Implementation of streamlining measures in selecting and prioritising complex cases for the cancer multidisciplinary team meeting: a mini review of the recent developments.

In January 2020, NHS England and NHS Improvement, in the United Kingdom, issued a permissive framework for streamlining cancer multidisciplinary (MDT) meetings. Streamlining is defined as a process whereby complex cases are prioritized for full discussion by an MDT in an MDT meeting (MDM), while the management of straightforward cases is expedited using Standards of Care (SoC). SoC are points in the pathway of patient management where there are recognized guidelines and clear clinical consensus on the options for management and should be regionally agreed and uniformly applied by regional Cancer Alliances. While this report marks the first major change in cancer MDT management since the Calman-Hine report in 1995, its implementation, nationally, has been slow with now nearly four years since its publication. It is argued however that streamlining is a necessary step in ensuring the viability of MDT processes, and therefore maintaining patient care in the current socioeconomic context of rising workload and cancer incidence, financial pressures, and workforce shortages. In this mini review, we offer a succinct summary of the recent developments around the implementation of the 2020 streamlining framework, including challenges and barriers to its implementation, and the potential future directions in this field, which we propose should increase utilisation of implementation science. We conclude that ensuring successful implementation of the framework and the SOC requires securing a buy-in from key stakeholders, including MDTs and hospital management teams, with clearly defined (a) management approaches that include triage (e.g. through a mini MDT meeting), (b) assessment of case complexity (something that directly feeds into the SOC), and (c) roles of the MDT lead and the members, while acknowledging that the SOC cannot be universally applied without the consideration of individual variations across teams and hospital Trusts.

Accuracy of Ex-vivo Fluorescence Confocal Microscopy in Margin Assessment of Solid Tumors: A Systematic Review.

Fluorescence confocal microscopy (FCM) is a novel technology that enables rapid high-resolution digital imaging of non-formalin-fixed tissue specimens and offers real-time positive surgical margin identification. In this systematic review, we evaluated the accuracy metrics of ex vivo FCM for intraoperative margin assessment of different tumor types. A systematic search of MEDLINE via PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus was performed for relevant papers (PROSPERO ID: CRD42022372558). We included 14 studies evaluating four types of microscopes in six different tumor types, including breast, prostate, central nervous system, kidney, bladder, and conjunctival tumors. Using the Quality Assessment of Diagnostic Accuracy Studies tool, we identified a high risk of bias in patient selection (21%) and index test (36%) of the included studies. Overall, we found that FCM has good accuracy metrics in all tumor types, with high sensitivity and specificity (>80%) and almost perfect concordance (>90%) against final pathology results. Despite these promising findings, the quality of the available evidence and bias concerns highlight the need for adequately designed studies to further define the role of ex vivo FCM in replacing the frozen section as the tool of choice for intraoperative margin assessment.

Protocol for a prospective study evaluating circulating tumour cells status to predict radical prostatectomy treatment failure in localised prostate cancer patients (C-ProMeta-1).

BACKGROUND: Treatment decisions in prostate cancer (PCa) rely on disease stratification between localised and metastatic stages, but current imaging staging technologies are not sensitive to micro-metastatic disease. Circulating tumour cells (CTCs) status is a promising tool in this regard. The Parsortix® CTC isolation system employs an epitope-independent approach based on cell size and deformability to increase the capture rate of CTCs. Here, we present a protocol for prospective evaluation of this method to predict post radical prostatectomy (RP) PCa cancer recurrence. METHODS: We plan to recruit 294 patients diagnosed with unfavourable intermediate, to high and very high-risk localised PCa. Exclusion criteria include synchronous cancer diagnosis or prior PCa treatment, including hormone therapy. RP is performed according to the standard of care. Two blood samples (20 ml) are collected before and again 3-months after RP. The clinical team are blinded to CTC results and the laboratory researchers are blinded to clinical information. Treatment failure is defined as a PSA ≥ 0.2 mg/ml, start of salvage treatment or imaging-proven metastatic lesions. The CTC analysis entails enumeration and RNA analysis of gene expression in captured CTCs. The primary outcome is the accuracy of CTC status to predict post-RP treatment failure at 4.5 years. Observed sensitivity, positive and negative predictive values will be reported. Specificity will be presented over time. DISCUSSION: CTC status may reflect the true potential for PCa metastasis and may predict clinical outcomes better than the current PCa progression risk grading systems. Therefore establishing a robust biomarker for predicting treatment failure in localized high-risk PCa would significantly enhance guidance in treatment decision-making, optimizing cure rates while minimizing unnecessary harm from overtreatment. TRIAL REGISTRATION: ISRCTN17332543.

