Retrospective analysis of metastatic colorectal cancer based on clinical cancer registry data. Tumor biology, treatment, and outcome

Metastatic colorectal cancer (mCRC) is one of the most common causes of cancer-related death with median overall survival (OS) between 26-36 months. Important prognostic factors are the localization and tumor biology. Systemic chemotherapy has been the main treatment approach for non resectable mCRC. A wide range of new therapies have been proposed owing to the identification of new targetable biomarkers. Although randomized controlled trials are indispensable for investigating efficacy of new treatment protocols, their validity outside of clinical trials can be limited. Evaluation of different treatment options based on real-world data may provide additional insight into the usefulness of different therapeutic strategies. The aim of the present study is to explore clinical and biological profile of mCRC as well as the disease treatment and patient outcome based on the data collected in the cancer registry of Baden-Wuertemberg state, Germany. Real-world treatment is compared with the current clinical guidelines and mCRC studies.

Records for patients with metastatic colorectal adenocarcinoma diagnosed in 2016-2022 were selected from the clinical Cancer Registry Database of the German Federal State Baden Württemberg (BW). Invasive disease-free survival (iDFS) and overall survival were assessed using Kaplan-Meier statistics and multivariable Cox proportional hazard models. The following parameters were considered: age, gender, tumor localization, BRAF and RAS mutations, MSI status, and systemic treatment.

A total of 2207 mCRC cases were identified. Among them, there are 808 rectal tumors, 729 left- and 670 right-sided colon carcinomas. For 1613 (840) patients RAS (BRAF) mutations and in 1077 cases MSI status was reported. All three markers are mostly associated with right-side-cancer. Around 12% of patients with reported BRAF status presents with BRAF alterations (25% of right-side-cancer, 7% of rectum and 12% of left-side-cancer). Overall survival of patients diagnosed with right-sided carcinoma was significantly worse compared to those with left-side and rectal carcinomas (23 months vs 33 and 30 months respectively, p < 0.001). BRAF mutation was the most significant prognostic factor: HR 1.89 (95% CI 1.21-3.0). The median overall survival of BRAF mutated carcinoma was 18 months. A variety of chemotherapy modalities, including VEGF- and EGFR-targeted therapy, as well as mono- or combined immunotherapy have been reported to the registry.

In the present study tumor biology, therapy modalities, and treatment outcomes were analyzed for mCRC cases in the Baden Württemberg state of Germany with a population of more than 11 million habitants. BRAF status was confirmed as the most important prognostic factor. BRAF and RAS mutations as well as MSI status were associated with right-sided colon cancer. Right-side tumor location was also associated with greater risk of death compared to left-side location and to rectal cancer. It is noteworthy, that these results represented a case distribution and routine clinical practice in a real-world patient population.

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