Treatment-related cardiovascular late effects and exercise training countermeasures in testicular germ cell cancer survivorship

Abstract

Background: Treatment of testicular germ cell cancer constitutes a major success story in modern oncology. Today, the vast majority of patients are cured by a therapeutic strategy using one or more highly effective components including surgery (orchiectomy), radiotherapy and/or chemotherapy. However, the excellent cancer-specific survival comes at considerable costs, as individuals with a history of germ cell cancer experience serious long-term complications, including markedly increased risk of cardiovascular morbidities and premature cardiovascular death. The factors responsible, as well as their mode of action, are not fully understood and there is a lack of knowledge concerning optimal evidence-based long-term follow-up strategies.

Results: Here, we present the growing body of evidence suggesting that germ cell cancer patients as a consequence of the different treatment components, are subjected to toxicities, which individually, and synergistically, can cause physiological impairments leading to sub-clinical or clinical cardiovascular disorders (i.e. the 'multiple-hit hypothesis'). Furthermore, we discuss the efficacy and utility of structured exercise training to ameliorate treatment-induced cardiovascular dysfunction to prevent premature onset of clinical cardiovascular disease in germ cell cancer survivors, with a view towards highlighting future directions of exercise-based survivorship research in the germ cell cancer setting.

Conclusion: As exercise training may have the potential to ameliorate and/or reverse long-term cardiovascular disease sequelae in germ cell cancer survivors, a strong rationale exists for the promotion of exercise oncology research in this setting, in order to provide exercise recommendations for optimal germ cell cancer survivorship.

Figure 1. The ‘Multiple-Hit Hypothesis”

The ’multiple-hit hypothesis’ applied to the germ cell cancer setting – adapted from Jones et al. 2007, J Am Coll Cardiol [31]. As patients move along the trajectory of germ cell cancer treatment they will be subjected to one or several of the treatment components associated with various toxicities. Individually, and synergistically, these toxicities can significantly impair cardiovascular function, which leaves the patient more susceptible to cardiovascular injuries, and ultimately higher risk of premature cardiovascular morbidities and mortality.