In contemporary urological practice periurethral abscesses are rare. We report the case of a 61-year-old presenting with a painless penile mass and urinary retention. He underwent imaging with ultrasonography, targeted antibiotics and successful source control through open incision and drainage. He has been symptom, recurrence and complication free at 24 months post intervention. Risk factors for abscesses include obstruction, trauma, urethral diverticula and urethral carcinoma. Inadequate detection and treatment may lead to urethral fistulae, strictures and rarely, necrotizing fasciitis. To our knowledge, this is the first report of a periurethral abscess presenting as a painless penile mass causing urinary retention.

Endoscopic Holmium Laser harvesting of bladder mucosal graft for substitution urethroplasty

ABSTRACT Introduction: Tissue transfer has been used in urethral reconstruction for decades, and several grafts have been described (1, 2). The ideal graft would have optimal tissue characteristics and lead to minimal morbidity at the donor site. Urethroplasty using bladder mucosa was first described by Memmelaar in 1947 (3). The main limitation in using bladder mucosal grafts has been the invasiveness of open harvesting (4). We describe an endoscopic technique using Holmium: YAG laser to harvest bladder mucosal graft for substitution urethroplasty. Methodology: A 33-year-old male with no history of urethral instrumentation, trauma, or infection presented with obstructive lower urinary tract symptoms. On retrograde urethrogram a 6cm bulbar urethral stricture was identified. Several options were discussed, and the patient opted for a one-sided onlay dorsal urethroplasty (5) using a bladder mucosal graft. Equipment used to harvest the graft included an 18.5Fr continuous flow laser endoscope with a Kuntz working element (RZ) and a 60W Holmium Laser (Quanta) with 550μm laser fiber. The procedure was started by making a perineal incision, urethral mobilization and incision of the stricture segment. The laser endoscope was then introduced via the perineum. Settings of 0.5J, 30 Hz, and long pulse were used and a 7 x 2.5cm graft was harvested from the posterior bladder wall. Hemostasis of the harvest site was performed. The bladder mucosal graft was thinned in similar fashion to a buccal mucosal graft and sutured as per previously described techniques. Conclusion: Endoscopic Holmium Laser harvesting of bladder mucosal graft is feasible and may allow this graft to become an alternative to buccal mucosa. Further studies are required to define its role in urethral reconstruction.

A National Analysis of Temporal Changes in Prescribing of Testosterone Replacement Therapy Considering Methods of Delivery and Government Regulation.

PURPOSE: Testosterone replacement therapy (TRT) is commonly used for various causes of androgen deficiency and subsidized by the Pharmaceutical Benefits Scheme (PBS) in Australia when appropriate. In response to a sharp increase in the prescribing of subsidized TRT, the Australian government instituted new, stricter prescription criteria in April 2015. We aim to demonstrate longitudinal changes in the prescription patterns of subsidized TRT over time. MATERIALS AND METHODS: The publicly available PBS database was accessed for TRT prescription data between 1992-2018. Population estimate data was collected from the Australian Bureau of Statistics for population-adjustment. Data analysis was performed according to class and specific formulation of TRT. Total and population-adjusted trends were considered, as was indexation to 2015 when restrictions were implemented. RESULTS: Longitudinal trends in subsidized TRT prescription demonstrated a progressive overall increase since 2000, according to total prescriptions and population-adjusted estimates, with greater use of topical formulations (gel, patch, cream/spray) and injections. Since 2015, a 37% decline in total population-adjusted prescriptions was observed (1,399-883 per 100,000 persons). Since 2015, relatively increased use of injections (50%) and 1% gel (30%) comprise the majority of contemporary TRT. Annual financial burden due to TRT was $AU16,768 per 100,000 persons prior to 2000 (mean cost 1992-2000), increasing to $AU112,539 in 2018 (due to use of injections). The rate of change in costs slowed after the restrictions were introduced in 2015. CONCLUSIONS: The restrictions in subsidized TRT eligibility enforced by the PBS have reduced overall TRT prescriptions and slowed the cumulative financial burden.

Transrectal versus transperineal prostate biopsy under intravenous anaesthesia: a clinical, microbiological and cost analysis of 2048 cases over 11 years at a tertiary institution.

