Health status and burden of late effects in very long-term testicular cancer survivors.

Depending on disease stage, testicular cancer (TC) treatment consists of an
orchidectomy, alone or followed by radiotherapy (RT) or platinum-based
chemotherapy (CT). TC survival rates are above 90% nowadays, which results in
growing TC survivor population. Because of the long life expectancy of these
survivors, prevention or early detection of late treatment effects has become
increasingly relevant. Yet known late effects are nephrotoxicity,
cardiovascular disease (CVD), secondary malignant neoplasms (SMN),
neurotoxicity, pulmonary toxicity, Raynaud*s phenomenon, hypogonadism, fatigue
and psychosocial problems. Nephrotoxicity is an important late effect, but data
is lacking in very long-term survivors, since performed studies have a
follow-up duration of 5-14 years. Decreased renal function is a known risk
factor for CVD development and also an association between renal function and
neurotoxicity via circulating platinum levels has been shown. We hypothesize
that treatment induced nephrotoxicity is prevalent in TC survivors and might be
a mediator for development of late effects. Our secondary aim is to assess
prevalence of late effects in very long-term TC survivors: until now, most data
have been collected through questionnaires in large epidemiological studies in
TC survivors till approximately 10 years after treatment. The prevalence of
late effects may increase over time: 10 years after treatment late effects may
not be present yet, whilst late effects can emerge just after 20 years.
Consequently, health status and possible late effects, resulting in morbidity,
are underestimated in patients who are 20-30 years after treatment. By
investigating health status of these very long-term survivors a more profound
insight in the prevalence and aetiology of these late effects and the
development over time can be assessed. Current treatment is very similar to TC
treatment 20-30 years ago and therefore knowledge on late effects is relevant
for currently treated patients. Furthermore, as a result of this study, we will
better understand which factors and issues should be watched closely during
follow-up, which TC survivors are at increased risk of developing late
treatment effects and how to detect early damage before overt morbidity occurs.

The aim of this study is to compare glomerular filtration rate (GFR) in very
long-term TC-survivors treated with chemotherapy, radiotherapy or surgery only
and non-cancer treated healthy controls. Furthermore, a secondary aim is to
assess prevalence of adverse late treatment effects in very long-term
TC-survivors treated with CT, RT or surgery only and investigate the
relationship between GFR parameters and these late effects.

We will perform an observational cross-sectional cohort study. Patients will be
invited for a single study visit, which consists of collection of urine during
24 hours, withdrawal of blood samples, filling in questionnaires, physical
examination, vascular function and structure tests, lung function tests,
digital cooling tests, neuropsychological assessment and a walk test.

Participants are asked to bring a single study visit of approximately three
hours. Venapuncture is the only invasive procedure, with low risk of adverse
effects. By inviting survivors who are not in any routine follow-up care,
research into late effects and risk factors can be combined with lifestyle
counselling regarding cardiovascular risk reduction. More knowledge about late
effects of TC treatment can lead to better prevention and earlier detection of
these late effects and to development of new follow-up strategies.