Clinical outcomes in men with prostate cancer who selected active surveillance using a clinical cell cycle risk score.
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ABSTRACT:
SUBMITTER: Kaul S
PROVIDER: S-EPMC7447833 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
Publications
Clinical outcomes in men with prostate cancer who selected active surveillance using a clinical cell cycle risk score.
Kaul Sanjeev S Wojno Kirk J KJ Stone Steven S Evans Brent B Bernhisel Ryan R Meek Stephanie S D'Anna Richard E RE Ferguson Jeffrey J Glaser Jeffrey J Morgan Todd M TM Lieb Jeremy J Yan Robert R Cohen Todd T Ehdaie Behfar B
Personalized medicine 20190904 6
<b>Aim:</b> To evaluate active surveillance (AS) selection, safety and durability among men with low-risk prostate cancer assessed using the clinical cell cycle risk (CCR) score, a combined clinical and molecular score. <b>Patients & methods:</b> Initial treatment selection (AS vs treatment) and duration of AS were evaluated for men with low-risk prostate cancer according to the CCR score and National Comprehensive Cancer Network guidelines. Adverse events included biochemical recurrence and met ...[more]
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Project description:Initial management of intermediate-risk prostate cancer is evolving, with no clear recommendation for treatment. Data on utilization of active surveillance for patients with newly diagnosed intermediate-risk prostate cancer may help clarify emerging trends. To further characterize US national trends of initial management of intermediate-risk prostate cancer. This cohort study included patients with intermediate-risk prostate cancer diagnosed from January 1, 2010, to December 31, 2020. Eligible patients were diagnosed in US hospitals included in the National Cancer Database; National Comprehensive Cancer Network risk stratification guidelines were used to characterize as favorable vs unfavorable intermediate risk. Analysis was performed in September 2023. Active surveillance vs intervention with surgery and/or radiation or no treatment. Temporal trends in demographic, clinical, and socioeconomic factors among men with intermediate-risk prostate cancer and their association with the use of active surveillance; further subgroup analysis was conducted for those with favorable vs unfavorable intermediate risk classification. In total, 289 584 men diagnosed with intermediate-risk prostate cancer were identified from 2010 to 2020 (46 147 Black [15.9%], 230 071 White [79.5%]). Among patients, 153 726 (53.1%) underwent prostatectomy, 107 152 (37.0%) underwent radiotherapy, and 15 847 (5.5%) underwent active surveillance as initial treatment strategy. Overall, active surveillance quadrupled from 418 of 21 457 patients (2.0%) in 2010 to 2428 of 28 192 patients (8.6%) in 2020 for the entire cohort (P < .001). Active surveillance increased from 317 of 12 858 patients (2.4%) in 2010 to 2020 of 12 902 patients (13.5%) in 2020 in men with favorable intermediate-risk prostate cancer (P < .001). In the unfavorable intermediate-risk cohort, active surveillance increased from 101 of 8181 patients (1.2%) in 2010 to 408 of 12 861 patients (3.1%) in 2020 (P < .001). On multivariable analysis, use of active surveillance was associated with increased age (age 70-80 years vs <50 years: odds ratio [OR], 3.09; 95% CI, 2.66-3.59), lower Gleason score (3 + 3 vs 3 + 4: OR, 3.45; 95% CI, 3.25-3.66), early T stage (T2c vs T1a through T2a: OR, 0.35; 95% CI, 0.32-0.38), treatment at an academic center (community vs academic center: OR, 0.72; 95% CI, 0.67-0.78), higher level of education (communities with 21% or higher population without high school vs less than 7%: OR, 0.73; 95% CI, 0.67-0.79), insurance type (Medicare or other governmental service vs private: OR, 1.11; 95% CI, 1.07-1.16), proximity to treatment facility (greater than 120 miles vs less than 60 miles: OR, 0.75; 95% CI, 0.68-0.84), facility location (South Atlantic vs New England: OR, 0.54; 95% CI, 0.46-0.53), and lower income (less than $38 000 vs $63 000 or greater: OR, 1.22; 95% CI, 1.14-1.31). These findings highlight increasing implementation of active surveillance in the initial management of intermediate risk prostate cancer. Prospective data with improved risk stratification incorporating genomics and digital pathology artificial intelligence as well as novel surveillance strategies may continue to better delineate optimal treatment recommendations in this patient population.
