Inferior vena cava involvement

One of the unique features of renal cell carcinoma (RCC) is its frequent pattern of growth intraluminally into the renal venous circulation, also known as venous tumor thrombus.

About 45%–70% of patients with RCC and inferior vena cava (IVC) thrombus can be cured with an aggressive surgical approach, including radical nephrectomy (RN) and IVC thrombectomy.

Staging of the level of IVC thrombus is as follows: I, adjacent to the ostium of the renal vein; II, extending up to the lower aspect of the liver and below the hepatic veins; III, involving the intrahepatic portion of the IVC but below the diaphragm; and IV, extending above the diaphragm.

In all series, a significant proportion of patients with level IV IVC thrombi are cured with surgical resection, typically in the absence of metastases and other adverse features.

Magnetic resonance imaging (MRI) is the preferred diagnostic study at many centers; however, recent literature indicates that an appropriately performed computed tomography (CT) can provide essentially equivalent information.

The surgical approach is tailored to the level of IVC thrombus but uniformly begins with early ligation of the arterial blood supply and in the process the kidney is gently mobilized, leaving it only attached via the renal vein.

Vascular control for level III and level IV IVC thrombi requires more extensive dissection, venovenous bypass, or cardiopulmonary bypass and hypothermic circulatory arrest. For level III thrombi, mobilization of the liver and exposure of the intrahepatic IVC often allows the thrombus to be mobilized caudad to the hepatic veins, and venous isolation can then proceed as for a level II thrombus ( Fig. 29.1 ). Patient selection is critical because many patients, especially those with metastatic disease, will have a limited life expectancy.

Schematics illustrating surgical techniques for management of inferior vena cava (IVC) thrombi according to level. (A) Level I IVC thrombus managed with a Satinsky clamp to achieve vascular isolation. (B) Level II IVC thrombus managed by sequential clamping of the lower IVC, contralateral renal vein, and cephalad IVC, along with mobilization of the IVC and occlusion of lumbar veins, allowing for vascular isolation. (C) Level III IVC thrombus managed by mobilization of the liver, providing exposure of the intrahepatic IVC and retraction of the thrombus to facilitate placement of the upper IVC clamp just below the level of the hepatic veins. Through this approach, vascular isolation is achieved in a manner similar to that in B. If the cephalad clamp must be placed above the level of the hepatic veins, a Pringle maneuver should be performed to temporarily occlude the hepatic blood flow.

(Reprinted with permission, Cleveland Clinic Center for Medical Art and Photography, Copyright 2007-2009. All rights reserved.)

However, surgery can impart a significant palliative benefit by preventing pulmonary emboli and minimizing disability from intractable edema, ascites, cardiac dysfunction, or associated local symptoms such as abdominal pain and hematuria.

Locally invasive renal cell carcinoma

In evaluation of patients with large, invasive retroperitoneal masses, a broad differential diagnosis should be considered, including adrenocortical carcinoma, urothelial carcinoma, sarcoma, and lymphoma, in addition to locally invasive RCC.

Because surgical therapy is the only potentially curative management for RCC, extended operations with en bloc resection of adjacent organs are occasionally indicated.

However, even with an aggressive surgical approach, the prognosis remains poor. Despite a significant likelihood of recurrence of RCC with poor-risk features, there is no established evidence of a benefit for adjuvant therapy in patients who appear to be cancer free after surgical resection, and observation remains the standard of care. Ongoing adjuvant clinical trials investigating targeted molecular agents, checkpoint inhibitors, and other novel systemic approaches should be supported in an effort to identify an efficacious adjuvant strategy.

Lymph node dissection for renal cell carcinoma

The presence of lymph node metastasis is an important prognostic factor and defines a high-risk subset of patients with advanced RCC.

Although lymphadenectomy for RCC provides accurate staging ( Table 29.1 , Fig. 29.2 ), the therapeutic benefits of routine lymphadenectomy are controversial.

Frequency of lymph node positivity detected at extended lymphadenectomy in patients with lymph node positive renal cancer at nephrectomy.

(From Crispen PL, Breau RH, Allmer C, et al. Lymph node dissection at the time of radical nephrectomy for high-risk clear cell renal cell carcinoma: indications and recommendations for surgical templates. Eur Urol 2011;59:18-23.)

Most important, the European Organization for Research and Treatment of Cancer (EORTC) 30881 randomized trial of lymphadenectomy at RN failed to show a survival advantage for most patients undergoing lymphadenectomy.

Lymphadenectomy may be performed in patients with clinically suspicious (radiographic or intraoperative) lymphadenopathy for staging purposes and, because of lack of data indicating a reliable therapeutic benefit, need not be performed routinely in patients with localized kidney cancer and clinically negative nodes.

Local recurrence after radical nephrectomy or nephron-sparing surgery

Local recurrence of RCC after RN, which includes recurrence in the renal fossa, ipsilateral adrenal gland, renal vein stump or adjacent IVC, or ipsilateral retroperitoneal lymph nodes, is an uncommon event, occurring in 2%–4% of cases.

Risk factors include locally advanced or node-positive disease and adverse histopathologic features.

Only about 20%–40% of local recurrences are isolated; the majority of patients with local recurrence also have systemic disease, and a thorough metastatic evaluation should be pursued.

Surgical resection of isolated local recurrence of RCC after RN should be considered because it can provide long-term cancer-free status for 30%–40% of patients.

Local recurrence in the remnant kidney after PN for RCC has been reported in 1.4%–10% of patients, and the main risk factors are advanced T stage or high tumor grade.

Patients with isolated local recurrence after PN can be considered for repeat PN, completion nephrectomy, TA, or AS.

Prognostic factors

Several clinical features, such as a long time interval between initial diagnosis and appearance of metastatic disease and presence of fewer sites of metastatic disease, have been associated with better outcome.

Poor performance status and the presence of lymph node and/or liver metastases have long been recognized to be associated with shorter survival.

A multivariate analysis showed a poor performance status (Karnofsky score <80), an elevated serum lactate dehydrogenase level (>1.5 times upper limit of normal), a low hemoglobin (less than the lower limit of normal), an elevated corrected calcium concentration (>10 g/dL), and lack of prior nephrectomy were independent predictors of a poor outcome ( Table 29.2 ).

Patients could be stratified into three distinct prognostic groups based on these five poor prognostic factors ( Table 29.3 ). The overall survival (OS) times in patients with no adverse factors (favorable-risk group), one to two risk factors (intermediate-risk group), and more than three risk factors (poor-risk group) were 20 months, 10 months, and 4 months, respectively.

The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) investigators confirmed the prognostic relevance of several components of the Memorial Sloan Kettering Cancer Center (MSKCC) model (performance status, hypercalcemia, anemia, and time from diagnosis to treatment); in addition, neutrophilia and thrombocytosis were identified as additional, independent predictors of poor outcome. Patients were divided into three risk categories ( Tables 29.4 and 29.5 ).

Table 29.5

Risk Stratification Based on Adverse Prognostic Factors in 849 Patients Treated with First-Line Vascular Endothelial Growth Factor–Targeted Therapy

Data from Heng DY, Xie W, Regan MM, et al. External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a population-based study. Lancet Oncol 2013;14(2):141-148.

RISK GROUP	NO. OF ADVERSE PROGNOSTIC FACTORS	MEDIAN OVERALL SURVIVAL (months)
Good	0	43.2
Intermediate	1–2	22.5
Poor	3–6	7.8

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