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Background: Lymph node invasion (LNI) represents a poor prognostic factor after primary radical prostatectomy (RP) for prostate cancer (PCa). However, the impact of LNI on oncologic outcomes in salvage radical prostatectomy (SRP) patients is unknown. Objective: To investigate the impact of lymph node dissection (LND) and pathological lymph node status (pNX vs. pN0 vs. pN1) on long-term oncologic outcomes of SRP patients. Patients and methods: Patients who underwent SRP for recurrent PCa between 2000 and 2021 were identified from 12 high-volume centers. Kaplan–Meier analyses and multivariable Cox regression models were used. Endpoints were biochemical recurrence (BCR), overall survival (OS), and cancer-specific survival (CSS). Results: Of 853 SRP patients, 87% (n = 727) underwent LND, and 21% (n = 151) harbored LNI. The median follow-up was 27 months. The mean number of removed lymph nodes was 13 in the LND cohort. At 72 months after SRP, BCR-free survival was 54% vs. 47% vs. 7.2% for patients with pNX vs. pN0 vs. pN1 (p < 0.001), respectively. At 120 months after SRP, OS rates were 89% vs. 81% vs. 41% (p < 0.001), and CSS rates were 94% vs. 96% vs. 82% (p = 0.02) for patients with pNX vs. pN0 vs. pN1, respectively. In multivariable Cox regression analyses, pN1 status was independently associated with BCR (HR: 1.77, p < 0.001) and death (HR: 2.89, p < 0.001). Conclusions: In SRP patients, LNI represents an independent poor prognostic factor. However, the oncologic benefit of LND in SRP remains debatable. These findings underline the need for a cautious LND indication in SRP patients as well as strict postoperative monitoring of SRP patients with LNI.

To determine the impact of the COVID-19 pandemic on diagnostic and treatment activity in 2020 across hospital providers of prostate cancer (PCa) care in the English National Health Service.Diagnostic and treatment activity between 23 March (start of first national lockdown in England) and 31 December 2020 was compared with the same calendar period in 2019. Patients newly diagnosed with PCa were identified from national rapid cancer registration data linked to other electronic healthcare datasets.There was a 30.8% reduction (22 419 vs 32 409) in the number of men with newly diagnosed PCa in 2020 after the start of the first lockdown, compared with the corresponding period in 2019. Men diagnosed in 2020 were typically at a more advanced stage (Stage IV: 21.2% vs 17.4%) and slightly older (57.9% vs 55.9% ≥ 70 years; P0.001). Prostate biopsies in 2020 were more often performed using transperineal (TP) routes (64.0% vs 38.2%). The number of radical prostatectomies in 2020 was reduced by 26.9% (3896 vs 5331) and the number treated by external beam radiotherapy (EBRT) by 14.1% (9719 vs 11 309). Other changes included an increased use of EBRT with hypofractionation and reduced use of docetaxel chemotherapy in men with hormone-sensitive metastatic PCa (413 vs 1519) with related increase in the use of enzalutamide.We found substantial deficits in the number of diagnostic and treatment procedures for men with newly diagnosed PCa after the start of the first lockdown in 2020. The number of men diagnosed with PCa decreased by about one-third and those diagnosed had more advanced disease. Treatment patterns shifted towards those that limit the risk of COVID-19 exposure including increased use of TP biopsy, hypofractionated radiation, and enzalutamide. Urgent concerted action is required to address the COVID-19-related deficits in PCa services to mitigate their impact on long-term outcomes.

Differential gene expression DESeq2 analysis for 16h Spheres vs Adh (Sheet #1) and 5d Spheres vs Adh

In many tumors, cells transition reversibly between slow-proliferating tumor-initiating cells (TIC) and their differentiated, faster-growing progeny. Yet, how transcriptional regulation of cell-cycle and self-renewal genes is orchestrated during these conversions remains unclear. In this study, we show that as breast TIC form, a decrease in cell-cycle gene expression and increase in self-renewal gene expression are coregulated by SOX2 and EZH2, which colocalize at CpG islands. This pattern was negatively controlled by a novel long noncoding RNA (lncRNA) that we named Stem Cell Inhibitory RNA Transcript (SCIRT), which was markedly upregulated in tumorspheres but colocalized with and counteracted EZH2 and SOX2 during cell-cycle and self-renewal regulation to restrain tumorigenesis. SCIRT specifically interacted with EZH2 to increase EZH2 affinity to FOXM1 without binding the latter. In this manner, SCIRT induced transcription at cell-cycle gene promoters by recruiting FOXM1 through EZH2 to antagonize EZH2-mediated effects at target genes. Conversely, on stemness genes, FOXM1 was absent and SCIRT antagonized EZH2 and SOX2 activity, balancing toward repression. These data suggest that the interaction of an lncRNA with EZH2 can alter the affinity of EZH2 for its protein-binding partners to regulate cancer cell state transitions.Significance:These findings show that a novel lncRNA SCIRT counteracts breast tumorigenesis by opposing transcriptional networks associated with cell cycle and self-renewal.See related commentary by Pardini and Dragomir, p. 535

