Evaluating the Combined Effect of Comorbidity and Prostate-Specific Antigen Kinetics on the Risk of Death in Men After Prostate-Specific Antigen Recurrence

PurposeWe examined whether time-dependent continuous prostate-specific antigen (PSA) velocity at recurrence was associated with all cause mortality (ACM) adjusting for comorbidity levels among men treated with definitive radiation therapy (RT) alone with or without androgen suppression therapy (AST) in the setting of a randomized controlled trial.Patients and MethodsFrom 1995 to 2001, 206 men with localized, unfavorable prostate cancer were randomly assigned to receive RT alone or RT and AST combined. Cox multivariate regression analysis was performed to evaluate the relationship between PSA velocity at recurrence and ACM, adjusting for known prostate cancer prognostic factors, including Adult Comorbidity Evaluation 27 comorbidity level.ResultsWith a median follow-up of 8.4 years, 89 biochemical recurrences and 74 ACM deaths occurred. Among all patients, higher PSA velocity was associated with increased ACM (hazard ratio [HR], 1.47; 95% CI, 1.07 to 1.44; P < .001) after adjusting for age, treatment arm, comorbidity score, and salvage AST. For 89 patients with biochemical recurrence, increasing PSA velocity at recurrence (HR, 1.60; 95% CI, 1.23 to 2.09; P ≤ .001) and moderate to severe comorbidity score (HR, 7.94; 95% CI, 1.55 to 40.52; P = .01) were associated with increased ACM. PSA velocity at recurrence was associated with significantly higher risk of ACM among patients with no or minimal comorbidity (P < .001), but not moderate to severe comorbidity (P = .12).ConclusionRapid PSA velocity at recurrence is significantly associated with an increased risk of ACM among patients with no or minimal comorbidity but not moderate to severe comorbidity. These findings support judicious use of salvage AST, particularly in men with moderate to severe comorbidities, where prospective surveillance protocols are needed.

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Natural History of Untreated Prostate Specific Antigen Radiorecurrent Prostate Cancer in Men with Favorable Prognostic Indicators

Prostate Cancer ◽

10.1155/2014/912943 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Neil E. Martin ◽

Ming-Hui Chen ◽

Clair J. Beard ◽

Paul L. Nguyen ◽

Marian J. Loffredo ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Doubling Time ◽

Cox Regression ◽

Specific Antigen ◽

Risk Of Death ◽

Psa Doubling Time ◽

Increased Risk ◽

Psa Failure ◽

Post Radiation

Background and Purpose. Life expectancy data could identify men with favorable post-radiation prostate-specific antigen (PSA) failure kinetics unlikely to require androgen deprivation therapy (ADT).Materials and Methods. Of 206 men with unfavorable-risk prostate cancer in a randomized trial of radiation versus radiation and ADT, 53 experienced a PSA failure and were followed without salvage ADT. Comorbidity, age and established prognostic factors were assessed for relationship to death using Cox regression analyses.Results. The median age at failure, interval to PSA failure, and PSA doubling time were 76.6 years (interquartile range [IQR]: 71.8–79.3), 49.1 months (IQR: 37.7–87.4), and 25 months (IQR: 13.1–42.8), respectively. After a median follow up of 4.0 years following PSA failure, 45% of men had died, none from prostate cancer and no one had developed metastases. Both increasing age at PSA failure (HR: 1.14; 95% CI: 1.03–1.25;P=0.008) and the presence of moderate to severe comorbidity (HR: 12.5; 95% CI: 3.81–41.0;P<0.001) were significantly associated with an increased risk of death.Conclusions. Men over the age of 76 with significant comorbidity and a PSA doubling time >2 years following post-radiation PSA failure appear to be good candidates for observation without ADT intervention.

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Limitation of prostate-specific antigen doubling time as a predictor of outcome in hormone-naive prostate cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4566 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4566-4566 ◽

Cited By ~ 3

Author(s):

J. B. Nelson ◽

D. J. Sleep ◽

J. D. Isaacson ◽

M. A. Carducci

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Doubling Time ◽

Controlled Trial ◽

Specific Antigen ◽

Controlled Study ◽

Primary Therapy ◽

Double Blind ◽

Psa Velocity ◽

Baseline Psa

4566 Background: Prostate-specific antigen doubling time (PSADT) is used to monitor progression after primary therapy for prostate cancer. Increasingly in this population, PSADT is an efficacy measure in therapeutic trials, many of which are uncontrolled. Examination of PSADT response on placebo in a randomized controlled study may evaluate the utility of PSADT as an outcome measure in patients with hormone-naive prostate cancer. Methods: Patients with biochemical failure post radical prostatectomy were enrolled in a randomized, double-blind, placebo-controlled trial of atrasentan 10 mg. Eligibility criteria included baseline PSA between 0.4 ng/mL and 5 ng/mL with a PSADT ≤12 months based on two PSA values at least 2 weeks apart. On-treatment PSADT was compared between treatment groups in patients with at least 3 on-treatment PSA values collected every 12 weeks while on study drug. Categorical analysis comparing PSADT between groups was performed using Cochran-Mantel-Haenszel methodology. Mean change from baseline in PSA velocity (log PSA vs time) was analyzed using a one-way analysis of variance with treatment as the factor. Results: Of 222 patients enrolled, 209 had 3 PSA values on study: N=107 for placebo; N = 102 for atrasentan. Baseline PSA was lower for patients in the placebo arm than for those in the atrasentan arm (mean of 1.4 ng/mL [SE 0.1] vs 1.8 ng/mL [SE 0.1] P =.012). On-treatment PSADT was similar between treatment arms (P =.363); the proportion of patients whose PSADT was >1 year on study was 55% with placebo and 51% with atrasentan. More notably, PSADT lengthened on study for most patients in both arms (76/107, 71% for placebo and 68/102, 64% for atrasentan). PSA velocity was also protracted for patients in both treatment arms (placebo: slope = 1.47 at baseline to 0.96, P < .001; atrasentan: slope = 1.56 at baseline to 1.26, P =.017). Conclusions: The fact that over 70% of patients receiving placebo experienced lengthened PSADT suggests that, in the absence of a control arm, changes in PSADT from baseline are not a reliable measure of treatment effect in trials in early prostate cancer. PSADT data from trials in this population should be interpreted with caution. [Table: see text]

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Prostate Cancer

10.1093/oso/9780190676827.003.0020 ◽

2018 ◽

Author(s):

Kathryn M. Wilson ◽

Lorelei Mucci

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Family History ◽

Prostate Specific Antigen ◽

Advanced Prostate Cancer ◽

Advanced Disease ◽

African Ancestry ◽

Specific Antigen ◽

Dietary Factors ◽

Increased Risk

Prostate cancer is among the most commonly diagnosed cancers among men, ranking second in cancer globally and first in Western countries. There are marked variations in incidence globally, and its incidence must be interpreted in the context of diagnostic intensity and screening. The uptake of prostate-specific antigen screening since the 1990s has led to dramatic increases in incidence in many countries, resulting in an increased proportion of indolent cancers that would never have come to light clinically in the absence of screening. Risk factors differ when studying prostate cancer overall versus advanced disease. Older age, African ancestry, and family history are established risk factors for prostate cancer. Obesity and smoking are not associated with risk overall, but are associated with increased risk of advanced prostate cancer. Several additional lifestyle factors, medications, and dietary factors are now emerging as risk factors for advanced disease.

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Absolute Prostate-Specific Antigen Value After Androgen Deprivation Is a Strong Independent Predictor of Survival in New Metastatic Prostate Cancer: Data From Southwest Oncology Group Trial 9346 (INT-0162)

Journal of Clinical Oncology ◽

10.1200/jco.2006.06.4246 ◽

2006 ◽

Vol 24 (24) ◽

pp. 3984-3990 ◽

Cited By ~ 312

Author(s):

Maha Hussain ◽

Catherine M. Tangen ◽

Celestia Higano ◽

Paul F. Schelhammer ◽

James Faulkner ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Proportional Hazards ◽

Strong Predictor ◽

Specific Antigen ◽

Androgen Deprivation ◽

Time To Death ◽

Cancer Data ◽

Risk Of Death ◽

Group Trial

Purpose To establish whether absolute prostate-specific antigen (PSA) value after androgen deprivation (AD) is prognostic in metastatic (D2) prostate cancer (PCa). Patients and Methods D2 PCa patients with baseline PSA of at least 5 ng/mL received 7 months induction AD. Patients achieving PSA of 4.0 ng/mL or less on months 6 and 7 are randomly assigned to continuous versus intermittent AD on month 8. Eligibility for this analysis required a prestudy PSA with at least two subsequent PSAs and that patients be registered at least 1 year before analysis date. Survival was defined as time to death after 7 months of AD. Associations were evaluated by proportional hazards regression models. Results One thousand one hundred thirty four of 1,345 eligible patients achieved a PSA of 4 ng/mL or less. At end of induction, 965 patients maintained PSA of 4 or less and 604 had a PSA of 0.2 ng/mL or less. After controlling for prognostic factors, patients with a PSA of 4 or less to more than 0.2 ng/mL had less than one third the risk of death (ROD) as those with a PSA of more than 4 ng/mL (P < .001). Patients with PSA of 0.2 ng/mL or less had less than one fifth the ROD as patients with a PSA of more than 4 ng/mL (P < .001) and had significantly better survival than those with PSA of more than 0.2 to 4 ng/mL or less (P < .001). Median survival was 13 months for patients with a PSA of more than 4 ng/mL, 44 months for patients with PSA of more than 0.2 to 4 ng/mL or less, and 75 months for patients with PSA of 0.2 ng/mL or less. Conclusion A PSA of 4 ng/mL or less after 7 months of AD is a strong predictor of survival. This data should be used to tailor future trial design for D2 prostate cancer.

