Dataset Information

Accelerating precision medicine in metastatic prostate cancer.

ABSTRACT: Despite advances in prostate cancer screening and treatment, available therapy options, particularly in later stages of the disease, remain limited and the treatment-resistant setting represents a serious unmet medical need. Moreover, disease heterogeneity and disparities in patient access to medical advances result in significant variability in outcomes across patients. Disease classification based on genomic sequencing is a promising approach to identify patients whose tumors exhibit actionable targets and make more informed treatment decisions. Here we discuss how we can accelerate precision oncology to inform broader genomically-driven clinical decisions for men with advanced prostate cancer, drug development and ultimately contribute to new treatment paradigms.

SUBMITTER: Mateo J

PROVIDER: S-EPMC8274325 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

Accelerating precision medicine in metastatic prostate cancer.

Mateo Joaquin J McKay Rana R Abida Wassim W Aggarwal Rahul R Alumkal Joshi J Alva Ajjai A Feng Felix F Gao Xin X Graff Julie J Hussain Maha M Karzai Fatima F Montgomery Bruce B Oh William W Patel Vaibhav V Rathkopf Dana D Rettig Matthew M Schultz Nikolaus N Smith Matthew M Solit David D Sternberg Cora C Van Allen Eliezer E VanderWeele David D Vinson Jake J Soule Howard R HR Chinnaiyan Arul A Small Eric E Simons Jonathan W JW Dahut William W Miyahira Andrea K AK Beltran Himisha H

Nature cancer 20201117 11

Despite advances in prostate cancer screening and treatment, available therapy options, particularly in later stages of the disease, remain limited and the treatment-resistant setting represents a serious unmet medical need. Moreover, disease heterogeneity and disparities in patient access to medical advances result in significant variability in outcomes across patients. Disease classification based on genomic sequencing is a promising approach to identify patients whose tumors exhibit actionabl ...[more]

PMID: 34258585

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Project description:BackgroundSystematic identification of data essential for outcome prediction in metastatic prostate cancer (mPC) would accelerate development of precision oncology.ObjectiveTo identify novel phenotypes and features associated with mPC outcome, and to identify biomarker and data requirements to be tested in future precision oncology trials.Design setting and participantsWe analyzed deep longitudinal clinical, neuroendocrine expression, and autopsy data of 33 men who died from mPC between 1995 and 2004 (PELICAN33), and related findings to mPC biomarkers reported in the literature.InterventionThirty-three men prospectively consented to participate in an integrated clinical-molecular rapid autopsy study of mPC.Outcome measurements and statistical analysisData exploration with correction for multiple testing and survival analysis from the time of diagnosis to time to death and time to first occurrence of severe pain as outcomes were carried out. The effect of seven complications on the modeled probability of dying within 2 yr after presenting with the complication was evaluated using logistic regression.Results and limitationsFeature exploration revealed novel phenotypes related to mPC outcome. Four complications (pleural effusion, severe anemia, severe or controlled pain, and bone fracture) predict the likelihood of death within 2 yr. Men with Gleason grade group 5 cancers developed severe pain sooner than those with lower-grade tumors. Surprisingly, neuroendocrine (NE) differentiation was frequently observed in the setting of high serum prostate-specific antigen (PSA) levels (≥30 ng/ml). In 4/33 patients, no controlled (requiring analgesics) or severe pain was detected, and strikingly, 14/15 metastatic sites studied in these men did not express NE markers, suggesting an inverse relationship between NE differentiation and pain in mPC. Intracranial subdural metastasis is common (36%) and is usually clinically undetected. Categorization of "skeletal-related events" complications used in recent studies likely obscures the understanding of spinal cord compression and fracture. Early death from prostate cancer was identified in a subgroup of men with a low longitudinal PSA bandwidth. Cachexia is common (body mass index <0.89 in 24/31 patients) but limited to the last year of life. Biomarker review identified 30 categories of mPC biomarkers in need of winnowing in future trials. All findings require validation in larger cohorts, preferably alongside data from this study.ConclusionsThe study identified novel outcome subgroups for future validation and provides "vision for mPC precision oncology 2020-2050" draft recommendations for future data collection and biomarker studies.Patient summaryTo better understand variation in metastatic prostate cancer behavior, we assembled and analyzed longitudinal clinical and autopsy records in 33 men. We identified novel outcomes, phenotypes, and aspects of disease burden to be tested and refined in future trials.

Dataset Information

Accelerating precision medicine in metastatic prostate cancer.

Publications

Accelerating precision medicine in metastatic prostate cancer.

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