Kidney cancer: diagnosis and management

Why the committee made the recommendations

Evidence on information needs for people with suspected or confirmed renal cell carcinoma (RCC) was limited. The committee used themes from the evidence and their experience to make recommendations.

The committee cross referred to other NICE guidelines that cover aspects of care that aligned with the committee's experience and the evidence on shared decision making, communicating information, taking patient views and preferences into account, and supporting people in social care to make decisions.

Based on their expertise and experience, the committee agreed that it was important for people with suspected or confirmed RCC to have access to a clinical nurse specialist with training and experience in kidney cancer to provide this support and information. They agreed that it is important that the clinical nurse specialist attends multidisciplinary team meetings and acts as a link between the urology and oncology teams to ensure continuity of care. They noted that, in some places, cancer care navigators are available and can take on some of the work of signposting people to support services and coordinating appointments. But they should not replace clinical nurse specialists.

The committee acknowledged that having a cancer diagnosis and undergoing treatments are likely to lead to stress and anxiety, and possibly depression, and that people will need support in dealing with these issues. In addition, people who are diagnosed with kidney cancer because of an incidental finding on a scan for a completely unrelated condition may experience high levels of stress and anxiety because their diagnosis was unexpected. The committee noted that people will need different levels of support and that this could be provided by voluntary, community and NHS services.

The committee agreed that it is important that people with RCC have opportunities to be involved in research, including clinical and non-clinical studies, to access new treatments before they are widely available, help improve the evidence base for treatments that will benefit others, and share their views and experiences of treatments. Opportunities should not be limited to their own centres, but the committee acknowledged that taking part in research in other centres may cause issues, such as having to travel further.

The committee noted the importance of improving the experiences of people with RCC. They suggested that quality improvement programmes could be informed by a patient satisfaction survey developed with input from people with lived experience to ensure that they capture what matters. Existing surveys for people with kidney cancer, such as Kidney Cancer UK's patient survey, could be used or adapted.

How the recommendations might affect practice

The availability of clinical nurse specialists varies across the country, and they may not all have training in kidney cancer. To consistently achieve this support for everyone with suspected or confirmed RCC, more clinical nurse specialists with training in kidney cancer may need to be recruited, and some of the existing staff may need specialist training.

The recommendation promoting research involvement could lead to an increase in people being involved in clinical and non-clinical studies.

Return to recommendations

Why the committee made the recommendations

The committee noted that many people are referred for investigations for RCC based on incidental findings on imaging done for other reasons. In these cases, it may not be necessary to repeat the imaging if the existing results provide sufficient information to inform the next steps.

The committee recommended using multiphasic contrast-enhanced CT (CECT) first because it can successfully identify RCC in most people, like contrast-enhanced MRI, but is less expensive. It is also less time consuming per scan than an MRI, and so more appointments are available and more people can get scans more quickly. CECT is also preferred over MRI for people with claustrophobia, because they are less enclosed, and people with some metal implants who cannot safely use MRI scanners.

The committee agreed that there are situations when MRI, ideally with contrast, should be used in addition to or instead of CECT. One situation is when CECT is not suitable, for example, for people with very reduced renal function or with allergies to the contrast agent being used. Another is when the renal lesion type, and so potential next steps, are still unclear after a CECT. The committee agreed that CECT or MRI of the abdomen would usually be enough to detect if a mass is present. CT of the chest and pelvis should then be offered to complete staging.

There are several potential results from initial imaging. When there is high confidence of a benign renal lesion, such as a Bosniak 1 or 2 (not a Bosniak 2F) cyst or an angiomyolipoma, the committee agreed that most people can be discharged. Some people may still benefit from continued monitoring or treatment of local symptoms outside of the cancer pathway though, such as people with a Bosniak 1 or 2 cyst that is causing pain, or women, trans men and non-binary people registered female at birth who are of childbearing age and have an angiomyolipoma. People with an angiomyolipoma made up of mostly blood vessels may also be at higher risk of complications. They also noted that there is no standard monitoring approach, and this would need to be tailored to the individual. But, if imaging is inconclusive or suggests a malignant renal lesion, the committee highlighted the importance of multidisciplinary team discussions to determine possible options and next steps. These might include additional imaging, a biopsy or treatment.

The committee did not review evidence for the diagnosis of metastases and so were unable to make any specific recommendations on this topic. But they cross referred to other NICE guidelines that cover diagnosing brain and spinal cord metastases.

Based on limited evidence and their expertise and experience, the committee agreed that contrast-enhanced ultrasound can guide next steps if needed. Contrast-enhanced ultrasound can help differentiate solid and cystic renal lesions and provide information about lesion characteristics and complexity. The 'inert' microbubble contrast agent used in contrast-enhanced ultrasound can be used for people who cannot have the contrast agents used for CT and MRI because of an allergy or poor renal function.

