Observed RET-Positive Findings Across Routine Comprehensive Genomic Profiling Platforms in Japan: A Nationwide Descriptive Benchmark

Background: RET fusion is an actionable tumor-agnostic biomarker, but its observed frequency in routine comprehensive genomic profiling (CGP) may vary across testing platforms and clinical contexts. We conducted a nationwide descriptive analysis to benchmark observed RET fusion frequency in Japanese routine practice. Methods: This retrospective descriptive study used anonymized aggregated data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), including CGP-tested cases through 31 March 2025. Observed RET fusion frequency was summarized overall, across five standardized CGP platforms, across 12 prespecified organ groups, and in pooled tissue-based versus liquid-based comparisons. Exact binomial 95% confidence intervals were calculated to provide descriptive precision for low-frequency estimates. Results: Among 97,343 cases, 257 were RET-positive, corresponding to an overall observed RET fusion frequency of 0.26%. Platform-specific frequencies were 0.29% (192/66,992) for FoundationOne CDx, 0.28% (42/14,878) for FoundationOne Liquid CDx, 0.14% (6/4235) for GenMineTOP, 0.16% (15/9196) for NCC oncopanel, and 0.10% (2/2042) for Guardant360. Thoracic tumors showed the highest observed frequency (1.39%, 94/6740), followed by head and neck/thyroid tumors (1.04%, 42/4030). In a crude pooled comparison not adjusted for organ mix or clinical context, tissue-based and liquid-based CGP yielded numerically similar crude pooled frequencies of 0.265% (213/80,423) and 0.260% (44/16,920), respectively. Conclusions: This nationwide analysis benchmarks how RET-positive findings are surfaced to clinicians across heterogeneous routine CGP implementations in Japan. The data support platform-aware interpretation of RET results in practice, but should not be construed as biologic prevalence estimates or comparative assay performance.