BACKGROUND:Wide-awake local anesthesia no tourniquet (WALANT) is increasingly used for flexor tendon repair, but comparative data versus general/regional anesthesia(GA/RA) are limited. The aims of the WAFER trial were to generate high quality comparative data on WALANT versus GA/RA for flexor tendon repair and assess the feasibility of performing a large multicenter trial of this nature. METHODS:WAFER was a multicenter, assessor-blinded, parallel-group RCT with embedded qualitative and health economic components across four major hand units. Patients were randomized on a 1:1 basis to have flexor tendon repair under GA/RA or WALANT. The primary feasibility outcomes were recruitment, retention and trial acceptability in addition to clinical outcomes which included range of motion (Total-active-motion score), grip/pinch strength, finger circumference, complications and patient reported outcome measures(PROMS) (Michigan-Hand-Questionnaire, EQ-5D-5L). Qualitative interviews were conducted with clinicians and participants to assess acceptability and equipoise. Economic analyses summarized intra-operative costs and impact on productivity. The primary analysis set was per-protocol. RESULTS:Sixty participants were randomized across all sites (30 WALANT; 30 GA/RA); 56 were analyzed per-protocol. At 6 months, mean TAM score(SE) for GA/RA was 67.6(5.6) vs 60.3(6.3) in the WALANT group. Tendon rupture was reported in two patients in the GA/RA group and three in the WALANT group. PROMs improved over time in both groups, patients in the WALANT arm reported consistently higher MHQ scores across domains. Participants in WALANT arm returned to work earlier than participants in GA/RA arm (mean 3.0 vs 6.7weeks). Intra-operative costs were lower with WALANT by 54% (-£398, 95% CI -£509 to -£287). CONCLUSIONS:A pragmatic comparison of WALANT versus GA/RA with tourniquet for primary flexor tendon repair is deliverable and safe. Inter-arm clinical differences were small; however, WALANT showed lower intra-operative costs and a signal for earlier return to work.

In many breast cancer radiotherapy trials, the results are presented in the form of cumulative incidence rates of local recurrence or Kaplan-Meier plots, in which deaths are censored. Censoring - using patients' length of follow up until the point when they had last been seen alive - is included in the statistical model, under the correct assumption that they will continue to have a risk of developing a local recurrence. Censoring should be non-informative and balanced. However, if shorter follow up is unbalanced between treatments, or if shorter follow up is due to death (from whatever cause), these assumptions and therefore the model is no longer valid. It is therefore ambiguous to statistically ignore deaths when reporting local recurrence, by censoring them. We illustrate, with examples from randomised trials, why and how such graphs cannot give patients and clinicians a clear indication of the effects of treatments or prognosis. For instance, in one of these examples, 60% of patients were alive at 10 years, so those alive without a local recurrence should inevitably be lower than 60%, rather than the 90% estimated using the above method. The simple way to avoid this error is to turn the analysis on its head, by reporting chances of success rather than failure, by reporting the probability of being free of local recurrence (i.e. both death and local recurrence are events). This estimate truly represents what really happens to patients in terms of local control and the relative effectiveness of treatment(s) comprehensively. It also conforms with the recommendations of ICH-GCP, European (DATECAN) and American (STEEP) guidelines.