Supplementary material and methods

Purpose External beam radiation therapy (EBRT) with brachytherapy boost reduces cancer recurrence in patients with prostate cancer compared with EBRT monotherapy. However, randomized controlled trials or large-scale observational studies have not compared brachytherapy boost types directly. Methods and Materials This observational cohort study used linked national cancer registry data, radiation therapy data, administrative hospital data, and mortality records of 54,642 patients with intermediate-risk, high-risk, and locally advanced prostate cancer in England. The records of 11,676 patients were also linked to results from a national patient survey collected at least 18 months after diagnosis. Competing risk regression analyses were used to compare gastrointestinal (GI) toxicity, genitourinary (GU) toxicity, skeletal-related events (SRE), and prostate cancer–specific mortality (PCSM) at 5 years with adjustment for patient and tumor characteristics. Linear regression was used to compare Expanded Prostate Cancer Index Composite 26-item version domain scores (scale, 0-100, with higher scores indicating better function). Results Five-year GI toxicity was significantly increased after low-dose-rate brachytherapy boost (LDR-BB) (32.3%) compared with high-dose-rate brachytherapy boost (HDR-BB) (16.7%) or EBRT monotherapy (18.7%). Five-year GU toxicity was significantly increased after both LDR-BB (15.8%) and HDR-BB (16.6%), compared with EBRT monotherapy (10.4%). These toxicity patterns were matched by the mean patient-reported bowel function scores (LDR-BB, 77.3; HDR-BB, 85.8; EBRT monotherapy, 84.4) and the mean patient-reported urinary obstruction/irritation function scores (LDR-BB, 72.2; HDR-BB, 78.9; EBRT monotherapy, 83.8). Five-year incidences of SREs and PCSM were significantly lower after HDR-BB (2.4% and 2.7%, respectively) compared with EBRT monotherapy (2.8% and 3.5%, respectively). Conclusions Compared with EBRT monotherapy, LDR-BB has worse GI and GU toxicity and HDR-BB has worse GU toxicity. HDR-BB has a lower incidence of SREs and PCSM than EBRT monotherapy.

Objectives To determine the safety of urological admissions and procedures during the height of the COVID‐19 pandemic using “hot” and “cold” sites. The secondary objective is to determine risk factors of contracting COVID‐19 within our cohort. Patients and methods A retrospective cohort study of all consecutive patients admitted from March 1 to May 31, 2020 at a high‐volume tertiary urology department in London, United Kingdom. Elective surgery was carried out at a “cold” site requiring a negative COVID‐19 swab 72‐hours prior to admission and patients were required to self‐isolate for 14‐days preoperatively, while all acute admissions were admitted to the “hot” site. Complications related to COVID‐19 were presented as percentages. Risk factors for developing COVID‐19 infection were determined using multivariate logistic regression analysis. Results A total of 611 patients, 451 (73.8%) male and 160 (26.2%) female, with a median age of 57 (interquartile range 44‐70) were admitted under the urology team; 101 (16.5%) on the “cold” site and 510 (83.5%) on the “hot” site. Procedures were performed in 495 patients of which eight (1.6%) contracted COVID‐19 postoperatively with one (0.2%) postoperative mortality due to COVID‐19. Overall, COVID‐19 was detected in 20 (3.3%) patients with two (0.3%) deaths. Length of stay was associated with contracting COVID‐19 in our cohort (OR 1.25, 95% CI 1.13‐1.39). Conclusions Continuation of urological procedures using “hot” and “cold” sites throughout the COVID‐19 pandemic was safe practice, although the risk of COVID‐19 remained and is underlined by a postoperative mortality.

In many tumors, cells transition reversibly between slow-proliferating tumor-initiating cells (TIC) and their differentiated, faster-growing progeny. Yet, how transcriptional regulation of cell-cycle and self-renewal genes is orchestrated during these conversions remains unclear. In this study, we show that as breast TIC form, a decrease in cell-cycle gene expression and increase in self-renewal gene expression are coregulated by SOX2 and EZH2, which colocalize at CpG islands. This pattern was negatively controlled by a novel long noncoding RNA (lncRNA) that we named Stem Cell Inhibitory RNA Transcript (SCIRT), which was markedly upregulated in tumorspheres but colocalized with and counteracted EZH2 and SOX2 during cell-cycle and self-renewal regulation to restrain tumorigenesis. SCIRT specifically interacted with EZH2 to increase EZH2 affinity to FOXM1 without binding the latter. In this manner, SCIRT induced transcription at cell-cycle gene promoters by recruiting FOXM1 through EZH2 to antagonize EZH2-mediated effects at target genes. Conversely, on stemness genes, FOXM1 was absent and SCIRT antagonized EZH2 and SOX2 activity, balancing toward repression. These data suggest that the interaction of an lncRNA with EZH2 can alter the affinity of EZH2 for its protein-binding partners to regulate cancer cell state transitions. Significance: These findings show that a novel lncRNA SCIRT counteracts breast tumorigenesis by opposing transcriptional networks associated with cell cycle and self-renewal. See related commentary by Pardini and Dragomir, p. 535