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Project description:Active surveillance (AS) is standard of care for patients with low-risk prostate cancer (PCa), but its feasibility in intermediate-risk patients is controversial. We compared outcomes of low- and intermediate-risk patients managed with multiparametric magnetic resonance imaging (mpMRI)-supported AS in a community hospital. Of the 433 patients enrolled in AS between 2009 and 2016, 358 complied with AS inclusion criteria (Cancer of the Prostate Risk Assessment (CAPRA) score ≤ 5, Gleason grade group (GGG) ≤ 2, clinical stage ≤ cT2 and prostate-specific antigen (PSA) ≤ 20 ng/ml) and discontinuation criteria (histological-, PSA-, clinical- or radiological disease reclassification). Of the 358 patients, 177 (49%) were low-risk and 181 (51%) were intermediate-risk. Median follow-up was 4.2 years. The estimated 5-year treatment-free survival (TFS) was 56% (95% confidence interval [CI] 51-62%). Intermediate-risk patients had significantly shorter TFS compared with low-risk patients (hazard ratio 2.01, 95% CI 1.47-2.76, p < 0.001). There were no statistically significant differences in the rate of adverse pathology, biochemical recurrence-free survival and overall survival between low- and intermediate-risk patients. Two patients developed metastatic disease and three died of PCa. These results suggest that selected patients with intermediate-risk PCa may be safely managed by mpMRI-supported AS, but longer follow-up is necessary.
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Project description:Clinical trials play a critical role in evidence-based medicine, when rigorous scientific methodology is utilized to discover and test the effectiveness and safety of new drugs to prevent or cure diseases, including cancer. Participation in clinical trials thus becomes key to successful completion of these trials. Although it is estimated that >70% of Americans are inclined to participate in clinical trials, less than 5% of adult cancer patients participate in clinical trials. There is thus a large gap between those inclined to participate in clinical trials and actual participation in clinical trials. As with trials targeting men with prostate cancer (PCa) on active surveillance (AS), where the target population is mostly over 50 years of age, others have observed several challenges with recruitment and accrual in clinical trials. The participation rate is currently unavailable for men on primary and secondary chemoprevention trials. Additionally, with unanticipated environmental factors such as a pandemic or other natural emergencies that may severely impact the economy, personal property, travel and person-to person contact for study-related procedures, there is a need to continuously identify these challenges and determine solutions to recruitment barriers in chemoprevention trials to ensure timely completion of early phase trials. Recent studies regarding the impact of the pandemic on clinical trial recruitment have shown that cancer prevention trials were relatively more negatively impacted compared to cancer treatment trials. The goal of this manuscript is to review our experience in continuously evaluating the protocol and patient level challenges to recruiting subjects on AS for PCa in this cancer chemoprevention trial conducted at the Comprehensive Cancer Center (CCC) and report the contemporary strategies that we are utilizing to continue to recruit subjects in this trial. We provide data from our current trial as an example while discussing future strategies to improve overall clinical trial recruitment. These strategies can inform future design of contemporary cancer chemoprevention trials and, additionally, better select, focus and invest in strategies that are the most productive and efficient for recruiting target populations.
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Project description:We assessed the effect of age, health status and patient preferences on outcomes of surgery vs active surveillance for low risk prostate cancer.We used Monte Carlo simulation of Markov models of the life courses of 200,000 men diagnosed with low risk prostate cancer and treated with surveillance or radical prostatectomy to calculate quality adjusted life expectancy, life expectancy, prostate cancer specific mortality and years of treatment side effects, with model parameters derived from the literature. We simulated outcomes for men 50 to 75 years old with poor, average or excellent health status (50%, 100% and 150% of average life expectancy, respectively). Sensitivity of outcomes to uncertainties in model parameters was tested.For 65-year-old men in average health, surgery resulted in 0.3 additional years of life expectancy, 1.6 additional years of impotence or incontinence and a 4.9% decrease in prostate cancer specific mortality compared to surveillance, for a net difference of 0.05 fewer quality adjusted life years. Increased age and poorer baseline health status favored surveillance. With greater than 95% probability, surveillance resulted in net benefits compared to surgery for age older than 74, 67 and 54 years for men in excellent, average and poor health, respectively. Patient preferences toward life under surveillance, biochemical recurrence of disease, treatment side effects and future discount rate affected optimal management choice.Older men and men in poor health are likely to have better quality adjusted life expectancy with active surveillance. However, specific individual preferences impact optimal choices and should be a primary consideration in shared decision making.
