title: Cytokine Panel for Response to Intravesical Therapy (CyPRIT): Nomogram of Changes in Urinary Cytokine Levels Predicts Patient Response to Bacillus Calmette-Guérin.
abstract: The response of non-muscle-invasive bladder cancer (NMIBC) to intravesical immunotherapy with bacillus Calmette-Guérin (BCG) depends on adequate stimulation of an immune response. Although BCG has been used for decades, we lack tools to accurately predict response in individual patients. To address this deficiency, we initiated a clinical trial in patients with intermediate- and high-risk NMIBC. BCG was administered according to the Southwest Oncology Group protocol. Urine samples were collected for cytokine assay at baseline, immediately before and after BCG instillation at 6 wk, and immediately before and after the third BCG instillation of the first maintenance course. Levels of 12 cytokines were measured, and changes from baseline were calculated after treatment. A total of 130 patients were enrolled. Increases in single cytokines correlated with recurrence, but the best predictor of recurrence was changes in a combination of cytokines. A nomogram (CyPRIT) constructed using urinary levels of nine inducible cytokines (IL-2, IL-6, IL-8, IL-18, IL-1ra, TRAIL, IFN-γ, IL-12[p70], and TNF-α) predicted the likelihood of recurrence with 85.5% accuracy (95% confidence interval 77.9–93.1%).” This cytokine panel and nomogram have potential for identifying patients at risk of tumor recurrence during BCG treatment to guide modification of the dose and duration of BCG immunotherapy.
  
  
  
  Clinicaltrials.gov NCT01007058.
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: akamat@mdanderson.org.
authors.forename: Ashish M
authors.initials: AM
authors.lastname: Kamat
authors.affiliation: Alere Inc., San Diego, CA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Briggman
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Urbauer
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Svatek
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Graciela M
authors.initials: GM
authors.lastname: Nogueras González
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Roosevelt
authors.initials: R
authors.lastname: Anderson
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: H Barton
authors.initials: HB
authors.lastname: Grossman
authors.affiliation: Department of Strategic Industry Ventures, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ferran
authors.initials: F
authors.lastname: Prat
authors.affiliation: Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Colin P
authors.initials: CP
authors.lastname: Dinney
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001500:BCG Vaccine / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000652:urine; D016207:Cytokines / Q000652:urine*; D005260:Female; D006801:Humans; D007378:Interleukins / Q000652:urine; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000652:urine*; D049451:Nomograms; D011237:Predictive Value of Tests; D011446:Prospective Studies; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000652:urine; D014409:Tumor Necrosis Factor-alpha / Q000652:urine; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery / Q000652:urine*
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D014408:Biomarkers, Tumor; D016207:Cytokines; D007378:Interleukins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha
keywords: Bacillus Calmette-Guérin response; Bladder cancer; Nomogram; Prediction; Urinary cytokines