Fannie Morin1, Jean-Mathieu Beauregard2, Michelle Bergeron1, Molière Nguile Makao1, Louis Lacombe1, Vincent Fradet1, Yves Fradet1, Frédéric Pouliot3. 1. Division of Urology, Department of Surgery and Cancer Research Center, Université Laval, Quebec City, Canada; Division of Urology, Department of Surgery and Oncology Axis of CHU de Québec Research Center, CHU de Québec-Université Laval, Quebec City, Canada. 2. Division of Nuclear Medicine, Department of Radiology and Nuclear Medicine and Cancer Research Center, Université Laval, Quebec City, Canada; Division of Nuclear Medicine, Department of Medical Imaging and Oncology Axis of CHU de Québec Research Center, CHU de Québec-Université Laval, Quebec City, Canada. 3. Division of Urology, Department of Surgery and Cancer Research Center, Université Laval, Quebec City, Canada; Division of Urology, Department of Surgery and Oncology Axis of CHU de Québec Research Center, CHU de Québec-Université Laval, Quebec City, Canada. Electronic address: frederic.pouliot@crchudequebec.ulaval.ca.
Abstract
Although intrapatient heterogeneity of prostate cancer (PCa) has recently been characterized via genomic and transcriptomic studies, the heterogeneity of systemic treatment responses has yet to be reported or imaged. Our objective was to evaluate the intrapatient intermetastasis response to systemic treatment among patients with metastatic PCa. We evaluated the metabolic response for each individual metastatic lesion (n=165) in 15 patients with metastatic PCa who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography before and at least 3 mo after initiation of a systemic therapy that did not change in that period. Intermetastasis heterogeneity was defined as opposite metabolic responses for at least two metastases from the same compartment (bone or soft tissue) between the two time points. We found intrapatient intermetastasis response heterogeneity in 40% of the cases in our retrospective series. Our results suggest that systemic therapies can induce heterogeneous responses among individual metastases in patients with PCa, supporting the polyclonal evolution of PCa in advanced disease. Molecular imaging may thus be useful in identifying clinical resistance early after therapy initiation and could also allow targeted biopsy of resistant clones for molecular analysis. PATIENT SUMMARY: Systemic therapies can lead to heterogeneous responses in individual metastases of prostate cancer in a patient. Molecular imaging may be useful for identifying heterogeneity and could allow targeted biopsy for molecular analysis or therapy.
Although intrapatient heterogeneity of prostate cancer (PCa) has recently been characterized via genomic and transcriptomic studies, the heterogeneity of systemic treatment responses has yet to be reported or imaged. Our objective was to evaluate the intrapatient intermetastasis response to systemic treatment among patients with metastatic PCa. We evaluated the metabolic response for each individual metastatic lesion (n=165) in 15 patients with metastatic PCa who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography before and at least 3 mo after initiation of a systemic therapy that did not change in that period. Intermetastasis heterogeneity was defined as opposite metabolic responses for at least two metastases from the same compartment (bone or soft tissue) between the two time points. We found intrapatient intermetastasis response heterogeneity in 40% of the cases in our retrospective series. Our results suggest that systemic therapies can induce heterogeneous responses among individual metastases in patients with PCa, supporting the polyclonal evolution of PCa in advanced disease. Molecular imaging may thus be useful in identifying clinical resistance early after therapy initiation and could also allow targeted biopsy of resistant clones for molecular analysis. PATIENT SUMMARY: Systemic therapies can lead to heterogeneous responses in individual metastases of prostate cancer in a patient. Molecular imaging may be useful for identifying heterogeneity and could allow targeted biopsy for molecular analysis or therapy.
Authors: Michael C Haffner; Wilbert Zwart; Martine P Roudier; Lawrence D True; William G Nelson; Jonathan I Epstein; Angelo M De Marzo; Peter S Nelson; Srinivasan Yegnasubramanian Journal: Nat Rev Urol Date: 2020-12-16 Impact factor: 14.432
Authors: Chellappagounder Thangavel; Maryna Perepelyuk; Ettickan Boopathi; Yi Liu; Steven Polischak; Deepak A Deshpande; Khadija Rafiq; Adam P Dicker; Karen E Knudsen; Sunday A Shoyele; Robert B Den Journal: Mol Pharm Date: 2018-04-04 Impact factor: 4.939