Serial urinary IL-2, IL-6, IL-8, TNFalpha, UBC, CYFRA 21-1 and NMP22 during follow-up of patients with bladder cancer receiving intravesical BCG.
BACKGROUND
We evaluated the potential role of serial preinstillation levels of several interleukins, TNFalpha and urinary tumor markers to monitor patients with bladder cancer receiving intravesical BCG.


METHODS
121 urine samples were collected from: patients with bladder cancer treated with BCG (group 1); patients with bladder cancer receiving other intravesical treatment (group 2) and patients with urinary tract infections (group 3). Cytokines [IL-2, IL6 and [L8] and TNFalpha and urinary tumor markers [UBC, CYFRA 21-1 and NMP22] were measured by immunoassays.


RESULTS
In 3 out of 15 BCG non-responders that recurred over the period of the study, no cytokine peak for IL-2, IL-6 or TNFa were detected. Urinary tumor markers increased in 2 out of 3 of these patients earlier than scheduled cystoscopies. Cytokine measurement was heterogeneous among 12 out of 15 BCG-responding patients: there were low levels of IL-6 and TNFalpha and peaks of IL-2 and IL-8 in 10 out of 12 and 4 out of 12 patients, respectively. During responding patients' follow-up we observed false-positive results in 7 out of 65 urine samples for UBC, 8 out of 65 for CYFRA 21-1 and 20 out of 65 for NMP22. Urinary tract infections were the main factor associated with non-specific elevations of IL-6 and IL-8 and urinary tumor markers in all groups of patients.


CONCLUSIONS
Although larger series are required to confirn our preliminary observations, our data argue for a potential predictive role for IL-2 of favourable response to BCG therapy. Monitoring BCG with urinary tumor markers could early detect recurrence in non-responding patients.
Sanchez-Carbayo
M
M
Servicio de Bioquimica, Hospital Universitario de Salamanca, Spain. mscarbayo@ibercom.com
Urrutia
M
M
Romani
R
R
Herrero
M
M
Gonzalez de Buitrago
J M
JM
Navajo
J A
JA
D000283:Administration, Intravesical; D000951:Antigens, Neoplasm / Q000652:urine*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001500:BCG Vaccine / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000652:urine*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000401:mortality / Q000628:therapy / Q000652:urine*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D016207:Cytokines / Q000652:urine*; D018450:Disease Progression; D006801:Humans; D007167:Immunotherapy; D007376:Interleukin-2 / Q000652:urine; D015850:Interleukin-6 / Q000652:urine; D016209:Interleukin-8 / Q000652:urine; D053539:Keratin-19; D007633:Keratins; D016685:Mitomycin / Q000008:administration & dosage; D009363:Neoplasm Proteins / Q000652:urine*; D009687:Nuclear Proteins / Q000652:urine; D013852:Thiotepa / Q000008:administration & dosage; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000652:urine; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000628:therapy / Q000652:urine*
D000951:Antigens, Neoplasm; D001500:BCG Vaccine; D014408:Biomarkers, Tumor; D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D016209:Interleukin-8; D053539:Keratin-19; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014409:Tumor Necrosis Factor-alpha; C440529:UBC antigen; C102012:antigen CYFRA21.1; C100379:nuclear matrix protein 22; D016685:Mitomycin; D007633:Keratins; D013852:Thiotepa