The evidence showed that 99mTc-sestamibi single-photon emission computed tomography CT (SPECT/CT) may provide useful information about whether a renal lesion is more likely to be malignant or benign. But the committee agreed that this test is only useful when a person does not wish to or cannot have a biopsy (for example, because of the lesion's position or because they are taking anticoagulant medication) and their initial imaging could not show whether the lesion was oncocytic. To try to improve the efficiency and effectiveness of the diagnostic process, the committee made a recommendation for research on combinations and sequences of diagnostic approaches to most accurately differentiate between benign and malignant renal lesions.

How the recommendations might affect practice

CECT is commonly used in current practice to help diagnose RCC. MRI is also commonly used, but availability may be more limited because of the longer scanning duration per person and competing demands on the machines from other disease specialities. The recommendations for CECT and MRI are not expected to change current practice.

The committee acknowledged that contrast-enhanced ultrasound is a test that must be done by a specialist who may not be available at all centres. But the machines used for contrast-enhanced ultrasound are readily available in most places. The recommendations for contrast-enhanced ultrasound may lead to an increase in its use, and so more demand for specialists. They also noted that 99mTc-sestamibi SPECT/CT is not commonly used for diagnosing kidney cancer in the NHS, but as it is used for imaging the parathyroid and the heart, there is likely to be some availability and expertise already in place. The recommendations for 99mTc-sestamibi SPECT/CT may lead to an increase in its use, although this is expected to be limited as it is only recommended in very specific circumstances.

Return to recommendations

Why the committee made the recommendations

Evidence supported biopsy as a diagnostic tool for suspected RCC for people with renal lesions 4 cm in diameter or smaller to guide management decisions and, in particular, prevent an unnecessary nephrectomy for people with benign or low-risk malignant lesions. The committee agreed that although biopsy is not routinely offered to people with renal lesions larger than 4 cm in diameter, there are some situations when biopsy could be used to support particular management options or to reassure the person.

The committee agreed that there are situations when biopsy may not be suitable, such as when a renal lesion has grown into the renal vein or inferior vena cava, because surgery is the only treatment option and delaying treatment for a biopsy is undesirable. Biopsy is also not suitable if the person cannot have any treatment because of comorbidities or if they are too frail. If a biopsy cannot obtain enough tissue (for example, because there is not a substantial solid component or the lesion is smaller than 2 cm in diameter), or if accessing the renal lesion would be difficult (for example, if the lesion's position makes it inaccessible to a biopsy needle), the committee agreed a biopsy should not be done. They also agreed that a biopsy should not be done when management will not change, such as when the person has decided to have surgery regardless of the biopsy results. If a person cannot have a biopsy, the committee agreed that it is essential to explain the reason for this. Otherwise, the person may feel confused or anxious if they learn about biopsy from other people with suspected RCC.

The committee agreed that a repeat biopsy could be an option if the first one fails. They also agreed that ensuring people are given the opportunity to have a biopsy even if they have previously declined one is important. This is particularly relevant for people undergoing active surveillance who want to move to treatment, because a biopsy would help determine the most suitable options.

How the recommendations might affect practice

Biopsy is not used consistently across the country. Many local centres are not currently able to offer biopsy or can only offer biopsy on a limited basis. This is because of historical service configurations where surgery was mainly done without biopsy. So, the infrastructure and staff needed to collect and analyse the biopsy samples were not established. The recommendations would lead to more biopsies taking place in some places and a corresponding resource impact. The committee advised that interventional radiology provision would need to increase in some places, including more staff, and ways of working would change because people would need to be monitored for several hours after a biopsy. To offer biopsy to more people, referrals to specialist centres may increase, or some local centres that do not currently offer biopsy may need additional training to be able to do so. There would also be implications for histopathology services in terms of staff and diagnostic resources after an increase in the numbers of biopsies. But an increase in the number of biopsies is expected to lead to fewer unnecessary surgeries, with associated cost savings.

Return to recommendations

Why the committee made the recommendations

Biopsy results could guide systemic anticancer therapy (SACT) decisions for people with suspected metastatic RCC who do not have a previous diagnosis of RCC, but this is not necessary if the person has surgery as their first treatment. This is because the same information can be obtained from pathological assessment of the removed renal lesion.

The decision whether to biopsy the renal lesion or the metastases is complex and depends on many factors, such as the location of the renal lesion. The committee agreed that biopsy of metastatic lesions may not be necessary if the person has previously had treatment for RCC with no metastatic disease and now has suspected metastases, as the metastatic lesions are likely to be the same RCC. But if there is suspicion that the metastases could be from another malignancy (for example, if the metastases are seen several years after the initial diagnosis or treatment, or if the person has or has had another type of cancer) then clinical judgement should be used to determine whether to do a biopsy.

The committee agreed that biopsy of the renal lesion or metastases would not be suitable when the results would not provide any information to guide treatment decisions (for example, when people cannot have SACT or other treatments) as the risks would outweigh any potential benefits.

How the recommendations might affect practice

The use of biopsy for people with suspected metastatic RCC varies, but it is current practice to do a biopsy in this population if it would guide treatment. The recommendations should standardise practice, leading to a small uptake in biopsy, but this would have limited resource implications as the group of people who would have a biopsy is very small.