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Project description:BackgroundA combined clinical cell-cycle risk (CCR) score that incorporates prognostic molecular and clinical information has been recently developed and validated to improve prostate cancer mortality (PCM) risk stratification over clinical features alone. As clinical features are currently used to select men for active surveillance (AS), we developed and validated a CCR score threshold to improve the identification of men with low-risk disease who are appropriate for AS.MethodsThe score threshold was selected based on the 90th percentile of CCR scores among men who might typically be considered for AS based on NCCN low/favorable-intermediate risk criteria (CCR = 0.8). The threshold was validated using 10-year PCM in an unselected, conservatively managed cohort and in the subset of the same cohort after excluding men with high-risk features. The clinical effect was evaluated in a contemporary clinical cohort.ResultsIn the unselected validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.7%, and the threshold significantly dichotomized low- and high-risk disease (P = 1.2 × 10-5). After excluding high-risk men from the validation cohort, men with CCR scores below the threshold had a predicted mean 10-year PCM of 2.3%, and the threshold significantly dichotomized low- and high-risk disease (P = 0.020). There were no prostate cancer-specific deaths in men with CCR scores below the threshold in either analysis. The proportion of men in the clinical testing cohort identified as candidates for AS was substantially higher using the threshold (68.8%) compared to clinicopathologic features alone (42.6%), while mean 10-year predicted PCM risks remained essentially identical (1.9% vs. 2.0%, respectively).ConclusionsThe CCR score threshold appropriately dichotomized patients into low- and high-risk groups for 10-year PCM, and may enable more appropriate selection of patients for AS.
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Project description:In the United States, 192,000 men were diagnosed as having prostate cancer in 2009, the majority with low-risk, clinically localized disease. Treatment of these cancers is associated with substantial morbidity. Active surveillance is an alternative to initial treatment, but long-term outcomes and effect on quality of life have not been well characterized.To examine the quality-of-life benefits and risks of active surveillance compared with initial treatment for men with low-risk, clinically localized prostate cancer.Decision analysis using a simulation model was performed: men were treated at diagnosis with brachytherapy, intensity-modulated radiation therapy (IMRT), or radical prostatectomy or followed up by active surveillance (a strategy of close monitoring of newly diagnosed patients with serial prostate-specific antigen measurements, digital rectal examinations, and biopsies, with treatment at disease progression or patient choice). Probabilities and utilities were derived from previous studies and literature review. In the base case, the relative risk of prostate cancer-specific death for initial treatment vs active surveillance was assumed to be 0.83. Men incurred short- and long-term adverse effects of treatment.Hypothetical cohorts of 65-year-old men newly diagnosed as having clinically localized, low-risk prostate cancer (prostate-specific antigen level <10 ng/mL, stage ?T2a disease, and Gleason score ?6).Quality-adjusted life expectancy (QALE).Active surveillance was associated with the greatest QALE (11.07 quality-adjusted life-years [QALYs]), followed by brachytherapy (10.57 QALYs), IMRT (10.51 QALYs), and radical prostatectomy (10.23 QALYs). Active surveillance remained associated with the highest QALE even if the relative risk of prostate cancer-specific death for initial treatment vs active surveillance was as low as 0.6. However, the QALE gains and the optimal strategy were highly dependent on individual preferences for living under active surveillance and for having been treated.Under a wide range of assumptions, for a 65-year-old man, active surveillance is a reasonable approach to low-risk prostate cancer based on QALE compared with initial treatment. However, individual preferences play a central role in the decision whether to treat or to pursue active surveillance.
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Project description:ObjectiveActive surveillance (AS) is an increasingly utilized strategy for monitoring men with low-risk prostate cancer (PCa) that allows them to defer active treatment (AT) in the absence of cancer progression. Studies have explored reasons for selecting AS and for then switching to AT, but less is known about men's experiences being on AS. We interviewed men to determine the clinical and psychological factors associated with selecting and adhering to AS protocols.MethodsWe conducted semi-structured interviews with men with a low-risk PCa at two academic medical centers. Subjects had either been on AS for ? 1 year or had opted for AT after a period of AS. We used an iterative, content-driven approach to analyze the interviews and to identify themes.ResultsWe enrolled 21 subjects, mean age 70.4 years, 3 racial/ethnic minorities, and 16 still on AS. Men recognized the favorable prognosis of their cancer (some had sought second opinions when initially offered AT), valued avoiding treatment complications, were reassured that close monitoring would identify progression early enough to be successfully treated, and trusted their urologists. Although men reported feeling anxious around the time of surveillance testing, those who switched to AT did so based only on evidence of cancer progression.ConclusionsOur selected sample was comfortable being on AS because they understood and valued the rationale for this approach. However, this highlights the importance of ensuring that men newly diagnosed with a low-risk PCa are provided sufficient information about prognosis and treatment options to make informed decisions.