BACKGROUND:Sparing the periprostatic neurovascular bundles during robot-assisted radical prostatectomy (RARP) improves postoperative erectile function and early urinary continence recovery. The NeuroSAFE technique, a standardised frozen section analysis, enables accurate real-time detection of positive surgical margins during nerve-sparing, increasing the likelihood of successful nerve preservation. However, the impact of the technique on patient outcomes remains uncertain. We aimed to assess the effect of NeuroSAFE-guided RARP versus standard RARP on erectile function and urinary continence. METHODS:NeuroSAFE PROOF was a multicentre, patient-blinded, randomised, controlled phase 3 trial done at five National Health Service hospitals in the UK. Key eligibility criteria were a diagnosis of non-metastatic prostate cancer deemed suitable to undergo RARP, good erectile function (defined as a score of ≥22 on the first 5 items of the International Index of Erectile Function [IIEF]) without medical erectile function assistance, and no previous prostate cancer treatment. No age limits were applied. Participants were randomly assigned (1:1) to standard RARP or NeuroSAFE-guided RARP using block randomisation, stratified by site. Masking of participants to allocation was maintained throughout, but patients were informed of their nerve-sparing status after the operation. Due to the nature of the intervention, operating teams were aware of treatment group. Nerve-sparing was guided by a preoperative plan in the standard RARP group and by intraoperative NeuroSAFE assessment in the NeuroSAFE group. The primary outcome was erectile function at 12 months, assessed using the IIEF-5 score, in the modified intention-to-treat population, which included all randomly assigned participants who had surgery. Secondary endpoints were urinary continence scores at 3 and 6 months, evaluated using the International Consultation on Incontinence Questionnaire (ICIQ), and the erectile function domain of the IIEF (IIEF-6) scores at 12 months. The trial is registered at ClinicalTrials.gov, NCT03317990. FINDINGS:Between Jan 6, 2019, and Dec 6, 2022, 407 patients were recruited, of whom 381 had surgery (190 participants in the NeuroSAFE group and 191 participants in the standard RARP group), and were included in the modified intention-to-treat population. Data for the primary outcome (IIEF-5 score at 12 months) were available for 344 participants (173 in the NeuroSAFE group and 171 participants in the standard RARP group). Median follow-up was 12·3 months (IQR 11·8-12·7). At 12 months, the mean IIEF-5 score was 12·7 (SD 8·0) in the NeuroSAFE group versus 9·7 (7·5) in the standard RARP group (adjusted mean difference 3·18 [95% CI 1·62 to 4·75]; p<0·0001). At 3 months, the ICIQ score was significantly lower in the NeuroSAFE group than the standard RARP group (adjusted mean difference -1·41 [95% CI -2·42 to -0·41]; p=0·006). At 6 months, no significant difference in ICIQ score was observed between groups (adjusted mean difference -0·37 [95% CI -1·35 to 0·62]; p=0·46). At 12 months, the mean IIEF-6 score was higher in the NeuroSAFE group than in the standard RARP group (15·3 [SD 9·7] vs 11·5 [SD 9·0]; adjusted mean difference 3·92 [95% CI 2·01 to 5·83]; p<0·0001). Serious adverse events occurred in six (3%) of 190 patients in the NeuroSAFE group, and and in five (3%) of 191 patients in the standard RARP group. All adverse events were postoperative complications; no serious adverse events or deaths were attributed to the study intervention. INTERPRETATION:The use of NeuroSAFE to guide nerve-sparing during RARP improves patient-reported IIEF-5 scores at 12 months and short-term urinary continence. The erectile function benefit is enhanced in patients who would not otherwise have undergone bilateral nerve-sparing by standard practice. FUNDING:National Institute of Healthcare Research, JP Moulton Charitable Foundation, UCLH Charity, St Peters Trust, and Rosetrees Trust.

INTRODUCTION:Children having surgery, and their parents, commonly have anxiety in the preoperative period, and this may impact longer-term health and quality of life. Psychological preparation can be expensive and time-consuming, and the type and effectiveness of preparatory interventions are variable. The aim of this randomised controlled trial (RCT) is to evaluate the clinical effectiveness of a preoperative smartphone psychological preparation application with virtual reality (VR) capability (the 'Little Journey app' (LJ)), at reducing anxiety and its sequelae in children and their carers. METHODS AND ANALYSIS:Multicentre, assessor-blinded, two-armed, parallel group, RCT in children aged between 3 and 12 years, undergoing ambulatory surgery and receiving their first general anaesthetic. Randomisation is one-to-one between an intervention and a control arm. Participants in the intervention arm are provided with access to the LJ app and a low-cost cardboard VR headset (to be used with a smartphone) to use in the weeks leading up to their operation. Children in the control arm receive the same VR headset and suggestions of unrelated VR games to play, but no access to the LJ app. To improve accessibility, smart devices are provided to children whose families do not have a smart phone, and the app content has been translated from English into multiple languages. Both groups receive standard perioperative care at the hospital where they are having treatment. The primary outcome measure is the modified Yale Preoperative Anxiety Scale-Short Form applied by independent blinded observers, immediately before induction of general anaesthesia. Secondary outcomes include process measures, psychological and socioeconomic outcomes for both children and parents/carers. The planned sample size was 304 participants, including an anticipated 15% attrition rate. An interim analysis was conducted when the trial was temporarily paused because of the COVID-19 pandemic, at which point 119 participants had been recruited. The trial steering committee and data monitoring committee recommended continuation of the trial, but the sample size was increased to 596 to account for differences between the previously anticipated and actual outcomes of recruited participants. ETHICS AND DISSEMINATION:The study was approved by Surrey Borders-Research Ethics Committee 251219, and all participating sites were in England. Results will be presented in academic manuscripts and presentations and summarised for diverse audiences (including clinicians and patients/public) in podcasts, infographics and other multimedia formats. TRIAL REGISTRATION NUMBER:NCT03797716.

Beta-blockers, originally developed for cardiovascular conditions, have been explored for their potential role in cancer treatment. Propranolol, a non-selective beta-blocker, has shown promise in inhibiting stress-induced signalling pathways associated with cancer progression. This systematic review aims to assess the evidence for the repurposing of propranolol as a treatment for various cancers, particularly breast cancer to answer the research question: Does propranolol improve cancer outcomes, including survival and recurrence? We conducted a systematic search of MEDLINE, EMBASE, Global Health, Web of Science, and the Cochrane Library, including studies up to July 2024. Randomised Controlled Trials (RCTs), systematic reviews, and meta-analyses were included if they assessed the effects of propranolol on cancer outcomes such as mortality, survival, recurrence, or biomarkers of tumour regression. A narrative synthesis was performed to summarise the findings. Thirty-one studies were included, consisting of 7 RCTs, 4 systematic reviews and 20 meta-analyses. The evidence suggests that propranolol may improve cancer outcomes, especially when administered perioperatively, by reducing recurrence risk. However, the results remain inconclusive regarding its use in combination with chemotherapy or radiotherapy, as studies showed mixed results. The timing of propranolol administration, alongside its combination with other cancer therapies, appears to be a key factor in its effectiveness. Propranolol has potential as an adjunctive therapy in cancer treatment, particularly in reducing recurrence risk during the perioperative period. However, further clinical trials are needed to better define its role in cancer therapy, particularly regarding optimal treatment regimens and patient populations.

BACKGROUND:Penile cancer is a rare male genital malignancy. Surgical excision of the primary tumour is followed by radical inguinal lymphadenectomy if there is metastatic disease detected by biopsy, fine needle aspiration cytology (FNAC) or following sentinel lymph node biopsy in patients with impalpable disease. However, radical inguinal lymphadenectomy is associated with a high morbidity rate, and there is increasing usage of a videoendoscopic approach as an alternative.METHODS:A pragmatic, UK-wide multicentre feasibility randomised controlled trial (RCT), comparing videoendoscopic radical inguinal lymphadenectomy versus open radical inguinal lymphadenectomy. Patients will be identified and recruited from supraregional multi-disciplinary team meetings (sMDT) and must be aged 18 or over requiring inguinal lymphadenectomy, with no contraindications to surgical intervention for their cancer. Participants will be followed up for 6 months following randomisation. The primary outcome is the ability to recruit patients for randomisation across all selected sites and the rate of loss to follow-up. Other outcomes include acceptability of the trial and intervention to patients and healthcare professionals assessed by qualitative research and obtaining resource utilisation information for health economic analysis.DISCUSSION:There are currently no other published RCTs comparing videoendoscopic versus open radical inguinal lymphadenectomy. Ongoing study is required to determine whether randomising patients to either procedure is feasible and acceptable to patients. The results of this study may determine the design of a subsequent trial.TRIAL REGISTRATION:Clinicaltrials.gov PRS registry, registration number NCT05592639. Date of registration: 13th October 2022, retrospectively registered.

OBJECTIVES:To understand the facilitators and barriers to the implementation of renal tumour biopsy (RTB) in the diagnostic pathway for renal tumours in England. PATIENTS AND METHODS:Participants consisted of patients who had a renal tumour diagnosed and/or treated at one of five tertiary centres in England, healthcare professionals involved in the direct care of patients diagnosed with renal tumours, and clinical service managers and commissioners. The study employed a mixed-methods research methodology consisting of individual interviews and an on-line survey that explored the types of facilitators and barriers individuals perceived and experienced and the frequency in which these were reported. A public dissemination event took place following the completion of data collection; to facilitate discussion of potential solutions to implementing RTB. RESULTS:There were 50 participant interviews (23 patients, 22 clinicians, and five health service commissioners/operations managers). The patient on-line survey received 52 responses, and the clinician survey received 22 responses. Patients most frequently reported influences in choosing whether to undergo RTB pertained to wanting to know the diagnosis of their kidney mass (40%), the advice or information provided by healthcare professionals (40%), and not wishing to delay treatment (23%). Clinicians most frequently reported barriers to recommending RTB related to their uncertainty of diagnostic accuracy (56%), availability of appointments or hospital beds (52%), concerns of risk of bleeding (44%), risk of seeding (41%), and delays in meeting national cancer pathway targets (41%). The dissemination event was attended by 18 participants (seven patients and 11 clinicians). Suggestions to improve implementation included reducing variation and promotion of standardisation of practice by a consensus statement, increasing the evidence base (clinicians) and improved communication by developing better patient aids such as videos and diagrams (patients and clinicians). CONCLUSION:Implementation of RTB may be dependent on the quality of information provided, its format and perceived reliability of the information. Increased utilisation of RTB may be improved by development of a consensus statement on the role of biopsy, with patients expressing a preference for alternative information aids such as patient videos.