BACKGROUND: Transrectal (TR) and transperineal (TP) approaches for prostate biopsy have different morbidity profiles. Our institution transitioned to a preference for multiparametric MRI-based triage and TP biopsy since 2014. The aim of this study was to compare clinical, microbiological and health economic outcomes between TR and TP prostate biopsy. METHODS: A consecutive cohort study considered prostate biopsies over an 11 year period. Hospital presentations across the region within 30 days of biopsy were analysed for details and subsequent outcomes according to biopsy approach. Cost for each encounter (routine and unplanned) were analysed and generalised linear models applied, as well as cost implications for inclusion of mpMRI-based triage and TP biopsy preference. RESULTS: In total, 2048 prostate biopsies were performed. Similar re-presentation rates per occurred for each biopsy approach (90 patients, TR 4.8%, TP 3.8%, p = 0.29), with 23 patients presenting more than once (119 total presentations). Presentations after TR biopsy were more likely to be of infectious aetiology (TR 2.92%, TP 0.26% de novo, p < 0.001) and result in hospital admission (TR 43/49, 93.4%; TP 14/24, 58.3%; p = 0.007) for similar rates of urinary retention (TR 2.76% vs TP 3.63%, p = 1). The mean overall cost (biopsy and re-presentations) was higher for the TP group (p < 0.001), adjusted for year and age, but reduced over time and was similar for patients who re-presented (p = 0.98). Incorporation of mpMRI (with subsequently avoided biopsies), TP biopsy and re-presentations resulted in AU$783.27 saving per biopsy. CONCLUSIONS: TR biopsy resulted in more infectious complications and hospital admissions than TP biopsy for similar rates of re-presentation and urinary retention. TP biopsy costs reduced over time and use in conjunction with mpMRI provides an overall cost saving. Routine TP biopsy is safe and feasible, with further cost savings expected with other approaches (local anaesthetic) under investigation.

Management of benign prostatic hyperplasia in the 21st century: temporal trends in Australian population-based data.

OBJECTIVE: To examine national trends in the medical and surgical treatment of benign prostatic hyperplasia (BPH) using Australian Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) population data from 2000 to 2018. PATIENTS AND METHODS: Annual data was extracted from the MBS, PBS and Australian Institute of Health and Welfare databases for the years 2000-2018. Population-adjusted rates of BPH procedures and medical therapies were calculated and compared in relation to age. Cost analysis was performed to estimate financial burden due to BPH. RESULTS: Overall national hospital admissions due to BPH declined between 2000 and 2018, despite an increased proportion of admissions due to private procedures (42% vs 77%). Longitudinal trends in the medical management of BPH showed an increased prescription rate of dutasteride/tamsulosin combined therapy (111 vs 7649 per 100 000 men) and dutasteride monotherapy (149 vs 336 per 100 000 men) since their introduction to the PBS in 2011. Trends in BPH surgery showed an overall progressive increase in rate of total procedures between 2000 and 2018 (92 vs 133 per 100 000 men). Transurethral resection of the prostate (TURP) remained the most commonly performed surgical procedure, despite reduced utilisation since 2009 (118 vs 89 per 100 000 men), offset by a higher uptake of photoselective vaporisation of prostate, holmium:YAG laser enucleation of prostate, and later likely due to minimally invasive surgical therapies including prostatic urethral lift and ablative technologies (including Rezum™). Financial burden due to BPH surgery has remained steady since 2009, whilst the burden due to medical therapy has risen sharply. CONCLUSION: Despite reduced national BPH-related hospitalisations, overall treatment for BPH has increased due to medical therapy and surgical alternatives to TURP. Further exploration into motivators for particular therapies and effect of medical therapy on BPH progression in clinical practice outside of clinical trials is warranted.

68Ga-PSMA PET/CT better characterises localised prostate cancer after MRI and transperineal prostate biopsy: Is 68Ga-PSMA PET/CT guided biopsy the future?

BACKGROUND: 68Ga prostate specific membrane antigen PET/CT (68Ga-PSMA PET/CT) may be superior to multiparametric MRI (mpMRI) for localisation of prostate cancer tumour foci, however the concordance and differences between 68Ga-PSMA PET/CT and mpMRI when applied to all biopsied patients and potential benefit in patients with negative mpMRI is unclear. METHODS: Retrospective analysis of patients undergoing mpMRI, prostate biopsy and 68Ga-PSMA PET/CT over a 3-year period. Diagnostic performance of 68Ga-PSMA PET/CT and mpMRI were assessed using biopsy histopathology for the entire cohort and radical prostatectomy specimen in a subset of patients. Lesion concordance and additional detection of each modality were determined, including in a dedicated cohort of patients with mpMRI PIRADS 2 scans. RESULTS: A total of 144 patients were included in the study. Index lesion/foci detection was similar between 68Ga-PSMA PET/CT and mpMRI (sensitivity 83.1% vs 90.1%; p = 0.267), however lesions missed by mpMRI were larger (1.66 cm3 vs 0.72 cm3; p = 0.034). Lesion detection rates were similar across the biopsy histopathology and radical prostatectomy specimen subset, with a high concordance for index (80.1%) and a moderate concordance for total (67%) lesions between the 2 imaging modalities. The additional detection yield favoured 68Ga-PSMA PET/CT over mpMRI for index (13.5% vs 4.3%) and total (18.2% vs 5.4%) lesions; both modalities missed 2.1% and 12.3% of index and total lesions, respectively. 68Ga-PSMA PET/CT identified 9 of 11 patients with PIRADS 2 mpMRI but subsequently diagnosed with Gleason ≥ 3 + 4 disease. CONCLUSIONS: Despite high concordance rates, 68Ga-PSMA PET/CT incrementally improved tumour localisation compared with mpMRI. These results suggest that 68Ga-PSMA PET/CT may have an incremental value to that of mpMRI in the diagnostic process for prostate.

