Abstract
Simple SummaryAround 30–40% of patients with early stage colorectal cancer (eCRC) experience relapse after surgery. Current recommendations for adjuvant therapy are based on suboptimal risk-stratification tools. In elderly patients, risk of relapse assessment is particularly important to ultimately avoid unnecessary chemotherapy-related toxicity in this frailer population. Serum metabolomics via NMR spectroscopy may improve risk stratification by identifying patients with residual micrometastases after surgery and thus at higher risk of relapse. We evaluated the serum metabolomic fingerprints of 94 elderly patients with eCRC (65 relapse free and 29 relapsed), and of 75 elderly patients with metastatic disease. Metabolomics efficiently discriminated patients with relapse-free eCRC from those with metastatic disease, correctly predicting relapse in 69% of relapsed eCRC patients. The metabolomic score was strongly and independently associated with prognosis. Our data suggest metabolomics as a valid addition to standard tools to refine risk stratification for eCRC and warrant further investigation.Adjuvant treatment for patients with early stage colorectal cancer (eCRC) is currently based on suboptimal risk stratification, especially for elderly patients. Metabolomics may improve the identification of patients with residual micrometastases after surgery. In this retrospective study, we hypothesized that metabolomic fingerprinting could improve risk stratification in patients with eCRC. Serum samples obtained after surgery from 94 elderly patients with eCRC (65 relapse free and 29 relapsed, after 5-years median follow up), and from 75 elderly patients with metastatic colorectal cancer (mCRC) obtained before a new line of chemotherapy, were retrospectively analyzed via proton nuclear magnetic resonance spectroscopy. The prognostic role of metabolomics in patients with eCRC was assessed using Kaplan–Meier curves. PCA-CA-kNN could discriminate the metabolomic fingerprint of patients with relapse-free eCRC and mCRC (70.0% accuracy using NOESY spectra). This model was used to classify the samples of patients with relapsed eCRC: 69% of eCRC patients with relapse were predicted as metastatic. The metabolomic classification was strongly associated with prognosis (p-value 0.0005, HR 3.64), independently of tumor stage. In conclusion, metabolomics could be an innovative tool to refine risk stratification in elderly patients with eCRC. Based on these results, a prospective trial aimed at improving risk stratification by metabolomic fingerprinting (LIBIMET) is ongoing.
Highlights
Colorectal cancer (CRC) is the second most common cancer in developed countries, with approximately two-thirds of patients having resectable primary disease at diagnosis.30–40% of these patients will eventually experience relapse after surgery [1].CRC is a heterogeneous entity that presents with different characteristics of clinical onset and individual treatment response, even at the same pathological stage
Colon cancer is defined as early stage, localized, resectable disease without distant metastases at time of diagnosis, while metastatic colorectal cancer is defined as advanced disease, not resectable, with distant metastases
169 elderly patients aged ≥ 70 years with CRC prospectively enrolled in three onco-geriatric clinical trials were included in this study (Figure 1)
Summary
Colorectal cancer (CRC) is the second most common cancer in developed countries, with approximately two-thirds of patients having resectable primary disease at diagnosis.30–40% of these patients will eventually experience relapse after surgery [1].CRC is a heterogeneous entity that presents with different characteristics of clinical onset and individual treatment response, even at the same pathological stage. The assessment of recurrence risk in colon cancer is based primarily on pathological stage as defined by the TNM system based on the depth of tumor wall invasion, lymph node involvement, and distant metastasis [2,3]. This staging system is clinically useful and is highly associated with 5-year overall survival (OS), ranging from 92% in stage I disease to 11% at stage IV. Patients with stage II and III CRC comprise a largely heterogeneous group, with 5-year OS ranging between 50% and 90% [4]
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