Background and purpose Little is known about the functional outcomes and health-related quality of life (HRQoL) following external beam radiation therapy (EBRT) combined with a high-dose rate brachytherapy boost (EBRT-BB) for the treatment of prostate cancer. We aimed to compare patient-reported outcomes of EBRT to those of EBRT-BB. Methods and materials Patients diagnosed with intermediate-risk, high-risk or locally advanced prostate cancer (April 2014 to September 2016), who received EBRT in the English National Health Service within 18 months of diagnosis and responded to a national patient questionnaire, were identified from the National Prostate Cancer Audit. Adjusted linear regression was used to estimate differences in functional EPIC-26 domains and HRQoL (EQ-5D-5L) between treatment groups. Non-inferiority of EBRT-BB was determined if the lower 95% confidence limit did not exceed the established minimal clinically important difference (MCID). Results Of the 13,259 included men, 12,503 (94.3%) received EBRT and 756 (5.7%) received EBRT-BB. EBRT-BB was non-inferior compared to EBRT for the urinary incontinence, sexual, bowel and hormonal EPIC-26 domains. EBRT-BB resulted in significantly worse urinary irritation/obstruction scores than EBRT (−6.1; 95% CI: −8.8 to −3.4) but uncertainty remains as to whether this difference is clinically important (corresponding MCID of 5). Conclusions There is no evidence to suggest that EBRT-BB results in any clinically important detriment in functional outcomes or HRQoL compared to men receiving EBRT only. Whilst statistically significantly worse urinary irritation/obstruction outcomes were reported in the EBRT-BB cohort, the threshold for a clinically significant difference was not exceeded and further research is required for confirmation.

The COVID‐19 pandemic is impacting all urological cancer services. On March 19th the British Association of Urological Surgeons (BAUS) provided pragmatic guidance for prostate cancer diagnostic services (Table 1).(1)

Aims Randomised controlled trials have shown comparable early oncological outcomes after hypofractionated and conventionally fractionated radiotherapy in the radical treatment of prostate cancer (PCa). The effect of hypofractionation on treatment-related gastrointestinal and genitourinary toxicity remains uncertain, especially in older men and those with locally advanced PCa. Materials and methods A population-based study of all patients treated with radical conventionally fractionated radiotherapy (n = 9106) and hypofractionated radiotherapy (n = 3027) in all radiotherapy centres in the English National Health Service between 2014 and 2016 was carried out. We identified severe gastrointestinal and genitourinary toxicity using a validated coding framework and compared conventionally fractionated and hypofractionated radiotherapy using a competing-risks proportional hazards regression analysis. Results The median age in our cohort was 72 years old and most patients had locally advanced disease (65%). There was no difference in gastrointestinal toxicity (conventionally fractionated radiotherapy: 5.0 events/100 person-years; hypofractionated radiotherapy: 5.2 events/100 person-years; adjusted subdistribution hazard ratio: 1.00, 95% confidence interval: 0.89–1.13; P = 0.95) or genitourinary toxicity (conventionally fractionated radiotherapy: 2.3 events/100 person-years; hypofractionated radiotherapy: 2.3 events/100 person-years; adjusted subdistribution hazard ratio: 0.92, 95% confidence interval: 0.77–1.10; P = 0.35) between patients who received conventionally fractionated radiotherapy and those who received hypofractionated radiotherapy. Conclusions This national cohort study has shown that the use of hypofractionated radiotherapy in the radical treatment of PCa does not increase rates of severe gastrointestinal or genitourinary toxicity. Our findings also support the use of hypofractionated radiotherapy in older men and those with locally advanced PCa.

