Performance of a Prostate Cancer Genomic Classifier in Predicting Metastasis in Men with Prostate-specific Antigen Persistence Postprostatectomy

Daniel E. Spratt, Darlene L.Y. Dai, Robert B. Den, Patricia Troncoso, Kasra Yousefi, Ashley E. Ross, Edward M. Schaeffer, Zaid Haddad, Elai Davicioni, Rohit Mehra, Todd M. Morgan, Walter Rayford, Firas Abdollah, Edouard Trabulsi, Mary Achim, Elsa Li Ning Tapia, Mireya Guerrero, Robert Jeffrey Karnes, Adam P. Dicker, Mark A. HurwitzPaul L. Nguyen, Felix F.Y. Feng, Stephen J. Freedland, John W. Davis

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Prostate cancer patients who have a detectable prostate-specific antigen (PSA) postprostatectomy may harbor pre-existing metastatic disease. To our knowledge, none of the commercially available genomic biomarkers have been investigated in such men. Objective: To evaluate if a 22-gene genomic classifier can independently predict development of metastasis in men with PSA persistence postoperatively. Design, setting, and participants: A multi-institutional study of 477 men who underwent radical prostatectomy (RP) between 1990 and 2015 from three academic centers. Patients were categorized as detectable PSA (n = 150) or undetectable (n = 327) based on post-RP PSA nadir ≥0.1 ng/ml. Outcome measurements and statisitical analysis: Cumulative incidence curves for metastasis were constructed using Fine-Gray competing risks analysis. Penalized Cox univariable and multivariable (MVA) proportional hazards models were performed to evaluate the association of the genomic classifier with metastasis. Results and limitations: The median follow-up for censored patients was 57 mo. The median time from RP to first postoperative PSA was 1.4 mo. Detectable PSA patients were more likely to have higher adverse pathologic features compared with undetectable PSA patients. On MVA, only genomic high-risk (hazard ratio [HR]: 5.95, 95% confidence interval [CI]: 2.02-19.41, p = 0.001), detectable PSA (HR: 4.26, 95% CI: 1.16-21.8, p = 0.03), and lymph node invasion (HR: 12.2, 95% CI: 2.46-70.7, p = 0.003) remained prognostic factors for metastasis. Among detectable PSA patients, the 5-yr metastasis rate was 0.90% for genomic low/intermediate and 18% for genomic high risk (p <. 0.001). Genomic high risk remained independently prognostic on MVA (HR: 5.61, 95% CI: 1.48-22.7, p = 0.01) among detectable PSA patients. C-index for Cancer of the Prostate Risk Assessment Postsurgical score, Gandaglia nomogram, and the genomic classifier plus either Cancer of the Prostate Risk Assessment Postsurgical score or Gandaglia were 0.69, 0.68, and 0.82 or 0.81, respectively. Sample size was a limitation. Conclusions: Despite patients with a detectable PSA harboring significantly higher rates of aggressive clinicopathologic features, Decipher independently predicts for metastasis. Prospective validation of these findings is warranted and will be collected as part of the ongoing randomized trial NRG GU-002. Patient summary: Decipher independently predicted metastasis for patients with detectable prostate-specific antigen after prostatectomy. This article found that despite patients with a detectable prostate-specific antigen harboring significantly higher rates of aggressive clinicopathologic features, Decipher independently predicts for metastasis.

Original languageEnglish (US)
JournalEuropean Urology
DOIs
StateAccepted/In press - Jan 1 2017

Fingerprint

Prostate-Specific Antigen
Prostatic Neoplasms
Neoplasm Metastasis
Prostatectomy
Confidence Intervals
Nomograms
Preexisting Condition Coverage
Proportional Hazards Models
Sample Size
Biomarkers
Lymph Nodes
Odds Ratio

Keywords

  • Biomarker
  • Decipher
  • Detectable PSA
  • Genomic classifier
  • Persistent PSA
  • Prostate cancer
  • Prostatectomy
  • PSA

ASJC Scopus subject areas

  • Urology

Cite this

Performance of a Prostate Cancer Genomic Classifier in Predicting Metastasis in Men with Prostate-specific Antigen Persistence Postprostatectomy. / Spratt, Daniel E.; Dai, Darlene L.Y.; Den, Robert B.; Troncoso, Patricia; Yousefi, Kasra; Ross, Ashley E.; Schaeffer, Edward M.; Haddad, Zaid; Davicioni, Elai; Mehra, Rohit; Morgan, Todd M.; Rayford, Walter; Abdollah, Firas; Trabulsi, Edouard; Achim, Mary; Tapia, Elsa Li Ning; Guerrero, Mireya; Karnes, Robert Jeffrey; Dicker, Adam P.; Hurwitz, Mark A.; Nguyen, Paul L.; Feng, Felix F.Y.; Freedland, Stephen J.; Davis, John W.