BACKGROUND:Grade 4 astrocytomas are usually incurable due to their diffusely infiltrative nature. Photodynamic therapy (PDT) is a promising therapeutic option, but external light delivery is impractical when cancer cells infiltrate unknown areas of normal brain. Hence the search for endogenous sources to generate light at cancer cells. In vitro, astrocytoma cells, transfected with firefly luciferase, can be killed by bioluminescence-mediated PDT (bPDT). This study asks if bPDT can suppress tumour growth In vivo, when all components of treatment are administered systemically.METHODS:Transfected astrocytoma cells were injected subcutaneously or intra-cranially in athymic CD1 nu/nu mice. bPDT required ip bolus of mTHPC (photosensitiser) and delivery of the d-luciferin substrate over 7 days via an implanted osmotic pump. Control animals had no treatment, photosensitiser only or d-luciferin only. For subcutaneous tumours, size and BLI (light emitted after d-luciferin bolus) were measured before and every 2 days after PDT. For intracranial tumours, monitoring was weekly BLI.RESULTS:For subcutaneous tumours, there was significant suppression of the tumour growth rate (P<0.05), and absolute tumour size (P<0.01) after bPDT. Proliferation of subcutaneous and intracranial tumours (monitored by BrdU uptake) was significantly reduced in treated mice. (P<0.001) CONCLUSIONS: This study reports bPDT suppression of tumour growth from luciferase transfected astrocytoma cells with all components of treatment given systemically, as required for effective management of recurrent astrocytomas in unknown sites. However, research on systemic bPDT is needed to establish whether effects on non-transfected tumours can be achieved without any unacceptable effects on normal tissues.

You have accessJournal of UrologySurgical Technology & Simulation: Artificial Intelligence III (PD36)1 May 2024PD36-04 REMOTE DIGITAL SURVEILLANCE AND MACHINE LEARNING MODELLING TO PREDICT SURVIVAL FOLLOWING RADICAL CYSTECTOMY FOR BLADDER CANCER—A SECONDARY OUTCOME ANALYSIS OF THE IROC TRIAL Pramit Khetrapal, Yansong Liu, Gareth Ambler, Norman R. Williams, Ashwin Sridhar, Muhammad Shamim Khan, Imran Ahmad, Philip Charlesworth, Sanjeev Kotwal, Edward Rowe, Vishwanath Hanchanale, John McGrath, Nikhil Vasdev, Yukun Zhou, James W. F. Catto, Drobnjak Ivana, and John D. Kelly Pramit KhetrapalPramit Khetrapal , Yansong LiuYansong Liu , Gareth AmblerGareth Ambler , Norman R. WilliamsNorman R. Williams , Ashwin SridharAshwin Sridhar , Muhammad Shamim KhanMuhammad Shamim Khan , Imran AhmadImran Ahmad , Philip CharlesworthPhilip Charlesworth , Sanjeev KotwalSanjeev Kotwal , Edward RoweEdward Rowe , Vishwanath HanchanaleVishwanath Hanchanale , John McGrathJohn McGrath , Nikhil VasdevNikhil Vasdev , Yukun ZhouYukun Zhou , James W. F. CattoJames W. F. Catto , Drobnjak IvanaDrobnjak Ivana , and John D. KellyJohn D. Kelly View All Author Informationhttps://doi.org/10.1097/01.JU.0001008916.72488.6a.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Wearable devices allow for measurement of physical activity, potentially providing supplementary prognostic insights for predicting survival following radical cystectomy (RC), alongside commonly used conventional clinicopathological factors. The primary objective of this analysis is to assess the additional value of wearable device monitoring to pathological data in predicting survival. METHODS: The iROC randomised trial (NCT03049410) compared peri-operative recovery after intracorporeal robot-assisted RC (iRARC) vs open RC (ORC) for bladder cancer. Step-count data was collected using wrist-worn wearable devices, and maximum steps and average steps per day was calculated at baseline and 12 weeks post-RC. Stamina was measured using the 30 second chair-to-stand test at similar timepoints. Clinicopathological data and survival data was collected, and cross-sectional imaging was used to determine cancer recurrence. RESULTS: Among 338 patients in the iROC trial, 319 patients received RC. Overall survival following RC was 87% (319-41/319) patients and RFS was 82% (319-57/319) over a median follow-up of 33 months. Wearable device data was available for 165 patients for analysis. There was no significant reduction in maximum step-counts at baseline (mean 9388 , SD 4552) when compared with 3-months post-operatively (mean 8792, SD 4055). Using clinicopathological features including age, gender, BMI, pathological T-stage and surgical margin, we demonstrated an AUC of 74% to predict RFS which improved slightly to 76% on adding activity and stamina data. For prediction of OS, using clinicopathological features demonstrated an AUC of 71%, which improved to 81% with the addition of activity and stamina data. Kaplan Meier analysis with patients divided into low and high risk groups by the final model showed an increased PFS (99% vs 59%) and OS (98% vs 53%) in 33 months after surgery. CONCLUSIONS: Mobility data may offer information which could add value to traditional prognostic models for survival. With new wearable devices, activity data can be remotely collected alongside other biometric data such as heart rate which may further improve models to predict RFS and OS. Download PPT Source of Funding: The Urology Foundation and The Champniss Foundation © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e793 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Pramit Khetrapal More articles by this author Yansong Liu More articles by this author Gareth Ambler More articles by this author Norman R. Williams More articles by this author Ashwin Sridhar More articles by this author Muhammad Shamim Khan More articles by this author Imran Ahmad More articles by this author Philip Charlesworth More articles by this author Sanjeev Kotwal More articles by this author Edward Rowe More articles by this author Vishwanath Hanchanale More articles by this author John McGrath More articles by this author Nikhil Vasdev More articles by this author Yukun Zhou More articles by this author James W. F. Catto More articles by this author Drobnjak Ivana More articles by this author John D. Kelly More articles by this author Expand All Advertisement PDF downloadLoading ...

