Holten-Andersen, Mads

3576 Background: Identification of a marker with strong prognostic impact on clinical outcomes would aid in the management of pts with primary, curatively resected CRC. We conducted a pooled individual pt data analysis to confirm the prognostic value of pTIMP-1 for overall survival (OS) in stage II and III CRC. Methods: pTIMP-1 was determined in plasma using immunoassays. Samples and clinical data were included from 5 studies with a total of 1,042 stage II/III pts resected between 1991 – 2006 (Holten-Andersen (HA), 2000 [n=378], HA, 2004 [n=226], Waas, 2005 [52], Birgisson, 2010 [225], Nielsen, 2011[n=161]). To provide comparable measures across studies, pTIMP-1 values were rescaled using fractional ranks (FR, based on ranks and sample size). Pts were grouped by the median of the pTIMP-1 FR score. Stratified log-rank tests and multivariate Cox models assessed the association between OS and pTIMP-1 FR. Results: Overall, 59% were male; median age 69 years; 56% had stage II disease and 50% had colon cancer. The median follow-up was 5.5 years with 457 deaths. Continuous pTIMP-1 FR as a linear effect was significantly associated with OS (p < .0001, HR=1.38 for a 0.3 unit increase in FR score, 95% CI 1.25 to 1.52).Pts with pTIMP-1 FR above vs below the median had significantly shorter OS (HR, 1.72; 95% confidence interval[CI], 1.42 to 2.08, p <0.0001), which remained significant after adjusting for age, gender, stage, disease location, and serological CEA (HR, 1.31; 95%CI, 1.07 to 1.60; p = 0.009). Results by stage are shown in the table. No evidence of an interaction between pTIMP-1 and stage or disease location (colon vs. rectal) was observed (all p > 0.6). Conclusions: pTIMP-1 is a strong prognostic marker for predicting OS independent of age, gender, CEA, stage and site of disease in curatively resected stage II and III CRC. [Table: see text]

AbstractBackground: Updated National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed.Methods: Published reports relevant to use of tumor markers for 5 cancer sites—testicular, prostate, colorectal, breast, and ovarian—were critically reviewed.Results: For testicular cancer, α-fetoprotein, human chorionic gonadotropin, and lactate dehydrogenase are recommended for diagnosis/case finding, staging, prognosis determination, recurrence detection, and therapy monitoring. α-Fetoprotein is also recommended for differential diagnosis of nonseminomatous and seminomatous germ cell tumors. Prostate-specific antigen (PSA) is not recommended for prostate cancer screening, but may be used for detecting disease recurrence and monitoring therapy. Free PSA measurement data are useful for distinguishing malignant from benign prostatic disease when total PSA is &lt;10 μg/L. In colorectal cancer, carcinoembryonic antigen is recommended (with some caveats) for prognosis determination, postoperative surveillance, and therapy monitoring in advanced disease. Fecal occult blood testing may be used for screening asymptomatic adults 50 years or older. For breast cancer, estrogen and progesterone receptors are mandatory for predicting response to hormone therapy, human epidermal growth factor receptor-2 measurement is mandatory for predicting response to trastuzumab, and urokinase plasminogen activator/plasminogen activator inhibitor 1 may be used for determining prognosis in lymph node–negative patients. CA15-3/BR27–29 or carcinoembryonic antigen may be used for therapy monitoring in advanced disease. CA125 is recommended (with transvaginal ultrasound) for early detection of ovarian cancer in women at high risk for this disease. CA125 is also recommended for differential diagnosis of suspicious pelvic masses in postmenopausal women, as well as for detection of recurrence, monitoring of therapy, and determination of prognosis in women with ovarian cancer.Conclusions: Implementation of these recommendations should encourage optimal use of tumor markers.