Can tumor lysis syndrome (TLS) occur without chemotherapy?

Tumor Lysis Syndrome: Occurrence Without Chemotherapy

Yes, tumor lysis syndrome (TLS) can occur spontaneously without chemotherapy, although it is rare compared to treatment-induced TLS. 1

What is Tumor Lysis Syndrome?

Tumor lysis syndrome is a metabolic emergency characterized by:

• Rapid release of intracellular contents when tumor cells undergo lysis 1
• Metabolic derangements including hyperuricemia, hyperkalemia, hyperphosphatemia, and secondary hypocalcemia 2
• Potential clinical complications such as renal insufficiency, cardiac arrhythmias, and seizures 1

Spontaneous TLS

While TLS most commonly occurs after initiation of cytotoxic therapy, it can develop spontaneously in certain circumstances:

• Documented as a "rare" spontaneous event in multiple guidelines 1
• More likely in tumors with high proliferative rates and large tumor burden 2
• Has been reported in both hematologic malignancies and solid tumors 3

Risk Factors for Spontaneous TLS

Patients at higher risk for developing spontaneous TLS include those with:

• Hematologic malignancies with high proliferation rates (Burkitt's lymphoma, B-ALL) 1, 4
• Bulky disease with large tumor burden 2
• Elevated LDH levels (reflecting high tumor burden) 1, 5
• Pre-existing conditions: elevated uric acid, renal dysfunction, advanced age 2
• Extensive bone marrow involvement 1
• Solid tumors with high sensitivity to treatment and bulky disease 5

TLS in Solid Tumors

Though less common than in hematologic malignancies, TLS can occur in solid tumors:

• Reported in bulky small cell lung cancer and metastatic germ cell carcinoma 1
• Cases documented in breast cancer and other solid tumors 5, 3
• Higher mortality rate in solid tumors (approximately 35%) compared to hematologic malignancies 1
• Risk factors include bulky disease, liver metastases, and high tumor sensitivity 1

Prevention and Management

Even for patients at risk for spontaneous TLS:

• Risk assessment should be performed to identify high-risk patients 2
• Prophylaxis based on risk level:
  • High-risk: hydration and rasburicase 2
  • Intermediate-risk: hydration plus either allopurinol or rasburicase 2
  • Low-risk: hydration and oral allopurinol 2
• Monitoring of electrolytes, renal function, and uric acid levels 2
• Aggressive intervention for established TLS including possible dialysis 2

Clinical Pitfalls

Important considerations to avoid poor outcomes:

• Failure to recognize spontaneous TLS may lead to delayed treatment and increased mortality 5
• Solid tumor patients may not receive the same monitoring as hematologic patients, contributing to higher mortality 1
• Pre-existing renal dysfunction significantly worsens prognosis 2
• Patients with high tumor burden should be monitored even before starting treatment 2
• Spontaneous TLS in solid tumors like breast cancer can be fatal despite intervention 3