Metastatic Renal Cell Carcinoma: Relationship Between Initial Metastasis Hypoxia, Change After 1 Month's Sunitinib, and Therapeutic Response: An 18F-Fluoromisonidazole PET/CT Study

The aims of this cohort study were to evaluate initial tumor hypoxia in metastatic renal cell carcinoma (mRCC) and its changes after sunitinib treatment, using F-18-fluoromisonidazole PET/CT, and investigate the possible prognostic value of initial tumor hypoxia or its changes under sunitinib therapy. Methods: Antiangiogenic-naive patients with mRCC were prospectively enrolled in this cohort study. Before initiation of sunitinib, CT defined up to 10 targets that were assessed at 1 and 6 mo according to the response evaluation criteria in solid tumors (RECIST). Pretreatment target uptake of F-18-fluoromisonidazole was compared with uptake at 1 mo. Targets were considered hypoxic when their maximal standard uptake value was above mean blood value + 2 SDs. Hypoxic volumes were also computed. Relationships between initial hypoxia status, initial degree of hypoxia, its change at 1 mo, and overall or progression-free survival (OS and PFS, respectively) were assessed by survival analysis. Results: Fifty-three patients were included. Median follow-up was 16.8 mo. F-18-fluoromisonidazole uptake significantly decreased in initially hypoxic target metastases but did not change in others (-22%, P < 10(-4), vs. +1.5%, P = 0.77; P = 10(-3) between groups). Seventy-five percent of patients with hypoxic metastases were free of progressive disease at 4.8 mo (95% confidence interval, 2.99-11.83), compared with 11.3 mo (95% confidence interval, 3.08-36.9) for other patients (P = 0.02), whereas OS was not significantly different. Changes in tumor hypoxia were not related to PFS or OS. Conclusion: Sunitinib reduced hypoxia in initially hypoxic RECIST target metastases but did not induce significant hypoxia in nonhypoxic RECIST target metastases. Patients with initially hypoxic targets have shorter PFS than others.