Post-recurrence treatment in modern adjuvant or neoadjuvant soft-tissue sarcoma randomized trials: a perspective on evidence gaps

Post-recurrence treatment plays a crucial role in determining long-term outcomes in oncology, yet it is frequently underreported in clinical trials. A review of randomized, controlled trials (RCTs) across multiple cancers found that 43% failed to report recurrence data. This limitation is particularly evident in soft tissue sarcomas (STS). While perioperative therapies have demonstrated benefit in certain high-risk patients, the absence of structured post-recurrence treatment data complicates the interpretation of survival outcomes. This perspective discusses the challenges associated with the lack of post-recurrence data in modern STS trials. A systematic review was conducted in PubMed to identify RCTs evaluating adjuvant or neoadjuvant treatments in STS published between 1 January 2015 and 31 December 2024. Among 24 reviewed articles, 5 met the inclusion criteria. Disease-free survival was the primary endpoint in three trials, while overall survival was a secondary endpoint in all. Three trials evaluated neoadjuvant therapy, and two assessed neoadjuvant plus adjuvant therapy. Three compared cytotoxic chemotherapy regimens, one compared pazopanib plus chemotherapy versus chemotherapy alone, and another assessed pembrolizumab plus radiotherapy versus radiotherapy alone. None of the trials reported post-recurrence treatment data. A consistent lack of post-recurrence treatment data persists in STS perioperative RCTs, limiting evidence applicability and hindering the understanding of initial treatment's impact on disease management. Addressing this gap is essential to refining treatment guidelines, ensuring that perioperative therapy decisions in STS truly translate into meaningful survival benefits.