General
Epidemiology
Incidentaloma
A space-occupying lesion in the kidney that is discovered incidentally should be considered as potentially malignant and treated accordingly. Immediate treatment of an incidentaloma can prolong patient survival. Watchful waiting for incidentaloma does not appear to be justified, unless patient-related factors preclude surgical intervention.
Aetiology
Smoking cessation and weight loss are recommended for their overall health benefits, despite their limited benefit with regard to renal cell carcinoma.
Screening
No role has been established for routine screening for sporadically occurring renal cell carcinoma in the general population or subpopulations. One exception is patients with a hereditary renal tumour syndrome, who should be checked annually for the presence and development of solid or cystic kidney lesions using ultrasound or magnetic resonance imaging (MRI). Serial computed tomography (CT) scan is not preferred in this setting due to the radiation exposure. For lesions greater than 3 cm, nephron-sparing surgery should be performed whenever possible.
Diagnosis
Patient History/Laboratory Tests
Presenting symptoms and those which ultimately lead to the diagnosis of renal cell carcinoma should be recorded in the patient file.
Diagnostic assessment of paraneoplastic symptoms is useful in symptomatic patients with very advanced disease. In these cases, diagnostic assessment should coincide with the treatment plan and goals.
Diagnostic Imaging
CT/MRI
Routine work-up for staging of renal cell carcinoma includes a multiphase contrast CT (unenhanced, arterial phase, venous phase) and a chest x-ray. Ultrasound is also possible, but the results are dependent on the device and the weight and girth of the patient.
Chest x-rays should be used to screen for metastases. Patients who are suspected of having metastases and have some evidence of metastases should undergo a CT scan.
Patients with neurological symptoms suspected of having brain metastases should undergo a CT or, preferably, MRI scan. MRI is preferable for patients who are allergic to contrast media.
Skeletal Scintigraphy
Skeletal scintigraphy for the detection of bone metastases is not a routine part of the initial staging of patients with renal cell carcinoma.
Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)
Radiofluoride (18F) FDG PET is not a standard part of the primary staging of renal cell carcinoma
Pathological Assessment
Biopsy or Cytology
Biopsy or Cytology of the Primary Tumour
Histological needle biopsy or cytological needle aspirate may be useful in determining the nature of a malignant kidney lesion in individual cases, depending on the level of local cytological expertise. The morphology of the malignant lesion can also be determined to a limited degree. Immunological staining plays an important role in both techniques.
It is important to obtain a histo- or cytopathological diagnosis in patients with metastatic or unresectable renal cell carcinoma, and in those with both a confirmed primary tumour at another site and a space-occupying lesion in the kidney.
Frozen Section Analysis
Frozen Section Analysis During Nephron-Sparing Surgery
To aid in the pathological assessment and to enhance the value of surgical intervention for renal cell carcinoma, resected specimens should be labelled and demarcated adequately for pathological assessment.
Frozen Section Analysis in Differential Diagnosis
Intraoperative frozen section analysis is rarely indicated for renal tumours, but is preferably performed on the entire tumour.
Classification
The term Grawitz tumour is obsolete and should be replaced by renal cell carcinoma with subtype designation according to the World Health Organization (WHO) 2004 (see the original guideline document for the WHO classification system for renal cell carcinomas).
Grading
Nuclear grading of renal cell carcinoma should be reported according to the Fuhrman criteria (see original guideline document for the Fuhrman Grading System).
Staging
The TNM staging system of 2002 (or a more recent version) should be used for staging renal cell carcinoma.
Prognostic Factors
At this time, reporting the percentage of necrosis and microscopic venous invasion in renal cell carcinoma is optional.
Counselling and Communication
Diagnosis and Prognosis
It is important to take time for the bad news perception of the cancer patient.
The chance of cure should be stated clearly. Prospects (chance of cure, life expectancy, impact on daily living) should be given for both a favourable and less favourable course of disease.
Most cancer patients want as much information as possible on the diagnosis and prognosis. It is difficult to combine the delivery of bad news with a discussion of specific treatment options. The patient will be more receptive to new information after the initial emotional reaction has passed to some degree. Therefore, it is better to plan another time for a thorough discussion of treatment options. It should be made clear to the patient that they are involved in the decision process.
Decision Making
All cancer patients should be offered the opportunity to participate in the decision-making process in a timely manner, and allowed to determine their degree of participation. Given the positive effects that participating in the decision-making process has on patient satisfaction and disease acceptance, it is important to stimulate and support patient participation as much as possible.