Background The grim (<10% 5-year) survival rates for pancreatic ductal adenocarcinoma (PDAC) are attributed to its complex intrinsic biology and most often late-stage detection. The overlap of symptoms with benign gastrointestinal conditions in early stage further complicates timely detection. The suboptimal diagnostic performance of carbohydrate antigen (CA) 19-9 and elevation in benign hyperbilirubinaemia undermine its reliability, leaving a notable absence of accurate diagnostic biomarkers. Using a selected patient cohort with benign pancreatic and biliary tract conditions we aimed to develop a data analysis protocol leading to a biomarker signature capable of distinguishing patients with non-specific yet concerning clinical presentations, from those with PDAC. Methods 539 patient serum samples collected under the Accelerated Diagnosis of neuro Endocrine and Pancreatic TumourS (ADEPTS) study (benign disease controls and PDACs) and the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS, healthy controls) were screened using the Olink Oncology II panel, supplemented with five in-house markers. 16 specialized base-learner classifiers were stacked to select and enhance biomarker performances and robustness in blinded samples. Each base-learner was constructed through cross-validation and recursive feature elimination in a discovery set comprising approximately two thirds of the ADEPTS and UKCTOCS samples and contrasted specific diagnosis with PDAC. Results The signature which was developed using diagnosis-specific ensemble learning demonstrated predictive capabilities outperforming CA19-9, the only biomarker currently accepted by the FDA and the National Comprehensive Cancer Network guidelines for pancreatic cancer, and other individual biomarkers and combinations in both discovery and held-out validation sets. An AUC of 0.98 (95% CI 0.98-0.99) and sensitivity of 0.99 (95% CI 0.98-1) at 90% specificity was achieved with the ensemble method, which was significantly larger than the AUC of 0.79 (95% CI 0.66-0.91) and sensitivity 0.67 (95% CI 0.50-0.83), also at 90% specificity, for CA19-9, in the discovery set (p = 0.0016 and p = 0.00050, respectively). During ensemble signature validation in the held-out set, an AUC of 0.95 (95% CI 0.91-0.99), sensitivity 0.86 (95% CI 0.68-1), was attained compared to an AUC of 0.80 (95% CI 0.66-0.93), sensitivity 0.65 (95% CI 0.48-0.56) at 90% specificity for CA19-9 alone (p = 0.0082 and p = 0.024, respectively). When validated only on the benign disease controls and PDACs collected from ADEPTS, the diagnostic-specific signature achieved an AUC of 0.96 (95% CI 0.92-0.99), sensitivity 0.82 (95% CI 0.64-0.95) at 90% specificity, which was still significantly higher than the performance for CA19-9 taken as a single predictor, AUC of 0.79 (95% CI 0.64-0.93) and sensitivity of 0.18 (95% CI 0.03-0.69) (p = 0.013 and p = 0.0055, respectively). Conclusion Our ensemble modelling technique outperformed CA19-9, individual biomarkers and indices developed with prevailing algorithms in distinguishing patients with non-specific but concerning symptoms from those with PDAC, with implications for improving its early detection in individuals at risk.