Return to recommendations

Why the committee made the recommendations

Biopsy results could guide treatment decisions for people with suspicious renal lesions and a heritable RCC predisposition syndrome. The committee agreed that the decision to biopsy a suspicious renal lesion would depend on the type of syndrome. Renal lesions in people with von Hippel–Lindau (VHL) syndrome are almost always clear cell RCC, but there could be cases when the diagnosis is uncertain and a biopsy would be useful to determine the type of lesion. Biopsy should not be done for people with hereditary leiomyomatosis and RCC (HLRCC) syndrome. Instead, treatment of renal lesions should be expedited because of the risk of spread and the aggressive nature of lesions associated with this syndrome. But biopsy may be useful for people with Birt–Hogg–Dubé (BHD) syndrome and tuberous sclerosis complex (TSC).

How the recommendations might affect practice

The use of biopsy for people with suspected RCC and a heritable RCC predisposition syndrome varies but it is current practice to do a biopsy for some population subgroups to determine lesion type. The recommendations should standardise practice, leading to a small uptake in biopsy, but this would have limited resource implications as the group of people who would have a biopsy is very small.

Return to recommendations

Why the committee made the recommendation

Based on evidence supporting people's information needs about biopsy and it's diagnostic accuracy, the committee agreed that biopsy should be used when it is possible and can provide clinically useful information. They noted that people are often concerned about the risks of biopsy and this can put them off having one. They agreed that it is important to reassure people about the rarity of severe complications. People are also often anxious about cancer cells spreading along the path where the biopsy needle goes in. The committee emphasised that the likelihood of this happening is extremely low, and the only available evidence for this hypothesis comes from reports of case series studies with very small numbers of participants. They also noted that biopsy results sometimes differed from pathology results obtained from samples taken during or after surgery. But they stressed that this should not be seen as a reason not to have a biopsy because the situation is rare, and that if there was concern about the changing characteristics of a lesion believed to be benign then a biopsy can be repeated. The committee agreed that another reason people may decide not to have a biopsy is because it could take several weeks, from waiting for an appointment to getting the results. This can cause anxiety because people worry that the lesion could progress during the waiting period. They agreed that it is important to reassure people that the lesion is unlikely to progress in a way that would negatively impact their treatment options or outcomes. Finally, the committee noted that people who choose not to have a biopsy may be able to have one later, for example, to help guide treatment options if they have been undergoing active surveillance and are moving to treatment.

How the recommendation might affect practice

The committee noted that information sharing about biopsy varies, and that people with suspected RCC are often more aware of the potential risks of having a biopsy than the benefits. Improving the quality of the information given to people about biopsy and focusing on the benefits could increase uptake and this would have resource implications (see the rationale sections on biopsy for suspected localised or locally advanced RCC, biopsy for suspected metastatic RCC and biopsy for people with RCC who have a heritable RCC predisposition syndrome for more information). But an increase in the number of biopsies is expected to reduce unnecessary surgeries, with associated cost savings.

Return to recommendation

Why the committee made the recommendations

There was no evidence on active surveillance for oncocytomas or Bosniak 2F cysts of any size. So, the committee used their expertise and experience to make consensus recommendations that reflect best current practice.

How the recommendations might affect practice

The recommendations reflect current practice in some centres, but there may be some variation across England.

Return to recommendations

Why the committee made the recommendation

The recommendation on factors to discuss when choosing between non-pharmacological options for suspected or confirmed localised RCC and Bosniak 3 and 4 cysts is based on the evidence and the committee's experience. The committee noted that healthcare professionals should explain to people that there may be a lower risk of local recurrence with surgery compared to thermal ablation and stereotactic ablative radiotherapy (SABR). They were aware that risk of recurrence can also vary depending on the type of surgery or ablation, and lesion characteristics. But the evidence review was not designed to look at this specifically. By highlighting these points, the committee hope to improve the ability of people with RCC to choose a treatment option for themselves with support from their healthcare professional.

How the recommendation might affect practice

This recommendation should reflect current good practice but may help standardise this where practice varies.

Return to recommendation

Why the committee made the recommendations

The evidence on non-pharmacological interventions for people with localised RCC was for people with RCC that was proven or suspected on imaging. Studies did not specify whether the participants had renal lesions that were solid or cystic, and much of the evidence could not be split by the size of the person's lesion. The committee agreed that people with Bosniak 3 and 4 cysts have an increased chance of malignancy compared with Bosniak 1 and 2 cysts, and that Bosniak 4 cysts are more likely to be malignant than Bosniak 3 cysts. They agreed that, in many cases, management of Bosniak 4 cysts should be similar to management of solid masses. But they noted the lack of specific evidence about how to manage them. The committee used their expertise and experience to extrapolate from the evidence to make recommendations based on size and type of renal lesion, and included people with Bosniak 3 and 4 cysts in some recommendations along with people with solid renal masses.

