CUA CONSENSUS: SURGICAL MANAGEMENT OF RENAL CELL CARCINOMA 2014
*****All information below contained in more inclusive Open Kidney Cancer Surgery Chapter Notes
Evaluation: history, physical exam, CBC, creatinine, LFTs, markers of bone disease, CT abdo/pelvis, CXR/CT chest
- History and Physical Exam
- History
- Risk factors for renal cell carcinoma
- Symptoms
- Pain (bony and flank) and gross hematuria
- New onset coughing or other respiratory issues may suggest pulmonary metastases and new neurologic symptoms may suggest cerebral metastases
- Performance status should be assessed
- Physical exam
- Blood pressure
- Abdominal examination for masses and assessment for cervical lymphadenopathy and lower extremity edema, which may suggest inferior vena cava (IVC) involvement.
- Neurologic exam should be performed if there is any suggestion of cerebral or spinal metastases.
- Laboratory investigations
- Complete blood count (CBC)
- Renal function
- Liver function (transaminases)
- Markers of bone disease (alkaline phosphatase and corrected calcium)
- Markers of prognosis in patients with advanced disease (Lactic acid dehydrogenase [LDH], platelets, calcium, neutrophils, hemoglobin)
- Urine cytology in central tumours
- Imaging
- Primary tumour
- Triphasic CT abdo/pelvis (preferred)
- The evaluation of CT image includes staging of the primary tumour, determination of lymphadenopathy, abdominal metastatic disease and characterization of the contralateral kidney.
- Consider MRI, if patient pregnant, contrast allergy or renal insufficiency or CT suggests caval thrombus and level cannot be determined
- Doppler ultrasound is also a valuable tool to determine the extent of tumour involvement of the IVC
- Metastatic evaluation
- Chest X-ray, consider CT chest if ≥stage T2
- Bone scan, if clinically indicated (bony pain) or elevated alkaline phosphatase and serum calcium
- Brain CT or MRI if large volume metastatic disease or suspicion of brain metastases in cases with neurologic symptoms
- Isotope renogram may be useful in patients with compromised renal function, bilateral or multifocal disease for surgical planning and patient counselling.
- Positron emission tomography (PET) has no role in the primary assessment of RCC, its role in advanced RCC and assessment of tumour recurrence is evolving
Pretreatment prediction of tumour histology
- Nomograms and Classification trees have been developed and may be used to predict pretreatment histology of renal masses less than 4 cm in diameter.
- Biopsy of the localized renal mass
- Biopsy of SRMs for histologic characterization is an option and may guide treatment decisions
- Biopsy has a mean diagnostic rate of 83%. Histology concordance is good (73-98%), Fuhrman grade concordance is not robust (32-70%)
- In the case of a non-diagnostic initial biopsy, it may be expected that a diagnosis can be made with repeat biopsy, and that the rate of malignancy remains high.
- Indeterminate initial biopsy should not be taken as reassurance regarding the malignant potential of the mass.
- It is essential to identify tumour histology in the setting of metastatic disease, both to confirm that metastatic sites represent tumour spread (and not a second primary tumour) and to classify the histologic subtype as a guide to systemic therapy. In many cases in which cytoreductive nephrectomy will have been performed, the primary histology is known and widespread metastatic disease can comfortably be assumed to be similar. If cytoreductive nephrectomy is not performed prior to planned initiation of systemic therapy, percutaneous biopsy may help to guide therapy.
- In the setting of oligometastatic disease, the link between primary and secondary masses cannot be assumed reliably. Limited data are available with regards to the role of percutaneous biopsy in this setting.
- Biopsy of a renal mass or metastatic site in the setting of metastatic disease is important in guiding systemic therapy.
- In patients undergoing cytoreductive nephrectomy before systemic therapy, or surgical resection of metastatic site, a biopsy may not be necessary.
- Percutaneous biopsy is associated with a low risk of complications.
- Biopsy should be reserved for patients in whom the results might change management.
Treatment options
- Stage T1aN0M0
- Partial nephrectomy recommended. This can be done via open/laparoscopic/robotic procedures.
- EORTC 30904 was a multi-national trial randomizing 541 patients with tumours <5cm suspicious for RCC (and normal contralateral kidney) to RN vs. PN. Primary outcome was OS and CSS was a secondary outcome. In the intention to treat analysis, RN was associated with significant improvement in OS but not difference in CSS (only 2% of patients died of cancer). In the subgroup analysis of patients with RCC, associated for OS was extinguished. Cardiovascular deaths were less common in the RN group. RN favorable in terms of lower perioperative morbidity, while PN provided better renal functional outcomes. Numerous shortcomings of this study (such as premature study closure, trial designed as non-inferiority design but OS significance is based on superiority, patient comorbidity imbalances, cross-over, low statistical power, variable surgical technique and parenchymal sparing) have rendered its interpretation problematic.
