KEY POINTS
- This systematic evidence map screened 8,189 unique records and ultimately adjudicated 92 verified/supporting reports. The direct clinical evidence comprised 15 reports representing 14 independent studies, alongside 34 technical/platform reports.
- The clinical literature included two randomized phase III trials, one non-randomized comparative cervical study, ten uncontrolled series, and one case report, covering cervical, prostate, anal, vaginal, and mixed pelvic malignancies.
- In the randomized cervical cancer study, 224 patients were randomized and 205 analyzed. Three-year DFS was 67% with brachytherapy alone versus 60% with brachytherapy plus hyperthermia (p≈0.178), while local control was 84% versus 88% (p≈0.991); grade ≥3 late toxicity was also essentially identical (16.8% vs 16.6%).
- A second randomized trial in recurrent/persistent mixed tumors enrolled 184 patients, with 173 evaluable. Complete response was approximately 53% versus 55% and two-year survival 34% versus 35%, with no significant treatment benefit. Critically, only one patient met the predefined minimum criteria for adequate hyperthermia delivery, making this as much an intervention-fidelity failure as a negative efficacy trial.
- Non-randomized series demonstrate feasibility rather than comparative efficacy. For example, a later multicentre phase II salvage-prostate series of 109 patients reported 58.9% 5-year biochemical disease-free survival and 77.7% metastasis-free survival, with relatively limited serious late toxicity.
- The major translational problem is not simply generating heat but knowing where, for how long, and at what biologically relevant thermal dose tissue was heated. Historical studies frequently relied on sparse thermocouples or maximum-temperature readings, making spatial thermal exposure poorly characterized.
- The authors propose staged development rather than immediate clinical adoption: standardized multipoint thermometry, measurement-anchored spatial reconstruction, coupled radiation/thermal planning, platform qualification, prospective workflow validation, and only then disease-specific comparative efficacy trials.
CLINICAL TAKEAWAY
Brachytherapy-integrated hyperthermia has a plausible radiosensitizing rationale and decades of technical development, but there is currently no convincing randomized evidence that it improves pelvic cancer outcomes. The immediate research priority is reliable thermal dosimetry and reproducible delivery—not routine clinical adoption.