RESUMO
BACKGROUND AND OBJECTIVE: The source of tissue for genomic profiling of metastatic castration-resistant prostate cancer (mCRPC) is often limited to osseous metastases. To guide patient management, metastatic site selection and the technique for targeted bone biopsies are critical for identifying deleterious gene mutations. Our objective was to identify key parameters associated with successful large-panel DNA sequencing. METHODS: We analyzed parameters for 243 men with progressing mCRPC who underwent 269 bone biopsies for genomic profiling between 2014 and 2018. Univariate and multivariate analyses were performed for clinical, imaging (bone scan; fluorodeoxyglucose [FDG] positron emission tomography [PET]; computed tomography [CT]; magnetic resonance imaging), and technical (biopsy site, number of samples, needle gauge) features associated with successful genomic profiling. KEY FINDINGS AND LIMITATIONS: Overall, 159 of 269 biopsies (59%) generated sufficient tumor material for a genomic profile. Seventy (26%) of the failures were histopathologically negative for mCRPC and 40 (15%) had insufficient tumor for genomic profiling. Of 199 mCRPC samples submitted for molecular testing, 159 (80%) yielded a genomic profile. On univariate analysis, PSA, serum acid phosphatase, number of biopsy samples, FDG PET positivity, CT attenuation, and CT morphology were significantly associated with genomic profiling success. On multivariate analysis, higher FDG maximum standardized uptake value (odds ratio [OR] 7.51, 95% confidence interval [CI] 3.01-18.78; p < 0.001), higher number of biopsy samples (OR 4.73, 95% CI 1.49-15.02; p = 0.008), and lower mean CT attenuation (OR 0.4, 95% CI 0.18-0.89; p = 0.025) were significantly associated with sequencing success. CONCLUSIONS AND CLINICAL IMPLICATIONS: In patients with mCRPC, bone biopsies from sites with metabolic activity and lower CT attenuation are associated with higher success rates for genomic profiling via a large-panel DNA sequencing platform. PATIENT SUMMARY: We identified factors associated with successful genetic testing of bone tissue for patients with metastatic prostate cancer. Our findings may help in guiding the right scan technique and biopsy site for personalized treatment planning.
RESUMO
BACKGROUND: Cancers of unknown primary (CUP) have traditionally been treated empirically, with a dismal prognosis. Compared with standard diagnostic tests, including CT and MRI, imaging with 18F-fluorodeoxyglucose (FDG) PET or PET/CT has shown the capacity to better identify the primary tumour site and detect additional sites of metastasis. However, its clinical impact is not well established. We performed a systematic review and meta-analysis of prior studies to assess the impact of FDG-PET or PET/CT on the management of patients with CUP. MATERIALS AND METHODS: Pubmed and EMBASE databases were searched up to 4th February 2021. Studies that reported the proportion of patients with CUP who experienced a management change after FDG-PET or PET/ computed tomography (CT) were included and the proportions were pooled using the random-effects model. Study quality was assessed using QUADAS-2. Subgroup analysis was conducted to explore heterogeneity. RESULTS: Thirty-eight studies (involving 2795 patients) were included. The pooled proportion of patients with management changes was 35% (95% confidence interval 31%-40%). There was substantial heterogeneity among the studies (Q-test, p < 0.01; I2 = 82%). The specific reason for management change was more commonly detection of the primary site (22% [95% CI 18-28%]) than detection of additional metastatic sites (14% [95% CI 10-19%]). The pooled proportions of patients with management changes were similar among numerous subgroups (range, 32.8%-38.2%). CONCLUSION: FDG-PET or PET/CT had a meaningful impact on the management of patients with CUP. Approximately, a third of patients had their management changed because of FDG-PET or PET/CT results, and this finding was consistent across numerous subgroups.