- While the impact of a positive surgical margin on subsequent disease outcome has not definitively been shown to adversely affect survival outcomes, a negative surgical margin is always the goal of any nephron-sparing procedure.
- Pure or robot-assisted laparoscopic partial nephrectomy with experienced surgeons (transperitoneal or retroperitoneal).
- Consider laparoscopic radical nephrectomy for tumours not amenable to partial nephrectomy.
- Consider probe ablation by radiofrequency (RFA) or cryotherapy in patients with high surgical risk. A biopsy should be obtained before or at the time of ablation.
- Despite the lack of long-term recurrence and survival data, radiofrequency ablation (RFA) or cryotherapy performed either percutaneously under image guidance or laparoscopically, is a viable management option in patients with tumours less than 3 cm in diameter, with infrequent complications; they do, however, have a slightly higher risk of local recurrence compared to PN. Currently, patients considered for ablative approaches are those with severe medical comorbidities precluding surgical extirpation, or in patients with multiple bilateral lesions, possibly due to underlying genetic predispositions (Birt-Hogg-Dubé syndrome, Von Hippel-Lindau disease).
- Consider active surveillance in the elderly or infirm
- The long-term safety of initial active surveillance with delayed treatment for progression is not yet established. However, it is an alternative for managing SRMs that are asymptomatic and characteristic of RCC on imaging in the elderly and/or comorbid. It is not yet recommended for the young and fit.
- Patients must be counselled on the potential of systemic (1.1%) or local progression (12%) merits
- Follow-up must include serial imaging
- Stage T1bN0M0
- PN (open/laparoscopic/robotic) in cases where technically feasible
- Laparoscopic RN should be offered if a PN is not feasible
- Open RN if laparoscopic surgery not possible.
- Ablative modalities are not recommended for these tumours due to the high rate of incomplete ablation in lesions greater than 4 cm
- Stage T2N0M0
- RN – open/laparoscopic/robotic
- PN – open/laparoscopic/robotic
- The role of extended PN for tumours greater than 7 cm is controversial, and the consideration of such highly selected cases should be limited to experienced surgeons
- Stage T3
- Patients with tumours greater than 7 cm should raise suspicion of involvement of peri-renal tissues, such as Gerota’s fascia or renal sinus fat
- RN – open, laparoscopic or robotic assisted
- Resection of vascular thrombus when applicable (usually open)
- Resection of all gross disease including hilar or retroperitoneal extension
- PN may be attempted in highly selected cases by experienced surgeons
- IVC and renal vein thrombus
- In the presence or absence of distant metastases, tumour thrombus should be resected if technically feasible in appropriately selected patients
- It is recommended that these operations be performed in a centre with experience and with an availability of a multidisciplinary team as these complex procedures have significant risk of morbidity and mortality.
- Tumour thrombectomy with cytoreductive nephrectomy in the metastatic setting should be considered for all patients secondary to the poor outcome associated with untreated intravascular disease.
Special considerations
- Adrenalectomy
- The ipsilateral adrenal gland should be preserved at the time of the nephrectomy provided it appears normal on imaging and there is no sign of direct tumour invasion
- The incidence of ipsilateral adrenal involvement is 1.9% to 7.5%
- CT imaging has been shown to have as high as 99.4% specificity and a 99.4% negative predictive value.
- Ipsilateral adrenalectomy may be performed for patients with abnormal imaging, advanced stage (T3-4), or upper pole tumours greater than 7 cm.
- Lymphadenectomy
- Routine lymphadenectomy at the time of RN or PN is not routinely recommended in patients with clinical N0 disease.
- Lymphadenectomy is recommended in patients with clinical N1M0 disease.
- Lymphadenectomy may be performed for diagnostic purposes in patients with clinical N1M1 disease
- T4N0M0 (Local tumour extension to adjacent organs without metastatic disease)
- RN with resection of adjacent organs if feasible
- Remove all known disease, with possible concomitant resection of involved organs, such as the adrenal gland, liver, pancreas, diaphragm, and bowel.
- 5-year survival is poor and the oncological benefits of surgery should be carefully considered in the context of surgical morbidity.
- Regional lymphadenectomy should therefore be considered for adequate pathologic staging
- TanyN+M0 (Radiographic and clinical evidence of lymph node enlargement)
- RN and regional lymphadenectomy
- There are no randomized trials assessing the effect of lymphadenectomy for patients with RCC and clinical lymphadenopathy. However, a subset of patients with regional lymph node metastases will be cured, or experience prolonged survival following surgery.