NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Ip S, Dahabreh IJ, Chung M, et al. An Evidence Review of Active Surveillance in Men With Localized Prostate Cancer. Rockville (MD): Agency for Healthcare Research and Quality (US); 2011 Dec. (Evidence Reports/Technology Assessments, No. 204.)

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

Cover of An Evidence Review of Active Surveillance in Men With Localized Prostate Cancer

An Evidence Review of Active Surveillance in Men With Localized Prostate Cancer.

Show details


Prostate cancer epidemiology is affected by population-level trends, such as the aging of the United States population, but also by changes in the application of screening and diagnostic technologies among the population at risk. Keeping these caveats in mind, studies indicate that men in all racial/ethnic groups experienced increases in prostate cancer incidence since the mid-1980s. The incidence rate appears to have peaked in early-1990s. For all groups, incidence rates declined between the early-1990s and 1999. Studies consistently demonstrated that early-stage (localized and regional) prostate cancer cases were responsible for the observed increase in prostate cancer incidence from the mid-1980s up to the mid-1990s. Studies also demonstrated decreases in the prostate cancer-specific mortality rate for all age groups between the early-1990s and 1999. Mean age of diagnosis has also decreased over time from 72.2 years (1988 to 1989) to 67.2 years (2004 to 2005) for both blacks and whites. Another consistent trend over time in studies using the SEER database has been the decrease in low (corresponding to Gleason scores 2–4) and high grade (corresponding to Gleason score ≥7) tumors, and a concomitant increase in intermediate grade tumors (Gleason 5–6). It has been hypothesized that this effect is caused by changes in histopathological grading guidelines,245 a preference towards avoiding assigning Gleason 2–4 scores based on prostate cancer biopsy samples99,246,247, and the ability of the PSA test to detect moderately differentiated tumors with higher accuracy (compared to poorly-differentiated tumors). Most studies demonstrated decreasing trends in the proportion of patients being managed with strategies other than RP or RT throughout their respective time periods. Studies explicitly reporting on AS/WW-type strategies indicated decreases in the proportion of patients receiving such treatments over time; this was true even for subgroups of men with “low-risk disease.”

There is not yet consistency among clinicians or researchers as to the definitions or standardizations of AS. Eligibility criteria for AS based on disease and patient characteristics and followup protocols including defining triggers for active interventions have not been standardized. This is apparent looking at the 16 unique cohorts with formal protocols for monitoring triggers for curative treatment of prostate cancer (AS cohorts). In all, a variety of observational management strategies was offered to men with low-risk or clinically localized prostate cancer although no uniform criteria were used to identify these men, with the exception that no cohorts enrolled patients with clinical stage greater than T2. The strategies included different combinations of periodic DRE, PSA testing, rebiopsy and/or imaging findings to determine different thresholds used for seeking definitive treatments. Additional information was provided by 13 unique cohorts of men who initially received no treatment and who were subsequently treated only for symptomatic progression (WW cohorts). About half of these WW cohorts were formed in the pre-PSA screening era, enrolled men with more advanced disease, and tended to use regular prostate acid phosphatase (PAP) testing in followup.

Because of the nonstandardized usages of the terms AS and WW coupled with the fact that the primary intents of the observational management strategies reviewed were frequently not reported, at times it was difficult when reviewing the studies to know who had AS and who had WW.

Only two studies specifically examined factors related to men who were enrolled in an active monitoring protocol with triggers for curative treatments. The first found that the free to total PSA ratio and T stage were independent predictors of time to radical treatments in patients on the protocol, while initial PSA, PSA density, Gleason score, number of positive cores, and prostate volume were not independent predictors. The second study found that men with decreased baseline anxiety and higher socioeconomic status were associated with decreased probability of willingness to consent to randomization for AS versus definitive treatment (i.e., these men did not take a chance and proactively selected AS). The rest of the heterogeneous studies reported on men who did not receive treatments or initial treatments. Therefore, whether they were on AS or WW could not be readily discerned. The following patient and clinical variables are potentially important in increasing the probability that a patient receives WW or AS: older age, presence of comorbidities, lower Gleason score, lower tumor stage, lower diagnostic PSA, lower risk groups, or decreased baseline anxiety. The following patient and clinical variables are potentially important in increasing the probability that a patient interrupts WW or AS to seek definitive treatments: younger age, higher tumor stage, higher diagnostic PSA, higher PSA velocity, higher risk groups, or increased anxiety.