Treatment
Surgery
Radical Nephrectomy
The working group is of the opinion that radical nephrectomy, as described by Robson, is no longer the gold standard for the treatment of small (<7 cm) renal cell carcinomas.
The choice between a transperitoneal and extraperitoneal (translumbar) approach is determined largely by the extent and size of the tumour, as well as the preference and experience of the urologist.
Adrenalectomy
Routine removal of the adrenal gland during radical tumour nephrectomy is not longer justifiable. Adrenalectomy may be beneficial only in cases of abnormal findings by CT or large, upper-pole tumours. However, it is doubtful whether adrenalectomy improves survival in these settings.
Lymphadenectomy
At this time, lymphadenectomy has only diagnostic value in patients with renal cell carcinoma. Consequently it is useful for prognostic purposes only. Lymphadenectomy should not be performed routinely.
Thrombectomy
Tumour Thrombus and Thrombectomy
To ensure optimal care, patients with a supradiaphragmatic tumour thrombus should be treated in a treatment centre with expertise in cardiopulmonary surgical-technical protocols.
Laparoscopic Radical Nephrectomy
Laparoscopic nephrectomy is recommended for tumor stage T1, T2, and possibly T3 tumours. Preferably, this less invasive approach is performed in a specialised treatment centre.
Embolisation
Embolisation can be considered for the palliative treatment of massive haematuria and marked local pain in patients with inoperable or metastatic renal cell carcinoma, and for patients with poor physical condition.
Nephron-Sparing Treatment
The Indication for Nephron-Sparing Treatment of Renal Cell Carcinoma
Nephron-sparing treatment is indicated for a functional kidney with renal carcinoma, if technically possible, regardless of tumour size.
For a normal contralateral kidney, nephron-sparing treatment should be considered for tumours <4 cm.
After nephron-sparing treatment, monitoring should also include checking for possible local recurrence.
Open Partial Nephrectomy
Tumour resection via partial nephrectomy is preferred over radical nephrectomy for renal cell carcinomas with a diameter of 4 cm or less. The surgical margin of unaffected tissue should consist of a layer of macroscopically normal-appearing parenchyma.
Laparoscopic Partial Nephrectomy
A partial nephrectomy should be performed by an open procedure. Laparoscopic partial nephrectomy should be performed only in treatment centres with extensive experience with laparoscopic urological surgery.
Cryoablation
At this time, there is no role for cryoablation in the treatment of renal cell carcinoma outside the context of a clinical trial.
Radiofrequency Ablation
At this time, there is no role for radiofrequency ablation in the treatment of renal cell carcinoma outside the context of a clinical trial
Counselling and Psychosocial Care
Counselling for cancer patients should cover what they can expect specifically during treatment, opportunities for self-care, expected outcomes, and possible adverse events. Repeating information may be helpful, given the patient's level of unfamiliarity, insecurity, and anxiety.
Taking a receptive, empathetic approach to communication and providing time for questions and sharing emotions reduces patient stress and enhances self-efficacy. It is necessary to differentiate repeatedly between possible treatment-related adverse events and signs of disease progression or recurrence.
Recognition of stress is a crucial aspect of patient care. Coordination with care providers who specialise in psychosocial care is therefore desirable.
The palliative phase of cancer care requires adequate counselling, with particular attention given to the impact of treatment options on daily living. For good communication and decision making, it is essential to explore the patient's feelings, worries, and expectations and discuss aspects of quality of life explicitly.
Adjuvant Treatment Following Initial Therapy
Medical Technical
Systemic Therapy
The working group is of the opinion that, at this time, there is no role for adjuvant therapy in high-risk patients following nephrectomy, outside the context of a clinical trial.
Follow-Up
Medical Technical
The working group proposes systematic follow-up for patients with renal cell carcinoma as described, for example, in the European Association of Urology guidelines on renal cell carcinoma.
Check-ups should occur every 6 months for the first 3 years, and annually for the next 5-10 years, depending on tumour characteristics and patient factors. The check-up may include a chest x-ray and ultrasound of the remaining kidney.
Following partial nephrectomy, the operated kidney should be checked regularly by ultrasound or CT for the development of local recurrence. The duration of these checks depends on tumour characteristics and patient factors.
Counselling and Psychosocial Care
Counselling cancer patients on follow-up should provide clear information regarding the goal, value, and use of follow-up. It is important to provide oral and written information on the signs of relapse, so that they can be distinguished from other physical changes that may cause distress.
Discussions during consultation should not be limited to physical symptoms and test results. It should also cover anxiety, worries, and other topics related to quality of life.
