Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal.

Clear cell renal cell carcinoma (ccRCC) is characterized by near-universal loss of the short arm of chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal cell carcinoma. We find hotspots of point mutations in the 5' UTR of TERT, targeting a MYC-MAX-MAD1 repressor associated with telomere lengthening. The most common structural abnormality generates simultaneous 3p loss and 5q gain (36% patients), typically through chromothripsis. This event occurs in childhood or adolescence, generally as the initiating event that precedes emergence of the tumor's most recent common ancestor by years to decades. Similar genomic changes drive inherited ccRCC. Modeling differences in age incidence between inherited and sporadic cancers suggests that the number of cells with 3p loss capable of initiating sporadic tumors is no more than a few hundred. Early development of ccRCC follows well-defined evolutionary trajectories, offering opportunity for early intervention.

Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal.

The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. We observe up to 30 driver events per tumor and show that subclonal diversification is associated with known prognostic parameters. By resolving the patterns of driver event ordering, co-occurrence, and mutual exclusivity at clone level, we show the deterministic nature of clonal evolution. ccRCC can be grouped into seven evolutionary subtypes, ranging from tumors characterized by early fixation of multiple mutational and copy number drivers and rapid metastases to highly branched tumors with >10 subclonal drivers and extensive parallel evolution associated with attenuated progression. We identify genetic diversity and chromosomal complexity as determinants of patient outcome. Our insights reconcile the variable clinical behavior of ccRCC and suggest evolutionary potential as a biomarker for both intervention and surveillance.

Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal.

Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 metastatic biopsies across 100 patients with metastatic ccRCC, including two cases sampledat post-mortem. Metastatic competence was afforded by chromosome complexity, and we identify 9p loss as a highly selected event driving metastasis and ccRCC-related mortality (p = 0.0014). Distinct patterns of metastatic dissemination were observed, including rapid progression to multiple tissue sites seeded by primary tumors of monoclonal structure. By contrast, we observed attenuated progression in cases characterized by high primary tumor heterogeneity, with metastatic competence acquired gradually and initial progression to solitary metastasis. Finally, we observed early divergence of primitive ancestral clones and protracted latency of up to two decades as a feature of pancreatic metastases.

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors.

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology.

Radical cancer treatment is safe during COVID-19: the real-world experience of a large London-based Comprehensive Cancer Centre during the first wave.

BACKGROUND: During the COVID pandemic, there was a paucity of data to support clinical decision-making for anticancer treatments. We evaluated the safety of radical treatments which were delivered whilst mitigating the risks of concurrent COVID-19 infection. METHODS: Using descriptive statistics, we report on the characteristics and short-term clinical outcomes of patients undergoing radical cancer treatment during the first COVID-19 wave compared to a similar pre-pandemic period. RESULTS: Compared to 2019, the number of patients undergoing radical treatment in 2020 reduced by: 28% for surgery; 18% for SACT; and 10% for RT. Within SACT, 36% received combination therapy, 35% systemic chemotherapy, 23% targeted treatments, 5% immunotherapy and 2% biological therapy. A similar proportion of RT was delivered in 2019 and 2020 (53% vs. 52%). Oncological outcomes were also similar to pre-COVID-19. The COVID-19 infection rates were low: 12 patients were positive pre surgery (1%), 7 post surgery (<1%), 17 SACT patients (2%) and 3 RT patients (<1%). No COVID-19-related deaths were reported. CONCLUSIONS: Whilst there were fewer patients receiving radical anticancer treatments, those who did receive treatment were treated in a safe environment. Overall, cancer patients should have the confidence to attend hospitals and be reassured of the safety measures implemented.

Metastasectomy in renal cell carcinoma: where are we now?

PURPOSE OF REVIEW: Metastatic RCC has a variable natural history. Treatment choice depends on disease and patient factors, but most importantly disease burden and site of metastasis. This article highlights key variables to consider when contemplating metastasectomy for RCC and provide a narrative review on the evidence for metastasectomy in these patients. RECENT FINDINGS: Tumour subtype is associated with differing patterns of recurrence. Patients with single or few metastatic sites have better outcomes, and those with greater time interval from initial nephrectomy. Local recurrence is particularly amenable to minimally invasive surgical resection and is oncologically sound. Very well selected cases of liver or brain metastases may benefit from metastectomy, although lung and endocrine metastases have more favourable outcomes. Although site and burden of disease is important, the key determinate of outcome in metastasectomy depends mostly on the ability to achieve a complete resection. Adjuvant treatment is not currently advocated. SUMMARY: Metastasectomy should be generally reserved for cases where complete resection is achievable, unless the goal of treatment is to palliate symptoms. This field warrants ongoing research, particularly as systemic therapy and minimally invasive surgical techniques evolve. Elucidating tumour biology to inform patient selection will be important in future research.

