Rhabdomyosarcoma (RMS) is a typical tumour of childhood but can occur at any age. Several studies have reported that adolescent and young adult (AYA) patients with RMS have poorer survival than do younger patients. This review discusses the specific challenges in AYA patients with pediatric-type RMS, exploring possible underlying factors which may influence different outcomes. Reasons for AYA survival gap are likely multifactorial, and might be related to differences in tumor biology and intrinsic aggressiveness, or differences in clinical management (that could include patient referral patterns, time to diagnosis, enrolment into clinical trials, the adequacy and intensity of treatment), as well as patient factors (including physiology and comorbidity that may influence treatment tolerability, drug pharmacokinetics and efficacy). However, improved survival has been reported in the most recent studies for AYA patients treated on pediatric RMS protocols. Different strategies may help to further improve outcome, such as supporting trans-age academic societies and national/international collaborations; developing specific clinical trials without upper age limit; defining integrated and comprehensive approach to AYA patients, including the genomic aspects; establishing multidisciplinary tumor boards with involvement of both pediatric and adult oncologists to discuss all pediatric-type RMS patients; developing dedicated projects with specific treatment recommendations and registry/database.
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