The U Shape of Prostate-specific Antigen and Prostate Cancer-specific Mortality in High-grade Metastatic Prostate Adenocarcinoma

Purpose: To determine whether pretreatment risk groups shown to predict time to prostate cancer–specific mortality (PCSM) after treatment at a single institution retained that ability in a multi-institutional setting. Patients and Methods: From 1988 to 2002, 7,316 patients treated in the United States at 44 institutions with either surgery (n = 4,946) or radiation (n = 2,370) for clinical stage T1c-2, N0 or NX, M0 prostate cancer made up the study cohort. A Cox regression analysis was performed to determine the ability of pretreatment risk groups to predict time to PCSM after treatment. The relative risk (RR) of PCSM and 95% confidence intervals (CIs) were calculated for the intermediate- and high-risk groups relative to the low-risk group. Results: Estimates of non-PCSM 8 years after prostate-specific antigen (PSA) failure were 4% v 15% (surgery versus radiation; Plog rank = .002) compared with 13% v 18% (surgery versus radiation; Plog rank = .35) for patients whose age at the time of PSA failure was less than 70 as compared with ≥ 70 years, respectively. The RR of PCSM after treatment for surgery-managed patients with high- or intermediate-risk disease was 14.2 (95% CI, 5.0 to 23.4; PCox < .0001) and 4.9 (95% CI, 1.7 to 8.1; PCox = .0037), respectively. These values were 14.3 (95% CI, 5.2 to 24.0; PCox < .0001) and 5.6 (95% CI, 2.0 to 9.3; PCox = .0012) for radiation-managed patients. Conclusion: This study provided evidence to support the prediction of time to PCSM after surgery or radiation on the basis of pretreatment risk groups for patients with clinically localized prostate cancer managed during the PSA era.

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Prostate-specific antigen-based serial screening may decrease prostate cancer-specific mortality

Urology ◽

10.1016/j.urology.2006.02.030 ◽

2006 ◽

Vol 68 (2) ◽

pp. 342-347 ◽

Cited By ~ 32

Author(s):

Jason A. Efstathiou ◽

Ming-Hui Chen ◽

William J. Catalona ◽

David G. McLeod ◽

Peter R. Carroll ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Specific Antigen ◽

Specific Mortality ◽

Cancer Specific Mortality

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Time to Prostate-Specific Antigen Nadir After Androgen Suppression Therapy for Postoperative or Postradiation PSA Failure and Risk of Prostate Cancer-Specific Mortality

Yearbook of Urology ◽

10.1016/s0084-4071(08)79082-1 ◽

2008 ◽

Vol 2008 ◽

pp. 170-171

Author(s):

G.L. Andriole

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Specific Antigen ◽

Psa Failure ◽

Specific Mortality ◽

Cancer Specific Mortality ◽

Androgen Suppression

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Identification of low prostate-specific antigen, high Gleason prostate cancer as a unique hormone-resistant entity with poor survival: A contemporary analysis of 640,000 patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5080 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5080-5080

Author(s):

David Dewei Yang ◽

Brandon Arvin Virgil Mahal ◽

Christopher Sweeney ◽

Quoc-Dien Trinh ◽

Felix Yi-Chung Feng ◽

...

Keyword(s):

Prostate Cancer ◽

High Risk ◽

Prostate Specific Antigen ◽

Locally Advanced ◽

Specific Antigen ◽

Molecular Classification ◽

High Grade ◽

Biological Insight ◽

Cancer Specific Mortality ◽

New Treatment

5080 Background: The clinical implications of a low prostate-specific antigen (PSA) in high-grade prostate cancer are unclear. We examined the prognostic and predictive value of a low PSA in high-grade prostate cancer. Methods: We identified 642,975 patients in the National Cancer Database (n = 491,505) and Surveillance, Epidemiology, and End Results program (n = 151,470) with localized or locally advanced prostate cancer from 2004-2013. Patients were stratified by Gleason score (8-10 vs. ≤7) and PSA (≤2.5, 2.6-4.0, 4.1-10.0, 10.1-20.0, and > 20.0 ng/mL) for analyses. Multivariable Fine-Gray competing risks and Cox regressions were used to analyze prostate-cancer specific mortality (PCSM) and all-cause mortality (ACM), respectively. Results: 5.6% of Gleason 8-10 tumors were diagnosed with PSA ≤2.5 ng/mL. Among Gleason 8-10 disease using PSA 4.1-10.0 ng/mL as referent, PCSM was U-shaped with respect to PSA, with adjusted hazard ratio (AHR) of 1.75 (95% CI 1.05-2.92, P = 0.032) for PSA ≤2.5 ng/mL vs. 1.31, 0.88, and 1.60 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL. In contrast, PCSM was linear for Gleason ≤7 disease with AHR of 0.32 (95% CI 0.10-1.00, P = 0.050) for PSA ≤2.5 ng/mL vs. 1.13, 1.69, and 3.22 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL (PGleason*PSA interaction< 0.001). Gleason 8-10 disease with PSA ≤2.5 ng/mL had a much higher risk of PCSM than standard NCCN high-risk disease (AHR 1.92, 95% CI 1.18-3.14, P = 0.009; 47-month PCSM 14.0% vs. 10.5%). For Gleason 8-10 tumors treated with definitive radiotherapy, androgen deprivation therapy (ADT) was associated with decreased ACM for PSA > 2.5 ng/mL (AHR 0.87, 95% CI 0.81-0.94, P < 0.001) but trended toward increased ACM for PSA ≤2.5ng/mL (AHR 1.27, 95% CI 0.89-1.81, P = 0.194; PADT*PSA interaction= 0.026). Conclusions: Low PSA, high-grade prostate cancer appears to be a unique hormone-resistant entity with a high risk of PCSM that responds poorly to standard treatment. Further molecular classification and trials are urgently needed to develop biological insight into this entity and establish new treatment paradigms, potentially including chemotherapy or novel systemic agents.

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