Prostate cancer is an important cause of death in males. After lung cancer it is the second most important cause of cancer-related death in American males [1]. With the introduction of prostate-specific antigen (PSA) in the late 1980s, a screening tool became available that has been proven to detect prostate cancers earlier in the course of the disease [2]. One of the downsides of screening is a frequent diagnosis of low-risk cancers that would not have been detected during the man’s lifetime in the absence of screening (ie, overdiagnosis). As screening becomes globally more prevalent, the side effects such as overdiagnosis will increase as well. It can be calculated that, if all US men with PSA levels ≥2.5 ng/ml would be biopsied, 775,000 cancers would be diagnosed, which is 542,910 more than the estimated 232,090 cases to be diagnosed in 2005 in the United States and 25.6 times more than the 30,350 men expected to die of the disease [3]. A large proportion of these men will have insignificant cancers. Although men with these cancers are likely to die as a result of other causes, the majority of them are currently treated [4].
Active surveillance focuses on men for whom therapy is delayed until the tumor becomes progressive and curative treatment can be offered. It is distinct from watchful waiting as described in currently used guidelines in that the former has a curative intent [5]. Although several studies have examined the role of watchful waiting prior to the widespread use of PSA [6], [7], [8], the natural course of screen-detected prostate cancer is less well-known [9], [10]. Screen-detected prostate cancer differs from clinically diagnosed cancer. This is among other factors caused by lead- and length-time sampling bias.
Arguments to elect active surveillance include quality-of-life issues, costs associated with treatment, and ethical aspects. Little is known about the quality of life regarding active surveillance strategies. The SPCG-4 study has shown that the assignment of patients to watchful waiting or radical prostatectomy entails different risks of erectile dysfunction, urinary leakage, and urinary obstruction, but that, on average, the choice has little if any influence on well-being or the subjective quality of life after a mean follow-up of 4 yr [11]. Another argument is the costs of treatment. Although no literature is available, it seems obvious that active surveillance is less expensive than immediate treatment. The most important argument for active surveillance is probably an ethical argument: Our profession needs to decide what it considers an acceptable number of patients who need to be treated to prevent one prostate cancer death [12]. If any, the number of life-years gained will be small because of the fact that prostate cancer is a disease of older age. The potential benefit should be contrasted to the side effects of all applied treatments [13], [14].
To investigate the natural course of prostate cancers detected by screening, this report describes the baseline characteristics, PSA kinetics, deferred treatment, and outcome of all men diagnosed with prostate cancer within the first, second, and partial third screen rounds of the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam, who were initially managed with active surveillance.
The ERSPC was designed to study the feasibility of population-based screening for prostate cancer and its effect on prostate cancer mortality. Therefore, by the end of 2002, 183,000 men were randomized in eight European countries starting in 1993 [15]. In the Netherlands alone, 42,376 men were randomized to the screen (n = 21,210) or the control arm (n = 21,166) from June 1993 through December 1999. Men in the screening arm were enrolled in a screening program with a 4-yr interval. From start until
From 1993 through 1999, 21,210 men were randomized to the screen arm of the Rotterdam section of the ERSPC. During the first round of screening, 1078 men were diagnosed with prostate cancer (Fig. 1). Of those, 106 men (9.8%) elected active surveillance. In the second screening round, 550 prostate cancers were detected, and 134 (24.4%) of the men elected active surveillance. In the incomplete third round, 144 prostate cancers have been diagnosed, and 38 men (26.4%) have elected active
Of men diagnosed at the prevalence (ie, first) screening of the ERSPC screening program, 10.2% were safely managed by active surveillance: During the median follow-up of 6 yr, 18.1% had died, all of intercurrent diseases. Men diagnosed at repeated screening had more beneficial characteristics and were more likely to elect active surveillance. The latter is the result of an ongoing stage and grade shift, but is likely to be influenced by a time trend as well. Active surveillance has become a
Active surveillance plays an important role in the management of men with screen-detected prostate cancer detected within our screening program. Men detected at repeated screening are more likely to be on active surveillance. The cause-specific survival of our cohort was 100% at 5 yr. Although the exact value of PSA doubling time as a predictor of prostate cancer death needs to be established for untreated screen-detected men, an important proportion of men have prolonged PSA doubling times or
The authors have nothing to disclose. Prostate-specific antigen (PSA) screening occurs at an alarming rate among men who will gain no benefit from the diagnosis or treatment of prostate cancer [1]. It has been estimated that 30–50% of men diagnosed with prostate cancer today by PSA testing would otherwise have not known they had cancer during life in the absence of screening (ie, overdiagnosis) [2], [3]. Yet, >90% of Editorial Comment
The ERSPC is supported by grants from the Dutch Cancer Society, the Netherlands Organization for Health Research and Development, the European Union, and a grant from Beckman Coulter Hybritech Inc, San Diego, CA, USA.
This study received Erasmus MC and Ministry of Health institutional review board approval.
In the Scandinavian trial comparing radical prostatectomy to watchful waiting (without the option of definitive intervention), there was no difference in psychological functioning, anxiety, or depression between the two groups [39]. Nine prospective studies of AS have included about 10 000 men [38,40–48]. The largest most mature studies are summarized in Table 3.
