Early Tumor Shrinkage Under Treatment with First-line Tyrosine Kinase Inhibitors as a Predictor of Overall Survival in Patients with Metastatic Renal Cell Carcinoma: a Retrospective Multi-Institutional Study in Japan.
BACKGROUND
Prognostic significance of early tumor shrinkage following treatment with tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma (mRCC) has not been fully elucidated.


OBJECTIVE
The aim of this study was to assess the impact of early tumor shrinkage induced by first-line TKIs on overall survival (OS) in mRCC patients.


METHODS
This study retrospectively included 185 consecutive Japanese patients with mRCC treated with either sunitinib or sorafenib for at least 3 months as first-line molecular-targeted therapy between April 2011 and December 2014 at Kobe University Hospital and its affiliated institutions.


RESULTS
Median OS in the 185 patients was 33.6 months. At 12 weeks after the introduction of TKIs, 9 patients had achieved tumor shrinkage from -100 to -50 %, 43 from -49 to -25 %, 61 from -24 to 0 %, and the remaining 72 patients showed an increase in tumor size. The median OS stratified according to tumor shrinkage as shown above was 59.2, 39.1, 31.4, and 16.1 months, respectively. Univariate analysis identified prior nephrectomy, Memorial Sloan Kettering Cancer Center (MSKCC) risk classification, C-reactive protein (CRP) level, liver metastasis, number of metastatic organs, histological subtype, sarcomatoid feature, and early tumor shrinkage as significant predictors of OS. Of these significant factors, only the MSKCC classification, CRP level, liver metastasis, and early tumor shrinkage were shown to be independently associated with OS on multivariate analysis.


CONCLUSIONS
Early tumor shrinkage could be a useful predictor of OS in mRCC patients receiving TKIs as a first-line molecular-targeted agent.
Division of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. hideakimiyake@hotmail.com.
Hideaki
H
Miyake
Division of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Akira
A
Miyazaki
Division of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Satoshi
S
Imai
Division of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Ken-Ichi
K
Harada
Division of Urology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Masato
M
Fujisawa
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007564:Japan; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D011237:Predictive Value of Tests; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use; D012189:Retrospective Studies; D000077157:Sorafenib; D000077210:Sunitinib; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib