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Combined Longitudinal Clinical and Autopsy Phenomic Assessment in Lethal Metastatic Prostate Cancer : Recommendations for Advancing Precision Medicine
- Source :
- European Urology Open Science, EUROPEAN UROLOGY OPEN SCIENCE, European Urology Open Science, Vol 30, Iss, Pp 47-62 (2021), European Urology Open Science, 30, 47-62. Elsevier
- Publication Year :
- 2021
-
Abstract
- Background Systematic identification of data essential for outcome prediction in metastatic prostate cancer (mPC) would accelerate development of precision oncology. Objective To 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 participants We 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. Intervention Thirty-three men prospectively consented to participate in an integrated clinical-molecular rapid autopsy study of mPC. Outcome measurements and statistical analysis Data 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 limitations Feature 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<br />Take Home Message To 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.
- Subjects :
- Complications
Text mining
Urology
3122 Cancers
Metastasis
CONSENSUS CONFERENCE
SDG 3 - Good Health and Well-being
EVOLUTIONARY HISTORY
Medicine and Health Sciences
Electronic medical records
RC254-282
TREATMENT RESPONSE
AMERICAN-SOCIETY
Outcome
Prostate cancer
Prostate Cancer
Precision medicine
RADICAL PROSTATECTOMY
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
NATURAL-HISTORY
3126 Surgery, anesthesiology, intensive care, radiology
Diseases of the genitourinary system. Urology
CIRCULATING TUMOR-CELLS
PROGNOSTIC MODEL
3141 Health care science
Phenotyping
ANDROGEN DEPRIVATION THERAPY
SURVIVAL
RC870-923
Autopsy
3111 Biomedicine
Subjects
Details
- Language :
- English
- ISSN :
- 26661691 and 26661683
- Database :
- OpenAIRE
- Journal :
- European Urology Open Science, EUROPEAN UROLOGY OPEN SCIENCE, European Urology Open Science, Vol 30, Iss, Pp 47-62 (2021), European Urology Open Science, 30, 47-62. Elsevier
- Accession number :
- edsair.pmid.dedup....fc40236c21a64a7f691c2f570fcf533b