Guy's and St Thomas NHS Foundation active surveillance prostate cancer cohort: a characterisation of a prostate cancer active surveillance database.

BACKGROUND: The routine clinical use of serum prostatic specific antigen (PSA) testing has allowed earlier detection of low-grade prostate cancer (PCa) with more favourable characteristics, leading to increased acceptance of management by active surveillance (AS). AS aims to avoid over treatment in men with low and intermediate-risk PCa and multiple governing bodies have described several AS protocols. This study provides a descriptive profile of the Guy's and St Thomas NHS Foundation Trust (GSTT) AS cohort as a platform for future research in AS pathways in PCa. METHODS: Demographic and baseline characteristics were retrospectively collected in a database for patients at the GSTT AS clinic with prospective collection of follow-up data from 2012. Seven hundred eighty-eight men being monitored at GSTT with histologically confirmed intermediate-risk PCa, at least 1 follow-up appointment and diagnostic characteristics consistent with AS criteria were included in the profile. Descriptive statistics, Kaplan-Meier survival curves and multivariable Cox proportion hazards regression models were used to characterize the cohort. DISCUSSION: A relatively large proportion of the cohort includes men of African/Afro-Caribbean descent (22%). More frequent use of magnetic resonance imaging and trans-perineal biopsies at diagnosis was observed among patients diagnosed after 2012. Those who underwent trans-rectal ultrasound diagnostic biopsy received their first surveillance biopsy 20 months earlier than those who underwent trans-perineal diagnostic biopsy. At 3 years, 76.1% men remained treatment free. Predictors of treatment progression included Gleason score 3 + 4 (Hazard ratio (HR): 2.41, 95% Confidence interval (CI): 1.79-3.26) and more than 2 positive cores taken at biopsy (HR: 2.65, CI: 1.94-3.62). A decreased risk of progressing to treatment was seen among men diagnosed after 2012 (HR: 0.72, CI: 0.53-0.98). CONCLUSION: An organised biopsy surveillance approach, via two different AS pathways according to the patient's diagnostic method, can be seen within the GSTT cohort. Risk of patients progressing to treatment has decreased in the period since 2012 compared with the prior period with more than half of the cohort remaining treatment free at 5 years, highlighting that the fundamental aims of AS at GSTT are being met. Thus, this cohort is a good resource to investigate the AS treatment pathway.

How reliable are surgeon-reported data? A comparison of the British Association of Urological Surgeons radical prostatectomy audit with the National Prostate Cancer Audit Hospital Episode Statistics-linked database.

OBJECTIVES: To evaluate the accuracy and completeness of surgeon-reported radical prostatectomy outcome data across a national health system by comparison with a national dataset gathered independently from clinicians directly involved in patient care. PATIENTS AND METHODS: Data submitted by surgeons to the British Association of Urological Surgeons (BAUS) radical prostatectomy audit for all men undergoing radical prostatectomy between 2015 and 2016 were assessed by cross linkage to the National Prostate Cancer Audit (NPCA) database. Specific data items collected in both databases were selected for comparison analysis. Data completeness and agreement were assessed by percentages and Cohen's kappa statistic. RESULTS: Data from 4707 men in the BAUS and NPCA databases were matched for comparison. Compared with the NPCA, dataset completeness was higher in the BAUS dataset for type of nerve-sparing procedure (92% vs 42%) and postoperative margin status (89% vs 48%) but lower for readmission (87% vs 100%) and Charlson score (80% vs 100%). For all other variables assessed completeness was comparable. Agreement and data reliability were high for most variables. However, despite good agreement, the inter-cohort reliability was poor for readmission, M stage and Charlson score (κ < 0.30). CONCLUSIONS: For the first time in urology we show that surgeon-reported data from the BAUS radical prostatectomy audit can reliably be used to benchmark peri-operative radical prostatectomy outcomes. For comorbidity data, to assist with risk analysis, and longer-term outcomes, NPCA routinely collected data provide a more comprehensive source.

The management impact of 68gallium-tris(hydroxypyridinone) prostate-specific membrane antigen (68Ga-THP-PSMA) PET-CT imaging for high-risk and biochemically recurrent prostate cancer.

PURPOSE: To determine the impact on clinical management of patients with high-risk (HR) prostate cancer at diagnosis and patients with biochemical recurrence (BCR) using a new kit form of 68Ga-prostate-specific membrane antigen (PSMA), namely tris(hydroxypyridinone) (THP)-PSMA, with positron emission tomography-computed tomography (PET-CT). METHODS: One hundred eighteen consecutive patients (50 HR, 68 BCR) had management plans documented at a multidisciplinary meeting before 68Ga-THP-PSMA PET-CT. Patients underwent PET-CT scans 60-min post-injection of 68Ga-THP-PSMA (mean 159 ± 21.2 MBq). Post-scan management plans, Gleason score, prostate-specific antigen (PSA) and PSA doubling time (PSAdt) were recorded. RESULTS: HR group: 12/50 (24%) patients had management changed (9 inter-modality, 3 intra-modality). Patients with PSA < 20 µg/L had more frequent management changes (9/26, 34.6%) compared with PSA > 20 µg/L (3/24, 12.5%). Gleason scores > 8 were associated with detection of more nodal (4/16, 25% vs 5/31, 16.1%) and bone (2/16, 12.5% vs 2/31, 6.5%) metastases. BCR group: Clinical management changed in 23/68 (34%) patients (17 inter-modality, 6 intra-modality). Forty out of 68 (59%) scans were positive. Positivity rate increased with PSA level (PSA < 0.5 µg/L, 0%; PSA 0.5-1.0 µg/L, 35%; PSA 1.0-5.0 µg/L, 69%; PSA 5.0-10.0 µg/L, 91%), PSAdt of < 6 months (56% vs 45.7%) and Gleason score > 8 (78.9% vs 51.2%). CONCLUSIONS: 68Ga-THP-PSMA PET-CT influences clinical management in significant numbers of patient with HR prostate cancer pre-radical treatment and is associated with PSA. Management change also occurs in patients with BCR and is associated with PSA and Gleason score, despite lower scan positivity rates at low PSA levels < 0.5 µg/L.

Targeted and systematic cognitive freehand-guided transperineal biopsy: is there still a role for systematic biopsy?

OBJECTIVES: To assess whether targeted cognitive freehand-assisted transperineal biopsies using a PrecisionpointTM device still require additional systematic biopsies to avoid missing clinically significant prostate cancer, and to investigate the benefit of a quadrant-only biopsy approach to analyse whether a quadrant or extended target of the quadrant containing the target only would have been equivalent to systematic biopsy. PATIENTS AND METHODS: Patients underwent combined systematic mapping and targeted transperineal prostate biopsies at a single institution. Biopsies were performed using the Precisionpoint device (Perineologic, Cumberland, MD, USA) under either local anaesthetic (58%, 163/282), i.v. sedation (12%, 34/282) or general anaesthetic (30%, 85/282). A mean (range) of 24 (5-42) systematic and 4.2 (1-11) target cores were obtained. Magnetic resonance imaging (MRI) scans were reported using the Likert scale. Clinically significant cancer was defined as Gleason 7 or above. Histopathological results were correlated with the presence of an MRI abnormality within a spatial quadrant and the other adjoining or non-adjoining (opposite) quadrants. Histological concordance with radical prostatectomy specimens was analysed. RESULTS: A total of 282 patients were included in this study. Their mean (range) age was 66.8 (36-80) years, median (range) prostate-specific antigen level 7.4 (0.91-116) ng/mL and mean prostate volume 45.8 (13-150) mL. In this cohort, 82% of cases (230/282) were primary biopsies and 18% (52/282) were patients on surveillance. In all, 69% of biopsies (195/282) were identified to have clinically significant disease (Gleason ≥3 + 4). Any cancer (Gleason ≥3 + 3) was found in 84% (237/282) of patients. Of patients with clinically significant disease, the target biopsies alone picked up 88% (171/195), with systematic biopsy picking up the additional 12% (24/195) that the target biopsies missed. This altered with Likert score; 73% of Likert score 3 disease was detected by target biopsy, 92% of Likert score 4 and 100% of Likert score 5. Target biopsies with additional same-quadrant-only systematic cores picked up 75% (18/24) of significant cancer that was missed on target only, found in the same quadrant as the target. CONCLUSION: Systematic biopsy is still an important tool when evaluating all patients referred for prostate biopsy, but the need is decreased with increasing suspicion on MRI. Patients with very high suspicion of prostate cancer (Likert score 5) may not require systematic cores, unless representative surrounding biopsies are required for other specific treatments (e.g. focal therapy, or operative planning). More prospective studies are needed to evaluate this in full.

