Undetectable prostate-specific antigen after short-course androgen deprivation therapy for biochemically recurrent patients correlates with metastasis-free survival and prostate cancer-specific survival

Daniel M. Lim, Roman Gulati, Serge Aleshin-Guendel, Agnes Gawne, Jonathan T. Wingate, Heather H. Cheng, Ruth Etzioni, Evan Y. Yu

Research output: Contribution to journalArticle

Abstract

Background: Optimal utilization of novel therapies for advanced prostate cancer is challenging without a validated surrogate efficacy endpoint. Ongoing trials are using durable undetectable prostate-specific antigen (PSA) levels as a marker of efficacy. The clinical relevance of prolonged undetectable PSA after a short course of androgen deprivation therapy (ADT) is uncertain. Methods: The University of Washington Caisis database was queried for radical prostatectomy patients who received 6-12 months of ADT after biochemical recurrence (BCR), defined as PSA ≥0.2 ng/mL and no radiographically detectable metastasis. Proportions of men with undetectable PSA 12 and 24 months after ending ADT were compared to a hypothesized 5% rate using exact binomial tests. Associations with patient and tumor characteristics were examined using logistic regression, and associations with risk of subsequent metastasis and death were evaluated by log-rank tests. Results: After ineligibility exclusions, 23/93 (25%; 95%CI 16-35%; P < 0.001) and 14/93 (15%; 95%CI 9-24%; P < 0.001) had undetectable PSA 12 and 24 months after ending ADT, respectively. Detectable PSA at 12 months was associated with increased risk of metastasis (P = 0.006), prostate cancer-specific death (P = 0.028), and death from any cause (P = 0.065). Being 1 year older at diagnosis was associated with a 14% (95%CI 5-24%; P = 0.006) decrease in the odds of having a detectable PSA after controlling for PSA at diagnosis, PSA doubling time, grade group, and time from initial therapy to BCR. Conclusions: This single-institution retrospective analysis shows that it is not uncommon to have undetectable PSA 12 or 24 months after a short course of ADT. No baseline prognostic characteristic other than age was associated with a durable (12 month) undetectable PSA. Because a durable undetectable PSA was associated with lower risks of metastasis and prostate cancer-specific death, it may be a reasonable clinical trial endpoint.

Original languageEnglish (US)
Pages (from-to)1077-1083
Number of pages7
JournalProstate
Volume78
Issue number14
DOIs
StatePublished - Oct 1 2018
Externally publishedYes

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Prostate-Specific Antigen
Androgens
Prostatic Neoplasms
Neoplasm Metastasis
Survival
Therapeutics
Recurrence
Prostatectomy
Cause of Death
Biomarkers
Logistic Models
Clinical Trials
Databases

Keywords

  • endpoint
  • landmark
  • surrogate

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Undetectable prostate-specific antigen after short-course androgen deprivation therapy for biochemically recurrent patients correlates with metastasis-free survival and prostate cancer-specific survival. / Lim, Daniel M.; Gulati, Roman; Aleshin-Guendel, Serge; Gawne, Agnes; Wingate, Jonathan T.; Cheng, Heather H.; Etzioni, Ruth; Yu, Evan Y.

In: Prostate, Vol. 78, No. 14, 01.10.2018, p. 1077-1083.

Research output: Contribution to journalArticle

Lim, Daniel M. ; Gulati, Roman ; Aleshin-Guendel, Serge ; Gawne, Agnes ; Wingate, Jonathan T. ; Cheng, Heather H. ; Etzioni, Ruth ; Yu, Evan Y. / Undetectable prostate-specific antigen after short-course androgen deprivation therapy for biochemically recurrent patients correlates with metastasis-free survival and prostate cancer-specific survival. In: Prostate. 2018 ; Vol. 78, No. 14. pp. 1077-1083.
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abstract = "Background: Optimal utilization of novel therapies for advanced prostate cancer is challenging without a validated surrogate efficacy endpoint. Ongoing trials are using durable undetectable prostate-specific antigen (PSA) levels as a marker of efficacy. The clinical relevance of prolonged undetectable PSA after a short course of androgen deprivation therapy (ADT) is uncertain. Methods: The University of Washington Caisis database was queried for radical prostatectomy patients who received 6-12 months of ADT after biochemical recurrence (BCR), defined as PSA ≥0.2 ng/mL and no radiographically detectable metastasis. Proportions of men with undetectable PSA 12 and 24 months after ending ADT were compared to a hypothesized 5{\%} rate using exact binomial tests. Associations with patient and tumor characteristics were examined using logistic regression, and associations with risk of subsequent metastasis and death were evaluated by log-rank tests. Results: After ineligibility exclusions, 23/93 (25{\%}; 95{\%}CI 16-35{\%}; P < 0.001) and 14/93 (15{\%}; 95{\%}CI 9-24{\%}; P < 0.001) had undetectable PSA 12 and 24 months after ending ADT, respectively. Detectable PSA at 12 months was associated with increased risk of metastasis (P = 0.006), prostate cancer-specific death (P = 0.028), and death from any cause (P = 0.065). Being 1 year older at diagnosis was associated with a 14{\%} (95{\%}CI 5-24{\%}; P = 0.006) decrease in the odds of having a detectable PSA after controlling for PSA at diagnosis, PSA doubling time, grade group, and time from initial therapy to BCR. Conclusions: This single-institution retrospective analysis shows that it is not uncommon to have undetectable PSA 12 or 24 months after a short course of ADT. No baseline prognostic characteristic other than age was associated with a durable (12 month) undetectable PSA. Because a durable undetectable PSA was associated with lower risks of metastasis and prostate cancer-specific death, it may be a reasonable clinical trial endpoint.",
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T1 - Undetectable prostate-specific antigen after short-course androgen deprivation therapy for biochemically recurrent patients correlates with metastasis-free survival and prostate cancer-specific survival

AU - Lim, Daniel M.

AU - Gulati, Roman

AU - Aleshin-Guendel, Serge

AU - Gawne, Agnes

AU - Wingate, Jonathan T.

AU - Cheng, Heather H.

AU - Etzioni, Ruth

AU - Yu, Evan Y.

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AB - Background: Optimal utilization of novel therapies for advanced prostate cancer is challenging without a validated surrogate efficacy endpoint. Ongoing trials are using durable undetectable prostate-specific antigen (PSA) levels as a marker of efficacy. The clinical relevance of prolonged undetectable PSA after a short course of androgen deprivation therapy (ADT) is uncertain. Methods: The University of Washington Caisis database was queried for radical prostatectomy patients who received 6-12 months of ADT after biochemical recurrence (BCR), defined as PSA ≥0.2 ng/mL and no radiographically detectable metastasis. Proportions of men with undetectable PSA 12 and 24 months after ending ADT were compared to a hypothesized 5% rate using exact binomial tests. Associations with patient and tumor characteristics were examined using logistic regression, and associations with risk of subsequent metastasis and death were evaluated by log-rank tests. Results: After ineligibility exclusions, 23/93 (25%; 95%CI 16-35%; P < 0.001) and 14/93 (15%; 95%CI 9-24%; P < 0.001) had undetectable PSA 12 and 24 months after ending ADT, respectively. Detectable PSA at 12 months was associated with increased risk of metastasis (P = 0.006), prostate cancer-specific death (P = 0.028), and death from any cause (P = 0.065). Being 1 year older at diagnosis was associated with a 14% (95%CI 5-24%; P = 0.006) decrease in the odds of having a detectable PSA after controlling for PSA at diagnosis, PSA doubling time, grade group, and time from initial therapy to BCR. Conclusions: This single-institution retrospective analysis shows that it is not uncommon to have undetectable PSA 12 or 24 months after a short course of ADT. No baseline prognostic characteristic other than age was associated with a durable (12 month) undetectable PSA. Because a durable undetectable PSA was associated with lower risks of metastasis and prostate cancer-specific death, it may be a reasonable clinical trial endpoint.

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