Objective: A prospective pilot study in patients with metastatic renal cell cancer and the primary in situ to assess the feasibility of immunotherapy prior to nephrectomy and to evaluate the rationale for a future randomized trial to define the role of response to upfront immunotherapy as selection for cytoreductive surgery.
Patients and methods: Sixteen patients with synchronous multiple metastases were treated with the primary tumor in place and were evaluated with regard to age, sex, sites of extrarenal disease, morbidity, response, nephrectomy rate, time to progression and overall survival. Immunotherapy consisted of 2 courses low-dose IL-2 4MIU/m(2), subcutaneous GM-CSF 2.5 microg/kg and interferon-alpha (IFN-alpha) 5MU flat on day 1-13 and 22-34. Patients with either partial remission (PR) or stable disease (SD) underwent nephrectomy followed by a third and fourth course.
Results: No response was seen in the primary tumors. With regard to extrarenal sites SD was noted in nine cases, PR in two and progressive disease (PD) in five. Eleven patients underwent nephrectomy. No surgical complete response (CR) could be achieved. All patients with PD died after a median overall survival of 3 months versus 11.5 months (range 4-22) in those who underwent nephrectomy. Four patients are still alive at 10, 12, 18 and 19 months. Median duration of response was 6 months (range 2-10). One patient with SD following nephrectomy developed CR after two additional cycles, which is currently maintained for >10 months.
Conclusions: Absence of progression at metastatic sites following immunotherapy may be used as a selection for nephrectomy in this selected group. Non-responding patients can be spared from surgery. A randomized study is needed to assess the timing of nephrectomy in combination with immunotherapy with regard to morbidity, overall survival and quality of life.