Guideline adherence for the surgical treatment of T1 renal tumours correlates with hospital volume: an analysis from the British Association of Urological Surgeons Nephrectomy Audit.

OBJECTIVE: To assess European Association of Urology guideline adherence on the surgical management of patients with T1 renal tumours and the effects of centralisation of care. PATIENTS AND METHODS: Retrospective data from all kidney tumours that underwent radical nephrectomy (RN) or partial nephrectomy (PN) in the period 2012-2016 from the British Association of Urological Surgeons Nephrectomy Audit were retrieved and analysed. We assessed total surgical hospital volume (HV; RN and PN performed) per centre, PN rates, complication rates, and completeness of data. Descriptive analyses were performed, and confidence intervals were used to illustrate the association between hospital volume and proportion of PN. Chi- squared and Cochran-Armitage trend tests were used to evaluate differences and trends. RESULTS: In total, 13 045 surgically treated T1 tumours were included in the analyses. Over time, there was an increase in PN use (39.7% in 2012 to 44.9% in 2016). Registration of the Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) complexity score was included in March 2016 and documented in 39% of cases. Missing information on postoperative complications appeared constant over the years (8.5-9%).  A clear association was found between annual HV and the proportion of T1 tumours treated with PN rather than RN (from 18.1% in centres performing <25 cases/year [lowest volume] to 61.8% in centres performing ≥100 cases/year [high volume]), which persisted after adjustment for PADUA complexity. Overall and major (Clavien-Dindo grade ≥III) complication rate decreased with increasing HV (from 12.2% and 2.9% in low-volume centres to 10.7% and 2.2% in high-volume centres, respectively), for all patients including those treated with PN. CONCLUSION: Closer guideline adherence was exhibited by higher surgical volume centres. Treatment of T1 tumours using PN increased with increasing HV, and was accompanied by an inverse association of HV with complication rate. These results support the centralisation of kidney cancer specialist cancer surgical services to improve patient outcomes.

Predicting intra-operative and postoperative consequential events using machine-learning techniques in patients undergoing robot-assisted partial nephrectomy: a Vattikuti Collective Quality Initiative database study.

OBJECTIVE: To predict intra-operative (IOEs) and postoperative events (POEs) consequential to the derailment of the ideal clinical course of patient recovery. MATERIALS AND METHODS: The Vattikuti Collective Quality Initiative is a multi-institutional dataset of patients who underwent robot-assisted partial nephectomy for kidney tumours. Machine-learning (ML) models were constructed to predict IOEs and POEs using logistic regression, random forest and neural networks. The models to predict IOEs used patient demographics and preoperative data. In addition to these, intra-operative data were used to predict POEs. Performance on the test dataset was assessed using area under the receiver-operating characteristic curve (AUC-ROC) and area under the precision-recall curve (PR-AUC). RESULTS: The rates of IOEs and POEs were 5.62% and 20.98%, respectively. Models for predicting IOEs were constructed using data from 1690 patients and 38 variables; the best model had an AUC-ROC of 0.858 (95% confidence interval [CI] 0.762, 0.936) and a PR-AUC of 0.590 (95% CI 0.400, 0.759). Models for predicting POEs were trained using data from 1406 patients and 59 variables; the best model had an AUC-ROC of 0.875 (95% CI 0.834, 0.913) and a PR-AUC 0.706 (95% CI, 0.610, 0.790). CONCLUSIONS: The performance of the ML models in the present study was encouraging. Further validation in a multi-institutional clinical setting with larger datasets would be necessary to establish their clinical value. ML models can be used to predict significant events during and after surgery with good accuracy, paving the way for application in clinical practice to predict and intervene at an opportune time to avert complications and improve patient outcomes.