Improved detection and reduced biopsies: the effect of a multiparametric magnetic resonance imaging-based triage prostate cancer pathway in a public teaching hospital.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI) improves clinically significant prostate cancer (csPCa) detection by facilitating targeted biopsy (cognitive, fusion technology, or in-gantry MRI guidance) and reducing negative biopsies. This study sought to describe the feasibility of introducing an mpMRI-based triage pathway, including diagnostic performance, applicability to training, and cost analysis. METHODS: An observational retrospective cohort study of consecutive patients attending a large public tertiary referral training hospital who underwent mpMRI for suspicion of prostate cancer was considered. Standard clinical, MRI-related, histopathological, and financial parameters were collected for analysis of biopsy avoidance, diagnostic accuracy of biopsy approach, and operator (consultant and resident/registrar) and logistical (including financial) feasibility. RESULTS: 653 men underwent mpMRI, of which 344 underwent prostate biopsy resulting in a 47% biopsy avoidance rate. Overall, 240 (69.8%) patients were diagnosed with PCa, of which 208 (60.5%) were clinically significant, with higher rates of csPCa observed for higher PIRADS scores. In patients who underwent both systematic and targeted biopsy (stTPB), targeted cores detected csPCa in 12.7% and 16.6% in more men than systematic cores in PIRADS 5 and 4, respectively, whereas systematic cores detected csPCa in 5% and 3.2% of patients, where targeted cores did not. A high standard of performance was maintained across the study period and the approach was shown to be cost effective. CONCLUSIONS: Introdution of an mpMRI-based triage system into a large public tertiary teaching hospital is feasible, cost effective and leads to high rates of prostate cancer diagnosis while reducing unnecessary biopsies and detection of insignificant PCa.

Changing trends in surgical management of renal tumours from 2000 to 2016: a nationwide study of Medicare claims data.

BACKGROUND: Guidelines recommend nephron sparing surgery where possible for patients with T1 renal tumours. The trends of nephron sparing surgery outside the USA are limited, particularly since the introduction of robotic-assisted partial nephrectomy (RAPN). The aim of this study was to describe contemporary surgical management patterns of renal tumours in Australia according to Medicare claims data. METHODS: Claims data according to the Medicare Benefits Schedule on surgical management of renal tumours in adult Australians between January 2000 and December 2016 was collated. Analysis of absolute number, population-adjusted rate and renal cancer-adjusted rate of interventions according to age and gender were performed, as well as proportion of RAPN. RESULTS: Between 2000 and 2016, the rate of partial nephrectomy (PN) increased while radical nephrectomy (RN) remained stable (PN: 0.87-4.16, RN: 6.52-6.70 per 100 000 population). Since 2015, PN has become more common than RN in patients aged 25 to 44 years (0.98 versus 0.95 procedures per 100 000 population). Renal cancer-adjusted rate exhibited a trend towards increasing utilization of PN and reduced RN across all age groups. An increase in overall surgical treatment was observed (25%-41%), mainly due to increased treatment of patients older than 75 years. The proportion of RAPN was seen to rapidly increase (4.7% in 2010 to 58% in 2016). CONCLUSIONS: Treatment utilization for renal masses has markedly changed in Australia according to Medicare claims. PN is increasingly replacing RN in younger patients, and older patients are receiving more surgical treatment. The impact of increased RAPN utilization is yet to be determined.

A contemporary, nationwide analysis of surgery and radiotherapy treatment for prostate cancer.