The committee agreed that many factors need to be taken into account when choosing between non-pharmacological management options for localised solid renal masses and Bosniak 3 or 4 cysts. They made a recommendation covering some key points to help with decision making. The committee agreed that there should be biopsy confirmation of malignancy before using thermal ablation or SABR. But they noted that there may be rare situations when thermal ablation or SABR are used when biopsy has been attempted multiple times without confirmation of malignancy, and malignancy is strongly suspected by the multidisciplinary team.

How the recommendations might affect practice

Partial and total nephrectomy are the most common treatments for localised RCC in the UK. Partial nephrectomy is becoming more common, and the recommendations support this. The number of partial nephrectomies being offered varies, but this is because of differences in availability in local areas. The recommendations are expected to standardise practice, and a higher rate of partial nephrectomies may lead to increased referrals to centres with more expertise in these types of procedures. This would increase short-term costs, but some of these may be offset by long-term savings as more people benefit from preserved kidney function.

The recommendations may result in increased use of thermal ablation, SABR and active surveillance, but mainly in a population who cannot have surgery and would otherwise not have had treatment. The recommendations are not expected to replace many partial nephrectomies with non-surgical treatments. Practice varies, as these non-surgical treatments are not available everywhere. In particular, the use of SABR will require sign off in a uro-oncology multidisciplinary team meeting with the necessary expertise.

Return to recommendations

Why the committee made the recommendations

No evidence on active surveillance approaches (methods, duration, imaging frequency, and when to discharge) was identified. The committee relied on their expertise and experience to make consensus recommendations. They made a recommendation for research on active surveillance approaches for early detection of disease progression to try to address the evidence gap.

The committee agreed that it is important that people who are undergoing active surveillance are aware of the lack of evidence underlying active surveillance regimens and duration. They should agree a personalised care plan with their healthcare professional to help them understand their imaging schedule and how to seek help if they experience symptoms that concern them.

The committee agreed that although CT and MRI produce more detailed images of a lesion than ultrasound, reducing radiation exposure may justify using ultrasound as part of active surveillance. Also, some people may be unable to tolerate specific contrast agents, which may limit the imaging options available to them.

The committee suggested an active surveillance imaging schedule that could be tailored to individual needs. They agreed that the first scan should be 3 to 6 months after starting active surveillance, to detect early changes and reassure people who may feel anxious. Scan frequency could then be reduced unless there were changes to the renal lesion indicating the need for more frequent imaging or treatment.

How the recommendations might affect practice

The recommendations reflect current practice in some centres, but there is likely to be substantial variation. The types of imaging recommended reflect the imaging currently used, but when they are used may vary in practice. There is no single, established schedule or duration of active surveillance, and when people are discharged varies. The recommendations are expected to make it clearer when active surveillance may be suitable and increase people's confidence to select this option. So, it could increase imaging, but this may be balanced by fewer people having other treatments such as surgery.

Return to recommendations

Why the committee made the recommendations

No evidence on when to move from active surveillance to treatment or discharge was identified. The committee relied on their expertise and experience to make consensus recommendations. They highlighted the key factors that could lead to a discussion about moving from active surveillance to treatment. Bosniak 3 and 4 cysts are much more likely to be malignant than Bosniak 2F cysts, and so the committee agreed that deciding factors for moving from active surveillance to treatment should be similar to those for solid renal masses.

The committee agreed that stopping active surveillance should be discussed if no substantial changes have been recorded after 5 years because it is unlikely that a renal mass less than 4 cm in diameter will progress after this time. They noted that it may be helpful to explain the lack of evidence underlying the duration of active surveillance and to let them know when and how to seek help if needed. When people have no treatment options available, then active surveillance also becomes unnecessary.

How the recommendations might affect practice

These recommendations reflect current good practice but may help standardise practice where it varies.

Return to recommendations

Why the committee made the recommendation

The committee agreed that it is important that people with complex locally advanced RCC have their cases discussed and managed by a uro-oncology multidisciplinary team with specialist expertise to ensure that they have access to the expertise needed to provide their treatment. This team may take over the person's care completely, or alternatively, manage their surgery with oncology treatment carried out locally.

How the recommendation might affect practice

This recommendation reflects current good practice but may help standardise practice where it varies.

Return to recommendation

Why the committee made the recommendations

Most of the evidence evaluated surgical techniques for total nephrectomy for people with locally advanced RCC. The committee agreed that this reflected current practice and their experience, as it is very unlikely that a partial nephrectomy would be done in this population. They agreed that minimally invasive procedures for total nephrectomy are preferred in practice, as they are expected to minimise surgical complications and reduce length of hospital stay compared with open procedures. Although this was not clearly shown in the evidence, the committee noted the poor quality of the evidence (because of small studies with high risk of bias) and that the studies were done when minimally invasive techniques were being introduced. To address this uncertainty, the committee made a recommendation for research on different types of minimally invasive radical nephrectomy techniques compared to each other.