Salvage Radical Prostatectomy for Recurrent Prostate Cancer: Morbidity and Functional Outcomes from a Large Multicenter Series of Open versus Robotic Approaches.

PURPOSE: Salvage radical prostatectomy has historically yielded a poor functional outcome and a high complication rate. However, recent reports of robotic salvage radical prostatectomy have demonstrated improved results. In this study we assessed salvage radical prostatectomy functional outcomes and complications when comparing robotic and open approaches. MATERIALS AND METHODS: We retrospectively collected data on salvage radical prostatectomy for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers from 2000 to 2016. The Clavien-Dindo classification was applied to classify complications. Complications and functional outcomes were evaluated by univariable and multivariable analysis. RESULTS: We included 395 salvage radical prostatectomies, of which 186 were open and 209 were robotic. Robotic salvage radical prostatectomy yielded lower blood loss and a shorter hospital stay (each p <0.0001). No significant difference emerged in the incidence of major and overall complications (10.1%, p=0.16, and 34.9%, p=0.67), including an overall low risk of rectal injury and fistula (1.58% and 2.02%, respectively). However, anastomotic stricture was more frequent for open salvage radical prostatectomy (16.57% vs 7.66%, p <0.01). Overall 24.6% of patients had had severe incontinence, defined as 3 or more pads per day, for 12 or 6 months. On multivariable analysis robotic salvage radical prostatectomy was an independent predictor of continence preservation (OR 0.411, 95% CI 0.232-0.727, p=0.022). Limitations include the retrospective nature of the study and the absence of a standardized surgical technique. CONCLUSIONS: In this contemporary series to our knowledge salvage radical prostatectomy showed a low risk of major complications and better functional outcomes than previously reported. Robotic salvage radical prostatectomy may reduce anastomotic stricture, blood loss and hospital stay, and improve continence outcomes.

The global prevalence of erectile dysfunction: a review.

OBJECTIVE: To evaluate the global prevalence of erectile dysfunction (ED); as well as its association with physiological and pathological ageing by examining the relationship between ED and cardiovascular disease (CVD), benign prostatic hyperplasia (BPH), and dementia. We also aimed to characterise discrepancies caused by the use of different ED screening tools. METHODS: The Excerpta Medica dataBASE (EMBASE) and Medical Literature Analysis and Retrieval System Online (MEDLINE) were searched to find population-based studies investigating the prevalence of ED and the association between ED and CVD, BPH, and dementia in the general population. RESULTS: The global prevalence of ED was 3-76.5%. ED was associated with increasing age. Use of the International Index of Erectile Function (IIEF) and Massachusetts Male Aging Study (MMAS)-derived questionnaire identified a high prevalence of ED in young men. ED was positively associated with CVD. Men with ED have an increased risk of all-cause mortality odds ratio (OR) 1.26 (95% confidence interval [CI] 1.01-1.57), as well as CVD mortality OR 1.43 (95% CI 1.00-2.05). Men with ED are 1.33-6.24-times more likely to have BPH then men without ED, and 1.68-times more likely to develop dementia than men without ED. CONCLUSION: ED screening tools in population-based studies are a major source of discrepancy. Non-validated questionnaires may be less sensitive than the IIEF and MMAS-derived questionnaire. ED constitutes a large burden on society given its high prevalence and impact on quality of life, and is also a risk factor for CVD, dementia, and all-cause mortality.

Perioperative and oncological outcomes of radical prostatectomy for high-risk prostate cancer in the UK: an analysis of surgeon-reported data.

OBJECTIVES: To analyse the perioperative and oncological outcomes of all radical prostatectomies (RPs) performed for high-risk prostate cancer in the British Association of Urological Surgeons (BAUS) national registry from 2014 to 2015. PATIENTS AND METHODS: We identified and analysed outcomes of all RPs performed for high-risk prostate cancer (clinical stage >T2 and/or biopsy Gleason grade >7 and/or preoperative prostate-specific antigen level ≥20 ng/mL) in the national registry for 2014 and 2015. Surgeon reporting of data was mandated during this period. Institution and individual surgeon volume-outcome relationships were assessed. RESULTS: In total, 3671/13 947 (26.3%) patients underwent RP for high-risk prostate cancer over the 2-year period. Robot-assisted RP was the most prevalent approach (60.7%). In all, 39% of men received an extended pelvic lymph node dissection (LND), but over one-third (33.8%) had no LND. Minimally invasive techniques were associated with a significantly shorter length of stay. The reported rates of Clavien-Dindo ≥III complications within the dataset were low (2.0%), regardless of surgical modality or surgeon volume. No statistically significant surgeon volume-outcome relationships were identified when surgeon volume was stratified into tertiles. CONCLUSION: RP for high-risk prostate cancer in the UK appears safe, regardless of modality used or surgeon volume. No clear evidence that surgeon volume impacts on early perioperative outcomes was seen. Quality assurance of the surgeon-reported BAUS dataset is now required to drive quality improvement in national practice.