Introduction RECONCILE (ClinicalTrials.gov:NCT04340245) will identify molecular and radiomic markers associated with clinical progression and radiological progression events in a cohort of localised, newly diagnosed Gleason 3 + 4 tumours. Molecular markers will be correlated against standard of care MRI-targeted histology and oncological outcomes. Methods RECONCILE is an ethics approved (20/LO/0366) single centre, prospective, longitudinal, observational cohort study of recently diagnosed (within 12 months), organ-confined Gleason 3 + 4 cancers (MCCL ≤10mm) currently under active surveillance. 60 treatment-naïve participants with a concordant MRI lesion (Likert score 4 or 5) and PSA ≤ 15 ng/ml will be recruited. Blood, urine and targeted prostate tissue cores will be subject to next generation sequencing at baseline and one year in all participants. Semen will be collected from a specified sub-population. Baseline and interval MR images will be extracted from standard of care prostate MRI ahead of radiomic analysis. Data extracted from radiological and biological samples will be used to derive the association of molecular change and radiological progression, the primary outcome of the study. To compensate for spatial intratumoral heterogeneity and inherent sampling bias, a molecular index will be derived for each participant using the molecular profile of tumour tissue at both baseline (MolBL) and one year (MolFU). We will extract a ΔMolBL:MolFU score for each participant. Molecular progression will be defined as a MolBL:MolFU score >95% CI of the combined ΔMolBL scores. Radiological progression is defined as a PRECISE score of 4 or 5. The study is powered to detect an association with a statistical power of 80%. Results Recruitment began in July 2020 (n = 62). To date, 37 participants have donated tissue for analysis. Conclusion We have designed and implemented a prospective, longitudinal study to evaluate the underlying molecular landscape of intermediate risk, MR-visible prostate tumours. Recruitment is ongoing.

Background: Efforts to improve recovery after radical cystectomy (RC) are needed. Objective: To investigate wrist-worn wearable activity trackers in RC participants. Design, setting, and participants: An observational cohort study was conducted within the iROC randomised trial. Intervention: Patients undergoing RC at nine cancer centres wore wrist-based trackers for 7 days (d) at intervals before and after surgery. Outcome measurements and statistical analysis: Step counts were compared with participant and operative features, and recovery outcomes. Results and limitations: Of 308 participants, 284 (92.2%) returned digital activity data at baseline (median 17 d [interquartile range: 8-32] before RC), and postoperatively (5 [5- 6] d) and at weeks 5 (43 [38-43] d), 12 (94 [87-106] d), and 26 (192 [181-205] d) after RC. Compliance was affected by the time from surgery and a coronavirus disease 2019 pandemic lockdown (return rates fell to 0-7%, chi-square p < 0.001). Step counts dropped after surgery (mean of 28% of baseline), before recovering at 5 weeks (wk) (71% of baseline) and 12 wk (95% of baseline; all analysis of variance [ANOVA] p < 0.001). Baseline step counts were not associated with postoperative recovery or death. Patients with extended hospital stays had reduced postoperative step counts, with a difference of 2.2 d (95% confidence interval: 0.856-3.482 d) between the lowest third and highest two-third tertiles (linear regression analysis; p < 0.001). Additionally, they spent less time out of the hospital within 90 d of RC (80.3 vs 74.3 d, p = 0.013). Lower step counts at 5, 12, and 26 wk were seen in those seeking medical help and needing readmission (ANOVA p <= 0.002). Conclusions: Baseline step counts were not associated with recovery. Lower postoperative step counts were associated with longer length of stay at the hospital and postdischarge readmissions. Studies are required to determine whether low step counts can identify patients at a risk of developing complications.

