Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer

post hoc analysis of PREVAIL

Alan H Bryce, J. J. Alumkal, A. Armstrong, C. S. Higano, P. Iversen, C. N. Sternberg, D. Rathkopf, Y. Loriot, J. de Bono, B. Tombal, S. Abhyankar, P. Lin, A. Krivoshik, D. Phung, T. M. Beer

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background:Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested.Methods:Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups.Results:Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26–2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar.Conclusions:Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression.Prostate Cancer and Prostatic Diseases advance online publication, 24 January 2017; doi:10.1038/pcan.2016.71.

Original languageEnglish (US)
JournalProstate Cancer and Prostatic Diseases
DOIs
StateAccepted/In press - Jan 24 2017

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Castration
Prostatic Neoplasms
Disease Progression
Prostatic Diseases
Androgen Receptors
Disease-Free Survival
Publications
Clinical Trials
Confidence Intervals
Drug Therapy
Survival
MDV 3100
Serum

ASJC Scopus subject areas

  • Oncology
  • Urology
  • Cancer Research

Cite this

Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer : post hoc analysis of PREVAIL. / Bryce, Alan H; Alumkal, J. J.; Armstrong, A.; Higano, C. S.; Iversen, P.; Sternberg, C. N.; Rathkopf, D.; Loriot, Y.; de Bono, J.; Tombal, B.; Abhyankar, S.; Lin, P.; Krivoshik, A.; Phung, D.; Beer, T. M.

In: Prostate Cancer and Prostatic Diseases, 24.01.2017.

Research output: Contribution to journalArticle

Bryce, AH, Alumkal, JJ, Armstrong, A, Higano, CS, Iversen, P, Sternberg, CN, Rathkopf, D, Loriot, Y, de Bono, J, Tombal, B, Abhyankar, S, Lin, P, Krivoshik, A, Phung, D & Beer, TM 2017, 'Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer: post hoc analysis of PREVAIL', Prostate Cancer and Prostatic Diseases. https://doi.org/10.1038/pcan.2016.71
Bryce, Alan H ; Alumkal, J. J. ; Armstrong, A. ; Higano, C. S. ; Iversen, P. ; Sternberg, C. N. ; Rathkopf, D. ; Loriot, Y. ; de Bono, J. ; Tombal, B. ; Abhyankar, S. ; Lin, P. ; Krivoshik, A. ; Phung, D. ; Beer, T. M. / Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer : post hoc analysis of PREVAIL. In: Prostate Cancer and Prostatic Diseases. 2017.
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abstract = "Background:Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested.Methods:Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups.Results:Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95{\%} confidence interval 1.26–2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar.Conclusions:Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression.Prostate Cancer and Prostatic Diseases advance online publication, 24 January 2017; doi:10.1038/pcan.2016.71.",
author = "Bryce, {Alan H} and Alumkal, {J. J.} and A. Armstrong and Higano, {C. S.} and P. Iversen and Sternberg, {C. N.} and D. Rathkopf and Y. Loriot and {de Bono}, J. and B. Tombal and S. Abhyankar and P. Lin and A. Krivoshik and D. Phung and Beer, {T. M.}",
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T1 - Radiographic progression with nonrising PSA in metastatic castration-resistant prostate cancer

T2 - post hoc analysis of PREVAIL

AU - Bryce, Alan H

AU - Alumkal, J. J.

AU - Armstrong, A.

AU - Higano, C. S.

AU - Iversen, P.

AU - Sternberg, C. N.

AU - Rathkopf, D.

AU - Loriot, Y.

AU - de Bono, J.

AU - Tombal, B.

AU - Abhyankar, S.

AU - Lin, P.

AU - Krivoshik, A.

AU - Phung, D.

AU - Beer, T. M.

PY - 2017/1/24

Y1 - 2017/1/24

N2 - Background:Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested.Methods:Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups.Results:Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26–2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar.Conclusions:Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression.Prostate Cancer and Prostatic Diseases advance online publication, 24 January 2017; doi:10.1038/pcan.2016.71.

AB - Background:Advanced prostate cancer is a phenotypically diverse disease that evolves through multiple clinical courses. PSA level is the most widely used parameter for disease monitoring, but it has well-recognized limitations. Unlike in clinical trials, in practice, clinicians may rely on PSA monitoring alone to determine disease status on therapy. This approach has not been adequately tested.Methods:Chemotherapy-naive asymptomatic or mildly symptomatic men (n=872) with metastatic castration-resistant prostate cancer (mCRPC) who were treated with the androgen receptor inhibitor enzalutamide in the PREVAIL study were analyzed post hoc for rising versus nonrising PSA (empirically defined as >1.05 vs ⩽1.05 times the PSA level from 3 months earlier) at the time of radiographic progression. Clinical characteristics and disease outcomes were compared between the rising and nonrising PSA groups.Results:Of 265 PREVAIL patients with radiographic progression and evaluable PSA levels on the enzalutamide arm, nearly one-quarter had a nonrising PSA. Median progression-free survival in this cohort was 8.3 months versus 11.1 months in the rising PSA cohort (hazard ratio 1.68; 95% confidence interval 1.26–2.23); overall survival was similar between the two groups, although less than half of patients in either group were still at risk at 24 months. Baseline clinical characteristics of the two groups were similar.Conclusions:Non-rising PSA at radiographic progression is a common phenomenon in mCRPC patients treated with enzalutamide. As restaging in advanced prostate cancer patients is often guided by increases in PSA levels, our results demonstrate that disease progression on enzalutamide can occur without rising PSA levels. Therefore, a disease monitoring strategy that includes imaging not entirely reliant on serial serum PSA measurement may more accurately identify disease progression.Prostate Cancer and Prostatic Diseases advance online publication, 24 January 2017; doi:10.1038/pcan.2016.71.

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