Imaging modalities for characterising T1 renal tumours: A systematic review and meta-analysis of diagnostic accuracy.

Objectives: International guidelines recommend resection of suspected localised renal cell carcinoma (RCC), with surgical series showing benign pathology in 30%. Non-invasive diagnostic tests to differentiate benign from malignant tumours are an unmet need. Our objective was to determine diagnostic accuracy of imaging modalities for detecting cancer in T1 renal tumours. Methods: A systematic review was performed for reports of diagnostic accuracy of any imaging test compared to a reference standard of histopathology for T1 renal masses, from inception until January 2023. Twenty-seven publications (including 2277 tumours in 2044 participants) were included in the systematic review, and nine in the meta-analysis. Results: Forest plots of sensitivity and specificity were produced for CT (seven records, 1118 participants), contrast-enhanced ultrasound (seven records, 197 participants), [99mTc]Tc-sestamibi SPECT/CT (five records, 263 participants), MRI (three records, 220 participants), [18F]FDG PET (four records, 43 participants), [68Ga]Ga-PSMA-11 PET (one record, 27 participants) and [111In]In-girentuximab SPECT/CT (one record, eight participants). Meta-analysis returned summary estimates of sensitivity and specificity for [99mTc]Tc-sestamibi SPECT/CT of 88.6% (95% CI 82.7%-92.6%) and 77.0% (95% CI 63.0%-86.9%) and for [18F]FDG PET 53.5% (95% CI 1.6%-98.8%) and 62.5% (95% CI 14.0%-94.5%), respectively. A comparison hierarchical summary receiver operating characteristic (HSROC) model did not converge. Meta-analysis was not performed for other imaging due to different thresholds for test positivity. Conclusion: The optimal imaging strategy for T1 renal masses is not clear. [99mTc]Tc-sestamibi SPECT/CT is an emerging tool, but further studies are required to inform its role in clinical practice. The field would benefit from standardisation of diagnostic thresholds for CT, MRI and contrast-enhanced ultrasound to facilitate future meta-analyses.

Identifying the facilitators and barriers to implementation of renal tumour biopsy in the diagnostic pathway for small renal masses.

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.

Proteomic and phenotypic characteristics of memory-like natural killer cells for cancer immunotherapy.

BACKGROUND: Human and mouse natural killer (NK) cells have been shown to develop memory-like function after short-term exposure to the cocktail of IL-12/15/18 or to overnight co-culture with some tumor cell lines. The resulting cells retain enhanced lytic ability for up to 7 days as well as after cryopreservation, and memory-like NK cells (mlNK) have been shown to induce complete remissions in patients with hematological malignancies. No single phenotype has been described for mlNK and the physiological changes induced by the short-term cytokine or tumor-priming which are responsible for these enhanced functions have not been fully characterized. Here, we have generated mlNK by cytokine and tumor-priming to find commonalities to better define the nature of NK cell "memory" in vitro and, for the first time, in vivo. METHODS: We initiated mlNK in vitro from healthy donors with cytokines (initiated cytokine-induced memory-like (iCIML)-NK) and by tumor priming (TpNK) overnight and compared them by high-dimensional flow cytometry, proteomic and metabolomic profiling. As a potential mechanism of enhanced cytolytic function, we analyzed the avidity of binding of the mlNK to NK-resistant tumors (z-Movi). We generated TpNK from healthy donors and from cancer patients to determine whether mlNK generated by interaction with a single tumor type could enhance lytic activity. Finally, we used a replication-incompetent tumor cell line (INKmune) to treat patients with myeloid leukaemias to potentiate NK cell function in vivo. RESULTS: Tumor-primed mlNK from healthy donors and patients with cancer showed increased cytotoxicity against multiple tumor cell lines in vitro, analogous to iCIML-NK cells. Multidimensional cytometry identified distinct memory-like profiles of subsets of cells with memory-like characteristics; upregulation of CD57, CD69, CD25 and ICAM1. Proteomic profiling identified 41 proteins restricted to mlNK cells and we identified candidate molecules for the basis of NK memory which can explain how mlNK overcome inhibition by resistant tumors. Finally, of five patients with myelodysplastic syndrome or refractory acute myeloid leukemia treated with INKmune, three responded to treatment with measurable increases in NK lytic function and systemic cytokines. CONCLUSIONS: NK cell "memory" is a physiological state associated with resistance to MHC-mediated inhibition, increased metabolic function, mitochondrial fitness and avidity to NK-resistant target cells.

