Characteristics and risk factors of cisplatin-induced ototoxicity in testicular cancer patients detected by distortion product otoacoustic emission

Abstract

Objective: The characteristics and risk factors of the long-term ototoxic effect of cisplatin in testicular cancer patients was studied by measuring distortion product otoacoustic emissions (DPOAEs), which is a highly sensitive, new method for detecting high-frequency hearing loss.

Methods: 223 patients with a median follow-up time of 4.27 years (range 0.5-20 years) and a median age of 37 years (range 18-55 years) were assessed by DPOAE. 100 mg/m2 cisplatin were administered per cycle, in EP, BEP, VeIP, VIP or VPB regimens. The control group consisted of 40 testicular cancer patients without chemotherapy (median age 35 years, range 16-54 years). A detailed medical history evaluated audiological risk factors and hearing complaints. DPOAE was measured in eight frequencies from 750 to 8,000 Hz. Paired t test and Mann-Whitney test were used for statistical evaluation.

Results: Symptomatic ototoxicity was observed in 20% of the patients. In patients receiving <or=300 mg/m2 cisplatin, no amplitude changes were detected. Beyond this dose, hearing impairment proved to be dose dependent. Contrary to the literature, not only high frequencies were affected. In patients receiving >or=400 mg/m2, our method could detect significant hearing impairment at lower frequencies that are important for speech perception. At 400 mg/m2, significant amplitude change was detected at 3,000 Hz (p = 0.01); at 500-600 mg/m2, significant amplitude change was detected at 1,500, 2,000 and 3,000 Hz (p = 0.004, 0.0001 and 0.0002, respectively), and at 700 mg/m2 significant amplitude change was detected at 3,000 Hz (p = 0.01). We detected the lowest amplitudes in those 44 patients who had symptomatic ototoxicity. The only statistically significant risk factor was the cumulative dose of cisplatin; neither smoking nor noise exposure were independent risk factors.

Conclusion: DPOAE is a fast, noninvasive and reliable method in detecting late ototoxicity in testicular cancer patients. Contrary to the literature, not only high frequencies are affected. In patients receiving at least 400 mg/m2, using DPOAE we were able to detect significant hearing impairment at lower frequencies that are important for speech perception.