To assess the complications of transrectal (TR) compared to transperineal prostate (TP) biopsies.Men diagnosed with prostate cancer between 1 April 2014 and 31 March 2017 in England were identified in the National Prostate Cancer Audit. Administrative hospital data were then used to categorize the type of prostate biopsy and subsequent complications requiring hospital admission. Administrative hospital data were used to identify patients staying overnight immediately after biopsy and those readmitted separately for hospital admissions because of sepsis, urinary retention or haematuria. Procedure-related mortality and total length of hospital stay within 30 days were also recorded. Generalized linear models were used to calculate adjusted risk differences (aRDs).A total of 73 630 patients undergoing prostate biopsy were identified. Those undergoing TP biopsy (n = 13 723) were more likely to have an overnight hospital stay (12.3% vs 2.4%; aRD 9.7%, 95% confidence interval [CI] 7.1-12.3), were less likely to be readmitted because of sepsis (1.0% vs 1.4%; aRD -0.4%, CI -0.6 to -0.2), and were more likely to be readmitted with urinary retention (1.9% vs 1.0%; aRD 1.1%, CI 0.7-1.4) than those undergoing a TR biopsy (n = 59 907). There were no significant differences in the risk of haematuria or mortality.Our results showed that TP biopsy had a lower risk of readmission for sepsis but a higher risk of readmission for urinary retention than TR biopsy. Use of the TP route would prevent one readmission for sepsis in 278 patients at the cost of three additional patients readmitted for urinary retention.

INTRODUCTION: The treatment of prostate cancer varies between the United States (US) and England, however this has not been well characterised using recent data. We therefore investigated the extent of the differences between US and English patients with respect to initial treatment. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify men diagnosed with prostate cancer in the US and the treatments they received. We also used the National Prostate Cancer Audit (NPCA) database for the same purposes among men diagnosed with prostate cancer in England. Next, we used multivariable regression to estimate the adjusted risk ratio (aRR) of receiving radical local treatment for men with non-metastatic prostate cancer according to the country of diagnosis (US vs. England). The five-tiered Cambridge Prognostic Group (CPG) classification was included as an interaction term. RESULTS: We identified 109,697 patients from the SEER database, and 74,393 patients from the NPCA database, who were newly diagnosed with non-metastatic prostate cancer between April 1st 2014 and December 31st 2016 with sufficient information for risk stratification according to the CPG classification. Men in the US were more likely to receive radical local treatment across all prognostic groups compared to men in England (% radical treatment US vs. England, CPG1: 38.1% vs. 14.3% - aRR 2.57, 95% CI 2.47-2.68; CPG2: 68.6% vs. 52.6% - aRR 1.27, 95% CI 1.25-1.29; CPG3: 76.7% vs. 67.1% - aRR 1.12, 95% CI 1.10-1.13; CPG4: 82.6% vs. 72.4% - aRR 1.09, 95% CI 1.08-1.10; CPG5: 78.2% vs. 71.7% - aRR 1.06, 95% CI 1.04-1.07) CONCLUSIONS: Treatment rates were higher in the US compared to England raising potential over-treatment concerns for low-risk disease (CPG1) in the US and under-treatment of clinically significant disease (CPG3-5) in England.

ObjectivesTo test the feasibility of randomisation to radical prostatectomy (RP) plus pelvic lymphadenectomy in addition to standard-of-care (SOC) systemic therapy in men with newly diagnosed oligo-metastatic prostate cancer.Patients and MethodsA prospective, randomised, non-blinded, feasibility clinical trial with an embedded QuinteT Recruitment Intervention (QRI) to optimise recruitment was conducted in nine nationwide tertiary care centres undertaking high-volume robotic surgery. We aimed to randomise 50 men with synchronous oligo-metastatic prostate cancer within an 18-month recruitment period to SOC systemic therapy vs SOC plus RP (intervention arm). The main outcome measures were: ability to randomise patients, optimised by a QRI; EuroQoL five Dimensions five Levels (EQ-5D-5L) questionnaires to capture quality-of-life (QoL) data at baseline and 3 months post-randomisation; routine clinicopathological assessment to capture adverse events and prostate-specific antigen in both arms, plus standard perioperative parameters in the surgical arm.ResultsA total of 51 men were randomised within 14 months (one was subsequently deemed ineligible), with 60–83% accrual rate in centres that recruited at least two patients. All patients completed the trial follow-up; one patient in the intervention arm subsequently did not undergo the surgical intervention and one in the SOC arm refused all therapies. The QRI positively impacted recruitment. QoL data showed similarly high functioning in both study arms. Surgery for men with oligo-metastatic prostate cancer was found to be safe and had similar impact on early functional outcomes as surgery for standard indication.ConclusionIt is feasible to randomise men with synchronous oligo-metastatic prostate cancer to a surgical intervention in addition to standard systemic therapies. While surgery appeared safe with no substantial impact on QoL in this feasibility study, a large randomised controlled trial is now warranted to examine treatment effectiveness of this additional component in the multimodality management of oligo-metastatic prostate cancer.

