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


CONCLUSIONS
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.
Brydøy
Marianne
M
Department of Oncology, Haukeland University Hospital, N-5021 Bergen, Norway. marianne.brydoy@helse-bergen.no
Oldenburg
Jan
J
Klepp
Olbjørn
O
Bremnes
Roy M
RM
Wist
Erik A
EA
Wentzel-Larsen
Tore
T
Hauge
Erik R
ER
Dahl
Olav
O
Fosså
Sophie D
SD
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001299:Audiometry; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D034381:Hearing Loss / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D016017:Odds Ratio; D010292:Paresthesia / Q000139:chemically induced / Q000453:epidemiology; D015995:Prevalence; D011928:Raynaud Disease / Q000139:chemically induced* / Q000453:epidemiology*; D012044:Regression Analysis; D012107:Research Design; D018239:Seminoma / Q000188:drug therapy; D012678:Sensation Disorders / Q000139:chemically induced* / Q000453:epidemiology*; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D017741:Survivors / Q000706:statistics & numerical data*; D013736:Testicular Neoplasms / Q000188:drug therapy*; D014012:Tinnitus / Q000139:chemically induced / Q000453:epidemiology
D002945:Cisplatin