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Time to Prostate-specific Antigen Nadir and the Risk of Death From Prostate Cancer Following Radiation and Androgen Deprivation Therapy

Urology ◽

10.1016/j.urology.2018.11.056 ◽

2019 ◽

Vol 126 ◽

pp. 145-151 ◽

Cited By ~ 1

Author(s):

Luke R.G. Pike ◽

Jing Wu ◽

Ming-Hui Chen ◽

Marian Loffredo ◽

Andrew A. Renshaw ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Androgen Deprivation Therapy ◽

Specific Antigen ◽

Androgen Deprivation ◽

Risk Of Death

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Prostate-specific antigen response duration and risk of death for patients with hormone-refractory metastatic prostate cancer

Urology ◽

10.1016/j.urology.2005.03.083 ◽

2005 ◽

Vol 66 (3) ◽

pp. 571-576 ◽

Cited By ~ 10

Author(s):

Anthony V. D’Amico ◽

Ming-Hui Chen ◽

Michael C. Cox ◽

William Dahut ◽

William D. Figg

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Metastatic Prostate Cancer ◽

Specific Antigen ◽

Response Duration ◽

Risk Of Death ◽

Hormone Refractory

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The risk of death from prostate cancer in men with Gleason Score 3+4 prostate cancer treated using brachytherapy with or without a short course of androgen deprivation therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.330 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 330-330

Author(s):

David Dewei Yang ◽

Ming-Hui Chen ◽

Michelle H. Braccioforte ◽

Brian Joseph Moran ◽

Anthony Victor D'Amico

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Gleason Score ◽

Specific Antigen ◽

Androgen Deprivation ◽

Risk Of Death ◽

Short Course ◽

Increased Risk ◽

Adenocarcinoma Of The Prostate ◽

Biopsy Gleason Score

330 Background: We evaluated whether the intermediate-risk factors of percentage of positive biopsies (PPB), clinical tumor category, and prostate-specific antigen (PSA) level, in addition to age, were associated with the risk of prostate cancer-specific mortality (PCSM) among men with Gleason 3+4 prostate cancer treated with brachytherapy (BT) alone or BT and a short course of androgen deprivation therapy (ADT). Methods: We conducted a prospective cohort study of 1920 consecutively treated men with Gleason 3+4 adenocarcinoma of the prostate who received BT or BT and a median of 4 months of ADT between 10/14/1997 and 5/28/2013. Separate multivariable Fine and Gray competing risks regression models among men treated with BT or BT and ADT were used to assess whether PPB, cT2b-T2c, and PSA of 10.1-20.0 ng/ml, in addition to age greater than the median of 70 years, were associated with the risk of PCSM after adjustment for comorbidity. Results: After a median follow-up of 7.8 years (interquartile range 5.2-10.4 years), 284 men (14.8%) had died, including 31 (10.9% of deaths) from PC of which 18 (58.1%) and 13 (41.9%) occurred in men treated with BT or BT and ADT, respectively. For men treated with BT alone, increasing PPB, PSA of 10.1-20.0 vs 4.0-10.0 ng/mL, and age >70 vs ≤70 years were significantly associated with an increased risk of PCSM (adjusted hazard ratio [AHR] 1.015 95% confidence interval [CI] 1.000-1.031, P=0.048; AHR 5.55, 95% CI 2.01-15.29, P<0.001; and AHR 3.66, 95% CI 1.16-11.56, P=0.03, respectively). The respective results for men treated with BT and ADT were AHR 1.009, 95% CI 0.987-1.031, P=0.44; AHR 4.17, 95% CI 1.29-13.50, P=0.02; and AHR 3.74, 95% CI 0.87-16.05, P=0.08. The clinical tumor category was not significantly associated with the risk of PCSM. Conclusions: Among men with biopsy Gleason score 3+4 PC, both age >70 years and PSA of 10.1-20.0 ng/ml were significantly associated with an increased risk of PCSM following BT, and adding 4 months of ADT may not be sufficient to mitigate this risk. Advanced imaging and targeted biopsy of suspicious areas should be considered to personalize treatment in order to minimize the risk of PCSM in these men.

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