OBJECTIVE: To characterize national clinical practice trends in the treatment of prostate cancer (PCa) in Australia. PATIENTS AND METHODS: Population-level data were extracted from existing Medicare Benefits Schedule data for radical prostatectomy (RP) and brachytherapy (2002-2016), as well as external beam radiotherapy (EBRT; 2012-2016). Treatment rates were calculated relative to whole and PCa populations among privately treated patients. Overall age-related and geographical trends were analysed. RESULTS: The use of RP and low-dose-rate (LDR) brachytherapy increased between 2002 and 2009, but subsequently decreased to 124 and 6.9 per 100 000 men, respectively, in 2016. More dramatic decreases were observed for men aged <65 years. From 2012, rates of RP (15% drop) and LDR brachytherapy (58% drop) decreased, while the use of EBRT remained steady, falling by 5% to 42 per 100 000 men in 2016. Overall treatment increased in the age group 75-84 years, with the rate of RP increasing by 108%. CONCLUSION: National claims data indicate there has been a reduction in PCa treatment since 2009, which is mostly attributable to a reduction in the treatment of younger patients and reduced use of brachytherapy. RP is most commonly used and its use is rising in men aged >65 years.

Outcomes and learning curve for robotic-assisted radical cystectomy: an Australian experience.

BACKGROUND: This study aimed to describe perioperative, oncological and learning curve outcomes for robotic-assisted radical cystectomy (RARC) across the first 100 cases performed by an Australian high-volume, fellowship-trained robotic surgeon. METHODS: A retrospective cohort study was performed on a consecutive group of 100 patients who underwent RARC between 2010 and 2016 in Brisbane, Australia. Perioperative, oncological and survival data were collected. Demographic, survival and learning curve analyses were performed in MedCalc. RESULTS: A total of 100 patients underwent RARC over the study period. Median operative time was 389 min, with a reduction in median times from 420 to 330 min when comparing the first 50 versus the second 50 patients (P < 0.001). Median estimated blood loss was 500 mL, while urinary diversion was performed extracorporeally in 20 patients, intracorporeally in 69 patients and using a hybrid technique in 11 patients. Median length of hospital stay was 11 days. Post-operative complications occurred in 56% of patients (Clavien-Dindo classification I-II 32%, III-V 24%). Positive operative margins were 2% and median lymph node yield was 21 nodes. Overall recurrence-free survival was 50.3 months. CONCLUSION: Initial short-term experience with RARC shows favourable outcomes with regard to operative, perioperative and pathological indicators compared to open radical cystectomy and other RARC series.

Medical Management of Peyronie's Disease: Review of the Clinical Evidence.

Peyronie's disease is a condition that causes abnormal healing of the tunica albuginea, causing penile curvature. It is difficult to treat and its management is continuing to evolve. Proposed non-surgical treatments have included oral, topical, intralesional, extracorporeal shockwave, and traction therapy. The study of Peyronie's disease is made difficult by heterogeneity in the timing of presentation, severity and characteristics of deformity, and associated complaints. Moreover, meta-analyses of studies are difficult due to inconsistencies across study endpoints and the duration of treatments. This article reviews the current clinical evidence and guideline recommendations, with a focus on an improvement in penile curvature.

Robot-assisted laparoscopic prostatectomy versus open radical retropubic prostatectomy: 24-month outcomes from a randomised controlled study.

