Immunotherapy of renal cell carcinoma
- Daniel George, MD
Daniel George, MD
- Professor of Medicine and Surgery
- Duke University Medical Center
- Eric Jonasch, MD
Eric Jonasch, MD
- The University of Texas MD Anderson Cancer Center
Surgical resection of localized renal cell carcinoma (RCC) can be curative for localized disease, but many patients eventually recur. In addition, many RCCs are clinically silent for much of their course, and the initial diagnosis is often delayed until disease is either locally advanced and unresectable or metastatic. The prognosis for patients with advanced or metastatic RCC can vary widely from a few months to many years depending on the clinical, pathologic, laboratory, and radiographic features of disease.
Immunotherapy using high-dose interleukin-2 (IL-2) is a treatment option for carefully selected good-performance patients who have access to a facility able to manage the toxicity associated with this approach. Based upon results from a randomized phase III trial discussed below, immunotherapy with nivolumab, an anti-programmed cell death 1 (PD-1) agent, has a role for patients who were initially treated with a molecularly targeted agent. The integration of nivolumab into the management of patients with advanced or metastatic RCC is the subject of ongoing research.
This topic will review the data supporting the roles of IL-2 and the checkpoint inhibitor nivolumab. Interferon-alfa (IFNa) and other experimental approaches are discussed more briefly.
An overview of the treatment approach to RCC, prognostic factors in RCC, and the use of anti-angiogenic and molecularly targeted therapy are discussed separately. (See "Overview of the treatment of renal cell carcinoma" and "Anti-angiogenic and molecularly targeted therapy for advanced or metastatic clear-cell renal cell carcinoma".)
RATIONALE FOR IMMUNOTHERAPY
The fields of immunology and oncology have been linked since the late 19th century, when the surgeon William Coley reported that an injection of killed bacteria into sites of sarcoma could lead to tumor shrinkage. Since that time, exponential advances in the understanding of the intersection between immune surveillance and tumor growth and development have led to broad therapeutic advances that are now being studied in all cancer types. (See "Principles of cancer immunotherapy".)
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- RATIONALE FOR IMMUNOTHERAPY
- CHOICE OF THERAPY
- High-dose bolus IL-2
- Predictors of response
- - Clinical factors
- - Histology and carbonic anhydrase IX expression
- - Sarcomatoid RCC
- NIVOLUMAB AND CHECKPOINT INHIBITION
- Efficacy of nivolumab
- Nivolumab plus ipilimumab
- OTHER IMMUNOTHERAPY APPROACHES
- Other interleukins
- CYTOREDUCTIVE (DEBULKING) NEPHRECTOMY
- ADJUVANT IMMUNOTHERAPY
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS