What is considered a high lactate dehydrogenase (LDH) level in cancer?

What Constitutes High LDH in Cancer

In cancer patients, LDH levels above 1.5 times the upper limit of normal (ULN) are generally considered elevated and clinically significant, though specific thresholds vary by cancer type and carry distinct prognostic implications. 1

Cancer-Specific LDH Thresholds

Testicular Germ Cell Tumors

• LDH >1.5× ULN defines intermediate prognosis in non-seminomatous germ cell tumors 1
• LDH >2.5× ULN separates good from intermediate/poor prognosis groups, with 3-year progression-free survival dropping from 92-93% to 75-80% 1
• LDH >10× ULN defines poor prognosis with 5-year overall survival of only 67% 1
• These thresholds are incorporated into the International Germ Cell Cancer Collaborative Group (IGCCCG) classification for risk stratification 1

Osteosarcoma

• Any elevation above normal range is prognostically significant 2, 1
• Elevated LDH correlates strongly with metastatic disease at presentation 2
• 5-year disease-free survival is 39.5% with high LDH versus 60% with normal values 2, 1
• LDH levels are significantly higher in patients with metastatic versus localized disease 2

Multiple Myeloma

• LDH >500 U/L (when normal is <225 U/L) defines "high-grade myeloma" with lymphoma-like aggressive behavior 3
• LDH >300 U/L before or after high-dose chemotherapy identifies VAD-resistant disease with extraosseous features and poor prognosis 3
• Even high-normal LDH levels (versus <200 U/L) predict shorter survival regardless of tumor mass 3

Melanoma (Stage IV)

• LDH <1.5× ULN is associated with better outcomes and incorporated into AJCC staging 1, 4
• Patients with elevated LDH derive only marginal benefit even from the most effective modern therapies 5

Cancer of Unknown Primary

• Any LDH elevation above normal combined with ECOG performance status >1 defines poor prognosis 1
• Good prognosis requires both ECOG 0-1 AND normal LDH 1

Clinical Context and Interpretation

Important Caveats

• Numerous benign conditions elevate LDH, including hemolysis, liver disease, myocardial infarction, kidney disease, infections, and strenuous exercise 1
• Sample hemolysis falsely elevates LDH—always consider this artifact 1
• Tumor lysis during chemotherapy causes transient elevation; if LDH rises between day 1 of cycle 1 and day 1 of cycle 2, repeat testing midway through cycle 2 1

Prognostic Significance Beyond Tumor Burden

• LDH is not merely a marker of tumor burden but reflects activation of oncogenic signaling pathways, metabolic activity, invasiveness, and immunogenicity 5
• In lymphomas, LDH >250 U/L (when normal <225 U/L) is more frequent in high-grade (50%) and intermediate-grade (35%) than low-grade malignancies (6%) 6
• Elevated LDH in lymphomas correlates with bulky disease, B symptoms, bone marrow involvement, and leukemic syndrome 6

Measurement Timing

• Measure at diagnosis for baseline prognostic stratification 1
• Measure post-orchiectomy and before chemotherapy in testicular cancer 1
• Measure at treatment conclusion as rising tumor markers soon after therapy indicate progressive disease requiring salvage therapy 1
• Do NOT use LDH alone to guide treatment decisions in pure seminoma 1

Practical Algorithm

For known cancer patients:

1. Compare LDH to disease-specific thresholds (1.5× ULN for most cancers, 2.5× ULN for testicular cancer risk stratification) 1
2. Rule out benign causes (hemolysis, liver disease, recent exercise) 1
3. Integrate with other prognostic factors—LDH loses independent significance when histologic response to chemotherapy is considered in osteosarcoma 2
4. Use for risk stratification per disease-specific guidelines, not as sole treatment determinant 1