In: European Urology, 01.01.2017.

Research output: Contribution to journalArticle

Spratt, DE, Dai, DLY, Den, RB, Troncoso, P, Yousefi, K, Ross, AE, Schaeffer, EM, Haddad, Z, Davicioni, E, Mehra, R, Morgan, TM, Rayford, W, Abdollah, F, Trabulsi, E, Achim, M, Tapia, ELN, Guerrero, M, Karnes, RJ, Dicker, AP, Hurwitz, MA, Nguyen, PL, Feng, FFY, Freedland, SJ & Davis, JW 2017, 'Performance of a Prostate Cancer Genomic Classifier in Predicting Metastasis in Men with Prostate-specific Antigen Persistence Postprostatectomy', European Urology. https://doi.org/10.1016/j.eururo.2017.11.024
Spratt, Daniel E. ; Dai, Darlene L.Y. ; Den, Robert B. ; Troncoso, Patricia ; Yousefi, Kasra ; Ross, Ashley E. ; Schaeffer, Edward M. ; Haddad, Zaid ; Davicioni, Elai ; Mehra, Rohit ; Morgan, Todd M. ; Rayford, Walter ; Abdollah, Firas ; Trabulsi, Edouard ; Achim, Mary ; Tapia, Elsa Li Ning ; Guerrero, Mireya ; Karnes, Robert Jeffrey ; Dicker, Adam P. ; Hurwitz, Mark A. ; Nguyen, Paul L. ; Feng, Felix F.Y. ; Freedland, Stephen J. ; Davis, John W. / Performance of a Prostate Cancer Genomic Classifier in Predicting Metastasis in Men with Prostate-specific Antigen Persistence Postprostatectomy. In: European Urology. 2017.
@article{566dbd3464254688a94c0cb1ae9a233d,
title = "Performance of a Prostate Cancer Genomic Classifier in Predicting Metastasis in Men with Prostate-specific Antigen Persistence Postprostatectomy",
abstract = "Background: Prostate cancer patients who have a detectable prostate-specific antigen (PSA) postprostatectomy may harbor pre-existing metastatic disease. To our knowledge, none of the commercially available genomic biomarkers have been investigated in such men. Objective: To evaluate if a 22-gene genomic classifier can independently predict development of metastasis in men with PSA persistence postoperatively. Design, setting, and participants: A multi-institutional study of 477 men who underwent radical prostatectomy (RP) between 1990 and 2015 from three academic centers. Patients were categorized as detectable PSA (n = 150) or undetectable (n = 327) based on post-RP PSA nadir ≥0.1 ng/ml. Outcome measurements and statisitical analysis: Cumulative incidence curves for metastasis were constructed using Fine-Gray competing risks analysis. Penalized Cox univariable and multivariable (MVA) proportional hazards models were performed to evaluate the association of the genomic classifier with metastasis. Results and limitations: The median follow-up for censored patients was 57 mo. The median time from RP to first postoperative PSA was 1.4 mo. Detectable PSA patients were more likely to have higher adverse pathologic features compared with undetectable PSA patients. On MVA, only genomic high-risk (hazard ratio [HR]: 5.95, 95{\%} confidence interval [CI]: 2.02-19.41, p = 0.001), detectable PSA (HR: 4.26, 95{\%} CI: 1.16-21.8, p = 0.03), and lymph node invasion (HR: 12.2, 95{\%} CI: 2.46-70.7, p = 0.003) remained prognostic factors for metastasis. Among detectable PSA patients, the 5-yr metastasis rate was 0.90{\%} for genomic low/intermediate and 18{\%} for genomic high risk (p <. 0.001). Genomic high risk remained independently prognostic on MVA (HR: 5.61, 95{\%} CI: 1.48-22.7, p = 0.01) among detectable PSA patients. C-index for Cancer of the Prostate Risk Assessment Postsurgical score, Gandaglia nomogram, and the genomic classifier plus either Cancer of the Prostate Risk Assessment Postsurgical score or Gandaglia were 0.69, 0.68, and 0.82 or 0.81, respectively. Sample size was a limitation. Conclusions: Despite patients with a detectable PSA harboring significantly higher rates of aggressive clinicopathologic features, Decipher independently predicts for metastasis. Prospective validation of these findings is warranted and will be collected as part of the ongoing randomized trial NRG GU-002. Patient summary: Decipher independently predicted metastasis for patients with detectable prostate-specific antigen after prostatectomy. This article found that despite patients with a detectable prostate-specific antigen harboring significantly higher rates of aggressive clinicopathologic features, Decipher independently predicts for metastasis.",
keywords = "Biomarker, Decipher, Detectable PSA, Genomic classifier, Persistent PSA, Prostate cancer, Prostatectomy, PSA",
author = "Spratt, {Daniel E.} and Dai, {Darlene L.Y.} and Den, {Robert B.} and Patricia Troncoso and Kasra Yousefi and Ross, {Ashley E.} and Schaeffer, {Edward M.} and Zaid Haddad and Elai Davicioni and Rohit Mehra and Morgan, {Todd M.} and Walter Rayford and Firas Abdollah and Edouard Trabulsi and Mary Achim and Tapia, {Elsa Li Ning} and Mireya Guerrero and Karnes, {Robert Jeffrey} and Dicker, {Adam P.} and Hurwitz, {Mark A.} and Nguyen, {Paul L.} and Feng, {Felix F.Y.} and Freedland, {Stephen J.} and Davis, {John W.}",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/j.eururo.2017.11.024",
language = "English (US)",
journal = "European Urology",
issn = "0302-2838",
publisher = "Elsevier",

