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Introduction: Whereas tumor biopsy is the reference standard for genomic profiling of advanced NSCLC, there are now multiple assays approved by the Food and Drug Administration for liquid biopsy testing of circulating tumor DNA. Here, we study the incremental value that liquid biopsy comprehensive genomic profiling (CGP) adds to tissue molecular testing. Methods: Patients with metastatic NSCLC were enrolled in a prospective diagnostic study to receive circulating tumor DNA CGP; tissue CGP was optional in addition to their standard tissue testing. Focusing on nine genes listed per the National Comprehensive Cancer Network (NCCN) guidelines, liquid CGP was compared with available tissue testing results across three subcohorts: tissue CGP, standard-of-care testing of up to five biomarkers, or no tissue testing. Results: A total of 515 patients with advanced nonsquamous NSCLC received liquid CGP. Among 131 with tissue CGP results, NCCN biomarkers were detected in 86 (66%) with tissue CGP and 56 (43%) with liquid CGP (p < 0.001). Adding liquid CGP to tissue CGP detected no additional patients with NCCN biomarkers, whereas tissue CGP detected NCCN biomarkers in 30 patients (23%) missed by liquid CGP. Studying 264 patients receiving tissue testing of up to five genes, 102 (39%) had NCCN biomarkers detected in tissue, with an additional 48 (18%) detected using liquid CGP, including 18 with RET, MET, or ERBB2 drivers not studied in tissue. Conclusions: For the detection of patients with advanced nonsquamous NSCLC harboring 9 NCCN biomarkers, liquid CGP increases detection in patients with limited tissue results, but does not increase detection in patients with tissue CGP results available. In contrast, tissue CGP can add meaningfully to liquid CGP for detection of NCCN biomarkers and should be considered as a follow-up when an oncogenic driver is not identified by liquid biopsy.
RESUMO
Active surveillance (AS) is an accepted management strategy for some patients with renal cell carcinoma, but limited tools are available to identify optimal AS candidates. While renal mass biopsy provides diagnostic information, risk stratification based on biopsy is limited. In a retrospective, multi-institutional cohort that underwent renal mass biopsy followed by surgery, we assessed the ability of the cell cycle proliferation (CCP) score from clinical biopsy specimens to predict adverse surgical pathology (ie, grade 3-4, pT stage ≥3, metastasis at surgery, or papillary type II). Of 202 patients, 98 (49%) had adverse surgical pathology. When added to a baseline model including age, sex, race, lesion size, biopsy grade, and histology, CCP score was significantly associated with adverse pathology when modeled as a binary (odds ratio [OR]: 2.44 for CCP score >0, p = 0.02) and a continuous (OR: 1.72 per one unit increase, p = 0.04) variable. Discriminative performance measured by the area under the curve (AUC) improved from 0.73 in the baseline model to 0.75 and 0.76 in models including the CCP score. In the subgroup of patients with nephrectomy CCP score available (n = 67), the biopsy-based model outperformed the nephrectomy-based model (AUC 0.78 vs 0.75). These data support prospective assessment of biopsy CCP score to confirm clinical validity and assess potential utility in AS-eligible patients. PATIENT SUMMARY: In patients with localized renal cell carcinoma who underwent renal mass biopsy followed by surgery, the cell cycle proliferation score from clinical biopsy specimens could predict adverse surgical pathology.