BACKGROUND: Previous trials have found similar early outcomes after robot-assisted laparoscopic prostatectomy and open radical retropubic prostatectomy. We report functional and oncological postoperative outcomes up to 24 months after surgery for these two surgical techniques. METHODS: In this randomised controlled phase 3 study, men who had newly diagnosed clinically localised prostate cancer and who had chosen surgery as their treatment approach, and were aged between 35 years and 70 years were eligible and recruited from the Royal Brisbane and Women's Hospital (Brisbane, QLD, Australia). Participants were randomly assigned (1:1) to have either robot-assisted laparoscopic prostatectomy or open radical retropubic prostatectomy. Randomisation was computer generated and occurred in blocks of ten. This was an open trial; however, study investigators involved in data analysis were masked to each patient's surgical treatment. Primary outcomes were urinary function (urinary domain of Expanded Prostate Cancer Index Composite [EPIC]) and sexual function (sexual domain of EPIC and International Index of Erectile Function Questionnaire [IIEF]) at 6 months, 12 months, and 24 months and oncological outcome (biochemical recurrence and imaging evidence of progression). The trial was powered to assess health-related and domain-specific quality-of-life outcomes over 24 months. All analyses were done on a per-protocol basis. The trial was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000661976. FINDINGS: Between Aug 23, 2010, and Nov 25, 2014, 326 men were enrolled, of whom 163 were randomly assigned to robot-assisted laparoscopic prostatectomy and 163 to open radical retropubic prostatectomy. 18 withdrew (12 assigned to radical retropubic prostatectomy and six assigned to robot-assisted laparoscopic prostatectomy); thus, 151 in the radical retropubic prostatectomy group and 157 in the robot-assisted laparoscopic prostatectomy group proceeded to surgery. At the 24-month follow-up time point, 150 men remained in the robot-assisted laparoscopic prostatectomy group and 146 remained in the open radical retropubic prostatectomy group. Urinary function scores did not differ significantly between robot-assisted laparoscopic prostatectomy and open radical retropubic prostatectomy at 6 months post-surgery (88·68 [95% CI 86·79-90·58] vs 88·45 [86·54-90·36]; p1<0·0001, p2<0·0001), 12 months post-surgery (90·76 [88·89-92·62] vs 91·53 [90·07-92·98]; p1<0·0001, p2<0·0001), or 24 months post-surgery (91·33 [89·64-93·03] vs 90·86 [89·01-92·70]; p1<0·0001, p2<0·0001). Sexual function scores were not significantly different between robot-assisted laparoscopic prostatectomy and open radical retropubic prostatectomy at 6 months post-surgery (EPIC: 37·40 [33·60-41·19] vs 38·63 [34·76-42·49], p1=0·0001, p2<0·0001; IIEF: 29·75 [26·66-32·84] vs 29·78 [26·41-33·16], p1<0·0001, p2<0·0001), 12 months post-surgery (EPIC: 42·28 [38·05-46·51] vs 42·51 [38·29-46·72], p1<0·0001, p2<0·0001; IIEF: 33·10 [29·59-36·61] vs 33·50 [29·87-37·13], p1=0·0002, p2<0·0001), or 24 months post-surgery (EPIC: 45·70 [41·17-50·23] vs 46·90 [42·20-51·60], p1=0·0003, p2<0·0001; IIEF: 33·95 [30·11-37·78] vs 33·89 [29·82-37·96], p1=0·0003, p2=0·0004). Equivalence testing on the difference between the proportion of biochemical recurrences between the two groups (13 [9%] in the open radical retropubic prostatectomy group vs four [3%] in the robot-assisted laparoscopic prostatectomy group) showed that equality between the two techniques could not be established based on a 90% CI with a prespecified margin of 10%. However, a superiority test showed that the two proportions were significantly different (p=0·0199). Equivalence testing on the proportion of patients who had imaging evidence of progression revealed that the two groups were not significantly different (p=0·2956). INTERPRETATION: Robot-assisted laparoscopic prostatectomy and open radical retropubic prostatectomy yielded similar functional outcomes at 24 months. We advise caution in interpreting the oncological outcomes of our study because of the absence of standardisation in postoperative management between the two trial groups and the use of additional cancer treatments. Clinicians and patients should view the benefits of a robotic approach as being largely related to its minimally invasive nature. FUNDING: Cancer Council Queensland.

Design and Clinical Verification of Surface-Enhanced Raman Spectroscopy Diagnostic Technology for Individual Cancer Risk Prediction.

The use of emerging nanotechnologies, such as plasmonic nanoparticles in diagnostic applications, potentially offers opportunities to revolutionize disease management and patient healthcare. Despite worldwide research efforts in this area, there is still a dearth of nanodiagnostics which have been successfully translated for real-world patient usage due to the predominant sole focus on assay analytical performance and lack of detailed investigations into clinical performance in human samples. In a bid to address this pressing need, we herein describe a comprehensive clinical verification of a prospective label-free surface-enhanced Raman scattering (SERS) nanodiagnostic assay for prostate cancer (PCa) risk stratification. This contribution depicts a roadmap of (1) designing a SERS assay for robust and accurate detection of clinically validated PCa RNA targets; (2) employing a relevant and proven PCa clinical biomarker model to test our nanodiagnostic assay; and (3) investigating the clinical performance on independent training ( n = 80) and validation ( n = 40) cohorts of PCa human patient samples. By relating the detection outcomes to gold-standard patient biopsy findings, we established a PCa risk scoring system which exhibited a clinical sensitivity and specificity of 0.87 and 0.90, respectively [area-under-curve of 0.84 (95% confidence interval: 0.81-0.87) for differentiating high- and low-risk PCa] in the validation cohort. We envision that our SERS nanodiagnostic design and clinical verification approach may aid in the individualized prediction of PCa presence and risk stratification and may overall serve as an archetypical strategy to encourage comprehensive clinical evaluation of nanodiagnostic innovations.