Paired Tissue and Plasma Comprehensive Genomic Profiling in Advanced Solid Tumors: A Retrospective Study from India

Background: Tissue and plasma comprehensive genomic profiling (CGP) sample different compartments and may yield nonoverlapping clinically relevant findings. We assessed the added patient-level yield of paired testing in a pan-cancer cohort from India. Methods: This retrospective, single-institution study included patients with stage IV solid tumors who underwent paired tissue and plasma CGP between November 2022 and October 2024. The primary endpoint was detection in a patient of an OncoKB Level 1 or Level 2 or R1 alteration, high tumor mutational burden, or microsatellite instability. Molecularly informed therapy and laboratory turnaround time were assessed descriptively. Results: Of 158 patients, 123 matched evaluable pairs were analyzed. Either modality detected a clinically relevant finding in 46 of 123 patients (37.4%; 95% confidence interval, 29.4–46.2%): tissue CGP in 33 (26.8%), plasma CGP in 35 (28.5%), both in 22 (17.9%), tissue only in 11 (8.9%) and plasma only in 13 (10.6%). This complementarity remained bidirectional across exploratory analyses, including a subgroup that excluded non-small cell lung cancer (33.0%), all 139 technically successful pairs (33.8%), all 158 paired sample sets (32.3%), and even when the endpoint was restricted to OncoKB alterations (22.0%). Among 91 patients with therapy-alignment data, 25 (27.5%) received molecularly informed therapy. Median laboratory turnaround time was 7 days for plasma and 13 days for tissue CGP. Conclusions: Tissue and plasma CGP were complementary rather than interchangeable in this selected cohort: either modality alone would have missed clinically relevant findings. Whether this improves outcomes is untested; prospective studies linking testing strategy to treatment delivery and survival are needed.