Based on the evidence and their expertise and experience, the committee agreed that minimally invasive procedures for total nephrectomy should be done when technically and clinically possible. They noted that minimally invasive techniques would not be possible or adequate in more complex cases, and that open total nephrectomy should be used instead.

The committee also highlighted that people with locally advanced RCC and inferior vena cava thrombus should have an abdominal MRI to show the extent of tumour thrombus before the type of surgery can be decided. Minimally invasive procedures may sometimes be possible in this population, but they agreed that open total nephrectomy should be used otherwise. In all cases, they agreed that the surgical approach should be decided by a uro-oncology multidisciplinary team, which may also include expertise from specialities such as cardiothoracic, vascular and hepatobiliary surgeons. In addition, the committee noted the importance of liaising with local renal services when there any expectations that a person with RCC may need dialysis after surgery so they can access this treatment quickly.

The committee agreed that it is very important that people with locally advanced RCC have surgery in a timely manner to reduce the risk of progression to metastatic disease. There was no evidence identified for using SABR in this population.

How the recommendations might affect practice

Minimally invasive techniques for total nephrectomy, including robot-assisted and laparoscopy-assisted techniques, are the preferred method for total nephrectomy for people with locally advanced RCC. It is not anticipated that these recommendations will result in changes in practice. Additional expertise may be needed to use these techniques for people who have locally advanced RCC and inferior vena cava thrombus, and this may not currently be readily available in all centres.

Return to recommendations

Why the committee made the recommendation

Based on the evidence and their expertise, the committee agreed that people need as much information as possible about their treatment options to be able to make an informed decision. So, they recommended some key points for healthcare professionals to discuss, or share in another format, with people before surgery. These are in addition to information about the benefits and risks of surgery, and the short-term side effects (such as pain), which should be covered routinely as part of any discussion about treatment options.

How the recommendation might affect practice

The committee noted that it is standard practice to provide people with information before surgery but that what information is given to people varies. The recommendations are expected to standardise practice as they reinforce best practice and highlight what is important to people.

Return to recommendation

Why the committee made the recommendations

The evidence supported the usefulness of some risk prediction tools in classifying people with non-metastatic RCC into different risk groups for recurrence and that this could be used to help decide follow-up schedules and future treatment options. There was only evidence for the most common RCC subtypes, namely clear cell RCC, papillary RCC, and chromophobe RCC. Clear cell RCC had the most evidence.

The evidence for risk tools that predict a 5-year risk of recurrence of clear cell RCC showed that the Leibovich 2003, SSIGN, UISS, Karakiewicz, Kattan and Sorbellini models demonstrated a poor to good ability at discriminating between people at high and low risk of recurrence. The evidence supported the use of any of these tools, so the committee decided not to recommend a single specific tool. The evidence showed that the VENUSS tool had a fair discriminative ability and was superior to other risk prediction tools at predicting papillary RCC recurrence.

The evidence for predicting chromophobe RCC recurrence was limited to the Leibovich 2003 tool and showed a poor discriminative ability. But the committee noted that tumour grading, which is included in the Leibovich 2003 risk model, is not strictly applicable to this tumour subtype and this limits the usefulness of this tool for people with chromophobe RCC. So, the committee were not able to recommend this tool and instead made a recommendation for research on the development of a tool appropriate for this subtype. The committee did not recommend using the Leibovich 2018 tool because it predicted progression-free survival rather than recurrence.

The committee agreed that a risk prediction tool should not be used in isolation because they are not completely accurate. Clinical judgement should also be used, taking into account the person's clinical characteristics, which can also affect the risk of recurrence and are not included in the recommended risk tools. They noted that the risk prediction tools have not been validated in people with rarer forms of kidney cancer or heritable RCC predisposition syndromes (for example, VHL syndrome), so there is more uncertainty about the accuracy of these tools in these populations.

People included in the studies had a nephrectomy to remove the primary renal lesion, and pathology information from a surgical specimen was used to calculate risk of recurrence. The committee recognised that it may also be possible for the tools to use pathology data from biopsy samples, but the results may be less accurate and reliable.

Since no risk prediction tools were identified that were designed to estimate the risk of recurrence in people who have had SABR or thermal ablation rather than nephrectomy, the committee drafted a recommendation for research on risk prediction tools for people with localised RCC having thermal ablation or SABR to address this gap in the evidence. They also drafted a recommendation for research to develop a risk prediction tool to estimate the risk of progression in people who are undergoing active surveillance for a localised RCC.

Adjuvant treatment is now available for people at increased risk of recurrence after surgery for non-metastatic RCC. The committee acknowledged that, in the future, eligibility for SACT may depend on risk stratification using a specific risk prediction tool stated in NICE technology appraisal guidance or NHS commissioning criteria. So, they agreed that these risk prediction tools should be used in addition to any other tool mentioned in the recommendations when SACT is indicated for people with localised or locally advanced RCC.

