Dataset Information

Randomized trial finds that prostate cancer genetic risk score feedback targets prostate-specific antigen screening among at-risk men.

ABSTRACT:

Background

Prostate-specific antigen (PSA) screening may reduce death due to prostate cancer but leads to the overdiagnosis of many cases of indolent cancer. Targeted use of PSA screening may reduce overdiagnosis. Multimarker genomic testing shows promise for risk assessment and could be used to target PSA screening.

Methods

To test whether counseling based on the family history (FH) and counseling based on a genetic risk score (GRS) plus FH would differentially affect subsequent PSA screening at 3 months (primary outcome), a randomized trial of FH versus GRS plus FH was conducted with 700 whites aged 40 to 49 years without prior PSA screening. Secondary outcomes included anxiety, recall, physician discussion at 3 months, and PSA screening at 3 years. Pictographs versus numeric presentations of genetic risk were also evaluated.

Results

At 3 months, no significant differences were observed in the rates of PSA screening between the FH arm (2.1%) and the GRS-FH arm (4.5% with GRS-FH vs. 2.1% with FH: χ² = 3.13, P = .077); however, PSA screening rates at 3 months significantly increased with given risk in the GRS-FH arm (P = .013). Similar results were observed for discussions with physicians at 3 months and PSA screening at 3 years. Average anxiety levels decreased after the individual cancer risk was provided (P = .0007), with no differences between groups. Visual presentation by pictographs did not significantly alter comprehension or anxiety.

Conclusions

This is likely the first randomized trial of multimarker genomic testing to report genomic targeting of cancer screening. This study found little evidence of concern about excess anxiety or overuse/underuse of PSA screening when multimarker genetic risks were provided to patients. Cancer 2016;122:3564-3575. © 2016 American Cancer Society.

SUBMITTER: Turner AR

PROVIDER: S-EPMC5247411 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Publications

Randomized trial finds that prostate cancer genetic risk score feedback targets prostate-specific antigen screening among at-risk men.

Turner Aubrey R AR Lane Brian R BR Rogers Dan D Lipkus Isaac I Weaver Kathryn K Danhauer Suzanne C SC Zhang Zheng Z Hsu Fang-Chi FC Noyes Sabrina L SL Adams Tamara T Toriello Helga H Monroe Thomas T McKanna Trudy T Young Tracey T Rodarmer Ryan R Kahnoski Richard J RJ Tourojman Mouafak M Kader A Karim AK Zheng S Lilly SL Baer William W Xu Jianfeng J

Cancer 20160719 22

<h4>Background</h4>Prostate-specific antigen (PSA) screening may reduce death due to prostate cancer but leads to the overdiagnosis of many cases of indolent cancer. Targeted use of PSA screening may reduce overdiagnosis. Multimarker genomic testing shows promise for risk assessment and could be used to target PSA screening.<h4>Methods</h4>To test whether counseling based on the family history (FH) and counseling based on a genetic risk score (GRS) plus FH would differentially affect subsequent ...[more]

PMID: 27433786

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Project description:BackgroundDespite higher risks associated with prostate cancer, young African American men are poorly represented in prostate-specific antigen (PSA) trials, which limits proper evidence-based guidance. We evaluated the impact of PSA screening, alongside primary care provider utilization, on prostate cancer outcomes for these patients.MethodsWe identified African American men aged 40-55 years, diagnosed with prostate cancer between 2004 and 2017 within the Veterans Health Administration. Inverse probability of treatment-weighted propensity scores were used in multivariable models to assess PSA screening on PSA levels higher than 20, Gleason score of 8 or higher, and metastatic disease at diagnosis. Lead-time adjusted Fine-Gray regression evaluated PSA screening on prostate cancer-specific mortality (PCSM), with noncancer death as competing events. All statistical tests were 2-sided.ResultsThe cohort included 4726 patients. Mean age was 51.8 years, with 84-month median follow-up. There were 1057 (22.4%) with no PSA screening prior to diagnosis. Compared with no screening, PSA screening was associated with statistically significantly reduced odds of PSA levels higher than 20 (odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.49 to 0.63; P < .001), Gleason score of 8 or higher (OR = 0.78, 95% CI = 0.69 to 0.88; P < .001), and metastatic disease at diagnosis (OR = 0.50, 95% CI = 0.39 to 0.64; P < .001), and decreased PCSM (subdistribution hazard ratio = 0.52, 95% CI = 0.36 to 0.76; P < .001). Primary care provider visits displayed similar effects.ConclusionsAmong young African American men diagnosed with prostate cancer, PSA screening was associated with statistically significantly lower risk of PSA levels higher than 20, Gleason score of 8 or higher, and metastatic disease at diagnosis and statistically significantly reduced risk of PCSM. However, the retrospective design limits precise estimation of screening effects. Prospective studies are needed to validate these findings.

