Absolute Effect of Prostate Cancer Screening: Balance of Benefits and Harms by Center within the European Randomized Study of Prostate Cancer Screening

Abstract

Purpose The balance of benefits and harms in prostate cancer screening has not been sufficiently characterized. We related indicators of mortality reduction and overdetection by center within the European Randomized Study of Prostate Cancer Screening. Experimental Design We analyzed the absolute mortality reduction expressed as number needed to invite (NNI=1/absolute risk reduction; indicating how many men had to be randomized to screening arm to avert a prostate cancer death) for screening and the absolute excess of prostate cancer detection as number needed for overdetection (NNO=1/absolute excess incidence; indicating the number of men invited per additional prostate cancer case), and compared their relationship across the seven ERSPC centers. Results Both absolute mortality reduction (NNI) and absolute overdetection (NNO) varied widely between the centers: NNI 200-7000 and NNO 16-69. Extent of overdiagnosis and mortality reduction were closely associated (correlation coefficient r=0.76, weighted linear regression coefficient β=33, 95% 5-62, R2=0.72). For an averted prostate cancer death at 13 years of follow-up, 12-36 excess cases had to be detected in various centers. Conclusions The differences between the ERSPC centers likely reflect variations in prostate cancer incidence and mortality, as well as in screening protocol and performance. The strong interrelation between the benefits and harms suggests that efforts to maximize the mortality effect are bound to increase overdiagnosis, and might be improved by focusing on high-risk populations. The optimal balance between screening intensity and risk of overdiagnosis remains unclear.

Patients’ perceptions of the negative effects following different prostate cancer treatments and the impact on psychological well-being: a nationwide survey

“…An on-going debate exists regarding how and whether to actively treat patients with early-stage prostate cancer (Denberg et al , 2006; Bul et al , 2013; Wever et al , 2013; Carter et al , 2015; Klotz et al , 2015). A related discussion concerns the appropriateness of population PSA screening for prostate cancer (van Leeuwen et al , 2013; Schröder et al , 2014; Auvinen et al , 2016). …”

“…Many men with localised prostate cancer do not benefit from definitive treatment (European Association of Urology Prostate Cancer Guidelines), and not all early local or locoregional prostate cancers require active treatment (Bul et al , 2013; Wever et al , 2013; Carter et al , 2015). In addition, the harms and benefits of population PSA screening are currently widely discussed (Auvinen et al , 2016). Screening with PSA detects some early prostate cancers that would never cause significant clinical problems during a man's lifetime.…”

Mutational load of the mitochondrial genome predicts pathological features and biochemical recurrence in prostate cancer

“…Currently, elevated serum prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE) are used as the rationale for a needle biopsy and histopathological diagnosis and Gleason scoring, which is a grading system based on prostate gland histological architecture and used for prognosis [4,5]. Although the only biomarker in routine clinical use, PSA testing has led to over-diagnosis and overtreatment with no definitive mortality benefit [6,7]. Ultimately, the effective treatment of prostate cancer requires novel molecular biomarkers that provide early detection of lethal disease associated with metastasis, while appropriate detection of indolent disease is required to prevent overtreatment and, in turn, improve patient quality of life [8].…”

What's new in screening in 2015?

“…[17] This was confirmed by analyses on the entire ERSPC where it was found that the number needed to invite (NNI) and a novel metric – the number needed to overdiagnose (NNO) to prevent one PC death – varied greatly between ERSPC centers mainly due to differences in background risk and screening protocols; NNI varied between 200 to 7,000 and NNO between 16 to 69. [18] Further, the previously found reduction of metastatic PC both at diagnosis and during follow-up[19] was confirmed and was found to precede the reduction in PC mortality by about 3 years. [20]…”