The recommended risk prediction tools rely on information provided in pathology reports and other clinical characteristics in some cases. The committee noted that pathology reports containing all the pathology information needed to calculate risk of recurrence using the recommended tools varies in practice. Making this information available and including the calculated risk score in pathology reports, when possible, would save time during the multidisciplinary team meetings.

To reduce variation in practice and promote the use of risk prediction tools, the committee noted the importance of recording the risk score on the person's clinical record before deciding follow-up schedules or future treatment options. They agreed that it is important that people understand their risk of recurrence and how it is calculated using the risk prediction tools so that they can be fully involved in these decisions.

How the recommendations might affect practice

Risk prediction tools for localised and locally advanced RCC are currently used in the UK, but the specific tools used vary. Leibovich 2003 is commonly used for clear cell and other types of RCC. Additional tools are recommended for clear cell RCC, although there is scope in the recommendations to choose from multiple tools. This may impact on practice less if centres decide to continue using Leibovich 2003. VENUSS may not be used currently for calculating the risk of recurrence of papillary RCC in all centres. The recommendations may reflect a change in practice and lead to a standardisation of tools used for papillary RCC.

The recommendation to provide all the relevant pathology information and to report calculated risk scores on pathology reports is expected to change practice in some areas but is already happening in others.

Return to recommendations

Why the committee made the recommendation

The committee highlighted that healthcare professionals should tell people with RCC that although adjuvant SACT may be an option for them, its use after surgery for localised or locally advanced RCC may affect which treatments they can have in the future. This is because prior immunotherapy use may affect eligibility for future immunotherapy if they developed metastatic disease. People with RCC may also be able to take part in clinical trials of adjuvant SACT that are still in development, although if it is a randomised trial then they may not be assigned to the group receiving the new treatment.

How the recommendation might affect practice

This recommendation reflects current good practice but may help standardise practice where it varies.

Return to recommendation

Why the committee made the recommendations

Very limited evidence was identified on follow-up approaches (methods, duration, imaging frequency, and when to discharge) for localised and locally advanced renal cell carcinoma (RCC). The committee relied on their expertise and experience to make consensus recommendations. They also made a recommendation for research on follow-up strategies to fill this gap in the evidence base.

The committee agreed that people should be told to seek help if they have symptoms that could indicate recurrence of the RCC or metastasis. These would likely be persistent, rather than acute, symptoms lasting for several weeks. Telling people who have had treatment for RCC in advance about their expected duration of follow-up if there is no sign of recurrence may help to manage their expectations and any anxiety.

How the recommendations might affect practice

The recommendations reflect current practice in some areas but the duration and timing of follow-up imaging varies across the UK. Most follow-up imaging is cross sectional, mainly CECT. The recommendations are expected to standardise follow-up schedules and duration. Imaging frequency may increase in some centres and decrease in others. The recommendations will also make it clearer to people that they have a named contact for any information needs during follow up. This is standard practice and should not have any implications on how often services are accessed.

Return to recommendations

Why the committee made the recommendations

Based on their expertise and experience, the committee recommended that multidisciplinary teams be involved in discussions about the potential integration of pharmacological and non-pharmacological treatments. Identifying suitable treatment options can be very complex because these decisions are based on many factors. Factors include the person's performance status, number and location of metastases, baseline risk group, general health and comorbidities. The committee recognised that in some situations, additional specialist input may be needed based on the site of metastases, as the site could affect what treatments are suitable (for example, the potential for surgical resection).

How the recommendations might affect practice

The recommendations reflect current good practice but may result in a slight increase in referrals to specialist multidisciplinary teams in places where this is not happening.

Return to recommendations

Why the committee made the recommendations

Most of the available evidence focused on the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center (MSKCC) risk prediction tools applied before first-line SACT for adults with clear cell metastatic RCC. The committee agreed that using risk prediction tools for these people aligned with current clinical practice. The discriminative ability for predicting overall survival was similar and poor for both IMDC and MSKCC. Despite this, the committee agreed that using a prediction tool alongside clinical judgement might be helpful. They preferred the IMDC because it:

So, although the IMDC alone is not very accurate at classifying people into risk groups, the committee agreed to consider using the IMDC tool to guide decisions around management options. They emphasised that this risk prediction tool should be used with clinical judgement, including consideration of individual clinical characteristics such as fitness and comorbidities, because it is not very accurate on its own. This is particularly important for certain groups of people with rarer RCC subtypes, when there is less or no evidence about the accuracy of the tool in predicting overall survival, and when making decisions about second- or subsequent-line treatment, as prior interventions may potentially bias predictive results. The committee also made a recommendation for research on developing and testing new risk prediction tools for different RCC subtypes (including clear cell RCC) to predict outcomes for metastatic RCC.

The committee acknowledged that eligibility for SACT may depend on risk stratification using a specific risk prediction tool stated in relevant NICE technology appraisal guidance or NHS commissioning criteria. So, they agreed that these risk prediction tools should be used in addition to the IMDC when SACT is indicated.