Objectives To investigate whether patient-reported urinary incontinence and bother scores after radical prostatectomy result in subsequent intervention with incontinence surgery. Methods Men diagnosed with prostate cancer in the English National Health Service between April 2014 and January 2016 were identified. Administrative data were used to identify men who had undergone a radical prostatectomy and those who subsequently underwent a urinary incontinence procedure. The National Prostate Cancer Audit database was used to identify men who had also completed a post-treatment survey. These surveys included the Expanded Prostate Cancer Composite Index (EPIC-26). The frequency of subsequent incontinence procedures, within 6 months of the survey, was explored according to EPIC-26 urinary incontinence scores. The relationship between "good" (≥75) or "bad" (≤25) EPIC-26 urinary incontinence scores and perceptions of urinary bother was also explored (responses ranging from 'no problem' to 'big problem' with respect to their urinary function). Results We identified 11,290 men who had undergone a radical prostatectomy. The 3-year cumulative incidence of incontinence surgery was 2.5%. After exclusions, we identified 5,165 men who had also completed a post-treatment survey after a median time of 19 months (response rate 74%). 481 men (9.3%) reported a "bad" urinary incontinence score and 207 men (4.0%) also reported that they had a big problem with their urinary function. 47 men went on to have incontinence surgery within 6 months of survey completion (0.9%), of whom 93.6% had a "bad" urinary incontinence score. Of the 71 men with the worst urinary incontinence score (zero), only 11 men (15.5%) subsequently had incontinence surgery. Conclusion In England, there is a significant number of men living with severe, bothersome urinary incontinence following radical prostatectomy, and an unmet clinical need for incontinence surgery. The systematic collection of patient-reported outcomes could be used to identify men who may benefit from incontinence surgery.

Improvements in short-term outcomes have been reported for hospitals with higher radical prostatectomy (RP) volumes. However, the association with longer-term functional outcomes is unknown. All patients diagnosed with non-metastatic prostate cancer in the English NHS between 2014 and 2016 who underwent RP (N = 10,089) were mailed a survey ≥18 months after diagnosis. Differences in patient-reported urinary continence and sexual function (EPIC-26 on scale from 0 to 100) by hospital volume group (≤60, 61–100, 101–140, >140 RPs/year) were estimated using multilevel linear regression. Overall, 7702 men (76.3%) responded. There were no statistically significant differences in urinary continence (p = 0.08) or sexual function scores with increasing volume group (p = 0.2). When modelled as a linear function, we found a non-significant increase of 0.70 (95% CI −0.41 to 1.80; p = 0.22) in urinary continence and a significant increase of 1.54 (0.62–2.45; p = 0.001) in sexual function scores for a 100-procedure increase in hospital volume, which did not meet the threshold for a minimal clinically important difference (10–12 points). The results were similar for robotic-assisted RP (5529 men [71.8%]). These results do not support further centralisation of RP services beyond levels in England where four in five hospitals perform >60 RPs/year.

BACKGROUND: Many factors are implicated in the potential 'under-treatment' of prostate cancer but little is known about the between-hospital variation. METHODS: The National Prostate Cancer Audit (NPCA) database was used to identify high-risk localised or locally advanced prostate cancer patients in England, between January 2014 and December 2017, and the treatments received. Hospital-level variation in radical local treatment was explored visually using funnel plots. The intra-class correlation coefficient (ICC) quantified the between-hospital variation in a random-intercept multivariable logistic regression model. RESULTS: 53,888 men, from 128 hospitals, were included and 35,034 (65.0%) received radical local treatment. The likelihood of receiving radical local treatment was increased in men who were younger (the strongest predictor), more affluent, those with fewer comorbidities, and in those with a non-Black ethnic background. There was more between-hospital variation (P

Many factors are implicated in the potential ‘under-treatment’ of prostate cancer but little is known about the between-hospital variation. The National Prostate Cancer Audit (NPCA) database was used to identify high-risk localised or locally advanced prostate cancer patients in England, between January 2014 and December 2017, and the treatments received. Hospital-level variation in radical local treatment was explored visually using funnel plots. The intra-class correlation coefficient (ICC) quantified the between-hospital variation in a random-intercept multivariable logistic regression model. 53,888 men, from 128 hospitals, were included and 35,034 (65.0%) received radical local treatment. The likelihood of receiving radical local treatment was increased in men who were younger (the strongest predictor), more affluent, those with fewer comorbidities, and in those with a non-Black ethnic background. There was more between-hospital variation (P

INTRODUCTION AND OBJECTIVE:There is debate about the effectiveness and toxicity of pelvic lymph node (PLN) irradiation when used for disease recurrence following radical prostatectomy. This study c...

INTRODUCTION AND OBJECTIVE:No direct comparison has been made between England and the US with respect to the diagnosis and treatment of men with prostate cancer over one contemporary time period. W...

