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

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4566-4566 ◽  
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]

Autophagic cell death with hydroxychloroquine in patients with hormone-dependent prostate-specific antigen progression after local therapy for prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 102-102 ◽  
Author(s):  
Mridula Annette George ◽  
Tina M. Mayer ◽  
Dirk Moore ◽  
Chunxia Chen ◽  
Eileen White ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Growth ◽  
Prostate Specific Antigen ◽  
Hormonal Therapy ◽  
Doubling Time ◽  
Specific Antigen ◽  
Local Therapy ◽  
Primary Therapy ◽  
Response Change ◽  
Early Tumor

102 Background: For patients who have a rising prostate-specific antigen value after definitive local therapy, androgen deprivation is a commonly employed option. However, immediate hormonal therapy has not been shown to alter the progression of the disease. Prior studies showed the dependence of early tumor growth and progression on anaerobic metabolism through glycolysis. Autophagy is conserved, genetically controlled catabolic response to starvation and stress whereby cells self-digest intracellular proteins and organelles by targeting them for degradation in lysosomes to generate energy and mitigate damage, thereby supporting cancer cell survival. Our hypothesis was that the autophagic inhibitor, hydroxychloroquine, when utilized in prostate cancer, would interfere with defective autophagy such that tumor growth will be slowed or stopped. Methods: Patients had rising PSA after primary therapy for PC, no radiographic evidence of metastasis, no (neo)adjuvant ADT within 3 months of enrollment and testosterone > 150 ng/dL. Hydroxychloroquine was dosed at 400 mg/day (cohort 1) or 600 mg/day (cohort 2). Endpoints were PSA response (change in slope of PSA rise by at least 25%, when log (PSA) is plotted vs. time). Results: 64 patients (36 cohort 1; 28 patients cohort 2) with median age 71(55-94) and baseline PSA was 3.25ng/ml (0.24- 45.69ng/ml) were enrolled in the study. 39 patients completed 6 months of hydroxychloroquine therapy and 44 patients completed 5 months of treatment. Out of 64 patients, 52 had at least 5 PSA measurements after the start of treatment, and we restrict our analysis to these patients. In 33 patients of these 52 (63%), the doubling time decreased after treatment began. In 12 of these 52 (23%), the “doubling time” turned negative, consistent with decreasing PSA value. Most common adverse events were diarrhea (26%), nausea (12%) and rash (12%). Conclusions: Hydroxychloroquine appears to have some activity in PSA progression after localized therapy with minimal toxicity. Given that hydroxychloroquine has limited side effects, this drug has the potential to augment responses to hormonal therapy or chemotherapy. Clinical trial information: NCT00726596.

Prostate-specific antigen (PSA) kinetics in untreated, localized prostate cancer: PSA velocity vs PSA doubling time

2009 ◽  
Vol 103 (7) ◽  
pp. 872-876 ◽  
Author(s):  
Michael K. Ng ◽  
Nicholas Van As ◽  
Karen Thomas ◽  
Ruth Woode-Amissah ◽  
Alan Horwich ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Doubling Time ◽  
Specific Antigen ◽  
Localized Prostate Cancer ◽  
Psa Kinetics ◽  
Psa Doubling Time ◽  
Psa Velocity

scholarly journals Baseline Prostate-Specific Antigen Levels in Midlife Predict Lethal Prostate Cancer

2016 ◽  
Vol 34 (23) ◽  
pp. 2705-2711 ◽  
Author(s):  
Mark A. Preston ◽  
Julie L. Batista ◽  
Kathryn M. Wilson ◽  
Sigrid V. Carlsson ◽  
Travis Gerke ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Controlled Trial ◽  
Conditional Logistic Regression ◽  
Characteristic Curve ◽  
Specific Antigen ◽  
Health Study ◽  
Opportunistic Screening ◽  
Odds Ratios ◽  
Baseline Psa