Evaluating the impact of length of time from diagnosis to surgery in patients with unfavourable intermediate-risk to very-high-risk clinically localised prostate cancer.

OBJECTIVE: To evaluate the impact of length of time from diagnostic biopsy to radical prostatectomy (RP) on oncological outcomes amongst men diagnosed with unfavourable intermediate- to very-high-risk clinically localised prostate cancer. PATIENTS AND METHODS: We performed a retrospective review of men with a diagnosis of grade group (GG) ≥3 prostate cancer on biopsy, who underwent RP within 6 months of diagnosis, at our institution between 2005 and 2018. We assessed patient demographics, pre-biopsy disease characteristics, and receipt of neoadjuvant therapy. We categorised time between biopsy and RP into two intervals: <3 and 3-6 months. For each GG, we compared receipt of adjuvant therapy, pathological outcomes at RP (positive surgical margin [PSM], extraprostatic extension [EPE], seminal vesicle invasion [SVI], and lymph node involvement [LNI]), risk of 2- and 5-year biochemical recurrence-free survival (BCRFS), and 2-, 5-, and 10-year metastasis-free survival (MFS) between patients who underwent RP at <3 vs 3-6 months after diagnosis. RESULTS: Amongst 2303 men who met the study inclusion criteria, 1244 (54%) had GG 3, 608 (26%) had GG 4, and 451 (20%) had GG 5 disease. In all, 72% underwent RP at <3 months after diagnosis. For each diagnostic GG, there was no significant difference in rates of adjuvant therapy, PSM, EPE, SVI, or LNI in men who had RP at <3 vs 3-6 months after diagnosis. In all, 1568 men had follow-up after RP of >1 year. For each diagnostic GG, there was no significant difference in 2- and 5-year BCRFS between patients who had RP at <3 vs 3-6 months after diagnosis (GG 3: 78% vs 83% and 69% vs 66%, respectively, P = 0.6; GG 4: 68% vs 74% and 51% vs 57%, respectively, P = 0.4; GG 5: 58% vs 74% and 48% vs 54%, respectively, P = 0.2). Similarly, for each diagnostic GG, there was no significant difference in 2-, 5-, and 10-year MFS between patients who had RP at <3 vs 3-6 months after diagnosis, although we were not able to calculate 10-year MFS for patients with GG 5 disease due to limited follow-up in that group (GG 3: 98%, 92%, and 84% vs 97%, 95%, and 91%, respectively, P = 0.4; GG 4: 97%, 90%, and 72% vs 94%, 91%, and 81%, respectively, P = 0.8; GG 5: 89% and 81% vs 91% and 71%, respectively, P = 0.9). CONCLUSIONS: Waiting for RP up to 6 months after diagnosis is not associated with adverse outcomes amongst patients with unfavourable intermediate- to very-high-risk prostate cancer.

Robotic versus laparoscopic radical nephrectomy: a large multi-institutional analysis (ROSULA Collaborative Group).

