Elevated Lactate Dehydrogenase in Colon Cancer
Elevated LDH in colon cancer indicates poor prognosis with significantly reduced overall survival, particularly in metastatic disease, and serves as an independent adverse prognostic factor that should be measured at diagnosis for risk stratification. 1, 2
Prognostic Significance
Elevated LDH is strongly associated with worse survival outcomes in colorectal cancer patients:
In metastatic colorectal cancer (mCRC), elevated LDH independently predicts poor overall survival (OS), with median OS of approximately 16-20 months in high-LDH patients versus 25-35 months in low-LDH patients 2, 3, 4
High LDH levels correlate with reduced progression-free survival (PFS), with median PFS of 4.2 months versus 8 months in patients with high versus low LDH receiving chemotherapy alone 5
A meta-analysis of 8,261 patients confirmed that high LDH is associated with poor OS (HR 1.75,95% CI 1.52-2.02) in colorectal cancer patients 4
However, the prognostic value differs by disease stage:
In non-metastatic colorectal cancer, LDH alone has not demonstrated significant prognostic value (HR 1.21,95% CI 0.79-1.86), with sensitivity of only 76% and specificity of 46.5% 4, 6
The prognostic significance is most robust in metastatic disease, where elevated LDH combined with elevated serum lactate represents an independent prognostic factor for both PFS (HR 2.922) and OS (HR 3.187) 2
Clinical Risk Stratification
For patients with metastatic colon cancer, use a two-factor prognostic score combining ECOG performance status with LDH: 7, 1
- Good prognosis group: ECOG PS 0-1 AND normal LDH
- Poor prognosis group: ECOG PS >1 OR elevated LDH
This simple algorithm provides effective risk stratification without requiring complex molecular testing 7, 1
Additional Prognostic Context
Other independent adverse prognostic factors that compound the significance of elevated LDH include: 7, 2
- Reduced serum albumin (HR 0.417-0.459) 2
- Elevated alkaline phosphatase 7
- Presence of liver metastases 7
- Higher number of metastatically involved organs 7
Predictive Value for Treatment Response
Elevated LDH may predict differential benefit from bevacizumab-based therapy:
In patients with high LDH receiving bevacizumab plus chemotherapy, response rates improved to 58% versus 14% in low-LDH patients, suggesting bevacizumab may partially overcome the adverse prognosis associated with elevated LDH 5
Bevacizumab addition reduced progressive disease rates (16.4% vs 30.5%) and improved PFS specifically in the high-LDH subgroup (p=0.028) 3
However, the predictive value remains controversial, as not all studies confirmed improved outcomes with bevacizumab in high-LDH patients 5, 3
Clinical Measurement Recommendations
Measure total LDH at initial cancer diagnosis for prognostic stratification: 1
Ensure proper specimen handling to exclude hemolysis artifact, which falsely elevates LDH 1, 8
LDH isoenzyme fractionation is not recommended, as it adds no clinical value beyond total LDH measurement 8
Repeat measurements when treatment concludes, as rising LDH indicates progressive disease 1
Important Caveats
LDH elevation is not specific to malignancy and requires clinical context:
Mild elevations (<5× upper limit of normal) are commonly benign 1
Marked elevations suggest malignancy, high tumor burden, or tumor lysis syndrome 1
Age is significantly associated with increased LDH levels independent of cancer status 6
The prognostic value of LDH for PFS remains uncertain (HR 1.36,95% CI 0.98-1.87), with inconsistent results across studies 4