Project description:ImportanceContinuing prostate-specific antigen (PSA) screening after age 70 years might benefit men at high risk of prostate cancer-specific mortality (PCSM) or metastatic prostate cancer (mPCa), but the relative value of clinical factors (race and ethnicity, competing mortality, and PSA history) in identifying men at higher vs lower risk is unknown.ObjectiveTo examine the value of PSA levels, race and ethnicity, and competing mortality in risk stratification for PCSM and mPCa in men after age 70 years.Design, setting, and participantsIn this cohort study, clinical data of all men receiving health care through the Veterans Health Administration who turned age 70 years between 2008 and 2020 and had a normal screening PSA value between age 65 and 69 years (<4 ng/mL [baseline PSA]) and no prior history of prostate cancer or biopsy were examined. The data cutoff date was December 26, 2023.ExposureThe most recent screening PSA value from age 65 to 69 years, self-reported race and ethnicity, and competing mortality risk derived from a machine learning model.Main outcome and measuresThe 10-year absolute risk of PCSM and mPCa were determined using regression modeling.ResultsThe cohort included 921 609 men who turned 70 years between 2008 and 2020; 11% of whom self-reported as Black and 82% as White race. Between age 65 and 70 years, 45% of patients had a baseline PSA of less than 1.00 ng/mL, and 32% had a baseline PSA of 1.00 to 1.99 ng/mL. Most patients (87%) continued to undergo screening past age 70 years, with little variation by competing mortality risk or race and ethnicity. The 10-year cumulative incidence of PCSM was 0.26% overall, and 95% of men had a 10-year risk less than 0.73%. Higher baseline PSA level between age 65 and 69 years was associated with 10-year PCSM risk (0.79% for 3.00-3.99 ng/mL vs 0.10% for 0.20-0.99 ng/mL), race and ethnicity (0.36% for Black vs 0.25% for White), and competing mortality (0.24% for the highest quintile vs 0.21% for the lowest quintile). Similar results were found for mPCa. Low PSA (0.20-0.99 ng/mL) was associated with very low PCSM and mPCa risk, even among Black men in the healthiest quintile of competing mortality risk (10-year PCSM risk, 0.08% [95% CI, 0.01%-0.44%]; 10-year mPCa risk 0.24% [95% CI, 0.10%-0.52%]).Conclusions and relevanceIn this cohort study, the findings suggest that most men receiving care through the VHA continue PSA screening after age 70 years despite low absolute 10-year PCSM risks. The PSA values from age 65 to 69 years may be highly informative for adverse prostate cancer outcomes after age 70 years, with a PSA less than 1 ng/mL associated with a very low risk of long-term PCSM and mPCa.

Project description:PurposeProstate specific antigen velocity is an unreliable predictor of adverse pathology findings in patients on active surveillance for low risk prostate cancer. However, to our knowledge a new concept called prostate specific antigen velocity risk count, recently validated in a screening cohort, has not been investigated in an active surveillance cohort.Materials and methodsWe evaluated a cohort of men from 1995 to 2012 with prostate cancer on active surveillance. They had stage T1c disease, prostate specific antigen density less than 0.15 ng/ml, Gleason score 6 or less, 2 or fewer biopsy cores and 50% or less involvement of any core with cancer. The men were observed by semiannual prostate specific antigen measurements, digital rectal examinations and an annual surveillance biopsy. Treatment was recommended for biopsy reclassification. Patients with 30 months or greater of followup and 3 serial prostate specific antigen velocity measurements were used in primary analysis by logistic regression, Cox proportional hazards, Kaplan-Meier analysis and performance parameters, including the AUC of the ROC curve.ResultsPrimary analysis included 275 of 668 men who met very low risk inclusion criteria, of whom 83 (30.2%) were reclassified at a median of 57.1 months. Reclassification risk increased with risk count, that is a risk count of 3 (HR 4.63, 95% CI 1.54-13.87) and 2 (HR 3.73, 95% CI 1.75-7.97) compared to zero. Results were similar for Gleason score reclassification (HR 7.45, 95% CI 1.60-34.71 and 3.96, 95% CI 1.35-11.62, respectively). On secondary analysis the negative predictive value (risk count 1 or less) was 91.5% for reclassification in the next year. Adding the prostate specific antigen velocity risk count improved the AUC in a model including baseline prostate specific antigen density (0.7423 vs 0.6818, p = 0.025) and it outperformed the addition of overall prostate specific antigen velocity (0.7423 vs 0.6960, p = 0.037).ConclusionsProstate specific antigen velocity risk count may be useful for monitoring patients on active surveillance and decreasing the frequency of biopsies needed in the long term.

Project description:ObjectivesTo investigate men's values and preferences regarding prostate-specific antigen (PSA)-based screening for prostate cancer.DesignSystematic review.Data sourcesWe searched MEDLINE, EMBASE, PsycINFO and grey literature up to 2 September 2017.Eligibility criteriaPrimary studies of men's values and preferences regarding the benefits and harms of PSA screening.Data extraction and synthesisTwo independent reviewers extracted data and assessed risk of bias with a modified version of a risk of bias tool for values and preferences studies, the International Patient Decision Aid Standards instrument V.3 and the Cochrane Collaboration risk of bias tool.ResultsWe identified 4172 unique citations, of which 11 studies proved eligible. Five studies investigated PSA screening using a direct choice study design, whereas six used decisions aids displaying patient-important outcomes. The direct choice studies used different methodologies and varied considerably in the reporting of outcomes. Two studies suggested that men were willing to forego screening with a small benefit in prostate cancer mortality if it would decrease the likelihood of unnecessary treatment or biopsies. In contrast, one study reported that men were willing to accept a substantial overdiagnosis to reduce their risk of prostate cancer mortality. Among the six studies involving decision aids, willingness to undergo screening varied substantially from 37% when displaying a hypothetical reduction in mortality of 10 per 1000 men, to 44% when displaying a reduction in mortality of 7 per 1000. We found no studies that specifically investigated whether values and preferences differed among men with family history, of African descent or with lower socioeconomic levels.ConclusionThe variability of men's values and preferences reflect that the decision to screen is highly preference sensitive. Our review highlights the need for shared decision making in men considering prostate cancer screening.Trial registration numberCRD42018095585.

Dataset Information

Randomized trial finds that prostate cancer genetic risk score feedback targets prostate-specific antigen screening among at-risk men.

Background

Methods

Results

Conclusions

Publications

Randomized trial finds that prostate cancer genetic risk score feedback targets prostate-specific antigen screening among at-risk men.

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