}

TY - JOUR

T1 - Performance of a Prostate Cancer Genomic Classifier in Predicting Metastasis in Men with Prostate-specific Antigen Persistence Postprostatectomy

AU - Spratt, Daniel E.

AU - Dai, Darlene L.Y.

AU - Den, Robert B.

AU - Troncoso, Patricia

AU - Yousefi, Kasra

AU - Ross, Ashley E.

AU - Schaeffer, Edward M.

AU - Haddad, Zaid

AU - Davicioni, Elai

AU - Mehra, Rohit

AU - Morgan, Todd M.

AU - Rayford, Walter

AU - Abdollah, Firas

AU - Trabulsi, Edouard

AU - Achim, Mary

AU - Tapia, Elsa Li Ning

AU - Guerrero, Mireya

AU - Karnes, Robert Jeffrey

AU - Dicker, Adam P.

AU - Hurwitz, Mark A.

AU - Nguyen, Paul L.

AU - Feng, Felix F.Y.

AU - Freedland, Stephen J.

AU - Davis, John W.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background: Prostate cancer patients who have a detectable prostate-specific antigen (PSA) postprostatectomy may harbor pre-existing metastatic disease. To our knowledge, none of the commercially available genomic biomarkers have been investigated in such men. Objective: To evaluate if a 22-gene genomic classifier can independently predict development of metastasis in men with PSA persistence postoperatively. Design, setting, and participants: A multi-institutional study of 477 men who underwent radical prostatectomy (RP) between 1990 and 2015 from three academic centers. Patients were categorized as detectable PSA (n = 150) or undetectable (n = 327) based on post-RP PSA nadir ≥0.1 ng/ml. Outcome measurements and statisitical analysis: Cumulative incidence curves for metastasis were constructed using Fine-Gray competing risks analysis. Penalized Cox univariable and multivariable (MVA) proportional hazards models were performed to evaluate the association of the genomic classifier with metastasis. Results and limitations: The median follow-up for censored patients was 57 mo. The median time from RP to first postoperative PSA was 1.4 mo. Detectable PSA patients were more likely to have higher adverse pathologic features compared with undetectable PSA patients. On MVA, only genomic high-risk (hazard ratio [HR]: 5.95, 95% confidence interval [CI]: 2.02-19.41, p = 0.001), detectable PSA (HR: 4.26, 95% CI: 1.16-21.8, p = 0.03), and lymph node invasion (HR: 12.2, 95% CI: 2.46-70.7, p = 0.003) remained prognostic factors for metastasis. Among detectable PSA patients, the 5-yr metastasis rate was 0.90% for genomic low/intermediate and 18% for genomic high risk (p <. 0.001). Genomic high risk remained independently prognostic on MVA (HR: 5.61, 95% CI: 1.48-22.7, p = 0.01) among detectable PSA patients. C-index for Cancer of the Prostate Risk Assessment Postsurgical score, Gandaglia nomogram, and the genomic classifier plus either Cancer of the Prostate Risk Assessment Postsurgical score or Gandaglia were 0.69, 0.68, and 0.82 or 0.81, respectively. Sample size was a limitation. Conclusions: Despite patients with a detectable PSA harboring significantly higher rates of aggressive clinicopathologic features, Decipher independently predicts for metastasis. Prospective validation of these findings is warranted and will be collected as part of the ongoing randomized trial NRG GU-002. Patient summary: Decipher independently predicted metastasis for patients with detectable prostate-specific antigen after prostatectomy. This article found that despite patients with a detectable prostate-specific antigen harboring significantly higher rates of aggressive clinicopathologic features, Decipher independently predicts for metastasis.

