When is a pulmonary function test (PFT) indicated prior to administering bleomycin in patients with or without pre-existing lung disease or prior chest radiation?

Pulmonary Function Testing Prior to Bleomycin

Baseline pulmonary function tests (PFTs) should be considered where possible as a useful reference for future comparison, but should NOT be used to predict toxicity risk or to decide whether to treat with bleomycin. 1

Primary Recommendation

The British Journal of Cancer guidelines, based on prospective phase III randomized trial evidence, explicitly state that PFTs are only weakly correlated with increased toxicity and only at the end of treatment—not at baseline. 1 Therefore:

• Do NOT use baseline PFTs to predict which patients will develop bleomycin pulmonary toxicity 1
• Do NOT use PFTs in isolation to aid decisions about whether to treat with bleomycin 1
• Baseline PFTs can be performed if feasible to serve as a reference point for comparison if toxicity is later suspected 1

Clinical Context and Reasoning

The guideline's position reflects high-quality evidence showing that baseline PFT values do not reliably identify patients at risk. 1 A 2016 study demonstrated that using a 25% reduction in DLCO as a threshold for stopping bleomycin caused 30% of patients to receive less than two-thirds of their planned doses, with potentially worse outcomes, particularly in good or poor prognosis patients. 2 This suggests that routine PFT monitoring may cause more harm than benefit by leading to premature discontinuation of effective therapy.

Risk Stratification (Without PFTs)

Exercise caution with bleomycin in patients with: 1

• Age >40 years
• Significant smoking history
• Reduced renal function (GFR <80 ml/min)
• Pre-existing lung disease (particularly fibrosis or symptomatic pathology)

A 2003 study confirmed that GFR <80 ml/min (HR 3.3), age >40 years (HR 2.3), stage IV disease (HR 2.6), and cumulative bleomycin dose >300,000 IU (HR 3.5) independently predict increased toxicity risk. 3 However, there are no absolute contraindications to bleomycin use. 1

Role of PFTs in Suspected Toxicity

If bleomycin toxicity is suspected during treatment (new cough or dyspnea), HRCT is the investigation of choice—NOT PFTs. 1 PFTs should not be used as a first-line investigation for suspected lung toxicity. 1

PFTs may have a limited adjunctive role: 1

• To corroborate HRCT findings when there is diagnostic uncertainty
• With particular attention to DLCO (diffusing capacity for carbon monoxide)
• In consultation with a respiratory physician

Common Pitfalls to Avoid

Do not rely on chest X-ray—it has extremely low sensitivity for bleomycin toxicity. 1 Studies from the 1980s showed no correlation between chest radiograph changes and PFT changes. 4

Do not use routine serial PFTs during treatment to monitor for toxicity. 1, 2 The 2016 trial data showed this practice led to unnecessary dose reductions without preventing clinically significant toxicity. 2

Recognize that cough is the most sensitive symptom for predicting toxicity, not PFT changes. 1 New respiratory symptoms should trigger HRCT imaging, not repeat PFTs.

Practical Algorithm

Before starting bleomycin:

1. Assess clinical risk factors (age, renal function, smoking, pre-existing lung disease) 1
2. Consider baseline PFTs if readily available, but do not delay treatment to obtain them 1
3. Ensure baseline CT thorax for patients >40 years old 1

During treatment:

• Monitor clinically for new cough or dyspnea 1
• If new respiratory symptoms develop, obtain HRCT immediately 1
• Consider PFTs only as adjunctive testing if HRCT findings are equivocal 1