Dataset Information

Variation in serum prostate-specific antigen levels in men with prostate cancer managed with active surveillance.

ABSTRACT:

Objective

To describe fluctuations in prostate-specific antigen (PSA) levels in men managed with active surveillance (AS) to determine if a single PSA increase is a consistent measure to use to trigger intervention.

Patients and methods

We evaluated data on 541 patients undergoing AS between 1995 and 2011. PSA variation was described by studying the Kaplan-Meier probability of patients' PSA levels reaching 4 or 7 ng/mL, falling below those thresholds, and then rising to those thresholds again. We also examined PSA variation by calculating the Kaplan-Meier probability of a PSA change followed by an equal or greater change in the opposite direction.

Results

We analysed data on 541 patients undergoing AS with a median (interquartile range [IQR]) of 8 (6-12) PSA measurements and undergoing AS for a median (IQR) of 4 (2-6) years. The 5-year estimate of the probability of reaching a threshold PSA of 7 ng/mL was 40% (95% confidence interval [CI] 35-46%) and the 5-year estimate of subsequently falling below this threshold was 90% (95% CI 82-95%). The 5-year estimate of a PSA direction change was 95% (95% CI 93-97%) overall and 56% (95% CI 51-61%) for PSA direction changes of ≥1 ng/mL.

Conclusions

We observed a high probability of variability in PSA levels for patients on AS. The probability of changes in PSA, defined by an increase to the specified thresholds or a rise >1 ng/mL within 6 months and subsequent decrease of equal or greater value on a subsequent measurement, increases over time; therefore, a single change in PSA level is not a reliable endpoint for patients on AS.

SUBMITTER: Ehdaie B

PROVIDER: S-EPMC5523832 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Publications

Variation in serum prostate-specific antigen levels in men with prostate cancer managed with active surveillance.

Ehdaie Behfar B Poon Bing Ying BY Sjoberg Daniel D DD Recabal Pedro P Laudone Vincent V Touijer Karim K Eastham James J Scardino Peter T PT

BJU international 20151026 4

<h4>Objective</h4>To describe fluctuations in prostate-specific antigen (PSA) levels in men managed with active surveillance (AS) to determine if a single PSA increase is a consistent measure to use to trigger intervention.<h4>Patients and methods</h4>We evaluated data on 541 patients undergoing AS between 1995 and 2011. PSA variation was described by studying the Kaplan-Meier probability of patients' PSA levels reaching 4 or 7 ng/mL, falling below those thresholds, and then rising to those thre ...[more]

PMID: 26385021

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Project description:BackgroundFor men on active surveillance for prostate cancer, utility of prostate-specific antigen (PSA) kinetics (PSAk) in predicting pathologic reclassification remains controversial.ObjectiveTo develop prediction methods for utilizing serial PSA and evaluate frequency of collection.Design, setting, and participantsData were collected from men enrolled in the multicenter Canary Prostate Active Surveillance Study, for whom PSA data were measured and biopsies performed on prespecified schedules. We developed a PSAk parameter based on a linear mixed-effect model (LMEM) that accounted for serial PSA levels.Outcome measurements and statistical analysisThe association of diagnostic PSA and/or PSAk with time to reclassification (increase in cancer grade and/or volume) was evaluated using multivariable Cox proportional hazards models.Results and limitationsA total of 851 men met the study criteria; 255 (30%) had a reclassification event within 5 yr. Median follow-up was 3.7 yr. After adjusting for prostate size, time since diagnosis, biopsy parameters, and diagnostic PSA, PSAk was a significant predictor of reclassification (hazard ratio for each 0.10 increase in PSAk=1.6 [95% confidence interval 1.2-2.1, p<0.001]). The PSAk model improved stratification of risk prediction for the top and bottom deciles of risk over a model without PSAk. Model performance was essentially identical using PSA data measured every 6 mo to those measured every 3 mo. The major limitation is the reliability of reclassification as an end point, although it drives most treatment decisions.ConclusionsPSAk calculated using an LMEM statistically significantly predicts biopsy reclassification. Models that use repeat PSA measurements outperform a model incorporating only diagnostic PSA. Model performance is similar using PSA assessed every 3 or 6 mo. If validated, these results should inform optimal incorporation of PSA trends into active surveillance protocols and risk calculators.Patient summaryIn this report, we looked at whether repeat prostate-specific antigen (PSA) measurements, or PSA kinetics, improve prediction of biopsy outcomes in men using active surveillance to manage localized prostate cancer. We found that in a large multicenter active surveillance cohort, PSA kinetics improves the prediction of surveillance biopsy outcome.

Project description:BackgroundMelanoma and prostate cancer may share risk factors. This study examined the association between serum PSA levels, which is a risk factor for prostate cancer, and variants in some melanoma-associated pigmentary genes.MethodsWe studied participants, all aged 70+ years, in the Concord Health and Ageing in Men Project who had no history of prostatitis or received treatment for prostate disease (n = 1033). We genotyped variants in MC1R (rs1805007, rs1805008), ASIP (rs4911414, rs1015362), SLC45A2 (rs28777, rs16891982), IRF4 (rs12203592), TYRP1 (rs1408799), TYR (rs1126809, rs1042602), SLC24A2 (rs12896399), and OCA2 (rs7495174). Generalised linear dominant models with Poisson distribution, log link functions and robust variance estimators estimated adjusted percentage differences (%PSA) in mean serum PSA levels (ng/mL) between variant and wildtype (0%PSA = reference) genotypes, adjusting for age, body mass index, serum 25OHD levels and birth regions (Australia or New Zealand (ANZ), Europe or elsewhere).ResultsSerum PSA levels were strongly associated with advancing age and birth regions: mean PSA levels were lower in Europe-born (-29.7%) and elsewhere-born (-11.7%) men than ANZ-born men (reference). Lower %PSA was observed in men with variants in SLC45A2: rs28777 (-19.6;95%CI: -33.5, -2.7), rs16891982 (-17.3;95%CI:-30.4,-1.7) than in wildtype men (reference). There were significant interactions between birth regions and PSA levels in men with variants in MC1R (rs1805007; p-interaction = 0.0001) and ASIP (rs4911414; p-interaction = 0.007). For these genes %PSA was greater in ANZ-born men and lower in Europe- and elsewhere-born men with the variant than it was in wildtype men. In a post hoc analysis, serum testosterone levels were increased in men with MC1R rs1805007 and serum dihydrotestosterone in men with ASIP rs1015362.ConclusionMen with SNPs in SLC45A2, who have less sun sensitive skin, have lower PSA levels. Men with SNPs in MC1R and ASIP, who have more sun sensitive skin, and were born in ANZ, have higher PSA levels. Androgens may modify these apparent associations of pigmentary genes and sun exposure with PSA levels.ImpactPSA levels and possibly prostate cancer risk may vary with sun sensitivity and sun exposure, the effects of which might be modified by androgen levels.

Dataset Information

Variation in serum prostate-specific antigen levels in men with prostate cancer managed with active surveillance.

Objective

Patients and methods

Results

Conclusions

Publications

Variation in serum prostate-specific antigen levels in men with prostate cancer managed with active surveillance.

Similar Datasets

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