To reduce variation in practice and promote the use of risk prediction tools, the committee noted the importance of recording the risk scores on the person's clinical record before deciding future treatment options. To support shared decision making and reduce confusion, the committee included a recommendation that people with metastatic RCC are given certain information about the IMDC tool. They emphasised the importance of people understanding predictions about their life expectancy and the impact of potential treatment options so they can make fully informed decisions.

How the recommendations might affect practice

The IMDC prognostic tool is currently the preferred tool to predict survival and guide treatment decisions in people with metastatic RCC. So, it is not anticipated that these recommendations will change practice.

Return to recommendations

Why the committee made the recommendations

There was limited low to very low-certainty evidence comparing non-pharmacological interventions before SACT with non-pharmacological interventions after SACT has started. Evidence was also limited comparing non-pharmacological interventions before or after SACT with SACT alone. The only non-pharmacological intervention covered by this evidence was cytoreductive nephrectomy (CN), a type of surgery. So, although this section of the guideline covers advanced RCC, most of the recommendations do not apply to people with locally advanced inoperable RCC as CN would not be a suitable option for them.

It was difficult to assess from the included studies (1 randomised controlled trial and multiple observational studies) whether CN before SACT was better than SACT alone. The committee agreed, based on their expertise and experience, that people with oligometastatic RCC who do not have symptoms may benefit from surveillance before SACT when there is a low risk of progression and the disease is judged to be stable. Using surveillance in these cases will delay starting treatments that may have side effects that negatively affect people's quality of life until SACT is clinically indicated. They also agreed that people with widespread metastases are likely to benefit most from immediate treatment when SACT is indicated. So, any non-pharmacological interventions should be used after, not before, SACT has been started. But urgent treatment for symptoms, such as metastatic spinal cord compression, should not be delayed to start SACT.

How the recommendations might affect practice

Most people with metastatic RCC currently have SACT before a non-pharmacological intervention, and these recommendations support that. Small proportions of people have no non-pharmacological interventions at all, and these recommendations are not expected to change that. But they could provide some standardisation across settings.

Return to recommendations

Why the committee made the recommendation

The committee agreed that most of the principles underlying information sharing, communication and shared decision making in the section on information for healthcare professionals to support people with suspected or confirmed RCC also applied for people with advanced RCC. But these people and their healthcare professionals would also need to be aware of supportive and palliative care options when these become relevant. So, they cross referred to other NICE guidance on these topics.

How the recommendation might affect practice

It is standard practice to ensure that palliative care is discussed with people when appropriate, and that the relevant information and sources of support are given to them. There is currently some variation in what information is provided. The recommendations are expected to standardise practice by signposting to all the relevant existing NICE guidance.

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Why the committee made the recommendations

Genetic testing criteria for heritable RCC predisposition syndromes are described in the National Genomic Test Directory's (NGTD) rare and inherited disease eligibility criteria document. These criteria are regularly updated, and new criteria are added as new genetic variants are identified. The committee decided to cross refer to this, and so there was no evidence review to determine factors associated with these syndromes. As the NGTD includes many testing criteria covering multiple syndromes, the committee recommended key features for healthcare professionals to assess in people with a suspected heritable RCC syndrome (based on the testing criteria for R224 inherited renal cancer) that would then prompt consultation of the NGTD.

Most genetic testing is requested by clinical genetics teams, but other specialities can request genetic testing with the move towards 'mainstreaming', which is when genetic testing is requested by treating teams. The committee recommended following local policies and procedures to determine whether the healthcare professional who does the initial assessment should also do the detailed assessment and request testing following the NGTD, or if they should refer the person on to another team to do this.

Based on their experience and the evidence, the committee agreed that, before testing a person with RCC for a heritable RCC predisposition syndrome, it is important to explain the likelihood of having a positive test and what this could mean for the person and the family. They recognised that this is likely to be a very stressful time for the person with RCC and that they will need access to specialist genetic services for ongoing support and advice to help them understand and process the information they are given. The committee were aware that some people decline the test initially and wanted people with RCC to know that the test could be done later if they change their mind.

The committee agreed that it is important for people who have RCC who are then diagnosed with a heritable RCC predisposition syndrome to be managed by a specialist multidisciplinary team because they have complex conditions that need input from multiple specialties. The committee also recognised the importance of ensuring that these newly diagnosed people are given information and support at this stage and on an ongoing basis.

How the recommendations might affect practice

Local pathways for accessing genetic assessment of heritable RCC predisposition syndromes vary across the UK. These recommendations have been written to accommodate this and any changes that may occur in the future. So, they are not expected to change local pathways. The recommendation listing the factors to assess before doing a detailed assessment following the NGTD may help standardise the early stage of the genetic assessment process but is not expected to have a large resource impact, as the numbers of people being assessed is likely to be relatively small.

The committee noted that the information provided to people with RCC and a suspected or confirmed heritable RCC predisposition syndrome varies. The recommendations are expected to help standardise practice by providing people with some key points to cover before and after diagnosis, including the correct information on how to access specialist genetic services. This could mean that more people access these services, but providing this information is standard practice in many places and the number of people affected are small, so any resource impact would be minimal.