BACKGROUND:The role of multiparametric magnetic resonance imaging (MRI) for detecting recurrent prostate cancer after radiotherapy is unclear. OBJECTIVE:To evaluate MRI and MRI-targeted biopsies for detecting intraprostatic cancer recurrence and planning for salvage focal ablation. DESIGN, SETTING, AND PARTICIPANTS:FOcal RECurrent Assessment and Salvage Treatment (FORECAST; NCT01883128) was a prospective cohort diagnostic study that recruited 181 patients with suspected radiorecurrence at six UK centres (2014 to 2018); 144 were included here. INTERVENTION:All patients underwent MRI with 5 mm transperineal template mapping biopsies; 84 had additional MRI-targeted biopsies. MRI scans with Likert scores of 3 to 5 were deemed suspicious. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:First, the diagnostic accuracy of MRI was calculated. Second, the pathological characteristics of MRI-detected and MRI-undetected tumours were compared using the Wilcoxon rank sum test and chi-square test for trend. Third, four biopsy strategies involving an MRI-targeted biopsy alone and with systematic biopsies of one to two other quadrants were studied. Fisher's exact test was used to compare MRI-targeted biopsy alone with the best other strategy for the number of patients with missed cancer and the number of patients with cancer harbouring additional tumours in unsampled quadrants. Analyses focused primarily on detecting cancer of any grade or length. Last, eligibility for focal therapy was evaluated for men with localised (≤T3bN0M0) radiorecurrent disease. RESULTS AND LIMITATIONS:Of 144 patients, 111 (77%) had cancer detected on biopsy. MRI sensitivity and specificity at the patient level were 0.95 (95% confidence interval [CI] 0.92 to 0.99) and 0.21 (95% CI 0.07 to 0.35), respectively. At the prostate quadrant level, 258/576 (45%) quadrants had cancer detected on biopsy. Sensitivity and specificity were 0.66 (95% CI 0.59 to 0.73) and 0.54 (95% CI 0.46 to 0.62), respectively. At the quadrant level, compared with MRI-undetected tumours, MRI-detected tumours had longer maximum cancer core length (median difference 3 mm [7 vs 4 mm]; 95% CI 1 to 4 mm, p < 0.001) and a higher grade group (p = 0.002). Of the 84 men who also underwent an MRI-targeted biopsy, 73 (87%) had recurrent cancer diagnosed. Performing an MRI-targeted biopsy alone missed cancer in 5/73 patients (7%; 95% CI 3 to 15%); with additional systematic sampling of the other ipsilateral and contralateral posterior quadrants (strategy 4), 2/73 patients (3%; 95% CI 0 to 10%) would have had cancer missed (difference 4%; 95% CI -3 to 11%, p = 0.4). If an MRI-targeted biopsy alone was performed, 43/73 (59%; 95% CI 47 to 69%) patients with cancer would have harboured undetected additional tumours in unsampled quadrants. This reduced but only to 7/73 patients (10%; 95% CI 4 to 19%) with strategy 4 (difference 49%; 95% CI 36 to 62%, p < 0.0001). Of 73 patients, 43 (59%; 95% CI 47 to 69%) had localised radiorecurrent cancer suitable for a form of focal ablation. CONCLUSIONS:For patients with recurrent prostate cancer after radiotherapy, MRI and MRI-targeted biopsy, with or without perilesional sampling, will diagnose cancer in the majority where present. MRI-undetected cancers, defined as Likert scores of 1 to 2, were found to be smaller and of lower grade. However, if salvage focal ablation is planned, an MRI-targeted biopsy alone is insufficient for prostate mapping; approximately three of five patients with recurrent cancer found on an MRI-targeted biopsy alone harboured further tumours in unsampled quadrants. Systematic sampling of the whole gland should be considered in addition to an MRI-targeted biopsy to capture both MRI-detected and MRI-undetected disease. PATIENT SUMMARY:After radiotherapy, magnetic resonance imaging (MRI) is accurate for detecting recurrent prostate cancer, with missed cancer being smaller and of lower grade. Targeting a biopsy to suspicious areas on MRI results in a diagnosis of cancer in most patients. However, for every five men who have recurrent cancer, this targeted approach would miss cancers elsewhere in the prostate in three of these men. If further focal treatment of the prostate is planned, random biopsies covering the whole prostate in addition to targeted biopsies should be considered so that tumours are not missed.

There is a paucity of high-level evidence on small renal mass (SRM) management, as previous classical randomised controlled trials (RCTs) failed to meet accrual targets. Our objective was to assess the feasibility of recruitment to a cohort-embedded RCT comparing cryoablation (CRA) to robotic partial nephrectomy (RPN). A total of 200 participants were recruited to the cohort, of whom 50 were enrolled in the RCT. In the CRA intervention arm, 84% consented (95% confidence interval [CI] 64-95%) and 76% (95% CI 55-91%) received CRA; 100% (95% CI 86-100%) of the control arm underwent RPN. The retention rate was 90% (95% CI 79-96%) at 6 mo. In the RPN group 2/25 (8%) were converted intra-operative to radical nephrectomy. Postoperative complications (Clavien-Dindo grade 1-2) occurred in 12% of the CRA group and 29% of the RPN group. The median length of hospital stay was shorter for CRA (1 vs 2 d; p = 0.019). At 6 mo, the mean change in renal function was -5.0 ml/min/1.73 m2 after CRA and -5.8 ml/min/1.73 m2 after RPN. This study demonstrates the feasibility of a cohort-embedded RCT comparing CRA and RPN. These data can be used to inform multicentre trials on SRM management. PATIENT SUMMARY: We assessed whether patients with a small kidney tumour would consent to a trial comparing two different treatments: cryoablation (passing small needles through the skin to freeze the kidney tumour) and surgery to remove part of the kidney. We found that most patients agreed and a full trial would therefore be feasible.

