Image-Guided Brachytherapy for Rectal Cancer: Reviewing the Past Two Decades of Clinical Investigation

Simple Summary With the introduction of better-quality imaging for tumor visualization and treatment planning, a new conformed radiation treatment was introduced with high-dose-rate endorectal brachytherapy (HDREBT). The advantage of this treatment is allowing for better sparing of normal tissues surrounding the tumor during treatment while delivering higher dose to the tumor. This diminishes the number and severity of side effects and results in more effective treatment. This manuscript summarizes two decades of technological evolution and progress in clinical studies to validate this treatment concept from the pre-operative setting to prevent tumor recurrence and, more recently, the introduction of the objective of cure without surgery; i.e., non-operative management (NOM) for patients with curable rectal cancer. HDREBT is a conformed radiation modality, shown to be safe and efficient both in the pre-operative setting and is presently being explored with interest in NOM in a multicenter study. (1) Background: The introduction of total mesorectal excision (TME) for rectal cancer has led to improvement in local recurrence (LR) outcomes. Furthermore, the addition of preoperative external beam radiotherapy to TME reduces LR to less than 6%. As a trade-off to these gradual improvements in local therapies, the oncology community's work is now focusing on mitigating treatment-related toxicities. In other words, if a small proportion of 4-6% of rectal cancer patients benefit from additional local therapy beyond TME, the burden of acute and long-term side effects must be considered with care. (2) Methods: With the introduction of better-quality imaging for tumor visualization and treatment planning, a new conformed radiation treatment was introduced with high-dose-rate endorectal brachytherapy. The treatment concept was tested in phase I and II studies: first in the pre-operative setting, and then as a boost after external beam radiation therapy, as a dose-escalation study, to achieve higher local tumor control. (3) Results: HDREBT is safe and effective in achieving a high tumor regression rate and was well tolerated in a phase II multicenter and two matched-pair studies. (4) Conclusions: HDREBT is a conformed radiation therapy that is safe and effective, and is presently explored in a phase III dose-escalation study in the NOM of patients with operable rectal cancer.