'Active Surveillance' for Low-risk Prostate Cancer
Abstract & Commentary
By William B. Ershler, MD, Editor
Synopsis: The management options for low-risk prostate cancer include "watchful waiting," or "active surveillance" prior to initiating disease specific treatment. To determine the rate at which patients who elect such an approach progress to the point at which directed therapy is warranted, Dall'Era and colleagues provide a retrospective analysis of the experience at their institution. Of the 321 patients for low-risk prostate cancer and "active surveillance," 33% met criteria for progression (rising PSA level or Gleason score) by 3 years of follow-up. Thus, for selected individuals with early disease, active surveillance remains a reasonable approach. However, data are still not available describing the effect of delayed initial therapy on disease-free and overall survival.
Source: Dall'Era MA, et al. Active surveillance for the management of prostate cancer in a contemporary cohort. Cancer. 2008;112:2664-2670.
Like just about all illnesses that occur later in life, prostate cancer demonstrates remarkable heterogeneity in clinical presentation. For those with histologically confirmed adenocarcinoma, certain features, such as PSA level below 10 ng/mL, Gleason score of ≤ 6, or a T1/T2a tumor mass predict low risk.1, 2 In recent years, the proportion of prostate cancer patients diagnosed at a "low risk" has increased to almost 50% of all incident cases.3 Although "watchful waiting" (also known as "active surveillance") is a reasonable approach for such patients, the past decade has seen a relative decrease in selection of that approach in deference to androgen deprivation or brachytherapy.4 These treatments, although effective, are not without side effects,5 and the question of whether early intervention is necessary for all those with low risk disease has been raised.
To address this Dall'Era and colleagues from the Department of Urology at the University of California at San Francisco report their experience in a contemporary cohort of men with prostate cancer who were managed with active surveillance.
All men who were managed initially with active surveillance were identified through the authors' institutional database. Selection criteria for active surveillance included: prostate-specific antigen (PSA) <10 ng/mL, biopsy Gleason sum ≤ 6 with no pattern 4 or 5, cancer involvement of <33% of biopsy cores, and clinical stage T1/T2a tumor. Patients were followed with PSA measurements and digital rectal examination every 3 to 6 months and with transrectal ultrasound at 6- to 12-month intervals. Beginning in 2003, patients also underwent repeat prostate biopsy at 12 to 24 months. The primary outcome measured was active treatment. Evidence of disease progression, defined as an increase Gleason sum or PSA velocity (>0.75 ng/mL per year), was a secondary outcome.
Three hundred twenty-one men (mean age [± standard deviation]: 63.4 ± 8.5 years) selected active surveillance as their initial management. The overall median follow-up was 3.6 years (range, 1-17 years). The initial mean PSA level was 6.5 ± 3.9 ng/mL. One hundred twenty men (37%) met at least 1 criterion for progression. Overall, 38% of men had higher grade on repeat biopsy, and 26% of men had a PSA velocity >0.75 ng/mL per year. Seventy-eight men (24%) received secondary treatment at a median 3 years (range, 1-17 years) after diagnosis. Approximately 13% of patients with no disease progression elected to obtain treatment. PSA density at diagnosis and rise in Gleason score on repeat biopsy were associated significantly with receipt of secondary treatment. The disease specific survival rate was 100%.
Thus, the authors concluded that selected individuals with early-stage prostate cancer may be candidates for active surveillance. Specific criteria should be developed to select the most appropriate individuals for this form of management and to monitor disease progression. A small attrition rate can be expected because of men who are unable or unwilling to tolerate surveillance.
Commentary
In this retrospective/observational analysis of selected "low-risk" patients, it is apparent that "active surveillance" in a structured way is a reasonable first management approach. With the rapid growth of the geriatric population and the implementation of aggressive screening strategies we are likely to observe increasing numbers of "low-risk" prostate cancers. If the findings from this study are generally applicable, somewhere around one-third of those who choose active surveillance will meet criteria for progression, either by a rising PSA or by increased Gleason score upon rebiopsy, and for these, directed management may be warranted.
There are, however, a number of concerns, many of which were articulated by the authors. First, this was a retrospective analysis of what might have been a highly-selected population. The approach would only be as reliable as the patient is compliant with the follow-up evaluations and the recognition by the medical practitioner of the necessity to maintain a schedule of office visits, imaging and laboratory studies. Furthermore, for some, the anxiety associated with the diagnosis may counter any benefit from waiting to initiate therapy. In the current study, for example, 13% of the patients elected to start a directed therapy (ie, discontinue the program of active surveillance) despite having no evidence for cancer progression. Also, in a European study, of 293 men eligible for active surveillance only 64 chose this approach.6
Finally, the current study is of insufficient size, duration, and design to address the question whether overall survival would be influenced by initial "active surveillance." It is encouraging that in this series that the disease free survival was 100% for the entire group, but we need to recall that these were low-risk patients and the median duration of follow-up was only 3.6 years. Hopefully, prospective studies, such as the European effort mentioned above,6 will give us further reassurance.
References
1. Albertsen PC, et al. Long-term survival among men with conservatively treated localized prostate cancer. JAMA. 1995;274(8):626-631.
2. Johansson JE, et al. Fifteen-year survival in prostate cancer. A prospective, population-based study in Sweden. JAMA. 1997;277(6):467-471.
3. Cooperberg MR, et al. The changing face of low-risk prostate cancer: trends in clinical presentation and primary management. J Clin Oncol. 2004;22(11):2141-2149.
4. Cooperberg MR, et al. Patterns of practice in the United States: insights from CaPSURE on prostate cancer management. Curr Urol Rep. 2004;5(3):166-172.
5. Litwin MS, et al. Quality of life after surgery, external beam irradiation, or brachytherapy for early-stage prostate cancer. Cancer. 2007;109(11):2239-2247.
6. Roemeling S, et al. Management and survival of screen-detected prostate cancer patients who might have been suitable for active surveillance. Eur Urol. 2006;50(3):475-482.
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