Core Outcome Measures in Effectiveness Trials

Renal cancer Core Outcome Sets (R-COS) programme encompassing 1) localised renal cell carcinoma (RCC) 2) locally advanced RCC and 3) metastatic RCC

General Information

Summary:
Background

Prevalence and Incidence
Renal cell cancer represents 2-3% of all cancers with the highest incidence in Western countries. Over the last two decades the incidence of RCC increased by about 2%, both worldwide and in Europe. The incidence varies globally, with the highest rates in developed countries such as North America and Europe and the lowest rates in Asia and Africa. In Western European countries this incidence stabilised over the past decade. In 2012, there were approximately 84,400 new cases of RCC and 34,700 kidney-cancer-related deaths in the European Union. [1, 2]
In Europe, overall mortality rates for RCC increased up to the early 1990s, before stabilising or declining thereafter. [3] Mortality has decreased since the 1980s in Scandinavian countries and since the early 1990s in France, Germany, Austria, the Netherlands, and Italy. However, in some European countries (Croatia, Estonia, Greece, Ireland, Slovakia), mortality rates still show an upward trend. Data from the United States also show increased incidence [4] There is a 1.5:1 male predominance, with a peak incidence between 60 and 70 years.
Due to increased detection of tumours by ultrasound (US) and computed tomography (CT), the number of incidentally diagnosed RCCs has increased. These tumours are usually smaller and of lower stage. [5]

Description of condition and available treatments
Renal cell cancer (also called kidney cancer or renal cell adenocarcinoma) is a disease in which malignant (cancer) cells are found in the lining of tubules (very small tubes) in the kidney.

Nephrectomy: Surgery to remove part or all of the kidney is often used to treat renal cell cancer. The following types of nephrectomy may be used:
• Partial nephrectomy: A surgical procedure to remove the cancer within the kidney and some of the tissue around it. A partial nephrectomy may be done to prevent loss of kidney function when the other kidney is damaged or has already been removed.
• Radical nephrectomy: A surgical procedure to remove the kidney, the adrenal gland, surrounding tissue, and, usually, nearby lymph nodes.

Immunotherapy is a treatment that uses the patient's immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body's natural defences against cancer.

Targeted therapy uses drugs or other substances to identify and attack specific cancer cell mechanisms.

Ablative therapy: Renal ablative treatment uses the cell destroying properties of temperature (hot or cold) to bring about apoptosis in cancer cells. An ideal ablative treatment should be able to destroy all cancer cells, without affecting normal tissue and the zone of treatment should be under the control of the physician.

Why is it important to develop core outcome sets for RCC?
Heterogeneous outcome reporting in RCC trials has been reported in systematic reviews of intervention effectiveness and guidelines. [6-9] This situation hinders comparing and contrasting the results of individual trials as well as critical reviews of the evidence base and is open to the potential for selective outcome reporting bias. The knock-on effect is that making evidence based recommendations in guideline panels, and decision-making by clinicians and patients, is hampered.
Developing a core outcome set (COS) is a solution to reduce outcome heterogeneity, selective outcome reporting and ensures that all trials contribute useable information to the evidence base. A COS is an agreed standardised collection of outcomes which should be measured and reported, as a minimum, in all trials for a specific clinical area. [10]
To address outcome heterogeneity, we have initiated a collaboration to develop Renal cancer Core Outcome Sets (R-COS). The features of the disease, and the various treatments available for each stage, dictate that it is most likely that there is a need for 3 COS aligning with the 3 broad categories of disease: localised RCC (L-RCC), locally advanced RCC (LA-RCC) and metastatic RCC (M-RCC). The scope of each COS is detailed further below.

Scope of the localised RCC COS
Population
• Adult (=18 years) males and females with a renal mass which is suspect for localised renal cell cancer on cross sectional imaging, up to stage T2b, N0 M0.
Interventions (and comparators)
• Active Surveillance
• Radical nephrectomy (all types and approaches: open, laparoscopic, robotic, peritoneal, retroperitoneal etc.)
• Partial Nephrectomy (all types and approaches: open, laparoscopic, robotic, peritoneal, retroperitoneal etc.)
• Cryoablation
• Radiofrequency ablation
• Other ablation (microwave, laser, HIFU)
• Radiotherapy
• Associated procedures: adrenalectomy, Adjuvant lymph node dissection (LND), Embolization

Scope of the locally advanced RCC COS
Population
• Adult (=18 years) males and females with a renal mass which is suspect for locally advanced renal cell cancer on cross sectional imaging , N+ or T3-T4 N0 M0.
Interventions (and comparators)
• Radical nephrectomy (all types and approaches: open, laparoscopic, robotic, peritoneal, retroperitoneal etc.)
• Partial Nephrectomy (all types and approaches: open, laparoscopic, robotic, peritoneal, retroperitoneal etc.)
• Neoadjuvant systemic therapy (Targeted therapies, Immunotherapy)
• Adjuvant systemic therapy (Targeted therapies, Immunotherapy)
• Radiotherapy
• Associated procedures: LND, adrenalectomy

