A randomized trial of early detection of clinically significant prostate cancer (ProScreen): study design and rationale

Abstract

The current evidence of PSA-based prostate cancer screening shows a reduction in cause-specific mortality, but with substantial overdiagnosis. Recently, new developments in detection of clinically relevant prostate cancer include multiple kallikreins as biomarkers besides PSA, and multiparametric magnetic resonance imaging (mpMRI) for biopsy decision. They offer opportunities for improving the outcomes in screening, particularly reduction in overdiagnosis and higher specificity for potentially lethal cancer. A population-based randomized screening trial will be started, with 67,000 men aged 55-67 years at entry. A quarter of the men will be allocated to the intervention arm, and invited to screening. The control arm will receive no intervention. All men in the screening arm will be offered a serum PSA determination. Those with PSA of 3 ng/ml or higher will have an additional multi-kallikrein panel and those with indications of increased risk of clinically relevant prostate cancer will undergo mpMRI. Men with a malignancy-suspect finding in MRI are referred to targeted biopsies. Screening interval is 6 years for men with baseline PSA < 1.5 ng/ml, 4 years with PSA 1.5-3.0 and 2 years if initial PSA > 3. The main outcome of the trial is prostate cancer mortality, with analysis at 10 and 15 years. The statistical power is sufficient for detecting a 28% reduction at 10 years and 22% at 15 years. The proposed study has the potential to provide the evidence to justify screening as a public health policy if mortality benefit can be sustained with substantially reduced overdiagnosis.

Tamización poblacional para la detección temprana del cáncer de próstata: ¿Qué hemos aprendido en los últimos 10 años?

“…Tras la estrategia de búsqueda primaria se obtuvo un total de 23 referencias de las cuales se excluyeron 9 por no aportar datos relevantes para el objetivo del presente artículo. Se incluyen en la revisión los resultados de 14 referencias seleccionadas [5,6,[9][10][11][12][13][14][15][16][17][18][19]24].…”

“…Dadas las limitaciones y riesgos descritos de las estrategias para el cribado del CaP con PSA (sobrediagnóstico, diagnóstico de enfermedad indolente, complicaciones por diagnóstico y tratamiento de cáncer en estadio indolente entre otras), un grupo de investigadores en Finlandia diseño el estudio "ProScreen" 24 ; en este estudio intentarán reclutar 67000 hombres de entre 55 y 67 años aleatorizados 1:3 entre tamización vs grupo control. Los autores pretenden disminuir la tasa de detección de cáncer indolente con el cribado basado en PSA, para tal fin a los pacientes con PSA > 3 ng/ml les ejecutaran secuencialmente la prueba de 4 calicreínas y si ese resultado es positivo, ejecutarán resonancia multiparamétrica de próstata.…”

Prostate cancer screening: what can we learn from randomised trials?

“…Kallikrein panels such as Prostate Health Index (PHI) and 4Kscore and magnetic resonance imaging (MRI) hold promise for improving this ( 46 , 47 ), but their impact remains to be evaluated in randomised trials. One is on-going in Sweden and another being launched in Finland ( 48 ).…”

Screening for prostate cancer: are organized screening programs necessary?

“…This so-called STHLM3 MRI phase 2 study is almost completed and will include 9,000 men ( 45 ). In Finland a population-based randomized screening trial will be started, with 67,000 men aged 55–67 years at entry ( 46 ). A quarter of the men will be allocated to the intervention arm, have their PSA measured and in case of a PSA >3.0 ng/mL be tested with the so-called 4K test ( 47 ).…”