Purpose Prostate-specific antigen (PSA) level in midlife predicted future prostate cancer (PCa) mortality in an unscreened Swedish population. Our purpose was to determine if a baseline PSA level during midlife predicts lethal PCa in a US population with opportunistic screening. Materials and Methods We conducted a nested case-control study among men age 40 to 59 years who gave blood before random assignment in the Physicians’ Health Study, a randomized, placebo-controlled trial of aspirin and β-carotene among 22,071 US male physicians initiated in 1982 and then transitioned into a prospective cohort with 30 years of follow-up. Baseline PSA levels were available for 234 patients with PCa and 711 age-matched controls. Seventy-one participants who developed lethal PCa were rematched to 213 controls. Conditional logistic regression was used to estimate odds ratios and the area under the receiver operating characteristic curve, with 95% CIs, of the association between baseline PSA and risk of lethal PCa. Results Median PSA among controls was 0.68, 0.88, and 0.96 ng/mL for men age 40 to 49, 50 to 54, and 55 to 59 years, respectively. Risk of lethal PCa was strongly associated with baseline PSA in midlife: odds ratios (95% CIs) comparing PSA in the > 90th percentile versus less than or equal to median were 8.7 (1.0 to 78.2) at 40 to 49 years, 12.6 (1.4 to 110.4) at 50 to 54 years, and 6.9 (2.5 to 19.1) at 55 to 59 years. A total of 82%, 71%, and 86% of lethal cases occurred in men with PSA above the median at ages 40 to 49, 50 to 54, and 55 to 59 years, respectively. Conclusion PSA levels in midlife strongly predict future lethal PCa in a US cohort subject to opportunistic screening. Risk-stratified screening on the basis of midlife PSA should be considered in men age 45 to 59 years.

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

2009 ◽  
Vol 27 (35) ◽  
pp. 6000-6005 ◽  
Author(s):  
Jennifer Y. Wo ◽  
Ming-Hui Chen ◽  
Paul L. Nguyen ◽  
Andrew A. Renshaw ◽  
Marian J. Loffredo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Controlled Trial ◽  
Specific Antigen ◽  
Multivariate Regression Analysis ◽  
Comorbidity Score ◽  
Risk Of Death ◽  
Increased Risk ◽  
Severe Comorbidity ◽  
Psa Velocity

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.

scholarly journals Systematic Review of Pretreatment Prostate-Specific Antigen Velocity and Doubling Time As Predictors for Prostate Cancer

2009 ◽  
Vol 27 (3) ◽  
pp. 398-403 ◽  
Author(s):  
Andrew J. Vickers ◽  
Caroline Savage ◽  
M. Frank O'Brien ◽  
Hans Lilja
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Prostate Specific Antigen ◽  
Doubling Time ◽  
Clinical Decision Making ◽  
Predictive Accuracy ◽  
Specific Antigen ◽  
Definitive Treatment ◽  
Definitive Therapy ◽  
Psa Velocity

Purpose Pretreatment prostate-specific antigen (PSA) dynamics (PSA velocity and PSA doubling time) are widely advocated as useful prognostic markers in prostate cancer. We aimed to assess the published evidence for the clinical utility of PSA dynamics in this population. Methods We conducted a systematic review of studies published before March 2007 in which a PSA dynamic (velocity or doubling time) was calculated in patients before definitive treatment, a subsequent event (such as biopsy or recurrence) was ascertained, and the association between the two was analyzed. Our principal end point was the type of analysis reported, particularly whether the predictive accuracy of a statistical model that included both absolute PSA level and a PSA dynamic was compared with that of a model that included only PSA. Results Eighty-seven articles were eligible for analysis. The most common end points were biopsy (42 articles), and either recurrence (14 articles) or metastases or death (14 articles) after definitive therapy. Although PSA dynamics were generally found to be associated with outcome, only one article compared predictive accuracy of models with and without a PSA dynamic: this reported that PSA velocity improved prediction slightly (from 0.81 to 0.83), but was subject to verification bias. No article used decision analytic methods to examine the clinical impact of PSA dynamics. Conclusion There is little evidence that calculation of PSA velocity or doubling time in untreated patients provides predictive information beyond that provided by absolute PSA level alone. We see no justification for the use of PSA dynamics in clinical decision making before treatment in early-stage prostate cancer.

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