Scope of the advanced and metastatic RCC COS
• Adult (=18 years) males and females with metastatic RCC cancer stage T any N+ M+.
Interventions and comparators
• Systemic Therapy ( in 1st line, 2nd line, 3rd line, etc)
o Targeted therapies
o Immunotherapy
• Cytoreductive nephrectomy
• Radiotherapy (any type or dose LIST)
• Metastasectomy

References
1. American Cancer Society; Cancer Facts & Figures 2016. 2016.
2. Ferlay, J., et al., Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer, 2013. 49(6): p. 1374-403.
3. Levi, F., et al., The changing pattern of kidney cancer incidence and mortality in Europe. BJU Int, 2008. 101(8): p. 949-58.
4. King, S.C., et al., Continued increase in incidence of renal cell carcinoma, especially in young patients and high grade disease: United States 2001 to 2010. J Urol, 2014. 191(6): p. 1665-70.
5. Kato, M., et al., Natural history of small renal cell carcinoma: evaluation of growth rate, histological grade, cell proliferation and apoptosis. J Urol, 2004. 172(3): p. 863-6.
6. MacLennan, S., et al., Systematic review of oncological outcomes following surgical management of localised renal cancer. Eur Urol, 2012. 61(5): p. 972-93.
7. MacLennan, S., et al., Systematic review of perioperative and quality-of-life outcomes following surgical management of localised renal cancer. Eur Urol, 2012. 62: p. 1097-117.
8. Bex, A., et al., Updated European Association of Urology Guidelines for Cytoreductive Nephrectomy in Patients with Synchronous Metastatic Clear-cell Renal Cell Carcinoma. Eur Urol, 2018. 74(6): p. 805-809.
9. Kramar, A., et al., Guidelines for the definition of time-to-event end points in renal cell cancer clinical trials: results of the DATECAN projectdagger. Ann Oncol, 2015. 26(12): p. 2392-8.
10. Williamson, P.R., et al., The COMET Handbook: version 1.0. Trials, 2017. 18(Suppl 3): p. 280.


Contributors:
Steven MacLennan. Academic Urology Unit, University of Aberdeen, UK,
Lorenzo Marconi, Department of Urology, Coimbra University Hospital, Portugal
Mieke van Hemelrijck. Translational Oncology and Urology Research Group, Kings College London, London, UK.
Katharina Beyer. Translational Oncology and Urology Research Group, Kings College London, London, UK.
Axel Bex, University Medical Centre, Utrecht, The Netherlands

Further Study Information

Current Stage:
Ongoing
Date:
September 2019 - September 2025
Funding source(s):
None

Health Area

Disease Category
Urology

Disease Name
Renal cell cancer

Target Population

Age Range
18 -

Sex
Either


Nature / type of Intervention
Any

Method(s)

Consensus meeting
Delphi process
Interview
Systematic review

The methods for each of the three COS will follow broadly the same process.
1. To identify a long list of outcomes reported in prior RCC intervention studies: Systematic reviews of RCTs included in relevant clinical practice guidelines and/or systematic reviews of intervention effectiveness (one each and separately for L-RCC, LA-RCC and M-RCC).
2. To identify outcome considered as important by patients who have experience RCC and its treatments: Systematic reviews of qualitative studies reporting on the experiences of RCC patients and/or primary qualitative interview studies (one each and separately for L-RCC, LA-RCC and M-RCC).
3. Delphi surveys involving urologists, oncologists, cancer specialist nurses (grouped as health care professionals) and RCC patients who have received treatment, to score the importance of each outcome identified (one each and separately for L-RCC, LA-RCC and M-RCC).
4. Consensus meetings with representatives from each stakeholder group to discuss and vote on unclear results from the Delphi and to ratify the COS (one each and separately for L-RCC, LA-RCC and M-RCC).
5. Assess the definitions and measurements for clinician reported outcomes (for example recurrence, progression etc) and where there is no one clear most appropriate and feasible definition and measurement we will engage HCPs in a consensus processes to identify the most appropriate definitions and measurement for specific purposes such as RCTs and routine clinical data collection
6. Assess the psychometric properties of each PROM identified for L-RCC, LA-RCC and M-RCC and where there is no one clear ‘best’ and most feasible PROM we will engage HCPs in a consensus processes to identify the most appropriate PROM for specific purposes such as RCTs and routine clinical data collection


Stakeholders Involved

Charities
Clinical experts
Consumers (patients)
Methodologists
Patient/ support group representatives
Researchers

Study Type

COS for clinical trials or clinical research
COS for practice
Recommended outcome measures (measurement)

The site uses cookies, some may have been set already. Please refer to our privacy policy & cookie usage statement.
If you continue to use the site we'll assume you're happy to accept the cookies.