AB - Background: Prostate cancer patients who have a detectable prostate-specific antigen (PSA) postprostatectomy may harbor pre-existing metastatic disease. To our knowledge, none of the commercially available genomic biomarkers have been investigated in such men. Objective: To evaluate if a 22-gene genomic classifier can independently predict development of metastasis in men with PSA persistence postoperatively. Design, setting, and participants: A multi-institutional study of 477 men who underwent radical prostatectomy (RP) between 1990 and 2015 from three academic centers. Patients were categorized as detectable PSA (n = 150) or undetectable (n = 327) based on post-RP PSA nadir ≥0.1 ng/ml. Outcome measurements and statisitical analysis: Cumulative incidence curves for metastasis were constructed using Fine-Gray competing risks analysis. Penalized Cox univariable and multivariable (MVA) proportional hazards models were performed to evaluate the association of the genomic classifier with metastasis. Results and limitations: The median follow-up for censored patients was 57 mo. The median time from RP to first postoperative PSA was 1.4 mo. Detectable PSA patients were more likely to have higher adverse pathologic features compared with undetectable PSA patients. On MVA, only genomic high-risk (hazard ratio [HR]: 5.95, 95% confidence interval [CI]: 2.02-19.41, p = 0.001), detectable PSA (HR: 4.26, 95% CI: 1.16-21.8, p = 0.03), and lymph node invasion (HR: 12.2, 95% CI: 2.46-70.7, p = 0.003) remained prognostic factors for metastasis. Among detectable PSA patients, the 5-yr metastasis rate was 0.90% for genomic low/intermediate and 18% for genomic high risk (p <. 0.001). Genomic high risk remained independently prognostic on MVA (HR: 5.61, 95% CI: 1.48-22.7, p = 0.01) among detectable PSA patients. C-index for Cancer of the Prostate Risk Assessment Postsurgical score, Gandaglia nomogram, and the genomic classifier plus either Cancer of the Prostate Risk Assessment Postsurgical score or Gandaglia were 0.69, 0.68, and 0.82 or 0.81, respectively. Sample size was a limitation. Conclusions: Despite patients with a detectable PSA harboring significantly higher rates of aggressive clinicopathologic features, Decipher independently predicts for metastasis. Prospective validation of these findings is warranted and will be collected as part of the ongoing randomized trial NRG GU-002. Patient summary: Decipher independently predicted metastasis for patients with detectable prostate-specific antigen after prostatectomy. This article found that despite patients with a detectable prostate-specific antigen harboring significantly higher rates of aggressive clinicopathologic features, Decipher independently predicts for metastasis.

KW - Biomarker

KW - Decipher

KW - Detectable PSA

KW - Genomic classifier

KW - Persistent PSA

KW - Prostate cancer

KW - Prostatectomy

KW - PSA

UR - http://www.scopus.com/inward/record.url?scp=85037634954&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85037634954&partnerID=8YFLogxK

U2 - 10.1016/j.eururo.2017.11.024

DO - 10.1016/j.eururo.2017.11.024

M3 - Article

C2 - 29233664

AN - SCOPUS:85037634954

JO - European Urology

JF - European Urology

SN - 0302-2838

ER -