ImportanceThe value to payers of robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) when compared with open radical cystectomy (ORC) for patients with bladder cancer is unclear.ObjectivesTo compare the cost-effectiveness of iRARC with that of ORC.Design, Setting, and ParticipantsThis economic evaluation used individual patient data from a randomized clinical trial at 9 surgical centers in the United Kingdom. Patients with nonmetastatic bladder cancer were recruited from March 20, 2017, to January 29, 2020. The analysis used a health service perspective and a 90-day time horizon, with supplementary analyses exploring patient benefits up to 1 year. Deterministic and probabilistic sensitivity analyses were undertaken. Data were analyzed from January 13, 2022, to March 10, 2023.InterventionsPatients were randomized to receive either iRARC (n = 169) or ORC (n = 169).Main Outcomes and MeasuresCosts of surgery were calculated using surgery timings and equipment costs, with other hospital data based on counts of activity. Quality-adjusted life-years were calculated from European Quality of Life 5-Dimension 5-Level instrument responses. Prespecified subgroup analyses were undertaken based on patient characteristics and type of diversion.ResultsA total of 305 patients with available outcome data were included in the analysis, with a mean (SD) age of 68.3 (8.1) years, and of whom 241 (79.0%) were men. Robot-assisted radical cystectomy was associated with statistically significant reductions in admissions to intensive therapy (6.35% [95% CI, 0.42%-12.28%]), and readmissions to hospital (14.56% [95% CI, 5.00%-24.11%]), but increases in theater time (31.35 [95% CI, 13.67-49.02] minutes). The additional cost of iRARC per patient was £1124 (95% CI, −£576 to £2824 [US $1622 (95% CI, −$831 to $4075)]) with an associated gain in quality-adjusted life-years of 0.01124 (95% CI, 0.00391-0.01857). The incremental cost-effectiveness ratio was £100 008 (US $144 312) per quality-adjusted life-year gained. Robot-assisted radical cystectomy had a much higher probability of being cost-effective for subgroups defined by age, tumor stage, and performance status.Conclusions and RelevanceIn this economic evaluation of surgery for patients with bladder cancer, iRARC reduced short-term morbidity and some associated costs. While the resulting cost-effectiveness ratio was in excess of thresholds used by many publicly funded health systems, patient subgroups were identified for which iRARC had a high probability of being cost-effective.Trial RegistrationClinicalTrials.gov Identifier: NCT03049410

IntroductionTriple negative breast cancer (TNBC) is a subtype of breast cancer characterised by its high tumourigenic, invasive, and immunosuppressive nature. Photodynamic therapy (PDT) is a focal therapy that uses light to activate a photosensitizing agent and induce a cytotoxic effect. 5-aza-2’-deoxycytidine (5-ADC) is a clinically approved immunomodulatory chemotherapy agent. The mechanism of the combination therapy using PDT and 5-ADC in evoking an anti-tumour response is not fully understood.MethodsThe present study examined whether a single dose of 5-ADC enhances the cytotoxic and anti-tumour immune effect of low dose PDT with verteporfin as the photosensitiser in a TNBC orthotopic syngeneic murine model, using the triple negative murine mammary tumour cell line 4T1. Histopathology analysis, digital pathology and immunohistochemistry of treated tumours and distant sites were assessed. Flow cytometry of splenic and breast tissue was used to identify T cell populations. Bioinformatics were used to identify tumour immune microenvironments related to TNBC patients.ResultsFunctional experiments showed that PDT was most effective when used in combination with 5-ADC to optimize its efficacy. 5-ADC/PDT combination therapy elicited a synergistic effect in vitro and was significantly more cytotoxic than monotherapies on 4T1 tumour cells. For tumour therapy, all types of treatments demonstrated histopathologically defined margins of necrosis, increased T cell expression in the spleen with absence of metastases or distant tissue destruction. Flow cytometry and digital pathology results showed significant increases in CD8 expressing cells with all treatments, whereas only the 5-ADC/PDT combination therapy showed increase in CD4 expression. Bioinformatics analysis of in silico publicly available TNBC data identified BCL3 and BCL2 as well as the following anti-tumour immune response biomarkers as significantly altered in TNBC compared to other breast cancer subtypes: GZMA, PRF1, CXCL1, CCL2, CCL4, and CCL5. Interestingly, molecular biomarker assays showed increase in anti-tumour response genes after treatment. The results showed concomitant increase in BCL3, with decrease in BCL2 expression in TNBC treatment. In addition, the treatments showed decrease in PRF1, CCL2, CCL4, and CCL5 genes with 5-ADC and 5-ADC/PDT treatment in both spleen and breast tissue, with the latter showing the most decrease. DiscussionTo our knowledge, this is the first study that shows which of the innate and adaptive immune biomarkers are activated during PDT related treatment of the TNBC 4T1 mouse models. The results also indicate that some of the immune response biomarkers can be used to monitor the effectiveness of PDT treatment in TNBC murine model warranting further investigation in human subjects.

Breast cancer is a multifactorial disease that affects millions of women worldwide. Recent work has shown intriguing connections between microorganisms and breast cancer, which might have implications for prevention and treatment. This article analyzed 117 relevant breast cancer clinical studies listed on ClinicalTrials.gov selected using a bespoke set of 38 search terms focused on bacteria, viruses, and fungi. This was supplemented with 20 studies found from a search of PubMed. The resulting 137 studies were described by their characteristics such as geographic distribution, interventions used, start date and status, etc. The studies were then collated into thematic groups for a descriptive analysis to identify knowledge gaps and emerging trends.