Overdiagnosis and overtreatment of early detected prostate cancer

Early detection of prostate cancer is associated with the diagnosis of a considerable proportion of cancers that are indolent, and that will hardly ever become symptomatic during lifetime. Such overdiagnosis should be avoided in all forms of screening because of potential adverse psychological and somatic side effects. The main threat of overdiagnosis is overtreatment of indolent disease. Men with prostate cancer that is likely to be indolent may be offered active surveillance. Evaluation of active surveillance studies and validation of new biological parameters for risk assessment are expected

Gastrin-releasing peptide receptor-based targeting using bombesin analogues is superior to metabolism-based targeting using choline for in vivo imaging of human prostate cancer xenografts

Purpose: Prostate cancer (PC) is a major health problem. Overexpression of the gastrin-releasing peptide receptor (GRPR) in PC, but not in the hyperplastic prostate, provides a promising target for staging and monitoring of PC. Based on the assumption that cancer cells have increased metabolic activity, metabolism-based tracers are also being used for PC imaging. We compared GRPR-based targeting using the68Ga-labelled bombesin analogue AMBA with metabolism-based tar

Prostate-specific antigen testing accuracy in community practice

BACKGROUND: Most data on prostate-specific antigen (PSA) testing come from urologic cohorts comprised of volunteers for screening programs. We evaluated the diagnostic accuracy of PSA testing for detecting prostate cancer in community practice. METHODS: PSA testing results were compared with a reference standard of prostate biopsy. Subjects were 2,620 men 40 years and older undergoing (PSA) testing and biopsy from 1/1/95 through 12/31/98 in the Albuquerque, New Mexico metropolitan area. Diagnostic measures included the area under the receiver-operating characteristic curve, sensitivity, specificity, and likelihood ratios. RESULTS: Cancer was detected in 930 subjects (35%). The area under the ROC curve was 0.67 and the PSA cutpoint of 4 ng/ml had a sensitivity of 86% and a specificity of 33%. The likelihood ratio for a positive test (LR+) was 1.28 and 0.42 for a negative test (LR-). PSA testing was most sensitive (90%) but least specific (27%) in older men. Age-specific reference ranges improved specificity in older men (49%) but decreased sensitivity (70%), with an LR+ of 1.38. Lowering the PSA cutpoint to 2 ng/ml resulted in a sensitivity of 95%, a specificity of 20%, and an LR+ of 1.19. CONCLUSIONS: PSA testing had fair discriminating power for detecting prostate cancer in community practice. The PSA cutpoint of 4 ng/ml was sensitive but relatively non-specific and associated likelihood ratios only moderately revised probabilities for cancer. Using age-specific reference ranges and a PSA cutpoint below 4 ng/ml improved test specificity and sensitivity, respectively, but did not improve the overall accuracy of PSA testing

Active surveillance for prostate cancer: a narrative review of clinical guidelines

In the past decade active surveillance (AS) of men with localized prostate cancer has become an increasingly popular management option, and a range of clinical guidelines have been published on this topic. Existing guidelines regarding AS for prostate cancer vary widely, but predominantly state that the most suitable patients for AS are those with pretreatment clinical stage T1c or T2 tumours, serum PSA levels <10 ng/ml, biopsy Gleason scores of 6 or less, a maximum of one or two tumour-positive biopsy core samples and/or a maximum of 50% of cancer per core sample. Following initiation of an AS programme, most guidelines recommend serial serum PSA measurements, digital rectal examinations and surveillance biopsies to check for and identify pathological indications of tumour progression. Definitions of disease reclassification and progression differ among guidelines and multiple criteria for initiation of definitive treatment are proposed. The variety of descriptions of criteria for clinically insignificant prostate cancer indicates a lack of consensus on optimal AS and intervention thresholds. A single set of guidelines are needed in order to reduce variations in clinical practice and to optimize clinical decision-making. To enable truly evidence-based guidelines, further research that combines existing evidence, while also gathering information from more long-term studies is needed.This study is linked to a larger project, the Movember Foundation's Global Action Plan on active surveillance for low-risk prostate cancer (GAP3), which is collaboration between institutions, hospitals and research centres in Australia, Canada, France, Finland, Italy, Japan, Netherlands, UK and the USA. The Movember Foundation has invested €1,664,950 in the GAP3 project in order to create the largest centralized database on AS in men with prostate cancer to date, comprising around 40% of all global patient data on AS. The funder did not play any role in the study design, collection, analysis or interpretation of data, or in the drafting of this paper

The Movember Foundation's GAP3 cohort: a profile of the largest global prostate cancer active surveillance database to date

OBJECTIVES: The Movember Foundation launched the Global Action Plan Prostate Cancer Active Surveillance (GAP3) initiative to create a global consensus on the selection and monitoring of men with low‐risk prostate cancer (PCa) on active surveillance (AS). The aim of this study is to present data on inclusion and follow‐up for AS in this unique global AS database. PATIENTS AND METHODS: Between 2014 and 2016, the database was created by combining patient data from 25 established AS cohorts worldwide (USA, Canada, Australasia, UK and Europe). Data on a total of 15 101 patients were included. Descriptive statistics were used to report patients' clinical and demographic characteristics at the time of PCa diagnosis, clinical follow‐up, discontinuation of AS and subsequent treatment. Cumulative incidence curves were used to report discontinuation rates over time. RESULTS: At diagnosis, the median (interquartile range [IQR]) patient age was 65 (60–70) years and the median prostate‐specific antigen level was 5.4 (4.0–7.3) ng/mL. Most patients had clinical stage T1 disease (71.8%), a biopsy Gleason score of 6 (88.8%) and one tumour‐positive biopsy core (60.3%). Patients on AS had a median follow‐up time of 2.2 (1.0–5.0) years. After 5, 10 and 15 years of follow‐up, respectively, 58%, 39% and 23% of patients were still on AS. The current version of GAP3 has limited data on magnetic resonance imaging (MRI), quality of life and genomic testing. CONCLUSIONS: GAP3 is the largest worldwide collaboration integrating patient data from men with PCa on AS. The results will allow individual patients and clinicians to have greater confidence in the personalized decision to either delay or proceed with active treatment. Longer follow‐up and the evaluation of MRI, new genomic markers and patient‐related outcomes will result in even more valuable data and eventually in better patient outcomes