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Why the committee made the recommendations

Very little evidence was identified for this review, and it was of poor quality because only non-comparative studies were found. So, the committee used their expertise and experience to make consensus recommendations.

Because people with heritable RCC predisposition syndromes are likely to have multiple renal lesions in their life, treating RCC in this population aims to balance the risk of metastases with preserving renal function for as long as possible. Some syndromes associated with aggressive disease, such as HLRCC (where the RCC is typically a fumarate hydratase [FH]-deficient RCC), would ideally have the RCC treated promptly, without active surveillance. But this population may have competing clinical needs related to comorbidities, and so immediate treatment may not always be possible. The committee agreed that active surveillance may be suitable in these cases until it is possible to move to treatment. In contrast, people with syndromes associated with less aggressive disease, such as VHL syndrome, BHD syndrome and TSC, could have active surveillance until the lesion is 3 cm in diameter before moving to treatment.

People with a heritable RCC predisposition syndrome have imaging throughout their life as part of standard surveillance to identify renal and non-renal lesions and to monitor other complications associated with their syndrome. They may have some RCCs that are being monitored using active surveillance before any treatment, and other sites that are being monitored as part of follow-up after treatment. The committee agreed that active surveillance for RCC in this population should use MRI or ultrasound imaging, instead of CT, to limit long-term radiation exposure. They also emphasised the importance of clinicians coordinating imaging to prevent duplication and to minimise the person's hospital appointments.

The committee recommended the same active surveillance imaging schedule for these people as for people with sporadic RCC (RCC occurring without a heritable RCC predisposition syndrome) for the first year. From year 2 onwards, the specialist multidisciplinary team should tailor the schedule to ensure that the active surveillance imaging is not less frequent than renal imaging in the active surveillance protocol for sporadic RCC, which is usually every year. They agreed that people who have a renal lesion and a heritable RCC predisposition syndrome associated with more aggressive RCC who are undergoing active surveillance should have a more intensive imaging schedule than people with syndromes associated with less aggressive RCC. But were unable to specify exactly what this should be.

The information to give people during active surveillance, and criteria to trigger a discussion about moving from active surveillance to treatment, were also adapted from those for sporadic RCC, but using 3 cm in diameter as the lesion size cut off to reflect the threshold in recommendation 1.18.2.

How the recommendations might affect practice

Managing heritable RCC predisposition syndromes does not vary widely across the UK. It is standard practice to use active surveillance for people with a heritable RCC predisposition syndrome unless they have a syndrome associated with aggressive RCC. So, it is unlikely that the recommendations will have a large impact on practice, but they are expected to encourage standardisation where variation exists.

People with heritable RCC predisposition syndromes often have other indications that need monitoring. If recommendations for coordinating imaging for active surveillance and follow-up of RCC and non-RCC related imaging are considered alongside other appointments for other conditions, this could be an opportunity to create efficiencies and avoid appointment duplication.

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How the recommendations might affect practice

Managing heritable RCC predisposition syndromes does not vary widely across the UK. It is standard practice to use nephron-sparing treatments for people with a heritable RCC predisposition syndrome unless they have a syndrome associated with aggressive RCC. So, it is unlikely that the recommendations will have a large impact on practice. But they are expected to encourage standardisation where variation exists.

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Why the committee made the recommendations

No evidence on follow-up strategies for people with a hereditable RCC predisposition syndrome after treatment of an RCC was identified. So, the committee used their expertise and experience to make consensus recommendations. The information given is similar to what is given to people with sporadic RCC during follow-up.

The committee recommended abdominal MRI to reduce radiation exposure. This is because people with RCC who have a heritable RCC predisposition syndrome will have long-term imaging to monitor these renal lesions, and more imaging during standard surveillance for their non-RCC related conditions associated with the syndrome. But CT is needed for chest imaging because of the low resolution of chest MRI.

The committee agreed that the intermediate risk of recurrence follow-up imaging schedule for people who have had treatment for sporadic RCC should be used as a starting point for these people too and continued for at least 5 years. But the committee were aware that people with RCC who have a hereditable RCC predisposition syndrome are also under the care of other healthcare professionals who monitor their syndrome using standard surveillance imaging. There was no evidence on when to stop follow-up for a treated RCC and return solely to standard surveillance. The committee agreed that this should be decided based on the person's clinical needs, in discussion with the other healthcare professionals, and not based on a set follow-up duration. They noted that standard surveillance and follow-up schedules may overlap, but in practice it would be unlikely for a person to have a scan for surveillance if they just had a scan for follow-up. The committee highlighted, though, that the situation may be more complex than this, because people with hereditable RCC predisposition syndromes may have several renal lesions at different stages of treatment, active surveillance or follow-up.

How the recommendations might affect practice

Recommended follow-up schedules using MRI or CT imaging reflect current practice for treating RCC in people with a heritable RCC predisposition syndrome.

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