TITLE:
Carcinoma of Unknown Primary Site: Outcomes in Patients with a Colorectal Molecular Profile Treated with Site Specific Chemotherapy
AUTHORS:
F. Anthony Greco, Wayne J. Lennington, David R. Spigel, Gauri R. Varadhachary, John D. Hainsworth
KEYWORDS:
Carcinoma of Unknown Primary Site; Colorectal Cancer; Molecular Profiling
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.3 No.1,
February
16,
2012
ABSTRACT: Purpose: Accurate identification of carcinoma of unknown primary site (CUP) patients with colorectal sites of origin may improve outcomes by directing colorectal chemotherapy rather than empiric chemotherapy. Clinical features, standard pathologic evaluation, treatment response, and survival of CUP patients whose tumors had colorectal genetic signatures were examined. Patients and Methods: We prospectively tested paraffin-embedded biopsies from 213 CUP patients using mRNA-based RT-PCR assays, and identified patients with colorectal genetic signatures. Results: Assays were successful in 185 specimens (87%); 32 (17%) had colorectal genetic signatures. All 32 patients had carcinoma; colonoscopy was normal in 30 patients studied; 29 patients (90%) had typical metastatic sites; 17 (53%) had consistent IHC profiles (CK20+, CDX2+). Twenty-nine patients (90%) received first- and/or second-line colorectal chemotherapy regimens (response rates of 69% and 54%, respectively). Median, 2- and 4-year survivals for all 32 patients were 21 months, 42%, and 35%, respectively. Conclusion: The majority of CUP patients with colorectal molecular profile diagnoses responded to site-specific chemotherapy; median survival was similar to patients with known advanced colorectal carcinoma and superior to expected survival of CUP patients receiving empiric chemotherapy. Molecular profile assays can identify CUP patients with colorectal carcinoma; colorectal chemotherapy appears to improve outcomes.