Development and validation of a novel automated Gleason grade and molecular profile that define a highly predictive prostate cancer progression algorithm-based test.
Prostate Cancer Prostatic Dis
; 21(4): 594-603, 2018 11.
Article
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| MEDLINE
| ID: mdl-30087426
ABSTRACT
BACKGROUND:
Postoperative risk assessment remains an important variable in the effective treatment of prostate cancer. There is an unmet clinical need for a test with the potential to enhance the Gleason grading system with novel features that more accurately reflect a personalized prediction of clinical failure.METHODS:
A prospectively designed retrospective study utilizing 892 patients, post radical prostatectomy, followed for a median of 8 years. In training, using digital image analysis to combine microscopic pattern analysis/machine learning with biomarkers, we evaluated Precise Post-op model results to predict clinical failure in 446 patients. The derived prognostic score was validated in 446 patients. Eligible subjects required complete clinical-pathologic variables and were excluded if they had received neoadjuvant treatment including androgen deprivation, radiation or chemotherapy prior to surgery. No patients were enrolled with metastatic disease prior to surgery. Evaluate the assay using time to event concordance index (C-index), Kaplan-Meier, and hazards ratio.RESULTS:
In the training cohort (n = 306), the Precise Post-op test predicted significant clinical failure with a C-index of 0.82, [95% CI 0.76-0.86], HR6.7, [95% CI 3.59-12.45], p < 0.00001. Results were confirmed in validation (n = 284) with a C-index 0.77 [95% CI 0.72-0.81], HR = 5.4, [95% CI 2.74-10.52], p < 0.00001. By comparison, a clinical feature base model had a C-index of 0.70 with a HR = 3.7. The Post-Op test also re-classified 58% of CAPRA-S intermediate risk patients as low risk for clinical failure.CONCLUSIONS:
Precise Post-op tissue-based test discriminates low from intermediate high risk prostate cancer disease progression in the postoperative setting. Guided by machine learning, the test enhances traditional Gleason grading with novel features that accurately reflect the biology of personalized risk assignment.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
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Transcriptoma
Tipo de estudio:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Aged
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Prostate Cancer Prostatic Dis
Asunto de la revista:
ENDOCRINOLOGIA
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NEOPLASIAS
/
UROLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos