Renal Cell Carcinoma

8. FOLLOW UP

8.1. Introduction

Surveillance after treatment for RCC allows the urologist to monitor or identify:

• post-operative complications;
• renal function;
• local recurrence;
• recurrence in the contralateral kidney;
• distant metastases;
• cardiovascular events.

There is no consensus on follow-up strategies after RCC treatment, with limited evidence suggesting that more frequent post-operative imaging intervals do not provide any improvement for early detection of recurrence that would lead to improved survival [642]. As such, intensive radiological surveillance may not be necessary for all patients. Follow-up is also important to assess functional outcomes and to limit long-term sequelae such as renal function impairment, ESRD and cardiovascular events [644].

Currently, the key question is whether any recurrence detection during follow-up and subsequent treatment will lead to any meaningful change in survival outcome for these patients.

In contrast to high-grade and/or locally-advanced disease, the outcome after surgery for T1a low-grade tumours is almost always excellent. It is therefore reasonable to stratify follow-up, taking into account the risk of each different RCC to develop a local or distant recurrence. Although there is no randomised evidence, large studies have examined prognostic factors with long follow-up [197,645,646] (LE: 4). One study has shown a survival benefit in patients who were followed within a structured surveillance protocol vs. patients who were not [647]; patients undergoing follow-up seem to have a longer OS when compared to patients not undergoing routine follow-up [647].

Furthermore, an individualised and risk-based approach to RCC follow-up has recently been proposed. The authors used competing risk models, incorporating patient age, pathologic stage, relapse location and comorbidities, to calculate when the risk of non-RCC death exceeds the risk of RCC recurrence [648]. For patients with low-stage disease but with a Charlson comorbidity index > 2, the risk of non-RCC death exceeded that of abdominal recurrence risk already one month after surgery, regardless of patient age. As for pshylogical factors, a SR including 15 studies revealed that psychological distress (defined as anxiety, depression, or psychological distress at any time during treatment or follow-up) is also prevalent among renal cell carcinoma (RCC) patients, reaching up to 77% in non-metastatic cases [649].

The RECUR consortium, initiated by this Panel, collects similar data with the aim to provide comparators for guideline recommendations. Recently published RECUR data support a risk-based approach; more specifically a competing-risk analysis showed that for low-risk patients, the risk of non-RCC related death exceeded the risk of RCC recurrence shortly after the initial surgery. For intermediate-risk patients, the corresponding time point was reached around four to five years after surgery. In high-risk patients, the risk of RCC recurrence continuously exceeded the risk of non-RCC related death [650]. In the near future, genetic profiling may refine the existing prognostic scores and external validation in datasets from adjuvant trials have been promising in improving stratification of patient’s risk of recurrence [650,651].

Recurrence after PN is rare, but early diagnosis is relevant, as the most effective treatment is surgery [633,652]. Recurrence in the contralateral kidney is rare (1-2%) and can occur late (median 5-6 years) [653] (LE: 3). Follow-up can identify local recurrences or metastases at an early stage. At recurrence, extensive metastatic tumour growth can hinder the opportunity for surgical resection. In addition, early diagnosis of tumour recurrence may enhance the efficacy of systemic treatment if the tumour burden is low.

8.2. Which imaging investigations for which patients, and when?

• The sensitivity of chest radiography and US for detection of small RCC metastases is poor. The sensitivity of chest radiography is significantly lower than CT-scans, as proven in comparative studies including histological evaluation [654-656]. Therefore, follow-up for recurrence detection with chest radiography and US are less sensitive [657].
• Positron-emission tomography and PET-CT as well as bone scintigraphy should not be used routinely in RCC follow-up, due to their limited specificity and sensitivity [117,131].
• Surveillance should also include evaluation of renal function and cardiovascular risk factors [644].
• Outside the scope of regular follow-up imaging of the chest and abdomen, targeted imaging should be considered in patients with organ-specific symptoms, e.g., CT or MRI imaging of the brain in patients experiencing neurological symptoms [658].

Controversy exists on the optimal duration of follow-up. Some authors argue that follow-up with imaging is not cost-effective after five years; however, late metastases are more likely to be solitary and justify more aggressive therapy with curative intent. In addition, patients with tumours that develop in the contralateral kidney can be treated with NSS if the tumours are detected early. Several authors have designed scoring systems and nomograms to quantify the likelihood of patients to develop tumour recurrences, metastases, and subsequent death [250,252,659,660]. These models, of which the most utilised are summarised in Chapter 6 - Prognosis, have been compared and validated [661] (LE: 2). Using prognostic variables, several stage-based follow-up regimens have been proposed, although, none propose follow-up strategies after ablative therapies [662,663]. A post-operative nomogram is available to estimate the likelihood of freedom from recurrence at five years [247]. Recently, a pre-operative prognostic model based on age, symptoms and TNM staging has been published and validated [664] (LE: 3). A follow-up algorithm for monitoring patients after treatment for RCC is needed, recognising not only the patient’s risk of recurrence profile, but also the efficacy of the treatment given (Table 8.1). These prognostic systems can be used to adapt the follow-up schedule according to predicted risk of recurrence. Ancillary to the above, life-expectancy calculations based on comorbidity and age at diagnosis may be useful in counselling patients on duration of follow-up [665].

Table 8.1: Proposed follow-up schedule following treatment for localised RCC, taking into account patient risk of recurrence profile and treatment efficacy (based on expert opinion )

ccRCC = clear cell renal cell carcinoma; CT = computed tomography; mo = months; non-ccRCC = non clear cell renal cell carcinoma; yr = years.

The table above provides recommendations on follow-up strategies for low, intermediate and high risk ofrecurrence in patients curatively treated for localised RCC either with NSS or RN. Computed tomography in the table refers to imaging of both chest and abdomen. Alternatively, MRI of the abdomen can be performedinstead of a CT-scan.
* Risk of recurrence profiles should be based on validated prognostic models. The EAU RCC Guidelines Panel recommends the 2003 Leibovich model for ccRCC [250]. However, other validated models can be used by physicians based on their own national/regional recommendations. In a similar fashion, for curatively treated localised non-ccRCC, the Panel recommends the use of the University of California Los Angeles integrated staging system (UISS) to determine risk of recurrence [251].
** For all risk of recurrence profiles, functional follow-up, mainly monitoring renal and cardiovascular function, may continue according to specific clinical needs irrespective of the length of the oncological follow-up.
*** For low-risk profiles at > 3 years and intermediate-risk at > 5 years of follow-up respectively, consider counselling patients about terminating oncological follow-up imaging based on assessment of comorbidities, age, life expectancy and/or patient wishes.

8.3. Summary of evidence and recommendations for surveillance following RN or PN or ablative therapies in RCC

8.4. Patient involvment in kidney cancer treatment

One RCT has indicated that patient involvement in reporting their symptoms during management of a variety of metastatic solid tumours, can improve clinical outcomes, including OS [666].

A large-scale global survey of patients with renal cell carcinoma (RCC), identified geographic variations in patient education, experience, awareness, access to care, best practices, quality of life, and unmet psychosocial needs [667]. A total of 1,983 patients from 43 countries revealed that at diagnosis, 43% of all respondents had no understanding of their RCC subtype, 29% of all patients reported no involvement in their treatment decision and 96% of respondents reported psychosocial impacts, with only 50% disclosing it to their health care team, with 90% indicated they would be interested in participating in clinical trails.

8.5. Recommendation on patient involvement and shared decision making