There are few data on the outcomes and toxicity of radical prostatectomy (RP) among men experiencing local recurrence of prostate cancer (PC) following focal therapy (FT). To characterise perioperative, oncological, and functional outcomes after salvage robot-assisted RP (S-RALP) and determine the risk factors for S-RALP failure, we conducted a multicentre cohort study of 82 patients undergoing S-RALP after FT. All had histological confirmation of PC recurrence, with metastatic disease excluded using pelvic magnetic resonance imaging, a bone scan, and/or positron emission tomography/computed tomography. Progression-free survival was 74%, 48%, and 36% at 12, 24, and 36mo after surgery, respectively. The 12-mo continence rate was 83%. There were no intraoperative complications and no major postoperative complications. On multivariable analysis, only infield recurrence (hazard ratio [HR] 3.77, 95% confidence interval [CI] 1.11-12.85; p=0.03) and pT3b stage (HR 5.0, 95% CI 1.53-16.39; p=0.008) were independent predictors of recurrence. This study represents the largest series of salvage surgery after FT and shows that this approach is safe with no increase in toxicity when compared to primary RALP. Men identified as having infield recurrence after FT appear to have phenotypically aggressive disease and should be counselled regarding the potential need for a multimodal therapeutic approach. PATIENT SUMMARY: Robotic surgery after focal therapy for prostate cancer is safe and achieves postoperative continence results similar to those for robotic radical prostatectomy in treatment-naïve patients. However, if the cancer recurrence is within the previously treated field, the oncological prognosis seems to be worse.

Background The National Prostate Cancer Audit (NPCA) reports publicly performance indicators for all hospitals in England and Wales providing radical prostate cancer treatment, identifying those with results that fall outside the ‘accepted range’ as ‘potential negative outliers’. Hospitals with outlying results are requested to provide a formal response. This ‘outlier process’, targeting a limited number of hospitals, mirrors a ‘high-risk approach’ of preventing poor quality care in contrast to a ‘population approach’ that would target all hospitals. We invited clinicians to a national workshop to learn how the outlier process contributes to quality improvement. Methods The workshop started with presentations on reducing the ‘toxicity’ of radical prostate cancer treatment. Then, clinicians from three hospitals identified as outliers shared their experience of the process and the changes in practice they had made as a result. We collected data in three ways. First, an online platform was used to gather comments from participants during the workshop. Second, a number of participants were interviewed about the outlier process as a means to improve quality of care. Third, feedback was sought after the workshop from all participants. Responses were collated and analysed for themes. Results Sixty-nine clinicians attended including urologists, oncologists, radiographers and nurses, representing a spread of hospitals across England and Wales. There were 6 interviews, 21 online comments and 31 responses after the workshop. The clinicians representing outlying hospitals highlighted the negative (stigma, work load, negative impact on reputation) and the positive impact (detailed review of procedures, implementation of targeted approaches) of the outlier process. Participants felt that sharing experiences of outlying hospitals helps others to improve. They also suggested a ‘buddy system’ between better and worse performing hospitals. Many highlighted the importance of ‘networks’ to share experiences, either good or bad, as a vehicle for improving practice. Discussion The outlier process was generally accepted as a possible mechanism to improve practice. However, participants indicated that effective dissemination is key to ensuring that identifying poor outcomes in some hospitals (e.g. high-risk approach) can stimulate country-wide quality improvement (population approach).

BackgroundContracting COVID-19 peri-operatively has been associated with a mortality rate as high as 23%, making prevention vital.ObjectivesThe primary objective is to determine safety of surgical admissions and procedures during the height of the COVID-19 pandemic using ‘hot’ and ‘cold’ sites. The secondary objective is to determine risk factors of contracting COVID-19.Design, Setting and ParticipantsA retrospective cohort study of all consecutive patients admitted from 1st March – 31st May 2020 at a high-volume tertiary urology department in London, United Kingdom. Elective surgery was carried out at a ‘cold’ site requiring a negative COVID-19 swab 72 hours prior to admission and to self-isolate for 14 days pre-operatively, whilst all acute admissions were admitted to the ‘hot’ site.Outcome Measurements and Statistical AnalysisComplications related to COVID-19 were presented as percentages. Risk factors for developing COVID-19 infection were determined using multivariate logistic regression analysis.Results and LimitationsA total of 611 patients, 451 (73.8%) male and 160 (26.2%) female, with a median age of 57 (interquartile range 44-70) were admitted under the urology team; 101 (16.5%) on the ‘cold’ site and 510 (83.5%) on the ‘hot’ site. Procedures were performed in 495 patients of which 8 (1.6%) contracted COVID-19 post-operatively with 1 (0.2%) post-operative mortality due to COVID-19. Overall, COVID-19 was detected in 20 (3.3%) patients with 2 (0.3%) deaths. Length of stay was associated with contracting COVID-19 in our cohort (OR 1.25, 95% CI 1.13-1.39). Limitations include possible under reporting due to post-operative patients presenting elsewhere.ConclusionsContinuation of surgical procedures using ‘hot’ and ‘cold’ sites throughout the COVID-19 pandemic was safe practice, although the risk of COVID-19 remained and is underlined by a post-operative mortality.Patient SummaryUsing ‘hot’ and ‘cold’ sites has allowed the safe continuation of urological practice throughout the height of the COVID-19 pandemic.

