Optimal timing of cancer treatments: a call for emerging evidence from clinical trials and real-world studies

Abstract

Cancer treatment has entered the era of personalised or precision medicine. Biomarker-driven therapies provide improved treatment efficacy and manageable toxicity profiles compared to systemic standard-of-care therapies. They also drive the development of combining non-surgical treatments, extending indications to early-stage tumours and further refining treatment lines with more precise options. The current treatment landscape, however, has introduced a complexity of approaches to cancer treatment, including the optimal timing of when to initiate and discontinue these treatments. Of note, treatment timing usually lacks evaluation in clinical trials and can be variable in real-world settings due to the impacts of medical, healthcare, and social factors. Given that more patients can benefit from multi-modality strategies, a better understanding of the prognostic impact of treatment-to-treatment intervals (TTIs) - the intervals between combined treatments and between treatment lines - is needed. Studies for this purpose can rely on existing trial and real-world data and be context-specific for treatment options, therapeutic settings, cancer types and biomarkers, healthcare settings or systems. This perspective article calls for emerging evidence of the optimal timing of cancer treatments. We anticipate that new studies on the optimal timing will bring new insights into how to better use cancer treatments, further improving treatment efficacy.

Fig. 1. Non-linear association between time interval and patient outcome.

Example of treatment-to-treatment interval (between surgery and adjuvant radiotherapy) associated with all-cause mortality (a) and disease-free survival (b) [21]. WPRT Whole pelvic radiotherapy, HR Hazard ratio, CI Confidence interval.