Analysis of Molecular Differences in Metastatic Colorectal Cancers and Their Impact on Prognosis Metastatik Kolorektal Kanserlerde Moleküler Farklılıkların Analizi ve Prognostik Sonuçları
Medical Journal of Bakirkoy, cilt.21, sa.1, ss.24-30, 2025 (ESCI, Scopus, TRDizin)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 21 Sayı: 1
- Basım Tarihi: 2025
- Doi Numarası: 10.4274/bmj.galenos.2024.2023.3-8
- Dergi Adı: Medical Journal of Bakirkoy
- Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, CINAHL, EMBASE, TR DİZİN (ULAKBİM)
- Sayfa Sayıları: ss.24-30
- Anahtar Kelimeler: Colorectal cancer, metastasis, KRAS, NRSAS, BRAF, monoclonal antibodies, prognosis
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Objective: Colorectal malignancies are the third most common cancer types according to the World Health Organization and the second leading cause of cancer-related deaths. It is the most common type of cancer that results in mortality in lung and prostate cancer and after lung and breast cancer. Improvements in screening programs, an increase in their availability, and new developments in treatment strategies have resulted in better survival outcomes in the modern era. In terms of treatment; surgery, chemotherapy, targeted therapies, and immunotherapy can be used for colon cancer management. Combination regimens of fluoropyrimidine provide a survival advantage over the best supportive care in the treatment of metastatic colorectal cancer. In addition, adding targeted therapies to standard chemotherapy provided better survival than chemotherapy alone. As with many other malignancies, better survival outcomes are achieved in colorectal cancers with treatments tailored according to the molecular characteristics of the tumor. In this study, we aimed to analyze the effects of selected treatments on survival that are tailored according to molecular differences in metastatic colorectal cancers. Methods: Patients aged 18 years or older, with pathologically confirmed metastatic colorectal cancer diagnosis, and who are suitable for intensive combination chemotherapy [Eastern Cooperative Oncology Group 0-2 (ECOG 0-2)], are enrolled in the study. Demographic findings (age, gender, ECOG performance status), clinical status (metastatic site, systemic treatments administered initially or in further steps, progression-free survival and overall survival), molecular findings [presence of Kirsten rat sarcoma viral oncogene homolog (KRAS), NRSAS, and BRAF mutations] and pathology-related data (histological type, differentiation, tumor location, microsatellite instability status, T and N stage, lymphovascular invasion, perineural invasion for early stage cancers at diagnosis which became metastatic later) were extracted from patients’ files and evaluated retrospectively. The prognostic status was estimated using the Kaplan-Meier curve. Results: The median survival time was 33.80±4.83 and the 5-year survival rate was 38%. The median survival time was observed as 29.32±5.33 in patients with KRAS mutant and 134.17±68.66 in patients with wild KRAS (p=0.005). While the median survival time in patients with neuroblastoma rat sarcoma (NRAS) mutant is 19.02±0.00, it is 33.80±4.83 in patients with Nras wild (p=0.62). While the median survival time was 26.28±12.14 in patients with BRAF mutant, it was 33.80±8.39 in patients with BRAF wild (p=0.055). Conclusion: Survival without treatment is extremely low in patients with metastatic colorectal cancer, and new treatment strategies can be applied according to the molecular behavior of the tumor. Monoclonal antibodies are the most preferred targeted therapies. Examples of these antibodies are bevacizumab and aflibercept, which target vascular endothelial growth factor (VEGF), and cetuximab and panitumumab, which target epidermal growth factor receptor (EGFR). Among these treatments, anti-VEGF molecules are effective regardless of the presence of molecular biomarkers, whereas anti-EGFR treatments are only effective in the absence of mutations in the EGFR-RAS-RAF-MEK pathway.