The COVID‐19 pandemic is impacting all urological cancer services. On March 19th the British Association of Urological Surgeons (BAUS) provided pragmatic guidance for prostate cancer diagnostic services (Table 1).(1)

INTRODUCTION AND OBJECTIVE:Use of freehand-guided transperineal prostate biopsy has allowed biopsies to be performed under local anesthesia (LA) or IV sedation (IVS) with less analgesia requirement...

Purpose Little is known about the toxicity of additional pelvic lymph node irradiation in men receiving intensity modulated radiation therapy (IMRT) for prostate cancer. The aim of this study was to compare patient-reported outcomes after IMRT to the prostate only (PO-IMRT) versus the prostate and pelvic lymph nodes (PPLN-IMRT). Methods and Materials Patients who received a diagnosis of high-risk or locally advanced prostate cancer in the English National Health Service between April 2014 and September 2016 who were treated with IMRT were mailed a questionnaire at least 18 months after diagnosis. Patient-reported urinary, sexual, bowel, and hormonal functional domains on a scale from 0 to 100, with higher scores indicating better outcomes, and generic health-related quality of life were collected using the Expanded Prostate Cancer Index Composite 26-item version and EQ-5D-5L. We used linear regression to compare PPLN-IMRT versus PO-IMRT with adjustment for patient, tumor, and treatment characteristics. Results Of the 7017 men who received a questionnaire, 5468 (77.9%) responded; 4196 (76.7%) had received PO-IMRT and 1272 (23.3%) PPLN-IMRT. Adjusted differences in the Expanded Prostate Cancer Index Composite 26-item version domain scores were smaller than 1 (P always >.2), except for sexual function, with men who had PPNL-IMRT reporting a lower mean score (adjusted difference, 2.3; 95% confidence interval, 0.9-3.7; P = .002). This did not represent a clinically relevant difference. There was no significant difference in health-related quality of life (P = .5). Conclusions Additional pelvic lymph node irradiation does not lead to clinically meaningful increases in the toxicity of IMRT for prostate cancer according to patient-reported functional outcomes and health-related quality of life.

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.

Background People with Diabetes Mellitus (DM) are at increased risk of postoperative complications if their HbA1C readings are not well controlled. In the UK, there are clear national guidelines requiring all people with DM to have HbA1C blood testing within 6months before undergoing surgery and that these readings should be below 69 mmol/mol if this is safe to achieve. The aim of this study was to determine whether hospitals in the region were compliant with the guidelines. Methods Data were prospectively collected from seven hospitals across the East of England region from 1st October 2017 to 31st March 2018 (6 months) in all people with DM undergoing elective day case procedures in General and Vascular surgery for benign disease. Results A total of 181 people with DM were included in the study, of whom 77.9% were male patients and the median age was 63 years. The three most commonly performed operations were laparoscopic cholecystectomy (20.9%, n = 38/181), inguinal hernia repair (20.4%, n = 37/181) and umbilical/para-umbilical hernia repair (11.0%, n = 20/181). In keeping with the national guidelines, only 86.7% (n = 157/181) of patients had an HbA1C tested within 6 months prior to their surgery date. Of the patients who had a preoperative HbA1C, 14 (n = 14/157, 8.9%) had an HbA1C ≥ 69 mmol/mol, and 12 (n = 12/14, 85.7%) of these proceeded to surgery without optimisation of their HbA1C. Conclusion A significant proportion of people with diabetes undergoing elective day case procedures in our region do not have HbA1C testing within 6 months of their procedure as recommended by the national guidelines. In patients who do have a high HbA1C, the majority still undergo surgery without adequate control of their DM. Greater awareness amongst healthcare workers and robust pathways are required for this vulnerable group of patients if we are to reduce the risk of developing postoperative complication rates.