Renal mass biopsy - a practical and clinicopathologically relevant approach to diagnosis.

Advancements in imaging modalities have increased the frequency of renal mass discovery. Imaging has typically been considered sufficient to guide management for a large proportion of these tumours, but renal mass biopsies (RMBs) have an increasing role in determining malignancy and can be a valuable tool for preventing unnecessary surgery in patients with benign tumours. A structured approach should be used to help to navigate the expanding repertoire of renal tumours, many of which are molecularly defined. In terms of tumour subtyping, the pathologist's strategy should focus on stratifying patients into clinically different prognostic groups according to our current knowledge of tumour behaviour, including benign, low-grade or indolent, intermediate malignant or highly aggressive. Crucial pathological features and morphological mimicry of tumours can alter the tumour's prognostic group. Thus, pathologists and urologists can use RMB to select patients with tumours at a reduced risk of progression, which can be safely managed with active surveillance within a tailored imaging schedule, versus tumours for which ablation or surgical intervention is indicated. RMB is also crucial in the oncological setting to distinguish between different high-grade tumours and guide tailored management strategies.

Diagnostic Biopsy for Small Renal Tumours: A Survey of Current European Practice.

Background and objective: Renal tumour biopsy (RTB) can help in risk stratification of renal tumours with implications for management, but its utilisation varies. Our objective was to report current practice patterns, experiences, and perceptions of RTB and research gaps regarding RTB for small renal masses (SRMs). Methods: Two web-based surveys, one for health care providers (HCPs) and one for patients, were distributed via the European Association of Urology Young Academic Urologist Renal Cancer Working Group and the European Society of Residents in Urology in January 2023. Key findings and limitations: The HCP survey received 210 responses (response rate 51%) and the patient survey 54 responses (response rate 59%). A minority of HCPs offer RTB to >50% of patients (14%), while 48% offer it in <10% of cases. Most HCPs reported that RTB influences (61.5%) or sometimes influences (37.1%) management decisions. Patients were more likely to favour active treatment if RTB showed high-grade cancer and less likely to favour active treatment for benign histology. HCPs identified situations in which they would not favour RTB, such as cystic tumours and challenging anatomic locations. RTB availability (67%) and concerns about delays to treatment (43%) were barriers to offering RTB. Priority research gaps include a trial demonstrating that RTB leads to better clinical outcomes, and better evidence that benign/indolent tumours do not require active treatment. Conclusions and clinical implications: Utilisation of RTB for SRMs in Europe is low, even though both HCPs and patients reported that RTB results can affect disease management. Improving timely access to RTB and generating evidence on outcomes associated with RTB use are priorities for the kidney cancer community. Patient summary: A biopsy of a kidney mass can help patients and doctors make decisions on treatment, but our survey found that many patients in Europe are not offered this option. Better access to biopsy services is needed, as well as more research on what happens to patients after biopsy.

2022 WUOF/SIU International Consultation on Urological Diseases: Active Surveillance for Small Renal Masses.

With greater awareness of indolence underlying small renal masses (SRM ≤ 4 cm) and the morbidity of invasive treatment, active surveillance for SRM patients is being increasingly utilized on an international level. This synopsis summarizes the 2022 review and expert opinion recommendations provided to the International Consultation of Urological Diseases (ICUD) by 10 urologists from high-volume active surveillance practices at international centers. Topics reviewed include SRM biology and clinical behavior, current national and international guidelines for active surveillance of SRM patients, active surveillance utilization patterns and barriers to implementation, outcomes and limitations of the active surveillance literature, criteria for active surveillance patient selection, protocols for active surveillance management including frequency/modality of imaging and the role of renal tumor biopsy, triggers for delayed intervention during active surveillance including tumor factors and patient factors, and pathological outcomes of delayed intervention. We conclude that despite limitations of the current literature, active surveillance is a safe initial management strategy for many SRM patients. The slow growth and low metastatic potential of SRMs, combined with no evidence to suggest oncologic compromise with delay to treatment, should provide confidence to both patients and providers who are considering active surveillance. Future research for prioritization should include characterization of long-term active surveillance outcomes including rates of metastasis and delayed intervention, standardization of objective tumor progression criteria for triggering delayed intervention, and further delineation of the role for active surveillance in young and healthy patients.