How to manage elevated procalcitonin (PCT) levels in patients with malignancy?

From the Guidelines

Elevated procalcitonin (PCT) levels in patients with malignancy should be managed by interpreting PCT levels in the context of clinical assessment, and considering discontinuation of antibiotics if PCT decreases by >80% from peak or falls below 0.5 ng/mL, cultures remain negative, and clinical improvement occurs, as suggested by the most recent guidelines 1. When encountering elevated PCT in cancer patients, it is essential to obtain blood cultures and appropriate imaging studies to rule out bacterial infection before initiating antibiotics.

• If infection is suspected, start empiric broad-spectrum antibiotics while awaiting culture results, typically using a combination like piperacillin-tazobactam (4.5g IV q6h) or meropenem (1g IV q8h) plus vancomycin (15-20mg/kg IV q8-12h) 1.
• Monitor PCT levels serially every 24-48 hours, as declining values suggest effective treatment.
• Consider discontinuing antibiotics if PCT decreases by >80% from peak or falls below 0.5 ng/mL, cultures remain negative, and clinical improvement occurs, as supported by recent studies [1, @111@, @112@].
• For persistently elevated PCT without identified infection, investigate tumor progression or paraneoplastic production.
• The threshold for initiating antibiotics should be lower in neutropenic patients (consider treatment at PCT >0.5 ng/mL) compared to non-neutropenic patients (consider at PCT >1.0 ng/mL), as PCT elevation occurs primarily in bacterial infections. It is crucial to note that PCT and CRP provide only supportive and complementary information to clinical assessment, and decisions on initiating, altering, or discontinuing antimicrobial therapy should not be made solely based on changes in PCT or CRP levels 1. Recent studies have demonstrated that PCT-guided antibiotic treatment in ICU patients with infection and sepsis patients resulted in improved survival and lower antibiotic treatment duration [@111@, @112@]. However, it is essential to consider the limitations of these studies, including the risk of bias and indirectness of effect, and to use PCT levels in conjunction with clinical assessment to guide antibiotic therapy 1.

From the Research

Procalcitonin Elevation in Malignancy

• Procalcitonin (PCT) is an inflammatory marker that can be elevated in patients with malignancy, particularly in those with bacteremia and bacterial pneumonia 2.
• A study found that PCT elevation above 0.5 ng/mL was significantly associated with diagnosed infection in patients with malignancy, including those with solid tumor malignancies and hematologic malignancies 2.
• However, PCT elevation was not associated with diagnosed infection in some subpopulations, such as patients with primary lung cancer, lung metastases, neuroendocrine tumors, febrile neutropenia, or history of bone marrow transplant (BMT) 2.

Diagnostic Utility of Procalcitonin

• PCT has been shown to be a useful diagnostic marker for distinguishing between infection and non-infectious acute-phase reactions in patients with malignant diseases 3.
• A study found that PCT concentration was a significant discriminator between having and not having infection, having infection and being in the tumor group, and having infection and being in the drug group 3.
• However, the diagnostic performance of PCT can be limited by its lack of specificity, and values must be interpreted cautiously and considering clinical context 2, 3.

Procalcitonin-Producing Tumors

• There have been reports of abnormal procalcitonin-producing metastatic pancreatic neuroendocrine tumors, which can lead to elevated PCT levels in the absence of infection 4.
• Immunohistochemistry has been used to demonstrate that PCT can be secreted by pancreatic neuroendocrine tumors (PanNET) 4.

Management of Elevated Procalcitonin Levels

• The management of elevated PCT levels in patients with malignancy should involve a comprehensive evaluation to determine the underlying cause of the elevation, including infection, tumor burden, or other non-infectious causes 2, 3.
• PCT-guided therapy has been shown to be a helpful approach to guide antibiotic therapy and surgical interventions, particularly in intensive care unit patients with severe sepsis and septic shock 5.
• However, the use of PCT-guided therapy should be individualized and based on clinical judgment, taking into account the patient's underlying condition, comorbidities, and other diagnostic markers 2, 3, 5.