Purpose To compare, in a national population-based study, severe genitourinary (GU) and gastrointestinal (GI) toxicity in patients with prostate cancer who were treated with radical intensity modulated radiation therapy (IMRT) or 3-dimensional conformal radiation therapy (3D-CRT). Methods and Materials Patients treated with IMRT (n=6933) or 3D-CRT (n=16,289) between January 1, 2010 and December 31, 2013 in the English National Health Service were identified using cancer registry data, the National Radiotherapy Dataset, and Hospital Episodes Statistics, the administrative database of care episodes in National Health Service hospitals. We developed a coding system that identifies severe toxicity (at least grade 3 according to the National Cancer Institute Common Terminology Criteria for Adverse Events scoring system) according to the presence of a procedure and a corresponding diagnostic code in patients' Hospital Episodes Statistics records after radiation therapy. A competing risks regression analysis was used to estimate hazard ratios (HRs), comparing the incidence of severe GI and GU complications after IMRT and 3D-CRT, adjusting for patient, disease, and treatment characteristics. Results The use of IMRT, as opposed to 3D-CRT, increased from 3.1% in 2010 to 64.7% in 2013. Patients who received IMRT were less likely than those receiving 3D-CRT to experience severe GI toxicity (4.9 vs 6.5 per 100 person-years; adjusted HR 0.66; 95% confidence interval 0.61-0.72) but had similar levels of GU toxicity (2.3 vs 2.4 per 100 person-years; adjusted HR 0.94; 95% confidence interval 0.84-1.06). Conclusions Prostate cancer patients who received radical radiation therapy using IMRT were less likely to experience severe GI toxicity, and they had similar GU toxicity compared with those who received 3D-CRT. These findings in an unselected “real-world” population support the use of IMRT, but further cost-effectiveness studies are urgently required.

Objectives Despite the rapid adoption of robot-assisted radical prostatectomy (RARP), there is little evidence about the occurrence of medium-term urinary complications with this type of surgery compared to laparoscopic (LRP) or retropubic open radical prostatectomy (ORP). The aim of this study was to evaluate the occurrence of severe urinary complications within two years of surgery in men undergoing RARP, LRP or ORP. Patients and Methods Population-based cohort study of men who underwent RARP (n=4,947), LRP (n= 5,479), or ORP (n=6,873) between 2008 and 2012 in the English National Health Service (NHS) using national cancer registry records linked to Hospital Episodes Statistics – an administrative database of admissions to NHS hospitals. We identified the occurrence of any severe urinary or severe stricture-related complication within two years of surgery using a validated tool. Multi-level regression modelling was used to determine the association between the type of surgery and occurrence of complications with adjustment for patient and surgical factors. Results Men undergoing RARP were least likely to experience any urinary complication (10.5%) or a stricture-related complication (3.3%) compared to those who had LRP (15.8% any or 5.7% stricture-related) or ORP (19.1% any or 6.9% stricture-related). The impact of the type of surgery on the occurrence of any urinary or stricture-related complications remained statistically significant with adjustment for patient and surgical factors (p < 0.01). Conclusion Men who underwent RARP have the lowest risk of developing severe urinary complications within two years of surgery. This article is protected by copyright. All rights reserved.

PURPOSE There is a debate about the effectiveness and toxicity of pelvic lymph node (PLN) irradiation for the treatment of men with high-risk prostate cancer. This study compared the toxicity of intensity-modulated radiation therapy (IMRT) to the prostate and the pelvic lymph nodes (PPLN-IMRT) with prostate-only IMRT (PO-IMRT). MATERIALS AND METHODS Patients with high-risk localized or locally advanced prostate cancer treated with IMRT in the English National Health Service between 2010 and 2013 were identified by using data from the Cancer Registry, the National Radiotherapy Dataset, and Hospital Episode Statistics, an administrative database of all hospital admissions. Follow-up was available up to December 31, 2015. Validated indicators were used to identify patients with severe toxicity according to the presence of both a procedure code and diagnostic code in patient Hospital Episode Statistics records. A competing risks regression analysis, with adjustment for patient and tumor characteristics, estimated subdistribution hazard ratios (sHRs) by comparing GI and genitourinary (GU) complications for PPLN-IMRT versus PO-IMRT. RESULTS Three-year cumulative incidence in the PPLN-IMRT (n = 780) and PO-IMRT (n = 3,065) groups was 14% for both groups for GI toxicity, and 9% and 8% for GU toxicity, respectively. Patients receiving PPLN-IMRT and PO-IMRT had similar levels of severe GI (adjusted sHR, 1.00; 95% CI, 0.80 to 1.24; P = .97) and GU (adjusted sHR, 1.10; 95% CI, 0.83 to 1.46; P = .50) toxicity rates. CONCLUSION Including PLNs in radiation fields for high-risk or locally advanced prostate cancer is not associated with increased GI or GU toxicity at 3 years. Additional follow-up is required to answer questions about its impact on late GU toxicity. Results from ongoing trials will provide insight into the anticancer effectiveness of PLN irradiation.