NeuroSAFE PROOF: study protocol for a single-blinded, IDEAL stage 3, multi-centre, randomised controlled trial of NeuroSAFE robotic-assisted radical prostatectomy versus standard robotic-assisted radical prostatectomy in men with localized prostate cancer.

BACKGROUND: Robotic radical prostatectomy (RARP) is a first-line curative treatment option for localized prostate cancer. Postoperative erectile dysfunction and urinary incontinence are common associated adverse side effects that can negatively impact patients' quality of life. Preserving the lateral neurovascular bundles (NS) during RARP improves functional outcomes. However, selecting men for NS may be difficult when there is concern about incurring in positive surgical margin (PSM) which in turn risks adverse oncological outcomes. The NeuroSAFE technique (intra-operative frozen section examination of the neurovascular structure adjacent prostate margin) can provide real-time pathological consult to promote optimal NS whilst avoiding PSM. METHODS: NeuroSAFE PROOF is a single-blinded, multi-centre, randomised controlled trial (RCT) in which men are randomly allocated 1:1 to either NeuroSAFE RARP or standard RARP. Men electing for RARP as primary treatment, who are continent and have good baseline erectile function (EF), defined by International Index of Erectile Function (IIEF-5) score > 21, are eligible. NS in the intervention arm is guided by the NeuroSAFE technique. NS in the standard arm is based on standard of care, i.e. a pre-operative image-based planning meeting, patient-specific clinical information, and digital rectal examination. The primary outcome is assessment of EF at 12 months. The primary endpoint is the proportion of men who achieve IIEF-5 score ≥ 21. A sample size of 404 was calculated to give a power of 90% to detect a difference of 14% between groups based on a feasibility study. Oncological outcomes are continuously monitored by an independent Data Monitoring Committee. Key secondary outcomes include urinary continence at 3 months assessed by the international consultation on incontinence questionnaire, rate of biochemical recurrence, EF recovery at 24 months, and difference in quality of life. DISCUSSION: NeuroSAFE PROOF is the first RCT of intra-operative frozen section during radical prostatectomy in the world. It is properly powered to evaluate a difference in the recovery of EF for men undergoing RARP assessed by patient-reported outcome measures. It will provide evidence to guide the use of the NeuroSAFE technique around the world. TRIAL REGISTRATION: NCT03317990 (23 October 2017). Regional Ethics Committee; reference 17/LO/1978.

E-Consent-a guide to maintain recruitment in clinical trials during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has posed daunting challenges when conducting clinical research. Adopting new technologies such as remote electronic consent (e-Consent) can help overcome them. However, guidelines for e-Consent implementation in ongoing clinical trials are currently lacking. The NeuroSAFE PROOF trial is a randomized clinical trial evaluating the role of frozen section analysis during RARP for prostate cancer. In response to the COVID-19 crisis, recruitment was halted, and a remote e-Consent solution was designed. The aim of this paper is to describe the process of implementation, impact on recruitment rate, and patients' experience using e-Consent. METHODS: A substantial amendment of the protocol granted the creation of a remote e-Consent framework based on the REDCap environment, following the structure and content of the already approved paper consent form. Although e-Consent obviated the need for in-person meeting, there was nonetheless counselling sessions performed interactively online. This new pathway offered continuous support to patients through remote consultations. The whole process was judged to be compliant with regulatory requirements before implementation. RESULTS: Before the first recruitment suspension, NeuroSAFE PROOF was recruiting an average of 9 patients per month. After e-Consent implementation, 63 new patients (4/month) have been enrolled despite a second lockdown, none of whom would have been recruited using the old methods given restrictions on face-to-face consultations. Patients have given positive feedback on the use of the platform. Limited troubleshooting has been required after implementation. CONCLUSION: Remote e-Consent-based recruitment was critical for the continuation of the NeuroSAFE PROOF trial during the COVID-19 pandemic. The described pathway complies with ethical and regulatory guidelines for informed consent, while minimizing face-to-face interactions that increase the risk of COVID-19 transmission. This guide will help researchers integrate e-Consent to ongoing or planned clinical trials while uncertainty about the course of the pandemic continues. TRIAL REGISTRATION: NeuroSAFE PROOF trial NCT03317990 . Registered on 23 October 2017. Regional Ethics Committee reference 17/LO/1978.