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Single EBUS-TBNA passes yield DNA of high quantity and quality with high accuracy for molecular profiling, irrespective of tumor cell content.

Malignant pleural effusion (MPE) may be diagnosed by cytologic evaluation of pleural fluid, though false negative results can occur. Pleural effusions may provide a source of tumour material for genotyping in lung cancer patients. Detection of MPE may be improved through use of highly sensitive molecular techniques. We identified five patients with non-small cell lung cancer (NSCLC) with initial pleural fluid samples that were non-malignant on cytology, but were subsequently clinically confirmed to have MPE. Tumour mutation status was confirmed via routine testing of diagnostic clinical specimens. Cytologically negative pleural fluid cell-block specimens were analysed by amplicon-based parallel sequencing (APS) for somatic mutations commonly detected in NSCLC, and selected cases by improved and complete enrichment CO-amplification at lower denaturation temperature PCR (ICECOLD PCR) for known mutations. Mutations were detected in three out of three (sensitivity 100%) cytologically non-malignant pleural fluids from patients with a known mutation: two patients with known Kirsten rat sarcoma (KRAS) mutation demonstrated the same KRAS mutation in their pleural fluids by APS, both at approximately 2% mutant allele frequency. In one patient with a known KRAS mutation, ICECOLD PCR detected the same KRAS variant at 0.7% frequency. No mutations were detected in patients with wild-type findings from reference samples (specificity 100%). Sensitive DNA sequencing methods can detect cancerdriver mutations in cytologically non-malignant pleural fluid specimens from NSCLC patients with MPE. Our findings demonstrate the feasibility of sensitive molecular diagnostic techniques for improvement of diagnostic assessment of pleural effusions in patients with lung cancer.

Objectives To investigate the utility of Magnetic Resonance Imaging (MRI) for prostate cancer diagnosis in the Australian setting. Patients and methods All consecutive men who underwent a prostate biopsy (transperineal or transrectal) at Royal Melbourne Hospital between July 2017 to June 2019 were included, totalling 332 patients. Data were retrospectively collected from patient records. For each individual patient, the risk of prostate cancer diagnosis at biopsy based on clinical findings was determined using the European Randomized study of Screening for Prostate Cancer (ERSPC) risk calculator, with and without incorporation of MRI findings. Results MRI has good diagnostic accuracy for clinically significant prostate cancer. A PI‐RADS 2 or lower finding has a negative predictive value of 96% for clinically significant cancer, and a PI‐RADS 3, 4 or 5 MRI scan has a sensitivity of 93%. However, MRI has a false negative rate of 6.5% overall for clinically significant prostate cancers. Pre‐ biopsy MRI may reduce the number of unnecessary biopsies, as up to 50.0% of negative or ISUP1 biopsies have MRI PI‐RADS 2 or lower. Incorporation of MRI findings into the ERSPC calculator improved predictive performance for all prostate cancer diagnoses (AUC 0.77 vs 0.71, P = .04), but not for clinically significant cancer (AUC 0.89 vs 0.87, P = .37). Conclusion MRI has good sensitivity and negative predictive value for clinically significant prostate cancers. It is useful as a pre‐biopsy tool and can be used to significantly reduce the number of unnecessary prostate biopsies. However, MRI does not significantly improve risk predictions for clinically significant cancers when incorporated into the ERSPC risk calculator.

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