Multidisciplinary coordination is desirable to systematically flag psychosocial problems for the purpose of providing appropriate support.
Diagnosis of Local Recurrence/Metastases
Natural Course
Disease progression must be documented before initiating systemic therapy.
Medical Technical
Diagnostic Imaging
18F-FDG PET for Restaging of Renal Cell Carcinoma
Given its high specificity and ability to detect tumours independently of the presence of scar tissue or anatomical changes caused by prior treatment, 18F-FDG PET may be of value as a supplemental test in individual cases where CT is inconclusive. This applies to the detection of locoregionally recurring renal cell carcinoma and distant metastases for recurring renal cell carcinoma, provided that the results may affect treatment decisions
Pathological Analysis
Histological diagnosis is the preferred method for demonstrating metastatic renal cell carcinoma. The diagnosis may be made cytopathologically if adequate cytopathological expertise is available.
For cytological analysis of metastatic renal cell carcinoma, it is important that the pathology department has an adequate method for performing various immunological staining on the available cytological material; for example, cellular material embedded in blocks from which sections are cut for immunohistology is a valid and appropriate method.
Treatment of Local Recurrence/Metastases
Tumour Nephrectomy
For patients with metastatic renal cell carcinoma treated with immunotherapy, tumour nephrectomy is recommended if the performance status of the patients allows.
Metastasectomy and Radiotherapy
Metastasectomy can be considered and performed after multidisciplinary review for select patients with solitary or easily accessible pulmonary metastases, solitary resectable intra-abdominal metastases, a long disease-free interval after nephrectomy, or a partial response in metastases to immunotherapy. High-dose radiation (13 x 3 Gy or 16 x 2.5 Gy) may be used for solitary metastases that are unresectable or not completely resectable. However, the associated morbidity should be discussed with the patient and the potential survival benefit should be assessed on an individual basis.
For patients with myelum compression, immediate surgical decompression followed by radiotherapy should be considered after consulting with a neurosurgeon. Radiotherapy using a standard schema of 1 x 8 Gy, 5 x 4 Gy, or 6 x 4 Gy is a good choice for metastases of renal cell carcinoma if the goal is palliation only. For patients with bone metastases, surgical resection and osteosynthetic stabilisation with postoperative radiotherapy (5 x 4 Gy) may be considered.
Palliative Radiotherapy for Brain Metastases
Patients with renal cell carcinoma, more than 4 brain metastases, and good Karnofsky performance status are candidates for whole brain radiotherapy (WBRT). Selected patients (Karnofsky Index >70%, maximal diameter 3-3.5 cm, no progressive extracranial tumour activity), are candidates for radiosurgery. At this time, the added value of WBRT to radiosurgery is unknown and should be performed only in the context of a clinical trial.
Systemic Therapy
Chemotherapy
Currently available cytotoxic agents are not effective in renal cell carcinoma. Therefore, it is recommended that treatment of patients with metastatic renal cell carcinoma with cytotoxic agents should take place within the context of a clinical trial only.
Immunotherapy
Identifying Candidates for Systemic Therapy
Outside the context of a clinical trial, only those patients with clear cell adenocarcinoma and an intermediate-to-favourable prognosis according to the Motzer criteria are candidates for immunotherapy.
Interferon-alpha (IFN-a)
Treatment with IFN-a can be considered for patients with metastatic renal cell carcinoma and a favourable prognostic profile, including a WHO performance score of 0-2.
For patients with metastatic renal cell carcinoma and good clinical condition, IFN-a monotherapy can be given for a maximum duration of 1 year.
Randomised Phase III Studies of IFN-a or Interleukin-2 (IL-2) Monotherapy Versus Combination Therapy
For patients with metastatic renal cell carcinoma and good clinical condition, IFN-a monotherapy can be considered for a maximum duration of 1 year.
Patients with renal cell carcinoma and an unfavourable risk profile (bone and liver metastases) but good clinical condition are candidates for high-dose intravenous IL-2 treatment when given at an experienced treatment centre. In the Netherlands, treatment with IL-2 is not operational. The data suggest that more attention should be given to this approach in the Netherlands.
Counselling and Psychosocial Care
It is important to tailor the provision of information and support to the personal needs and wishes of the patient. Patients should be asked explicitly whether they want to know all details or only general points; whether they want to hear the hard facts or if they prefer a more tactful approach; whether they would like to discuss their emotions and worries or find emotional support elsewhere; and, lastly, whether they would like to be involved in decision making or follow the advice of the physician.
