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Predicting time to castration resistance in hormone sensitive prostate cancer by a personalization algorithm based on a mechanistic model integrating patient data
Author(s) -
Elishmereni Moran,
Kheifetz Yuri,
Shukrun Ilan,
Bevan Graham H.,
Nandy Debashis,
McKenzie Kyle M.,
Kohli Manish,
Agur Zvia
Publication year - 2016
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23099
Subject(s) - prostate cancer , medicine , androgen deprivation therapy , algorithm , regimen , oncology , cancer , computer science
BACKGROUND Prostate cancer (PCa) is a leading cause of cancer death of men worldwide. In hormone‐sensitive prostate cancer (HSPC), androgen deprivation therapy (ADT) is widely used, but an eventual failure on ADT heralds the passage to the castration‐resistant prostate cancer (CRPC) stage. Because predicting time to failure on ADT would allow improved planning of personal treatment strategy, we aimed to develop a predictive personalization algorithm for ADT efficacy in HSPC patients. METHODS A mathematical mechanistic model for HSPC progression and treatment was developed based on the underlying disease dynamics (represented by prostate‐specific antigen; PSA) as affected by ADT. Following fine‐tuning by a dataset of ADT‐treated HSPC patients, the model was embedded in an algorithm, which predicts the patient's time to biochemical failure (BF) based on clinical metrics obtained before or early in‐treatment. RESULTS The mechanistic model, including a tumor growth law with a dynamic power and an elaborate ADT‐resistance mechanism, successfully retrieved individual time‐courses of PSA (R 2 = 0.783). Using the personal Gleason score (GS) and PSA at diagnosis, as well as PSA dynamics from 6 months after ADT onset, and given the full ADT regimen, the personalization algorithm accurately predicted the individual time to BF of ADT in 90% of patients in the retrospective cohort (R 2 = 0.98). CONCLUSIONS The algorithm we have developed, predicting biochemical failure based on routine clinical tests, could be especially useful for patients destined for short‐lived ADT responses and quick progression to CRPC. Prospective studies must validate the utility of the algorithm for clinical decision‐making. Prostate 76:48–57, 2016 . © 2015 Wiley Periodicals, Inc.