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Treatment of local-regional prostate cancer detected by PSA screening: benefits and harms according to prognostic factors.

ABSTRACT: Men with screen-detected prostate cancer can choose to undergo immediate curative treatment or enter into an expectant management programme. We quantified how the benefits and harms of immediate treatment vary according to the prognostic factors of clinical T-stage, Gleason score, and patient age.A microsimulation model based on European Randomized Study of Screening for Prostate Cancer data was used to predict the benefits and harms of immediate treatment versus delayed treatment of local-regional prostate cancer in men aged 55-74 years. Benefits included life-years gained and reduced probability of death from prostate cancer. Harms included lead time and probability of overdiagnosis.The ratio of mean lead time to mean life-years gained ranged from 1.8 to 31.2, and the additional number of treatments required per prostate cancer death prevented ranged from 0.3 to 11.6 across the different prognostic groups. Both harm-benefit ratios were lowest, most favourable, for men aged 55-59 years and diagnosed with moderate-risk prostate cancer. Ratios were high for men aged 70-74 years regardless of clinical T-stage and Gleason score.Men aged 55-59 years with moderate-risk prostate cancer are predicted to derive greatest benefit from immediate curative treatment. Immediate treatment is least favourable for men aged 70-74 years with either low-risk or high-risk prostate cancer.

SUBMITTER: Wever EM

PROVIDER: S-EPMC3670486 | biostudies-other | 2013 May

REPOSITORIES: biostudies-other

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Project description:The U.S. Preventive Services Task Force recently concluded that the harms of existing prostate-specific antigen (PSA) screening strategies outweigh the benefits.To evaluate comparative effectiveness of alternative PSA screening strategies.Microsimulation model of prostate cancer incidence and mortality quantifying harms and lives saved for alternative PSA screening strategies.National and trial data on PSA growth, screening and biopsy patterns, incidence, treatment distributions, treatment efficacy, and mortality.A contemporary cohort of U.S. men.Lifetime.Societal.35 screening strategies that vary by start and stop ages, screening intervals, and thresholds for biopsy referral.PSA tests, false-positive test results, cancer detected, overdiagnoses, prostate cancer deaths, lives saved, and months of life saved.Without screening, the risk for prostate cancer death is 2.86%. A reference strategy that screens men aged 50 to 74 years annually with a PSA threshold for biopsy referral of 4 µg/L reduces the risk for prostate cancer death to 2.15%, with risk for overdiagnosis of 3.3%. A strategy that uses higher PSA thresholds for biopsy referral in older men achieves a similar risk for prostate cancer death (2.23%) but reduces the risk for overdiagnosis to 2.3%. A strategy that screens biennially with longer screening intervals for men with low PSA levels achieves similar risks for prostate cancer death (2.27%) and overdiagnosis (2.4%), but reduces total tests by 59% and false-positive results by 50%.Varying incidence inputs or reducing the survival improvement due to screening did not change conclusions.The model is a simplification of the natural history of prostate cancer, and improvement in survival due to screening is uncertain.Compared with standard screening, PSA screening strategies that use higher thresholds for biopsy referral for older men and that screen men with low PSA levels less frequently can reduce harms while preserving lives.National Cancer Institute and Centers for Disease Control and Prevention.

Project description:Context and objectiveStandards for clinical practice guidelines require explicit statements regarding how values and preferences influence recommendations. However, no cancer screening guideline has addressed the key question of what magnitude of benefit people require to undergo screening, given its harms and burdens. This article describes the development of a new method for guideline developers to address this key question in the absence of high-quality evidence from published literature.Summary of methodThe new method was developed and applied in the context of a recent BMJ Rapid Recommendation clinical practice guideline for colorectal cancer (CRC) screening. First, we presented the guideline panel with harms and burdens (derived from a systematic review) associated with the CRC screening tests under consideration. Second, each panel member completed surveys documenting their views of expected benefits on CRC incidence and mortality that people would require to accept the harms and burdens of screening. Third, the panel discussed results of the surveys and agreed on thresholds for benefits at which the majority of people would choose screening. During these three steps, the panel had no access to the actual benefits of the screening tests. In step four, the panel was presented with screening test benefits derived from a systematic review of clinical trials and microsimulation modelling. The thresholds derived through steps one to three were applied to these benefits, and directly informed the panel's recommendations.ConclusionWe present the development and application of a new, four-step method enabling incorporation of explicit and transparent judgements of values and preferences in a screening guideline. Guideline panels should establish their view regarding the magnitude of required benefit, given burdens and harms, before they review screening benefits and make their recommendations accordingly. Making informed screening decisions requires transparency in values and preferences judgements that our new method greatly facilitates.

Project description:Lung cancer is the leading cause of cancer death. Most patients are diagnosed with advanced disease, resulting in a very low 5-year survival. Screening may reduce the risk of death from lung cancer.To conduct a systematic review of the evidence regarding the benefits and harms of lung cancer screening using low-dose computed tomography (LDCT). A multisociety collaborative initiative (involving the American Cancer Society, American College of Chest Physicians, American Society of Clinical Oncology, and National Comprehensive Cancer Network) was undertaken to create the foundation for development of an evidence-based clinical guideline.MEDLINE (Ovid: January 1996 to April 2012), EMBASE (Ovid: January 1996 to April 2012), and the Cochrane Library (April 2012).Of 591 citations identified and reviewed, 8 randomized trials and 13 cohort studies of LDCT screening met criteria for inclusion. Primary outcomes were lung cancer mortality and all-cause mortality, and secondary outcomes included nodule detection, invasive procedures, follow-up tests, and smoking cessation.Critical appraisal using predefined criteria was conducted on individual studies and the overall body of evidence. Differences in data extracted by reviewers were adjudicated by consensus.Three randomized studies provided evidence on the effect of LDCT screening on lung cancer mortality, of which the National Lung Screening Trial was the most informative, demonstrating that among 53,454 participants enrolled, screening resulted in significantly fewer lung cancer deaths (356 vs 443 deaths; lung cancer?specific mortality, 274 vs 309 events per 100,000 person-years for LDCT and control groups, respectively; relative risk, 0.80; 95% CI, 0.73-0.93; absolute risk reduction, 0.33%; P = .004). The other 2 smaller studies showed no such benefit. In terms of potential harms of LDCT screening, across all trials and cohorts, approximately 20% of individuals in each round of screening had positive results requiring some degree of follow-up, while approximately 1% had lung cancer. There was marked heterogeneity in this finding and in the frequency of follow-up investigations, biopsies, and percentage of surgical procedures performed in patients with benign lesions. Major complications in those with benign conditions were rare.Low-dose computed tomography screening may benefit individuals at an increased risk for lung cancer, but uncertainty exists about the potential harms of screening and the generalizability of results.

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Treatment of local-regional prostate cancer detected by PSA screening: benefits and harms according to prognostic factors.

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