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SWOG 8949

"Nephrectomy Plus Interferon Alfa-2b versus Interferon Alfa-2b Alone in Metastatic Renal-Cell Cancer"

Clinical Question

Does nephrectomy followed by interferon therapy result in longer survival than interferon therapy alone in patients with metastatic renal-cell cancer?

Bottom Line

Nephrectomy followed by interferon therapy results in longer survival among patients with metastatic renal-cell cancer than does interferon therapy alone.

Major Points

The Southwest Oncology Group conducted a randomized trial to determine whether nephrectomy affects survival in metastatic renal-cell cancer. The trial compared nephrectomy followed by interferon alfa-2b therapy with interferon alfa-2b therapy alone and found that the median survival was 11.1 months in the nephrectomy group, compared to 8.1 months in the interferon-only group.

Guidelines

As a result of this and related studies, nephrectomy followed by interferon therapy is considered a possible standard of care in metastatic renal-cell cancer, and should potentially be used in the control group of future phase 3 trials exploring treatments of this disease.

Design

- Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial
- N=241 eligible patients with metastatic renal-cell cancer and acceptable candidates for nephrectomy
- Randomization to radical nephrectomy plus interferon alfa-2b therapy or interferon alfa-2b therapy alone
- Mean follow-up: 368 days
- Primary endpoint: Overall survival
- Secondary endpoint: Response of tumor to treatment

Population

Inclusion Criteria:
- Confirmed diagnosis of metastatic renal-cell carcinoma
- Primary tumor considered resectable
- Performance status of 0 or 1 according to the Southwest Oncology Group (SWOG) criteria
- No prior treatment with chemotherapy, hormonal therapy, or biologic-response modifiers.

Exclusion Criteria:
- Uncontrolled cardiac arrhythmias
- History of other cancers within the last five years, with exceptions for certain treated skin cancers or in situ cervical cancer.

Interventions

- Radical nephrectomy through transabdominal, flank, or thoracoabdominal approach, followed by interferon alfa-2b therapy.
- Interferon alfa-2b therapy alone, without nephrectomy.

Outcomes

Primary Outcomes:
- Median survival: 11.1 months for nephrectomy group vs. 8.1 months for interferon-only group (P=0.05)

Secondary Outcome:
- Response rates to interferon therapy were low and similar in both groups (3.3% partial responses in the nephrectomy group vs. 3.6% complete/partial/unconfirmed responses in the interferon-only group).

Criticisms

- The reasons nephrectomy prior to systemic treatment may be beneficial are not well understood.
- Some argue the operative morbidity and mortality associated with nephrectomy may offset potential benefits, although this study showed low rates of complications.
- The study was not designed to evaluate which patients might most benefit from surgery.

Funding

Supported in part by Public Health Service Cooperative Agreements from the National Cancer Institute.