The combination of serum insulin, osteopontin, and hepatocyte growth factor predicts time to castration-resistant progression in androgen dependent metastatic prostate cancer- an exploratory study.
We hypothesized that pretreatment serum levels of insulin and other serum markers would predict Progression-free survival (PFS), defined as time to castration-resistant progression or death, in metastatic androgen-dependent prostate cancer (mADPC).



Serum samples from treatment-naïve men participating in a randomized phase 3 trial of ADT +/- chemotherapy were retrospectively analyzed using multiplex assays for insulin and multiple other soluble factors. Cox proportional hazards regression models were used to identify associations between individual factor levels and PFS.



Sixty six patients were evaluable (median age = 72 years; median prostate surface antigen [PSA] = 31.5 ng/mL; Caucasian = 86 %; Gleason score ≥8 = 77 %). In the univariable analysis, higher insulin (HR = 0.81 [0.67, 0.98] p = 0.03) and C-peptide (HR = 0.62 [0.39, 1.00]; p = 0.05) levels were associated with a longer PFS, while higher Hepatocyte Growth Factor (HGF; HR = 1.63 [1.06, 2.51] p = 0.03) and Osteopontin (OPN; HR = 1.56 [1.13, 2.15]; p = 0.01) levels were associated with a shorter PFS. In multivariable analysis, insulin below 2.1 (ln scale; HR = 2.55 [1.24, 5.23]; p = 0.011) and HGF above 8.9 (ln scale; HR = 2.67 [1.08, 3.70]; p = 0.027) levels were associated with longer PFS, while adjusted by OPN, C-peptide, trial therapy and metastatic volume. Four distinct risk groups were identified by counting the number of risk factors (RF) including low insulin, high HGF, high OPN levels, and low C-peptide levels (0, 1, 2, and 3). Median PFS was 9.8, 2.0, 1.6, and 0.7 years for each, respectively (p < 0.001).



Pretreatment serum insulin, HGF, OPN, and C-peptide levels can predict PFS in men with mADPC treated with ADT. Risk groups based on these factors are superior predictors of PFS than each marker alone.
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Dan L. Duncan Building (CPB7.3476), 1515 Holcombe Blvd., Unit 1374, Houston, TX, 77030, USA.
Farshid
F
Dayyani
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Dan L. Duncan Building (CPB7.3476), 1515 Holcombe Blvd., Unit 1374, Houston, TX, 77030, USA.
Amado J
AJ
Zurita
Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Graciela M
GM
Nogueras-González
Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Rebecca
R
Slack
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Dan L. Duncan Building (CPB7.3476), 1515 Holcombe Blvd., Unit 1374, Houston, TX, 77030, USA.
Randall E
RE
Millikan
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Dan L. Duncan Building (CPB7.3476), 1515 Holcombe Blvd., Unit 1374, Houston, TX, 77030, USA.
John C
JC
Araujo
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Dan L. Duncan Building (CPB7.3476), 1515 Holcombe Blvd., Unit 1374, Houston, TX, 77030, USA.
Gary E
GE
Gallick
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Dan L. Duncan Building (CPB7.3476), 1515 Holcombe Blvd., Unit 1374, Houston, TX, 77030, USA.
Christopher J
CJ
Logothetis
Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Dan L. Duncan Building (CPB7.3476), 1515 Holcombe Blvd., Unit 1374, Houston, TX, 77030, USA. pcorn@mdanderson.org.
Paul G
PG
Corn
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D005500:Follow-Up Studies; D017228:Hepatocyte Growth Factor / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D053495:Osteopontin / Q000097:blood*; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000175:diagnosis*; D012189:Retrospective Studies; D015996:Survival Rate
D014408:Biomarkers, Tumor; C066855:HGF protein, human; D007328:Insulin; C506895:SPP1 protein, human; D053495:Osteopontin; D017228:Hepatocyte Growth Factor
Castration resistance; Hepatocyte growth factor; Insulin; Metastatic prostate cancer; Osteopontin; Prognostic marker