Observational study of prevalence of long-term Raynaud-like phenomena and neurological side effects in testicular cancer survivors

Abstract

Background: Sensory neuropathy (paresthesias), tinnitus, hearing impairment, and Raynaud phenomena are side effects of cisplatin-based chemotherapy used to treat testicular cancer patients. We assessed the long-term occurrence of these side effects among testicular cancer survivors according to the treatment they received.

Methods: A total of 1814 men who were treated for unilateral testicular cancer in Norway during 1980-1994 were invited to participate in a national multicenter follow-up survey conducted during 1998-2002. The men were allocated to six groups according to the treatment they had received. Self-reported symptoms were assessed by a mailed questionnaire that included the Scale for Chemotherapy-Induced Neurotoxicity. A total of 1409 participants who responded to the questionnaire and/or underwent audiometry were assessable in this study. Respondents to the questionnaire (n = 1402) scored the relevant symptoms according to how troubled they were by each (not at all, a little, quite a bit, or very much). Hearing impairment was objectively assessed by audiometry at 4000 Hz in 755 men (seven of whom did not respond to the questionnaire). Group comparisons of symptom assessments were performed with chi2 or Kruskal-Wallis tests. Associations between relevant factors and self-reported symptoms or hearing impairment measured by audiometry were assessed using proportional odds ordinal logistic regression models and linear regression models, respectively. All statistical tests were two-sided.

Results: The median follow-up for the 1409 assessable men was 10.7 years (range = 4-21 years). All chemotherapy groups had statistically significantly higher odds for increasing severity of all assessed symptoms and inferior audiometric results compared with men who did not receive chemotherapy. Among chemotherapy-treated men, 39% (95% confidence interval [CI] = 35% to 43%) reported Raynaud-like phenomena (defined as white or cold hands or fingers [or feet or toes] on cold exposure), 29% (95% CI = 25% to 33%) reported paresthesias in the hands or feet, 21% (95% CI = 18% to 25%) reported hearing impairment, and 22% (95% CI = 19% to 26%) reported tinnitus as major symptoms troubling them quite a bit or very much. Hearing impairment (odds ratio [OR] = 5.3, 95% CI = 3.0 to 9.2) and tinnitus (OR = 7.1, 95% CI = 4.1 to 12.4) were particularly common in the dose-intensive chemotherapy group compared with the no chemotherapy group. Men who were treated with radiotherapy had higher odds of self-reported paresthesias in feet compared with those not treated with radiotherapy (OR = 1.5, 95% CI = 1.01 to 2.1, P = .04).

Conclusion: Long-term survivors of testicular cancer who were treated with cisplatin-based chemotherapy were more often troubled by dose-dependent neurological side effects and Raynaud-like phenomena compared with those who were not treated with chemotherapy.

Figure 1

Raynaud-like phenomena and paresthesias according to self-assessed severity and treatment. Self-reported Raynaud-like phenomena in the hands (A) and feet (B) and self-reported paresthesias in the hands (C) and feet (D) are grouped according to self-assessed symptom severity for each treatment group (P < .001 for the comparison between treatment groups for each symptom [two-sided Kruskal–Wallis tests]). Symptom severity coding: red = troubled very much, orange = troubled quite a bit, yellow = troubled a little, green = not troubled at all. Surv = surveillance; RPLND = retroperitoneal lymph node dissection; RT = radiotherapy.

Figure 2

Hearing impairment and tinnitus according to severity and treatment. Self-reported hearing impairment (A) and tinnitus (B) and assessed hearing impairment (C) grouped according to severity for each treatment group. The severity assessments in (A) and (B) are those reported by the participants; for the severity assessment for objective hearing loss measured at 4000 Hz for each testicular cancer survivor, the hearing impairment was classified according quartiles of the 4000-Hz hearing thresholds (averaged for both ears) that were measured in a large unscreened reference population of Norwegian men. (P < .001 the comparison between treatment groups for each symptom [two-sided Kruskal–Wallis tests]).

Figure 3

Relationship between reported and assessed hearing impairment. Box plot of impaired hearing in decibels (dB) measured by pure tone audiometry at 4000 Hz in relation to reported hearing impairment for 746 testicular cancer survivors for whom both assessments were available. The dark line within the box is the median value, the lower and upper boundaries of each box represent the 25th and 75th percentiles, respectively, and the whiskers represent the minimum and maximum values.