As most of these tentative conclusions are drawn from multivariable analyses of large databases that did not specifically address the factors that affect the offer, acceptance, and adherence of AS, whether different treatment options were offered to the patients, whether they accepted those options, and whether they adhered to their initial choices could only be inferred from whether they received the treatments or not. In addition, retrospective studies (without a priori definitions of AS, eligibility criteria, or choice of variables of interest) could not provide adequate data for unbiased analyses, because patient characteristics are strongly associated with initial treatment choice.

No trial has published results on comparisons of AS with RP, or RT in men with localized diseases. One trial reported that men on RP had lower mortality than men on WW; one trial reported that there was no difference in mortality comparing men in RP with men in WW. Retrospective studies suggest that men on conservative management had a higher prostate cancer-specific mortality than men treated with RP. Men who had RP had more urinary complications than men on WW. Retrospective studies also reported that men treated with RT had lower mortality than men on WW. They also reported higher rates of urinary strictures in men treated with RT compared with men on WW. It should be noted that confounding is likely in many retrospective analyses of large databases. The following example is instructive in illustrating the potential for confounding bias in observational studies of treatment effectiveness. Giordano 2008248 replicated a previously published analysis208 comparing overall survival between men who received active treatment (RP or RT) with men who were on WW, and performed additional analyses on mortality from non-prostate-specific causes (e.g., heart disease, other cancers, and chronic obstructive pulmonary disease). The study confirmed that patients with prostate cancer who underwent RP had better survival than those on WW but also suggested that patients treated with RP had improved survival compared to a randomly selected control population without cancer (matched with the RP population on the distributions of year of diagnosis and age at diagnosis). Further analysis showed that the patients who underwent RP had significantly improved their survival for many non-prostate-specific causes of death (including diabetes-, cardiovascular disease-, and chronic obstructive pulmonary disease-related death) as well, compared to those who had observational management. Because these causes of death are unlikely to be affected by prostate surgery, but conditions related to them (for example chronic angina or low exercise tolerance) are in fact used by urologists to decide fitness for surgery, the results suggest that the findings of improved overall survival in the RP group compared to the WW group reported by the previous analysis may have been affected by residual confounding by covariates that were not measured or not controlled for in the analysis.

Definitive conclusions for men with low-risk disease on AS or WW versus RP or RT will have to await results from two ongoing trials: Prostate cancer Intervention Versus Observation Trial (PIVOT: observation vs. RPa) and Prostate Testing for Cancer and Treatment trial (ProtecT: AS vs. RP or RTb). PIVOT recruited 731 patients (364 randomized to RP, 367 to observation); initial results were presented in the 2011 American Urological Association annual meeting (,18082#). ProtecT has finished recruitment (>2500 men, about 700 men each were offered AS, RP, or RT) and is now in the followup phase.c A brief description of these studies is provided in Appendix Table B.

Although cost calculations using retrospective data were performed using different methods and followup durations in each study, overall it appears that WW is associated with lower treatment costs compared with active treatment. However, a cost analysis based on the ICER model indicates that with long-term followup, the costs of AS may exceed those of RP and BT; and may be lower than those of intensity modulated RT (IMRT) or proton beam RT.

Limitations in our approaches in this report largely concern the breadth of literature covered. For example, studies identified for the question on factors relevant to the practice of AS were primarily found from our literature search conducted specifically for AS, we did not do a general search on specific topics like insurance or patient compliance. Undoubtedly, there are studies on some of these factors in patients with other cancers and their findings could potentially be informative here.

In conclusion, more men are being diagnosed with early stage prostate cancer. Whether active monitoring with a curative intent is an appropriate option for these men remains unclear. A standard, universally agreed-upon definition of AS that clearly distinguishes it from WW and other observational management strategies is needed to help clarify scientific discourse in this field. Ongoing clinical trials may provide information on the comparative effectiveness of AS compared to immediate active treatment, but will require long term followup.



Available at; last accessed September 30, 2011.


Available at http:​//clinicaltrials​.gov/ct2/show/NCT00632983; last accessed September 30, 2011.



  • PubReader
  • Print View
  • Cite this Page
  • PDF version of this title (3.0M)

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...