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Shrem et al

Management recommendations agement with vasodilators, such as calcium channel
• Primary prevention of bleomycin pulmonary toxicity blockers, selective serotonin reuptake inhibitors, and
should be considered by selecting chemotherapy angiotensin receptor blockers. 41
regimens that omit bleomycin for TCS age >40 years,
impaired kidney function, pre-existing lung disease, Cognitive impairment
significant smoking history, and planned pulmonary
surgery. 27,28,31,37 Cognitive impairment, including problems with memory,
• TCS should be educated to stop smoking during and executive functioning, attention, and/or processing speed,
post-chemotherapy. have been reported in survivors with non-central nervous
44
• Clinicians and TCS should be vigilant in monitoring for system cancers, primarily post-chemotherapy. This toxicity
symptoms of BPT during and shortly after completing is particularly concerning for TCS, as most are young and
chemotherapy. Bleomycin should be held when signs cognitive function is crucial for independent activities of daily
or symptoms of BPT develop, and the chemotherapy living, employment, social life, and well-being for many years
regimen should be re-evaluated. 37 to come. Studies have demonstrated cognitive impairment in
45
• There is no strong evidence suggesting that pre- or post- TCS; however, there are conflicting results as to the contribu-
chemotherapy changes in PFTs or DCLO are predictive tion of chemotherapy vs. other TC treatments.
of BPT. PFTs, however, may be useful as a baseline pre- To determine the prevalence of cognitive impairment in
therapy or as an investigation in symptomatic patients. 37 TCS compared to normative data, 72 TCS (36 post-orchiec-
• TCS who require surgery in the future must inform tomy ± radiation therapy and 36 postorchiectomy + chemo-
their anesthetist that they have had prior bleomycin therapy) were evaluated 2–7 years post-treatment with a bat-
therapy. 27,31 tery of neuropsychological tests to assess multiple cognitive
• If TCS plan to scuba dive, they should wait at least 6–12 domains (attention and working memory, processing speed,
months post-bleomycin treatment, seek medical advice verbal fluency, learning and memory, and executive func-
prior, and may require assessment by a dive medicine tion). Over 60% of the TCS were classified as having cogni-
specialist. 38,39 tive impairment, significantly exceeding the expected 25%
of the normal population; however, no association was found
Raynaud’s phenomenon between treatment modality and cognitive impairment.
46
In contrast, a study by Stouten-Kemperman et al exam-
Raynaud’s phenomenon is a condition in which spasm of ined cognitive impairment in TCS using questionnaires,
small arteries causes episodes of reduced blood flow, typ- neurocognitive tests, and 3T magnetic resonance imaging
ically in the fingers, and less commonly the toes. Symptoms (MRI) at an average of 14 years post-treatment. The 28
may consist of numbness, pain, and pallor, followed by a chemotherapy-treated TCS demonstrated significantly
red flash. It can last minutes to hours and in severe cases, lower performance scores compared to the 23 surgery-only
can lead to skin sores or gangrene. Raynaud’s phenomenon TCS. Further, a significantly higher percentage of memory
is primarily a dose-dependent bleomycin toxicity and less complaints were reported in the chemotherapy group (35.7
frequently associated with cisplatin and vinca-alkaloids. vs. 4.3%). Although chemotherapy affected white matter
Raynaud’s phenomenon can occur in up to 30–40% of microstructure on imaging, this was unrelated to cognitive
men receiving chemotherapy (OR 2.9 for four cycles BEP performance.
47
compared with no chemotherapy). 8,40-43 It can be chronic Similarly, Wefel et al performed longitudinal neuropsych-
8
but is only persistently bothersome in about 10% of TCS. ological assessment to determine if adjuvant chemotherapy
Concurrent smoking may increase the risk of developing was associated with cognitive impairment in TCS with non-
Raynaud’s phenomenon in TCS. 40 seminoma histology treated with orchiectomy and surveil-
lance (14 patients), low-exposure chemotherapy (≤3 cycles)
Management recommendations (25 patients), or high-exposure chemotherapy (≥4 cycles) (30
• Avoiding triggers of Raynaud’s phenomenon, such as patients). Compared to the orchiectomy group, TCS treated
cold and keeping hands warm, could minimize the phe- with chemotherapy had higher rates of cognitive decline
nomenon, although there is little evidence to support at 12 months (surveillance=0%, low-exposure=52%, high-
41
this. exposure= 67%) in a dose-dependent manner. Younger age
• TCS should be educated on smoking cessation to pre- was associated with greater incidence of overall cognitive
48
vent Raynaud’s phenomenon. decline at 12 months.
• For TSC with persistent and bothersome symptoms of
Raynaud’s phenomenon, clinicians should consider a
referral to a rheumatologist for pharmacological man-

260 CUAJ • August 2022 • Volume 16, Issue 8