OBJECTIVE: To compare the outcomes of robotic radical nephrectomy (RRN) to those of laparoscopic radical nephrectomy (LRN) for large renal masses. METHODS: This was a retrospective analysis of RRN and LRN cases performed for large (≥ cT2) renal masses from 2004 to 2017 and collected in the multi-institutional international database (ROSULA: RObotic SUrgery for LArge renal masses). Peri-operative, functional, and oncologic outcomes were compared between each approach. Descriptive analyses were performed and presented as medians with interquartile ranges. Inverse probability of treatment weighting-adjusted multivariable analyses were used to identify predictors of peri-operative complications. Kaplan-Meier analysis and Cox regression models were used to assess survival outcomes. RESULTS: A total of 941 patients (RRN = 404, LRN = 537) were identified. There was no difference in terms of gender, age, and clinical tumor size. Over the study period, RRN had an annual increase of 11.75% (95% CI [7.34, 17.01] p < 0.001) and LRN had an annual decline of 5.39% (95% CI [-6.94, -3.86] p < 0.001). Patients undergoing RRN had higher BMI (27.6 [IQR 24.8-31.1] vs. 26.5 [24.1-30.0] kg/m2, p < 0.01). Operative duration was longer for RRN (185.0 [150.0-237.2] vs. 126 [90.8-180.0] min, p < 0.001). Length of stay was shorter for RRN (3.0 [2.0-4.0] vs. 5.0 [4.0-7.0] days, p < 0.001). RRN cases presented more advanced disease (higher pathologic staging [pT3-4 52.5 vs. 24.2%, p < 0.001], histologic grade [high grade 49.3 vs. 30.4%, p < 0.001], and rate of nodal disease [pN1 5.4 vs. 1.9%, p < 0.01]). Surgical approach did not represent an independent risk factor for peri-operative complications (OR 1.81 95% CI [0.97-3.39], adjusted p = 0.2). The main study limitation is the retrospective design. CONCLUSIONS: This study represents the largest known multi-center comparison between RRN and LRN. The two procedures seem to offer similar peri-operative outcomes. Notably, RRN has been increasingly utilized, especially in the setting of more advanced and surgically challenging disease without increasing the risk of peri-operative complications.

Introducing new technology safely into urological practice.

PURPOSE: Surgical innovation is necessary to ensure continued improvement in patient care. However, several challenges unique to the surgical craft are encountered during the development and validation of such new technology. This article highlights some of these challenges and gives an overview of existing solutions. METHODS: A Pubmed review was performed about the "introduction of new technology" to identify challenges. Cross-referencing was used to explore the possible solutions per challenge. RESULTS: Several characteristics of the surgical craft itself limit our ability to establish randomised controlled trials and hence provide clear categorical evidence. Existing certification bodies for new technology often use unstructured regulations and allow fast-track bypassing systems. Consequently the IDEAL framework (innovation, development, exploration, assessment, long-term follow-up) proposes an objective scientific approach whilst defining stakeholder responsibilities. The selection of which new modality to implement is heavily influenced by third parties unrelated to the best patient outcomes and thus professional organisations can aid in this decision-making. Appropriate training of surgeons and their teams until proficiency is achieved is essential prior to credentialling. Finally long-term surveillance of outcomes in the form of registries is an increasing responsibility of the urological community to maintain our role in directing the adoption or rejection of these innovations. CONCLUSION: Urological innovation is a dynamic and challenging process. Increasing efforts are identified within the urological community to render the process more reliable and transparent.

Development of a technical checklist for the assessment of suturing in robotic surgery.

BACKGROUND: With the increased use of simulation for surgical training, there is a need for objective forms of assessment to evaluate trainees. The Global Evaluative Assessment of Robotic Skills (GEARS) is widely used for assessing skills in robotic surgery, but there are no recognised checklist scoring systems. This study aimed to develop a checklist for suturing in robotic surgery. METHODS: A suturing checklist for needle driving and knot tying was constructed following evaluation of participants performing urethrovesical anastomoses. Key procedural steps were identified from expert videos, while assessing novice videos allowed identification of common technical errors. 22 novice and 13 expert videos were marked on needle driving, while 18 novices and 10 experts were assessed on knot tying. Validation of the finalised checklist was performed with the assessment of 39 separate novices by an expert surgeon and compared to GEARS scoring. RESULTS: The internal consistency of the preliminary checklist was high (Cronbach's alpha = 0.870 for needle driving items; 0.736 for knot tying items), and after removal of poorly correlating items, the final checklist contained 23 steps. Both the needle driving and knot tying categories discriminated between novices and experts, p < 0.005. While the GEARS score demonstrated construct validity for needle driving, it could not significantly differentiate between novices and experts for knot tying, p = 0.286. The needle driving category significantly correlated with the corresponding GEARS scores (rs = 0.613, p < 0.005), but the correlation for knot tying was insignificant (rs = 0.296, p = 0.127). The pilot data indicates the checklist significantly correlated with the GEARS score (p < 0.005). CONCLUSION: This study reports the development of a valid assessment tool for suturing in robotic surgery. Given that checklists are simple to use, there is significant scope for this checklist to be used in surgical training.