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Project description:For patients with low-risk prostate cancer (PCa), active surveillance (AS) may produce oncologic outcomes comparable to those achieved with radical prostatectomy (RP). Health-related quality-of-life (HRQoL) outcomes are important to consider, yet few studies have examined HRQoL among patients with PCa who were managed with AS. In this study, the authors compared longitudinal HRQoL in a prospective, racially diverse, and contemporary cohort of patients who underwent RP or AS for low-risk PCa.Beginning in 2007, HRQoL data from validated questionnaires (the Expanded Prostate Cancer Index Composite and the 36-item RAND Medical Outcomes Study short-form survey) were collected by the Center for Prostate Disease Research in a multicenter national database. Patients aged ?75 years who were diagnosed with low-risk PCa and elected RP or AS for initial disease management were followed for 3 years. Mean scores were estimated using generalized estimating equations adjusting for baseline HRQoL, demographic characteristics, and clinical patient characteristics.Of the patients with low-risk PCa, 228 underwent RP, and 77 underwent AS. Multivariable analysis revealed that patients in the RP group had significantly worse sexual function, sexual bother, and urinary function at all time points compared with patients in the AS group. Differences in mental health between groups were below the threshold for clinical significance at 1 year.In this study, no differences in mental health outcomes were observed, but urinary and sexual HRQoL were worse for patients who underwent RP compared with those who underwent AS for up to 3 years. These data offer support for the management of low-risk PCa with AS as a means for postponing the morbidity associated with RP without concomitant declines in mental health.
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Project description:BackgroundProstate cancer (PCa) is characterized by its tendency to be multifocal. However, few studies have investigated the endogenous factors that explain the multifocal disease. The primary objective of the current study is to test whether inherited PCa risk is associated with multifocal tumors in PCa patients.MethodsSubjects in this study were PCa patients of European ancestry undergoing active surveillance at Johns Hopkins Hospital (N = 805) and NorthShore University HealthSystem (N = 432). The inherited risk was measured by genetic risk score (GRS), an odds ratio-weighted and population-standardized polygenic risk score based on known risk-associated single nucleotide polymorphisms. PCa multifocality was indirectly measured by the number and laterality of positive tumor cores from a 12-core systematic biopsy.ResultsIn the combined cohort, 35.7% and 66.3% of patients had ≥2 tumor cores at the initial diagnostic biopsy and on at least one subsequent surveillance biopsy, respectively. For tumor laterality, 7.8% and 47.8% of patients had bilateral tumor cores at diagnostic and surveillance biopsies, respectively. We found, for the first time, that patients with higher numbers of positive cores at diagnostic and surveillance biopsies, respectively, had significantly higher mean GRS values; p = .01 and p = 5.94E-04. Additionally, patients with bilateral tumors at diagnostic and surveillance biopsies, respectively, had significantly higher mean GRS values than those with unilateral tumors; p = .04 and p = .01. In contrast, no association was found between GRS and maximum core length of tumor or tumor grade at diagnostic/surveillance biopsies (all p > .05). Finally, we observed a modest trend that patients with higher GRS quartiles had a higher risk for tumor upgrading on surveillance biopsies. The trend, however, was not statistically significant (p > .05).ConclusionsThe associations of GRS with two measurements of PCa multifocality (core numbers and laterality) provide novel and consistent evidence for the link between inherited PCa risk and multifocal tumors.
| S-EPMC8827243 | biostudies-literature
Project description:BackgroundTo assess the utility of urinary prostate cancer antigen 3 (PCA3) as both a one-time and longitudinal measure in men on active surveillance (AS).MethodsThe Johns Hopkins AS program monitors men with favorable-risk prostate cancer with serial PSA, digital rectal examination (DRE), prostate magnetic resonance imaging and prostate biopsy. Since 2007, post-DRE urinary specimens have also been routinely obtained. Men with multiple PCA3 measures obtained over ⩾3 years of monitoring were included. Utility of first PCA3 score (fPCA3), subsequent PCA3 (sPCA3) and change in PCA3 were assessed for prediction of Gleason grade reclassification (GR, Gleason score >6) during follow-up.ResultsIn total, 260 men met study criteria. Median time from enrollment to fPCA3 was 2 years (interquartile range (IQR) 1-3) and from fPCA3 to sPCA3 was 5 years (IQR 4-6). During median follow-up of 6 years (IQR 5-8), 28 men (11%) underwent GR. Men with GR had higher median fPCA3 (48.0 vs 24.5, P=0.007) and sPCA3 (63.5 vs 36.0, P=0.002) than those without GR, while longitudinal change in PCA3 did not differ by GR status (log-normalized rate 0.07 vs 0.06, P=0.53). In a multivariable model including age, risk classification and PSA density, fPCA3 remained significantly associated with GR (log(fPCA3) odds ratio=1.77, P=0.04).ConclusionsPCA3 scores obtained during AS were higher in men who underwent GR, but the rate of change in PCA3 over time did not differ by GR status. PCA3 was a significant predictor of GR in a multivariable model including conventional risk factors, suggesting that PCA3 provides incremental prognostic information in the AS setting.
| S-EPMC5555773 | biostudies-literature